text stringlengths 8 5.77M |
|---|
Namespace myapp
#Import "<std>"
#Import "<mojo>"
#Import "<mojo3d>"
'uncomment this to create a mojo3d scene file in monkey2 dir!
'#Reflect mojo3d
#Import "assets/duck.gltf/@/duck.gltf"
Using std..
Using mojo..
Using mojo3d..
Class MyWindow Extends Window
Field _scene:Scene
Method New( title:String="Simple mojo app",width:Int=640,height:Int=480,flags:WindowFlags=WindowFlags.Resizable )
Super.New( title,width,height,flags )
CreateScene()
End
Method CreateGround()
Local box:=New Boxf( -50,-1,-50,50,0,50 )
Local material:=New PbrMaterial( Color.Green,0,1 )
Local model:=Model.CreateBox( box,1,1,1,material )
model.CastsShadow=False
End
Method CreateDucks()
Local duck:=Model.Load( "asset::duck.gltf/Duck.gltf" )
duck.Mesh.FitVertices( New Boxf( -1,1 ) )
Local root:=duck.Copy()
root.Move( 0,10,0 )
root.Scale=New Vec3f( 3 )
root.AddComponent<RotateBehaviour>().Speed=New Vec3f( 0,-.01,0 )
For Local m:=0.0 To 1.0 Step .125
For Local i:=0.0 Until 360.0 Step 24
Local copy:=duck.Copy( root )
copy.RotateY( i )
copy.Move( 0,0,6+m*16 )
copy.Scale=New Vec3f( 1 )
Local materials:=copy.Materials.Slice( 0 )
For Local j:=0 Until materials.Length
Local material:=Cast<PbrMaterial>( materials[j].Copy() )
material.MetalnessFactor=m
material.RoughnessFactor=i/360.0
materials[j]=material
Next
copy.Materials=materials
Next
Next
duck.Destroy()
End
Method CreateScene()
'create scene
'
_scene=New Scene( True )
'for softer shadows
'
_scene.ShadowAlpha=.6
'create camera
'
Local camera:=New Camera( Self )
camera.AddComponent<FlyBehaviour>()
camera.Move( 0,15,-20 )
'create light
'
Local light:=New Light
light.CastsShadow=True
light.Rotate( 90,0,0 )
CreateGround()
CreateDucks()
If _scene.Editable _scene.Save( "ducks-scene.mojo3d","modules/mojo3d/tests/assets/" ) ; _scene=Scene.Load( "ducks-scene.mojo3d" )
End
Method OnRender( canvas:Canvas ) Override
RequestRender()
_scene.Update()
_scene.Render( canvas )
canvas.DrawText( "FPS="+App.FPS,Width,0,1,0 )
End
End
Function Main()
New AppInstance
New MyWindow
App.Run()
End
|
Transmissible cancers in an evolutionary context.
Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers. |
defmodule GroupherServer.Repo.Migrations.CreatePinedPosts do
use Ecto.Migration
def change do
create table(:pined_posts) do
add(:post_id, references(:cms_posts, on_delete: :delete_all), null: false)
add(:community_id, references(:communities, on_delete: :delete_all), null: false)
add(:topic_id, references(:topics, on_delete: :delete_all), null: false)
timestamps()
end
create(unique_index(:pined_posts, [:post_id, :community_id, :topic_id]))
end
end
|
[Role of intestinal lymphatic pathway in pathogenesis of intestine-derived bacteria/endotoxin translocation in rats in shock].
To observe the changes of toxic substances in mesenteric lymph and portal vein blood of rats in hemorrhagic shock, and the influence of mesenteric lymph duct ligation on level of endotoxin (ET) in organs and bacterial contents in mesenteric lymph nodes (MLN) and spleen in rats with hemorrhagic shock, and to evaluate the role of lymphatic pathway in pathogenesis of intestine-derived bacteria/endotoxin translocation (BET) in rats with shock. Twenty-four male Wistar rats were randomly divided into the shock group and control group. A model of serious hemorrhagic shock was reproduced by blood shedding to maintain the blood pressure at 40 mm Hg (1 mm Hg=0.133 kPa) for 90 minutes under aseptic condition, and MLN and portal vein blood were harvested. The specimens were also obtained in control group. The contents of ET, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined in them. Thirty male Wistar rats were randomly divided into the sham operation group, shock group and lymphatic duct ligation group. Mesenteric lymph ducts were ligated after resuscitation. All rats were sacrificed, and lung, liver, heart and kidney were removed and homogenized for determination of the content of ET. MLN and spleen homogenates were subjected to bacterial culture. The contents of ET, TNF-alpha and IL-6 in lymph were significantly higher than those of plasma in shock group, and also higher than that in normal plasma and normal lymph (all P<0.01). In shock group the contents of ET in lung, liver, heart and renal homogenate 3 and 6 hours after transfusion and resuscitation were significantly higher than those of sham operation group and ligation group (P<0.05 or P<0.01). Bacterial culture of MLN and spleen in shock group rats 3 and 6 hours after transfusion and resuscitation was positive, but it was not in ligation group. The results demonstrate that the intestinal lymphatic pathway plays an important role after compromise of gut barrier function in carrying out BET after hemorrhagic shock. |
Why Use Sunscreen?
Why use sunscreen? As a strong advocate of sun protection, I always include sunscreen as part of my patient education in the field of aesthetics especially amongst people who wanted to get rid of their sun spots, dark spots, melasma, or other related aesthetic issues. While lasers and IPL therapies can help address sun spots, they cannot prevent reoccurrence; thus I can’t stress enough sunscreen and other sun protection measures. The pathogenesis of melasma is not clearly understood; while it can be traced to genetics and hormones, sun exposure triggers overproduction of melanocytes, the cells responsible for melanin. There are many resources available on the internet when it comes to sunscreens and sun protections; there are differing opinions as to which offers the best form of protection thus I felt compelled to share my opinion. As always, my point of view should not replace your doctor’s. Do your research and settle for the one that conforms to your lifestyle.
Is it true that the higher the SPF, the more protected you are? No. The American Academy of Dermatology recommends at least SPF 30 which blocks about 97% of UV rays. There is no proof that higher SPFs can block 100% of UV rays or that you can stay out longer. The single most important thing to remember about sunscreen is REAPPLICATION every two hours (if staying out longer in the sun) or each time you get wet or sweaty.
What’s the difference between UVA and UVB? UVA (aging rays) has the longest wavelength and can penetrate the skin’s deeper layer. It contributes to photo damage (premature wrinkling), aging and immediate tanning. UVB (burning rays) has medium wavelength and is the main culprit to sunburn. Both UV rays contribute to melanoma or skin cancer.
I work in the office, do I still need to apply sunscreen? Yes. UV rays penetrate glass and windows. While some can filter UVB, you are still exposed to UVA rays. You drive going to the office, you walk going to the office, all these things contribute to sun exposure.
My makeup has SPF 20, do I still need to apply sunscreen? Yes. Unless you apply a dollop of makeup or 1 oz (shot glass) to exposed areas which is the recommendation to get adequate protection, then by all means you need to apply a separate sunscreen.
What kind of sunscreen should I use? cream, lotion, spray, stick? If you have dry skin, use cream-based. For oily and combination, use lotion. For small areas such as around the eyes, use stick. Personally, I avoid spray type because it is hard to configure whether you have applied enough. Sunscreen should be broad spectrum so you can get protection from both UVA and UVB.
How much sunscreen should I apply? The most common mistake people do is under-application, meaning we apply less than the standard recommendation. For my face, I do apply a dollop and for all other exposed body areas, at least an ounce or equivalent to one shot glass.
Which is better, physical sunscreen or chemical sunscreen? Physical sunscreen (zinc oxide, titanium dioxide) blocks the UV rays. There is no need to wait for 15 minutes before going out. However, it is deemed to be not cosmetically appealing because it’s harder to blend and leaves a white cast. Chemical sunscreen absorb UV rays which prevents it from penetrating the skin. It typically combines ingredients such as avobenzone, oxybenzone, octinoxate, octisalate to maintain its stability. The ingredients in chemical sunscreen are generally safe although there have been reported incidence of irritation (including myself). Bottomline, it all boils down to personal preference.
So what’s my favorite sunscreen to-date? Hands down, those physical sunscreens from eltaMD. I prefer the tinted version UV Elements SPF 44 because it has titanium dioxide and zinc oxide plus sodium hyaluronate for hydration. I use the sheer version SPF 45 for my neck, ears and other exposed body areas. Don’t forget your lips, currently I am loving Lather’s unscented lip balm which has broad spectrum SPF 15.
After reading your post the other day about eltaMD sunscreen, I ordered a sample last night to go along with the Mirabella mascara I ordered. Eager to try it out. My question and problem is how to reapply sunscreen on top of my makeup? I usually use a cream sunscreen (Coola, Exuviance, Marini, for example), and I apply my makeup on top of that. What to do when it's time to reapply my sunscreen? What do you do that doesn't smear or ruin your foundation etc?
Thanks Allison! Good question. When I know that I am spending longer time out, I skip foundation and just wear tinted sunscreen so it is easy to reapply. I lightly set it with a powder using a fan brush so it does not look cakey, that way it is also to reapply.
Love hearing about these Elta MD products! What's your take on the UV Clear Broad Spectrum SPF 46? I've gone through more bottles of it than I can count, but lately have had some concerns and might switch. Firstly, the stuff isn't designed to last all day, so I'm unsure if I'm reapplying it enough. Second, I'm concerned about the niacinamide in it interacting with vit c. Thoughts?
Thanks for your questions. Are you reapplying it every 2 hours? That's how sunscreens are. Use a dollop too, I am very generous in application because most common mistake is under application. As for the interaction, I know there are several anecdotal resources on the internet that say you can't mix it. Unfortunately there are very limited clinical studies in the realm of skincare. I use Vitamin C and another eltaMD sunscreen w/o niacinamide in it, you may want to explore that
Well the vit c/b info is a bit confusing right now, so maybe it is best to separate them. I usually just reapply sunscreen around lunch when I'm indoors all day. It doesn't seem like enough, but reapplying every 1-2 hrs from dawn til dusk is gonna be a tough lifestyle adjustment. I'm confident that I apply enough- 1 pump of the spf 46 is ~a teaspoon. It's easy to reapply something like colorscience powder every hour, but it's usually not a full application. Maybe I need to peruse some of the light as air Japanese sunscreens. There are way worse problems to have- thx for the advice!
Reapplication every 2 hrs is when you're staying out longer in the sun or whenever you get wet or sweaty. Yes, you can space out Vit C and Niacinamide. In the morning, I apply Vit C and eltaMD Barrier Complex, have coffee (I spend 30 mins looking over emails, etc) then prepare to get ready for work. That's when I apply sunscreen |
Q:
Accessing views of other element of ListView from some element
I have a ListView whose each element is a custom layout. The layout consist of two frames: first one is just a TextView, second one is a LinearLayout consist of two images. What I am trying to do is, if i click an element of ListView, if the LinearLayout is "gone", it gets "visible" and TextView gets disable. If LinearLayout is "visible", it gets "gone" and TextView gets disable. Here is my following code:
Code:
ListView lvw = (ListView) layout.findViewById(R.id.formats);
formatAdapter adapter = new formatAdapter(act, arr); //act is context and arr is an array of String
lvw.setAdapter(adapter);
lvw.setOnItemClickListener(new OnItemClickListener() {
@Override
public void onItemClick(AdapterView<?> arg0, View arg1,
int arg2, long arg3) {
TextView tev = (TextView) arg1
.findViewById(R.id.formatN);
LinearLayout extraB = (LinearLayout) arg1
.findViewById(R.id.extraButtons);
if (extraB.getVisibility() == View.GONE) {
extraB.setVisibility(View.VISIBLE);
tev.setEnabled(false);
} else {
extraB.setVisibility(View.GONE);
tev.setEnabled(true);
}
}
});
formatAdapter.java
public class formatAdapter extends BaseAdapter {
LayoutInflater Inflater;
Context con;
String[] names;
public formatAdapter(Context c, String[] s) {
con = c;
names = s;
Inflater = (LayoutInflater) con
.getSystemService(Context.LAYOUT_INFLATER_SERVICE);
}
@Override
public int getCount() {
return names.length;
}
@Override
public Object getItem(int arg0) {
return null;
}
@Override
public long getItemId(int arg0) {
return 0;
}
@Override
public View getView(int arg0, View arg1, ViewGroup arg2) {
View v1 = arg1;
v1 = Inflater.inflate(R.layout.adapter_formats, null);
TextView tv = (TextView) v1.findViewById(R.id.formatN);
tv.setText(names[arg0]);
return v1;
}
}
adapter_formats.xml
<?xml version="1.0" encoding="utf-8"?>
<FrameLayout xmlns:android="http://schemas.android.com/apk/res/android"
android:layout_width="match_parent"
android:layout_height="match_parent" >
<TextView
android:id="@+id/formatN"
android:layout_width="fill_parent"
android:layout_height="wrap_content"
android:padding="10dp" />
<LinearLayout
android:id="@+id/extraButtons"
android:layout_width="wrap_content"
android:layout_height="wrap_content"
android:layout_gravity="center_horizontal"
android:orientation="horizontal"
android:visibility="gone">
<ImageView
android:id="@+id/play"
android:layout_width="wrap_content"
android:layout_height="wrap_content"
android:contentDescription="@string/cD"
android:src="@drawable/img_29" />
<View
android:layout_width="50dp"
android:layout_height="0dp"
android:contentDescription="@string/cD" />
<ImageView
android:id="@+id/download"
android:layout_width="wrap_content"
android:layout_height="wrap_content"
android:src="@drawable/img_31" />
</LinearLayout>
</FrameLayout>
Now, I want that if for any element, the LinearLayout is visible, and if I click on some other element, that elements LinearLayout gets gone and TextView gets enable(default layout). Let me explain with example: If I cliked the first element, its LinearLayout gets visible. I want that if I click on 2nd element, the linear layout of first element gets gone automatically. I tried to explain well but sorry if I was unable to explain good. Can anyone help me with this?
A:
Just found a way to do this and I feel awesome :) though this way is not genuine :P
To hide the views of other lists, I took a view globally in my class and initialize it to null(the view is same class which I want to hide, for example, here I want to make the linear layout of previous list element to gone, so i took a global linear layout). Then inside each onItemClickListener, I put the following code at beginning:
if(myGlobalView!=null)
{
myGlobalView.hide();
}
Also, when I make the view of other list element visible, I assign that view to my global view by following code:
myGlobalView = myCurrentView;
Hope it help other people :)
|
Christian churches and churches of Christ
The group of Christians known as the Christian Churches or Churches of Christ are congregations within the Restoration Movement (also known as the Stone-Campbell Movement and the Reformation of the 19th Century) that have no formal denominational affiliation with other congregations, but still share many characteristics of belief and worship. Churches in this tradition are strongly congregationalist and have no formal denominational ties, and thus there is no proper name that is agreed to apply to the movement as a whole. Most (but not all) congregations in this tradition include the words "Christian Church" or "Church of Christ" in their congregational name. Due to the lack of formal organization between congregations, there is a lack of official statistical data, but the 2016 Directory of the Ministry documents some 5000 congregations in the USA and Canada; some estimate the number to be over 6,000 since this directory is unofficial.
These congregations share historical roots with other, similarly named congregations within the Restoration Movement, including congregations organized within formal fellowships, such as the "Christian Church (Disciples of Christ)" or the "Churches of Christ". The congregations discussed in this article, however, have chosen to remain fully autonomous. Further distinguishing these congregations is their use of instrumental music within their worship, unlike the "Churches of Christ" who do not use instrumental music. The instrumental congregations discussed here and the a cappella "Churches of Christ" are otherwise very similar but have little contact with each other in most communities, although there is some cooperation among some larger churches and also in some educational institutions.
Congregational nomenclature
The churches are independent congregations and typically go by the name "Christian Church", but often use the name "church of Christ" as well. Though isolated exceptions may occur, it is generally agreed within the movement that no personal or family names should be attached to a congregation which Christ purchased and established with his own blood, though geographical labels are acceptable. Thus, it is common for a congregation to be known as "[City Name] Christian Church," but in some areas they may be known as "[The/First] Christian Church [of/at] [City, Community, or Other Location Name]." In recent history, individual congregations have made the decision to change their formal name to break with traditional nomenclature and to adopt more generic names like "Christ's Church [of/at] [City Name]", "[City Name] Community Christian Church", or "[City Name] Community Fellowship". The tendency in Restoration churches to choose names such as "Christian Church" and "Church of Christ" can cause difficulties in identifying the affiliation (if any) of an individual church based solely on its name. Furthermore, it is not uncommon for churches outside of the Restoration Movement to use similar names (see Church of Christ (disambiguation)).
Separation from the Disciples of Christ
The separation of the independent Christian churches and churches of Christ from the Christian Church (Disciples of Christ) (DoC) occurred over an extended period of time. The roots of the separation date back to a polarization that occurred during the early twentieth century as the result of three significant controversies. These controversies surrounded theological modernism, the impact of the ecumenical movement, and open membership (recognizing as full members individuals who had not been baptized by immersion).
The Disciples of Christ were, in 1910, a united, growing community with common goals Support by the United Christian Missionary Society of missionaries who advocated open membership became a source of contention in 1920. Efforts to recall support for these missionaries failed in a 1925 convention in Oklahoma City and a 1926 convention in Memphis, Tennessee. Many congregations withdrew from the missionary society as a result.
A new convention, the North American Christian Convention, was organized by the more conservative congregations in 1927. An existing brotherhood journal, the Christian Standard, also served as a source of cohesion for these congregations. From the 1960s on, newer unaffiliated missionary organizations like the Christian Missionary Fellowship (today, Christian Missionary Fellowship International) were working more on a national scale to rally Christian Church/Church of Christ congregations in international missions. By this time the division between liberals and conservatives was well established.
The official separation between the independent Christian Churches/Churches of Christ and the Christian Church (Disciples of Christ) is difficult to date. Suggestions range from 1926 to 1971 based on the events outlined below:
1926: The first North American Christian Convention (NACC) in 1927 was the result of disillusionment at the DoC Memphis Convention.
1944: International Convention of Disciples elects as president a proponent of open membership
1948: The Commission on Restudy, appointed to help avoid a split, disbands
1955: The Directory of the Ministry was first published listing only the "Independents" on a voluntary basis.
1968: Final redaction of the Disciples Year Book removing Independent churches
1971: Independent churches listed separately in the Yearbook of American Churches.
Identity
Because the Christian churches and churches of Christ are independent congregations there is no set creed, but The Directory of the Ministry contains the following general description:
Members of Christian Churches and churches of Christ believe in the deity and Lordship of Jesus Christ, the inspiration of the Bible, and the autonomy of local congregations. Following the basic principles of the 'Restoration Movement', they accept and teach believers' baptism by immersion into Christ for the forgiveness of sins; they assemble for worship on the first day of the week, making the observance of the Lord's Supper a focal point in such worship. They seek the unity of all believers on the basis of faith in and obedience to Christ as the divine Son of God and the acceptance of the Bible particularly the New Testament as their all-sufficient rule of faith and practice.
Baptism
Of the principles cited above, one characteristic marks most Christian Churches and Churches of Christ as distinctly different from other modern Evangelical Christian groups today. That is the teaching that a person receives the remission of sins, during his baptism. Baptism is:
by immersion,
for publicly confessing believers in Jesus Christ [Acts 8:37],
a work of God's grace, not a work of man [Col 2:12],
a promise received through obedient submission [Acts 2:40, 41],
necessarily accompanied with confession of sinfulness and repentance [Acts 2:38; Acts 3:19; Rom 10:9,10],
the occasion when one receives God's forgiveness for their sins [Acts 2:36-37; Acts 2:40-41],
the occasion when one calls on His name for salvation [Acts 22:16],
the occasion when the equipping, indwelling Holy Spirit is received as a seal and promise of heaven [Acts 2:38; Titus 3:5],
a "circumcision" or transformation of the believer's heart by the hands of Christ himself [Col 2:11,12],
foreshadowed in the Old Testament ceremonial washings, now fulfilled in a believer's shared experience with Christ [Heb 10:22],
sharing in the death, burial, and resurrection of Christ [Rom 6:4], and the only assurance of the hope of the resurrection from the dead [Rom 6:5-7],
specifically emphasized and commanded by Christ in his brief closing remarks ("The Great Commission") before ascending into heaven,
not only an outward sign of an inward change, but is both simultaneously [e.g. "born again" John 3:4, 5],
one baptism indeed, both physically in water and spiritually in the blood of Jesus [Eph 4:5; John 3:5],
entry into the body of Christ at large, and hence, the only viable entry into the membership of a local congregation of the Independent Christian Churches and Churches of Christ (as in the Church of Christ (non-instrumental), a candidate for membership is not usually required to be re-baptized if they have previously been "baptized into Christ" in accordance with the above general understanding and/or guidelines) [Eph 4:5].
Educational institutions
The Christian Churches/churches of Christ support a variety of Bible colleges and seminaries. Because there is no official "denominational" structure in the movement, the local colleges often serve as information centers and allow the local churches to maintain connections with each other.
Canada
Philippines
United States
Puget Sound Christian College, opened in 1950 but closed in 2007.
Slogans
A number of slogans have been used in the Restoration Movement to express some of the distinctive themes of the Movement. These include:
"Where the Scriptures speak, we speak; where the Scriptures are silent, we are silent."
"The church of Jesus Christ on earth is essentially, intentionally, and constitutionally one."
"We are Christians only, but not the only Christians."
"In essentials, unity; in opinions, liberty; in all things love."
"No creed but Christ, no book but the Bible, no law but love, no name but the divine."
"Call Bible things by Bible names."
See also
Christianity
Christian Church
Restoration Movement
Churches of Christ
Christian Church (Disciples of Christ)
Christian primitivism
Sponsoring church (Churches of Christ)
Churches of Christ (non-institutional)
References
Citations
Sources
Category:Restoration Movement
Category:Christian churches and churches of Christ
Category:Restoration Movement denominations
Category:arminian denominations |
Q:
Case insensitivity in nginx
We have several SEO pages like:
http://www.example.com/PageOne.html
Which we redirect in config like:
location = /PageOne.html {
rewrite ^/(.*) /seo.php?id=1 last;
}
Problem is if a user access this page by typing:
http://www.example.com/pageone.html
"Page Not Found" error is displaying. There are approximate 500+ seo pages. How to write rule for nginx to ignore case sensitivity in url? I want a common solution for all url.
A:
This solved my issue. Sad to say that there is not many articles related to these issues, even nginx doesn't provide user friendly Help/Tutorials.
location ~* ^/-PageOne.html {
rewrite ^ /seo.php?page_id=1 last;
}
Hope this helps!
|
{
"ver": "2.2.0",
"uuid": "513c898e-0901-4ef3-97e7-f722c94e49a3",
"type": "sprite",
"wrapMode": "clamp",
"filterMode": "bilinear",
"premultiplyAlpha": false,
"subMetas": {
"enemies_spritesheet": {
"ver": "1.0.3",
"uuid": "6d66601f-c896-4a90-a581-8f5301bd3093",
"rawTextureUuid": "513c898e-0901-4ef3-97e7-f722c94e49a3",
"trimType": "auto",
"trimThreshold": 1,
"rotated": false,
"offsetX": -0.5,
"offsetY": 0,
"trimX": 0,
"trimY": 0,
"width": 352,
"height": 153,
"rawWidth": 353,
"rawHeight": 153,
"borderTop": 0,
"borderBottom": 0,
"borderLeft": 0,
"borderRight": 0,
"subMetas": {}
}
}
} |
The second season of Jersey Shore promises to be action-packed! Saturday night, some guy was less-than-respectful to Snooki and JWoww, so Snickers slapped him, then threw food and booze at him. (He threw a drink on her, too).
Last night's episode finally got around to introducing Devorah Rose, who's used her invented status as editor-in-chief of a magazine we've never seen for sale anywhere to insinuate herself into society circles, as well as several different reality shows. »3/25/10 12:40pm 3/25/10 12:40pm |
Q:
Ubuntu 16.04 recognize external speakers as headphones
External speakers 2.1 are recognized as headphones, is it normal?
If not how can I fix it?
Notebook model: Dell Inspiron-3542
OS: Ubuntu 16.04 64-bit
Pop-up after connect external speakers 2.1
Recognized as headphones
A:
Yes, it's normal: if you already have speakers installed in your system in hardware, the second pair of speakers are recognized as "headphones" (as you very probably) plug them into the headphone port, not in the (internal) speaker port.
So unless you get your screw driver out and remove the internal speakers and hook up the external speakers to the internal port, just ignore it.
;-)
|
Chemotherapeutic treatments: a study of the interplay among drug resistance, toxicity and recuperation from side effects.
A system of differential equations for the control of tumor growth cells in a cycle nonspecific chemotherapy is analyzed. Spontaneously acquired drug resistance is taken into account, and a criterion for the selection of chemotherapeutic treatment is used. This criterion purports to describe the possibility of improvement of the patient's health when treatment is discontinued. Contrary to our early results which also take drug resistance into account, in this context strategies of continuous chemotherapy in which rest periods take part may be better than maximum drug concentration throughout the treatment (which appears to be in accordance with clinical practice). This bears out our previous conjecture that when drug resistance is accounted for, the imperfections in the usual modelling of treatment criteria, which in general do not allow for patient recuperation, ruled out the possibility of rest periods in optimal continuous chemotherapy. |
s the units digit of y(-17)?
9
Let r = 6 + -10. Let a(m) = -m**3 - 3*m**2 + 6*m + 3. Let z be a(r). What is the units digit of (-8)/20 - 112/z?
2
Suppose -3*m + 1598 = -a, 0 = -20*a + 15*a + 5. What is the hundreds digit of m?
5
Suppose -4*v - y - 36 = 17, -v = y + 14. Let b(c) be the first derivative of c**2/2 + 14*c - 1. What is the units digit of b(v)?
1
Let j be (3/3)/((-1)/(-2)). Let d(p) = p. Let a be d(j). Suppose 0 = a*h - 5*h + 99. What is the tens digit of h?
3
Let c = 9535 + -4409. What is the tens digit of c?
2
Let l(r) = -r**2 + 5*r + 3. Let w be l(0). Suppose x = -k + 168, -2*k + w*x + 534 = k. What is the units digit of k?
3
Let p = -34 + 39. Let d = 9 + -7. Suppose -i = 2*y - d*i - 11, -i - 32 = -p*y. What is the units digit of y?
7
Let l = 38 - -89. Suppose 11 - l = -4*v. Suppose 11 = 5*r - v. What is the units digit of r?
8
Let x = -7 - -5. Let a = x - 23. Let j = 39 + a. What is the tens digit of j?
1
Let a(j) be the third derivative of -29*j**5/120 + j**4/24 - 2*j**3/3 + 3*j**2. Let b(p) be the first derivative of a(p). What is the units digit of b(-1)?
0
Let q(m) = 17*m + 1. Let s(f) = f + 1. Let u be s(4). Suppose 7 = p + 3*t, -2*p - 2*t + 1 = -u. What is the tens digit of q(p)?
1
Let m(n) = n**2 - 10*n + 2. Let r(g) = g**3 + 6*g**2 - 2*g - 3. Let h be r(-6). Let i be m(h). Let j(x) = -x**2 - 10*x - 8. What is the units digit of j(i)?
3
Suppose -2*a + 2*p = -5*a + 5, -5*a + 3*p = -40. Let x(m) = 12*m + 16. What is the tens digit of x(a)?
7
Suppose 4*y - 4*u = 5*y - 736, 0 = -5*y + 4*u + 3800. What is the tens digit of y?
5
Let p = -36 + 40. What is the tens digit of (286 + 1)*p/14?
8
What is the hundreds digit of ((-2)/6)/((-4)/4236)?
3
Let h = 1919 + -913. What is the hundreds digit of h?
0
Let l(c) = -232*c + 1. Let b be l(1). Let o = -131 - b. Suppose y + 21 = 3*x - o, -3 = 3*y. What is the units digit of x?
0
Let j(i) = -3*i**3 + 38*i**2 - 6*i - 39. What is the tens digit of j(10)?
0
Suppose -45*k + 10341 + 40644 = 0. What is the thousands digit of k?
1
Suppose -3*o = -5*x + 10, 0 = -3*x + o + 10 - 0. Let j(p) be the third derivative of -p**6/120 + 7*p**5/60 + p**3/3 - 141*p**2. What is the tens digit of j(x)?
5
Let i be (-992)/10 - 72/90. Let w = i + 122. What is the tens digit of w?
2
Let x(r) = -4*r**2 - 38*r - 2. What is the tens digit of x(-7)?
6
Let g(k) = -2*k + 1 - 13*k**2 + 13*k**2 + 6*k**2 - 2. What is the tens digit of g(-2)?
2
Let u(i) = 19*i + 36. Let c be u(5). Let d = 8 + c. What is the units digit of d?
9
Let a = 743 - -2168. What is the units digit of a?
1
Let j = 351 + -198. What is the units digit of j?
3
Let t be (14 - (-2 - 0)) + 0. Let m be -11 + 13 - ((-3)/(-3) - 3). Let b = t - m. What is the tens digit of b?
1
Let j = 84 - 83. What is the units digit of ((-337)/(-3) - j)*9/6?
7
Let t(b) = -b + 30. Let a(v) = v**3 + 8*v**2 + 6*v + 1. Let y be a(-7). What is the tens digit of t(y)?
2
Let z(c) = -58*c**2 + 4 - 9 + 35*c**2 - 32*c + 29*c**2. What is the tens digit of z(7)?
6
Let w(h) = 7*h + 18. Let c be w(0). Suppose -c*g = -17*g - 93. What is the tens digit of g?
9
Let y(l) = -58*l - 1. What is the tens digit of y(-3)?
7
Suppose -3*m + 2*m + 5*w = 5, -w = 2*m - 45. What is the tens digit of 912/m - 12/(-30)?
4
Let s(i) = -i**3 - 16*i**2 + 7*i + 57. What is the tens digit of s(-19)?
0
Let s = 4626 + -1677. What is the tens digit of s?
4
Let x be 1/(-2) - 182/(-28). Let d = x + -5. What is the units digit of d?
1
Let b be -3*(-3 - 14/(-6)). Suppose -2*q = -0*m - b*m + 114, -4*m - 2*q = -198. What is the tens digit of m?
5
Let f be (-7)/(21/(-9)) - -22. Let k = f + -6. What is the tens digit of k?
1
Suppose 0 = 4*t + 2*h - 2942, 2*t + 31 - 1496 = 5*h. What is the tens digit of t?
3
Let r = -47 + 49. What is the tens digit of 0 + (-3 + r - -64)?
6
Let g = 566 - 37. What is the units digit of g?
9
Let k(a) = -3*a**2 - 25*a - 12. Let w be k(-14). Let n = w + 379. What is the hundreds digit of n?
1
Suppose 274 = 5*g - 81. Suppose -g = -y - 4*b, b + 6 = 3*b. What is the units digit of y?
9
Suppose 5*c = 11*k - 9*k + 1685, -c - 3*k + 337 = 0. What is the hundreds digit of c?
3
Let o be (-8)/(-32) + 78/8. Let r(a) = 6*a**2 + 0*a + a**3 - o*a - 10 + a**2. What is the units digit of r(-8)?
6
Let j = 400 + -250. What is the units digit of j?
0
Suppose 2*a + 2*s - 1070 = 0, -2170 = -4*a - 14*s + 16*s. What is the units digit of a?
0
Let u be 0 + 21*((-16)/(-12))/(-1). Let p(z) = -z**2 - 33*z - 6. What is the tens digit of p(u)?
3
Let j = 13 - -9. Suppose -6*p = -5*p - j. What is the tens digit of p?
2
What is the hundreds digit of ((-416)/3)/(15/(-45))?
4
Let z(u) = -u**3 + 9*u**2 - 2*u + 6. Let m be z(8). Suppose 3*x + 3*x + m = 0. Let r = x - -12. What is the units digit of r?
3
Let r = 2241 + -836. What is the tens digit of r?
0
Let c = 58 + -46. Suppose -c*k + 8*k = -292. What is the tens digit of k?
7
Let u = 29 + 30. Let n = 103 - u. Let t = -22 + n. What is the units digit of t?
2
Let s = 1021 - 24. What is the units digit of s?
7
Suppose -5*m - 5*k = -2*m - 13, -m + 3*k = -9. Suppose -v - 3*v - r + m = 0, 4*v = 3*r + 14. Suppose v*g - 6*g = -56. What is the units digit of g?
4
What is the thousands digit of (6321 - 1) + 6*(6 + -7)?
6
Let q = 62 - 38. Let a = 67 - -9. What is the units digit of a/14 - q/56?
5
What is the units digit of (7632/20)/((-21)/(-70))?
2
Let k(g) be the second derivative of g**4/12 + g**3/2 - 4*g. Let m be k(-4). Suppose -m*v = -14 - 2. What is the units digit of v?
4
Let c = -32 - -58. Let s = 20 - c. Let w(n) = n**2 - n + 8. What is the units digit of w(s)?
0
Let u be -1 - 0 - (2 - -22). Suppose c = 2*x + 3*x - 46, 4*c + 159 = -5*x. Let a = u - c. What is the units digit of a?
6
What is the hundreds digit of (26 + 0)*(-771)/(-6)?
3
Suppose 3*r = -2*j + 4227 - 321, -3906 = -2*j - 5*r. What is the tens digit of j?
5
Let f = -74 + 70. What is the tens digit of -2 - (0 - 69) - f?
7
Let h(z) = -z**3 - 3*z - 2. Let i be h(-1). Suppose 270 = i*s - 24. What is the tens digit of 1*-1*s/(-3)?
4
Let z(v) = -3*v**2 + 33*v - 15. What is the tens digit of z(8)?
5
Let o(d) = d**3 + 17*d**2 - 18*d - 12. What is the hundreds digit of o(-15)?
7
Let l(w) be the third derivative of 3/8*w**4 + 0*w + 11/6*w**3 + 0 + 2*w**2. What is the units digit of l(5)?
6
Let x(t) = -82*t + 42*t - 3*t**2 + 35*t + 4*t**2. What is the units digit of x(-7)?
4
Let t(h) = 233*h - 15. What is the units digit of t(9)?
2
Suppose 643 = 7*r - 141. What is the hundreds digit of r?
1
What is the units digit of 200/(-60)*546/(-4)?
5
Suppose -t - 3*z + 8*z + 7 = 0, t - 13 = 2*z. Suppose -b - 2*l = -t, 3*b - 51 = -l + 15. What is the tens digit of b?
2
Let b(l) = -8*l**2 - 242*l - 34. What is the tens digit of b(-25)?
1
Let z be (-3 - -3)/(-3) + 4. Suppose 0*s = z*s - 108. What is the units digit of s?
7
What is the units digit of 85 - 30/(-1 + -4)?
1
Let f = 11 - 15. What is the units digit of (-4456)/(-36) - f - (-4)/18?
8
Suppose 12*w + 5*u = 11*w + 580, -5*w = u - 2828. What is the hundreds digit of w?
5
Let l be 32/10 - 6/30. Suppose -x + 2*v = 2, 8*x - 2*v = l*x - 2. Suppose x = 15*q - 11*q - 96. What is the tens digit of q?
2
Suppose 0 = -3*l + l, -5*w + 5*l = 5. Let x(s) be the second derivative of -23*s**3/6 + s**2/2 - 68*s. What is the units digit of x(w)?
4
Let v = 120 + -69. Let m = 166 - v. What is the tens digit of m?
1
Let z be (-2 + (-33)/6)*-2. Let w be z/(-9) - 2/(-3). What is the units digit of 48/9 + w/3?
5
Let z(b) = -59*b + 61. What is the units digit of z(-7)?
4
Let p be -44*(-12)/(-28)*-7. Suppose 2*m - 66 = p. What is the tens digit of m?
9
Suppose -3 = -3*g - 0. Let d be -35*(2 - 3)/g. Let l = -13 + d. What is the units digit of l?
2
Suppose -7*h + 114 = -5*h. Suppose c - h = g, -c + 0*g = 2*g - 57. What is the tens digit of c?
5
Let k(o) = -o**2 + 11*o + 31. Let j be k(13). Suppose -h + 4 = -n + j, 3 = n. What is the units digit of h?
2
Suppose 6*t = -66 + 258. Let b = -27 + t. What is the units digit of b?
5
Let d(a) = 2*a**2 - 10*a - 7. Let w be d(6). Suppose -w*v + 128 = -257. What is the units digit of v?
7
Suppose y + 5*d - 128 = 1559, -2*y - 2*d + 3350 = 0. What is the thousands digit of y?
1
Let l = -42 + 20. Let m = 28 + l. Suppose 414 = -0*i + m*i. What is the units digit of i?
9
Let c |
For four years, I’ve asked the same question here: Who are the 50 best baseball players not in the Hall of Fame? It’s not 50 players who need to be enshrined tomorrow or ever, necessarily, just the 50 best not enshrined. As founder and editor of this website, it’s my pleasure to present the latest answer to this question.
UPDATE, JANUARY 4, 2016: I DID A NEW VERSION OF THIS PROJECT FOR SPORTING NEWS.
To anyone who’s new, four things:
1) This project is strictly voter-driven, with 208 ballots this year. I do little to no active campaigning and invite people to set their own criteria.
2) Everyone who votes is required to vote for 50 players. Next to each player a person selects, the voter is asked to put a “Yes” or “No” designating if the player belongs in the Hall of Fame. The latter component has no effect on ranking and is meant, in part, to signify that a player can be among the 50 best not in Cooperstown while having no business holding a plaque there. That said, were it up to voters from this project, seven players would be enshrined this coming summer, all from the 2014 writers ballot. In alphabetical order, these players are: Jeff Bagwell, Craig Biggio, Tom Glavine, Greg Maddux, Mike Piazza, Tim Raines and Frank Thomas.
3) I offered a ballot of more than 500 players at the start of voting. Full voting results are posted below, in alphabetical order of last name.
That being said, voters are not restricted to the ballot. Any player who hasn’t appeared in the majors in five years is eligible for this project. A player need not have played 10 seasons or even in the majors to be eligible here. A player is eligible until he is enshrined at Cooperstown’s annual summer ceremony.
I will likely cut the ballot down next year, as it has become unwieldy and confusing. Thus far, though, my aim has been not to omit any worthy player.
4) Please feel free check out the preceding three years of this project: Version 3.0, Version 2.0 and the debut of this project.
UPDATE, JANUARY 4, 2016: I DID A NEW VERSION OF THIS PROJECT FOR SPORTING NEWS.
All this being said, here’s how voting came out this year:
1. Tim Raines, 191 votes out of 208 (Does he belong in the Hall of Fame? 177 yes, 11 no, 3 N/A), written by Dan McCloskey of Left Field:
Only eight players in history have reached base 4,000 times, scored 1,500 runs, stolen 500 bases and were worth more than 60 Wins Above Replacement lifetime.
Six of them (Rickey Henderson, Joe Morgan, Barry Bonds, Ty Cobb, Eddie Collins and Honus Wagner) are unquestionably among the top five all-time at their respective positions. Of those six, only Bonds (due to PED questions) and Collins (due to the overcrowded ballot during the Hall’s early years) are not first-ballot Hall of Famers.
The seventh is Paul Molitor, who doesn’t quite fit into the top five all-time at his position category (unless you count DH), but is a first ballot inductee nonetheless.
The eighth, of course, is Tim Raines.
You can cherry-pick an argument for virtually any candidate, but there’s no reasonable debate against this straightforward comparison of Raines to seven upper tier Hall of Fame caliber players.
Lest anyone think he was just a compiler, his career WAR/162 of 4.455 ranks ahead of 55 Hall of Fame position players, including Brooks Robinson, Robin Yount, Reggie Jackson, Eddie Murray and Ernie Banks (h/t @BRefPlayIndex).
As the voters of this project have attested by ranking him in the top ten for the fourth year in a row, and No. 1 for the second straight year, Tim Raines is clearly one of the Hall of Fame’s most glaring omissions.
2. (Tie) Craig Biggio, 185 votes out of 208 (Does he belong in the Hall of Fame? 170 yes, 11 no, 4 N/A), written by Mark Kreidler, a voting member of the Baseball Writers Association of America. Kreidler explains here why he gave Biggio a vote in the BBWAA’s 2014 Hall of Fame election:
In an era of redrawn valuations, on a Hall of Fame list that grows more vexing each year, Biggio strikes me as one of the easiest Yes votes on the ballot – and he did so in 2013, when I voted for him in his first year of eligibility. A multi-position player whose up-the-middle metrics compare favorably with HOF standards, Biggio ranks 21st in MLB history in hits and 15th in runs scored, and he delivered more doubles than any RH hitter ever. (“Team guy” addendum: He was HBP more times than any player in the modern era.) He wound up with 3,060 hits, likely extending his career a year too long to do it – but even for those who aren’t milestone-fascinated, three thousand hits is something only 27 other players have achieved. It’s not nothing. And Biggio did this while earning four Gold Gloves, playing his entire career for a single organization, making 19 straight Opening Day starts, being honored as a Roberto Clemente Award recipient for community service, and being recognized – by teammate after teammate – as the lock-down, no-questions-asked leader of a Houston franchise that enjoyed its only run of sustained excellence on his watch. He goes in.
2. (Tie) Jeff Bagwell, 185 votes out of 208 (Does he belong in the Hall of Fame? 171 yes, 10 no, 4 N/A), written by Daren Willman of Baseball Savant:
Jeff Bagwell was the most dominant first baseman of the mid 90’s and is very worthy of the hall of fame. His numbers speak for themselves. In the 15 year period he played, he was second in RBI (1529), third in runs (1517), hits (2314), and walks (1401), and fifth in HR (449). Bagwell received MVP votes in 10 of his 15 years and won it in 1994. He’s one of only 12 players in MLB history to hit 400 HRs and steal 200 bases. While playing Bagwell was regarded as one of the smartest base runners in the league. His career stats compared to all players are equally as impressive 40th all-time in OBP, 36th in OPS+, and 63rd in career WAR. With all these things considered Jeff Bagwell should be a hall of famer.
4. Greg Maddux *New to ballot*, 183 votes out of 208 (Does he belong in the Hall of Fame? 179 yes, 1 no, 3 N/A), written by me:
Greg Maddux is the reason I will be trimming the ballot next year. I included more than 500 players on the ballot this year, making it somewhat unwieldy and indecipherable. On a clear, easy-to-read ballot, a player like Greg Maddux ought to get 100 percent of the vote. If the longtime Atlanta Braves ace, four-time Cy Young Award recipient and 355-game winner wasn’t the best pitcher of his generation or even baseball history, he isn’t far off.
5. Barry Bonds, 181 votes out of 208 (Does he belong in the Hall of Fame? 143 yes, 35 no, 3 N/A), written by Dan Szymborski of ESPN.com and Baseball Think Factory:
In a normal world, you would not be reading anything about Barry Bonds in this space. Based purely on the whole “playing baseball” thing, Bonds missing from Cooperstown is the equivalent of the Rock and Roll Hall of Fame leaving out the Beatles. They did take creativity-enhancing drugs after all…
But just in case you need to be reminded of the excellence of Barry Bonds, let’s run down the crazier parts of his resumé. 762 homers. a .298/.444/.607 career line for an OPS+ of 182, the latter number behind only Babe Ruth and Ted Williams, two sluggers whose names you should at least vaguely recall. 7 MVP awards, 8 Gold Gloves, 12 Silver Sluggers, and if there existed an award with Platinum or Diamond in the name, Bonds would probably have 10 of those too. Before performance-enhancing drugs became a concern in baseball, a half-century after their introduction into the sport, Bonds was infamous among casual fans for not playing well in the playoffs, which he eventually rectified to finish with a .936 career postseason OPS.
Bonds is one of the greatest players to ever play baseball. Not greatest in the sense that one would say “Wow, that was totally the greatest sandwich I ever ate!” but the kind of greatness that inspires generations. To write the story of 1990s/2000s baseball and not talk about the feats of Bonds is like writing a history of the Civil War and not mentioning Ulysses S. Grant. Come back here in a year’s time and again, Barry Bonds will top this list.
6. (Tie) Mike Piazza, 178 votes out of 208, (Does he belong in the Hall of Fame? 165 yes, 10 no, 3 N/A), written by Mike Gianella of Baseball Prospectus:
Writers often engage in hyperbole when discussing Hall of Fame candidates, but despite Piazza’s amazing offensive numbers as a catcher he hasn’t generated the same excitement that some all-time greats have when they reach the ballot. Some of this is a result of all of the negativity surrounding PEDs (even though Piazza has never been linked to steroids in any way whatsoever), but most of it probably is due to a misunderstanding of his value. His rWAR of 59.2 is low for a Hall of Famer, but when you compare Piazza only to other catchers, he sits right up there with all time greats like Johnny Bench, Yogi Berra, and Carlton Fisk, at least with the bat. Piazza’s 427 home runs and .308/.377/.545 slash are amazing numbers for an everyday catcher and even when you adjust for his era his career offensive WAR is on a par with Bench’s. It’s easy to make a Hall case for Piazza even with “simpler” numbers; he hit 30 home runs or more nine years out of 10 and .300 or better for 10 consecutive seasons. Piazza belongs in the Hall, and despite the current ballot logjam should eventually find his way to Cooperstown.
6. (Tie) Roger Clemens, 178 votes (Does he belong in the Hall of Fame? 139 yes, 36 no, 3 N/A), written by Michael Clair, who will be doing a charity blogathon for Doctors Without Borders this month. In lieu of donating to this project, please consider donating to Michael’s worthy cause:
There are those that say the horned minotaur is simply a creature of fiction, of myth, that there is no way a creature with the head of a bull and the body of a man could exist. Those people clearly never saw Roger Clemens pitch.
The fact that Clemens, weighing in at 205 lbs of ground chuck, spit, and vinegar, remains on this list, earning only 37.6% of the vote last year, is a shame. He has seven Cy Youngs awards, 354 victories, a 3.12 ERA. Seven times he lead the league in shutouts, another seven in ERA. Five times he lead the league in strikeouts, twice in innings. His 140.3 JAWS is third behind Walter Johnson and Cy Young. He even has his own Nintendo video game.
Clemens also had two separate peaks, his early years from 1986-1992, going 136-63 with a 2.66 ERA and his comeback with the Blue Jays, going 149-61 with a 3.22 ERA between 1997 and 2005. Just one of those is enough for a Hall of Fame career, two is simply overwhelming.
So while his performance can’t be denied, only Clemens’ use of performance enhancing drugs is keeping him out of Cooperstown. Forget that Clemens is arguably the greatest pitcher of all-time despite playing the second half of his career in a heightened offensive environment. Forget that much of his competition was also using drugs. Because Clemens was so successful, arrogant, and bull-headed, the voters have decided to trap Clemens in a labyrinth of fuzzy moral logic and out of Cooperstown.
And that’s more absurd than a creature with a bull’s head and a man’s body.
8. Alan Trammell, 177 votes out of 208 (Does he belong in the Hall of Fame? 148 yes, 22 no, 7 N/A), written by Joshua Pease:
Alan Trammell is inexorably linked with Lou Whitaker, who now rather famously failed to reach the 5 percent threshold in his only year on the Hall of Fame ballot. Thankfully, Trammell remains on the ballot, though he is now in his 13th year of eligibility and has yet to hit even 40 percent of the vote. Trammell debuted in 1977 and manned shortstop for the Tigers for the next 20 seasons, retiring in 1996. Over the course of his career, he proved to be an excellent all-around talent. He was an above average hitter (111 wRC+ and 3 Silver Sluggers), had good power for a shortstop (185 HR), was a good baserunner (236 SB), and played excellent defense (22 dWAR on Baseball Reference and 4 Gold Gloves). He was a better hitter than Ozzie Smith, as good a fielder as Cal Ripken, and a similar all-around player to Barry Larkin. The fact the Trammell was very good at everything but otherworldly at nothing may very well be what has kept Hall of Fame voters from enshrining him thus far.
I would vote for Alan Trammell if I had a Hall of Fame ballot.
9. Tom Glavine *New to ballot*, 176 votes out of 208 (Does he belong in the Hall of Fame? 170 yes, 3 no, 3 N/A), written by Eno Sarris of Fangraphs:
The word is “frustrating.” Both the numbers and the eyes agree on that one. Tom Glavine spent most years striking out batters at a well-below average rate. His walk rate was only slightly better than average. His ground-ball rate, though only measured in the twilight of his career, was basically average. He gave up a ton of hits — almost 4,300 by the time he hung it up. Somehow, he spent a career doing average things and getting great results. You still can’t ignore the 3.54 career ERA or the 305 wins just because he was on good teams and over-performed his peripherals. At some point, you just have to believe. Remember how frustrating it was to watch him hit that outside corner with fastball and changeup, time and time again. Remember how he stretched that outside corner as far as the umpire would let him. Remember how he just didn’t give up home runs with runners on base. These things all contribute to the confounding gap between his peripherals and results, and they even inspire us to re-examine some of our assumptions about pitching. So really all that frustration is just food for inspiration.
10. Shoeless Joe Jackson, 174 votes out of 208 (Does he belong in the Hall of Fame? 143 yes, 36 no, 5 N/A), written by Christopher Kamka of Comcast SportsNet Chicago:
Shoeless Joe Jackson is a player often distorted by myth and legend, but is best appreciated by simply examining the facts.
Joe could never exist today. Perhaps this is why he remains one of the more intriguing figures in baseball history. Can you imagine a guy playing an actual game in his socks? Even in the minors? For that matter, who was the last illiterate superstar to grace the diamond?
Consider the circumstances under which his career ended. A group of players throwing a World Series because they’re underpaid? Jackson’s 1919 salary was $6,000. Calculating for inflation, that translates to roughly $80,000, while today’s league minimum is more than six times that. Forget about it.
Jackson’s last season was 1920; his age 32 season. Plenty of good baseball left. His first sniff of the live ball era. What would he have done with league production trending like this:
American League average BA/SLG for the last five seasons of Jackson’s career
1916 .248/.324
1917 .248/.320
1918 .254/.322
1919 .268/.359
1920 .283/.387
AL average BA/SLG for the first five seasons after Jackson
1921 .292/.408
1922 .285/.398
1923 .283/.388
1924 .290/.397
1925 .292/.408
How many more .400 seasons? In the inflated offensive era of the 1920’s, many doubles & triples would turn into homers. Would White Sox fans not have had to wait until Bill Melton in 1971 for the first 30-HR season in franchise history? It’s a compelling thought because of his limited but incredible body of work.
Jackson hit .408, .395 & .378 in his first three full seasons – but thanks to Ty Cobb, he finished second in the American League each time.
Amazingly, he put up a .356 lifetime average (3rd all-time) without a single batting title. He had a .423 OBP, good for 16th all-time. Struck out only 234 times against 519 walks.
Jackson’s career OPS+ of 170 is tied with Dan Brouthers for 7th all-time. Only Babe Ruth, Ted Williams, Barry Bonds, Lou Gehrig, Rogers Hornsby, & Mickey Mantle are better.
He compiled 2,800 plate appearances for two original American League franchises (Indians & White Sox) and still owns the highest lifetime average for each (.375 for Cleveland, .340 for Chicago).
His game was not just limited to hitting. He could also run (202 SB), and throw (183 outfield assists).
This is a player who could conceivably make a list of the top 50 players period; not just limited to those not enshrined in Cooperstown.
Shoeless Joe Jackson (along with the other seven Black Sox) and John D. Rockefeller (a stunning $29 million fine imposed in 1907 on his Standard Oil in antitrust case) were the two most notable opponents taken down by Kenesaw Mountain Landis. The Standard Oil fine was overturned long ago. Isn’t it about time to give Joe his due?
11. Edgar Martinez, 170 votes out of 208 (Does he belong in the Hall of Fame? 134 yes, 31 no, 5 N/A), written by Bryan O’Connor of Replacement Level Blog:
We tend to talk about baseball players’ Hall of Fame candidacies in terms of greatness. The greatest players are cast in bronze, while the less great need a ticket to get into the museum. Greatness seems more closely tied to talent than it is to value, which reflects both talent and opportunity.
Taken on value, Edgar Martinez is a worthy Hall of Famer. His 68.3 WAR (per baseball-reference) rank 64th among eligible position players, well above the established standard and ahead of no-doubt Hall of Famers like Ernie Banks, Willie McCovey, and Dave Winfield.
Edgar’s case, though, is far stronger when measured by talent, irrespective of opportunity. Blocked by such legends as Jim Presley and Alvin Davis, Martinez didn’t crack the Mariners’ starting lineup until age 27 despite batting above .340 over his last three years in the minors. Defensively, he was an adequate third baseman, putting up positive Total Zone rankings more often than not until being banished to designated hitter duties in 1995, when Mike Blowers was ready to start butchering the position.
The original Papi’s 147 career OPS+ ranks 37th among Hall eligibles- 29th if we consider only players whose careers began after 1900. By this measure, he was a better hitter than Harmon Killebrew, Reggie Jackson, or Alex Rodriguez. He accumulated more adjusted batting runs than Carl Yastrzemski in more than 5,000 fewer plate appearances, and more than Hall of Famers Tony Perez and Johnny Bench combined.
Martinez, it seems, is outside the Hall of Fame now because he did not play in the field for three quarters of his career. McCovey and Killebrew were hitters of similar talent who cost their teams scores of runs by playing the field, only because the rules said they had to. His employers’ decisions should not cost Edgar Martinez the bronze bust he deserves.
12. Frank Thomas *New to ballot*, 168 votes out of 208 (Does he belong in the Hall of Fame? 158 yes, 7 no, 3 N/A), written by Dan Evans, currently a scout for the Toronto Blue Jays; former general manager of the Los Angeles Dodgers and assistant GM for the Chicago White Sox:
I was part of the White Sox staff involved in drafting Frank Thomas with the 7th selection overall in the 1989 draft. We thought his unique combination of zone awareness and power would develop into an impact bat. It turned out to be consistent excellence. Thomas had a legendary batting practice session in the old Comiskey Park shortly after signing in 1989 that tipped off his elite skills to others and seemingly NEVER gave up an at-bat. I worked for the White Sox through Thomas’s first 11 seasons and made sure I saw nearly every one of his plate appearances in that span.
One of the best right-handed hitters in MLB history, Thomas was a rare combination of high batting average, elite all-fields power, remarkable consistency, and an outstanding strike zone feel. His .301/.419/.555 career triple slash is matched or bettered in all three categories by only five players in history and his career .419 OBP is the best for a right-handed hitter since World War II.
Thomas is the only player ever with seven consecutive seasons of at least a .300 batting average, 100 walks, 100 runs, 100 RBI, and at least 20 homers, and it occurred in his initial seven full years (1991-1997). He won consecutive American League MVP Awards in 1993-94, placed in the top 10 in MVP balloting seven other times, and won the 1997 AL batting title. His .729 SLG and .487 OBP marks in 1994 were levels that had not been attained by an AL hitter since Ted Williams in 1957.
Nicknamed “The Big Hurt,” Thomas played the bulk of his career with the White Sox, and also played for Oakland and Toronto over his 19-year career. His 521 career homers rank 18th all-time, and more than one-half were hit to centerfield or right-center field. His #35 was retired by the White Sox in 2010.
Throughout Thomas’ career, he was outspoken about PED use among some of his peers. After hitting his 500th career homer, he said “This means a lot to me, because I did it the right way.” He was the only active player to voluntarily interview for the 2007 Mitchell Report.
I look forward to being in Cooperstown this summer when he is inducted into the Hall of Fame.
13. Pete Rose, 166 votes out of 208 (Does he belong in the Hall of Fame? 122 yes, 41 no, 3 N/A), written by Alex Putterman, assistant sports editor for the Daily Northwestern (Northwestern University):
Maybe Pete Rose belongs in the Hall of Fame — he’s the all-time hit king, of course, and achieved that distinction through an impressive peak and famous longevity. He is arguably the iconic player of his era, and Cooperstown is about nothing if not iconic players.
Or maybe he doesn’t belong in the Hall — he committed baseball’s cardinal sin, guilty of the most explicitly inexcusable offense of the time. He deserved punishment, and there’s no reason to commute his permanent sentence.
But the semantics of this project render that debate irrelevant. We’re looking for the best players not in the Hall, and all else aside, Rose is one of them. JAWs lists him as the fifth most Hall-worthy left-fielder ever (well ahead of Tim Raines, for example). He’s eighth among eligible non-Hall of Famers in WAR on Baseball-Reference and seventh in WAR on FanGraphs and in Hall Rating on HallofStats.com. Had Roseretired before a series of sub-replacement seasons he could rank even higher. It’s not unreasonable to argue using career value stats that he’s the fourth or fifth best player outside of the Hall.
Thus Rose, like a host of others here, is likely held down in voting for this project by non-baseball factors. Unlike those drug-accused others, his transgressions did not affect how good a baseball player he was.
This doesn’t necessarily mean Pete should have a place in the Hall of Fame. It does mean he should have a place very high up on this list.
14. Larry Walker, 161 votes out of 208 (Does he belong in the Hall of Fame? 119 yes, 37 no, 5 N/A), written by Brendan Bingham:
Most players perform better at home than on the road, but Larry Walker is an unusual case. His career numbers are dominated by the extreme park effects of pre-humidor Coors Field, making it difficult to compare him to other players of his day.
Limiting the analysis to road splits and choosing career slash line as the metric, let’s get a glimpse of the Larry Walker who would have existed had he never played for the Colorado Rockies. Slash line is a vast oversimplification, but it provides a quick and easy handle on hitting performance, especially when era and career length are controlled for. Like Walker, all of the players mentioned below played from the late 80s or early 90s through at least 2005, and all had at least 4000 plate appearances on the road.
As a hitter, Walker (.278/.370/.495) was a step ahead of Steve Finley (.273/.332/.447) and Ivan Rodriquez (.285/.322/.447), but no match for Manny Ramirez (.314/.409/.580), Frank Thomas (.297/.414/.511) or Jeff Bagwell (.291/.398/.521). Walker was somewhere in between, part of a cluster that includes Bernie Williams (.299/.378/.479), Luis Gonzalez (.283/.367/.489), Rafael Palmeiro (.291/.366/.502) and Ken Griffey, Jr. (.272/.355/.505).
Thanks to Coors Field, Walker was Superman at home and Jeff Kent (.290/.353/.504) on the road.
15. Mark McGwire, 158 votes out of 208 (Does he belong in the Hall of Fame? 99 yes, 56 no, 3 N/A), written by Susan Fornoff. Fornoff was instrumental in getting female reporters access to locker rooms and wrote a book about it. She covered McGwire and the Oakland Athletics’ beat for the Sacramento Bee in the 1980s and ’90s:
In the final round of a home-run derby pool in the spring of 1987, because no other name came to mind, I chose Mark McGwire. He wasn’t supposed to be a starter for the Oakland A’s that year, but, geez, he looked powerful and had hit three homers in an 18-game major-league cameo a year earlier. It was the last round, what the heck.
Needless to say, I cleaned up in that home-run pool when McGwire hit 49 homers, drove in 118 runs and hit .289 to coast to the Rookie of the Year award. All of us who watched him marveled at his seemingly limited potential.
We also marveled at his huge arms and neck the next spring. How on earth did he grow so much in just a few months?
McGwire excelled in the steroid era. If I represented him during so many years he stayed quiet thereafter, I probably would’ve advise him to just come out and say so. Say, “I’m sorry I used steroids. But I played in the era of the steroid. I did the best I could in the conditions of the game at the time.” Three years ago, he finally came clean.
With 15 seasons of 20 homers or more — and 12 of those over 30 — plus seven seasons of 100 RBIs or more, a respectable career batting average of .263 and a pretty nifty glove at first when he was healthy and at his best, McGwire deserves to be in the Hall of Fame. Apply a steroid tariff — 20 percent, even — and he’d make it in any other baseball era.
16. Curt Schilling, 157 votes out of 208 (Does he belong in the Hall of Fame? 127 yes, 27 no, 3 N/A), written by Amanda Gill:
Curt Schilling is most well known as a member of the Boston Red Sox for the infamous “Bloody Sock.” However, there was more to Schilling’s playing career than one postseason legend. Schilling spent time with five teams during his MLB career: the Orioles, Astros, Phillies, Diamondbacks, and Red Sox and he went to the World Series with the Phillies, Diamondbacks, and Red Sox, winning World Series Championships with Arizona (2001) and Boston (2004, 2007). Across his 20 years in the big leagues, Schilling amassed numerous impressive statistics including a career record of 216-146 with a 3.46 ERA, 3116 strikeouts to 711 walks, and an 11-2 record with a 2.23 ERA in postseason play. Schilling’s true lore lies in the postseason where he accumulated accolades including a NLCS MVP award with the Phillies in 1993, and a share of a World Series MVP with Randy Johnson when the Arizona Diamondbacks won in 2001. Curt Schilling deserves to be added into the National Baseball Hall of Fame. As a six-time All-Star and a three-time World Series champion, Schilling boasts a phenomenal combination of regular season and postseason success that he deserves to be enshrined for.
17. Dwight Evans, 155 votes out of 208 (Does he belong in the Hall of Fame? 98 yes, 51 no, 6 N/A), written by Dalton Mack of High Heat Stats:
Dewey never had the MVPs nor the widespread praise that outfield mates Fred Lynn or Jim Rice could lay claim to, was never the talk of Major League Baseball in his rookie season nor considered the “most feared hitter in baseball.” What Dwight Evans was however, was the 4th greatest position player in Red Sox history by Wins Above Replacement (WAR), behind only men named Williams, Yastrzemski and Boggs.
He only led the American League once in a traditional slash category (22 HRs in strike-shortened 1981), but where Evans excelled was in decidedly unsexy areas, like drawing walks and playing great defense. In fact, his 103 Fielding Runs from 1974-81 was, among outfielders, second only to Garry Maddox.
So why the lack of BBWAA support for Evans, who peaked at a tad over ten percent his second year on the ballot and fell off the following cycle? Likely for the same reason that keeps Alan Trammell from making Hall of Fame progress year after year—Evans did a host of things very well, without being truly outstanding at any particular one.
18. Dick Allen, 154 votes out of 208 (Does he belong in the Hall of Fame? 101 yes, 47 no, 6 N/A), written by Neal Kendrick of High Heat Stats:
The 1960’s and 70’s had some amazing players, all time greats like Mays, Aaron, & Frank Robinson. However there was one other great basher in that period that has largely been forgotten. Perhaps it’s because he was never a graceful fielder making dazzling plays, or maybe simply because he was traveling from city to city, but with the batDick Allen was right up there with anybody. Probably the best way to evaluate a player’s hitting ability is wRC+. It factors era, league, and home ballpark to give a true measure of a hitter’s performance, with 100 being average. Dick Allen had a 155 career wRC+. From 1963-1977, the length of Dick Allen’s career, that was tied with Frank Robinson for the best mark in baseball, ahead of pantheon guys like Mays, Aaron, Clemente, and Reggie Jackson. Allen was a dynamic all around hitter, who 3 times lead the league in Slugging Percentage, and twice in On-Base Percentage. He won an MVP award in 1972, receiving 21 of a possible 24 first place votes, in what arguably wasn’t even his best season. He had a slightly higher WAR in 1964 as a rookie. Dick Allen may not have been one of the most complete players of all-time, but he was certainly one of the best hitters of all-time. Across virtually the same timeframe Willie McCovey had .374 OBP and .515 SLG% with poor defense at first, while Dick Allen had a .378 OBP and .534 SLG% with poor defense at first and third. If McCovey can make it on the first ballot then Dick Allen should make it too.
19. Mike Mussina *New to ballot*, 150 votes out of 208 (Does he belong in the Hall of Fame? 125 yes, 22 no, 3 N/A), written by Jen Mac Ramos of Beyond the Box Score:
1999 was a good year for pitching. For one, Pedro Martinez was having a career year — one that lead to winning the AL Cy Young award. Everyone remembers Pedro. There’s Mariano Rivera, Bartolo Colon, David Cone, Jamie Moyer. They’re all easy to name. I know those were some of the first players I was aware of when I started following the game in 2007.
But then, there’s Mike Mussina. He kinda flew under the radar — pitching for the Orioles for more than half his career, and mostly on Orioles teams that were middlingin the AL East. That didn’t stop Mussina from throwing numbers worthy of the Hall of Fame: 3.68 ERA, 23 CGSHO, 3.58 K/BB, 0.95 HR/9, 82.8 RA9-WAR, 82.7 rWAR. He also averaged 34 games started for every 162 games his team played. Mike Mussina was a consistent pitcher, with some of the best numbers a career could have.
20. Lou Whitaker, 148 votes out of 208 (Does he belong in the Hall of Fame? 123 yes, 23 no, 2 N/A), written by Paul McCord of Braves Paul:
When “Sweet Lou” retired, he was one of only five second baseman ever with 200 homers, 1000 runs scored, and 1000 RBI (Alomar, Biggio, and Kent have since made Whitaker one of eight). His 74.8 career bWAR was highest among position players on the 2001 Hall of Fame ballot, including inductees Dave Winfield (64.0) and Kirby Puckett (50.8). He was clearly one of the best offensive second baseman in baseball history, and he was part of the most prolific double-play duo the game has ever seen. So why was Whitaker dismissed from Hall of Fame consideration so unceremoniously in his only year on the ballot?
Whitaker’s career numbers are remarkably similar to Ryne Sandberg’s (each is the other’s most similar batter in MLB history), which works well for this discussion since “Ryno” also played second base and wound up in the Hall of Fame. A comparison reveals that Whitaker’s consistency may actually have been his Hall of Fame weakness. He didn’t shine as brightly on consistently good Tigers teams as Sandberg did on consistently bad Cubs teams, and Whitaker’s lengthy peak that lasted late until his retirement simply lacked flair compared to Sandberg’s eye-popping numbers (and eventual flame-out).
21. Rafael Palmeiro, 146 votes out of 208 (Does he belong in the Hall of Fame? 80 yes, 57 no, 9 N/A), written by Mike Hllywa:
Let’s say you’re a General Manager, and you have the chance to add a player to your roster who averages a slash line of .288/.371/.515 for every 162 games played. That’s good for an OPS+ of 132. Would you do it? Of course you would. Who wouldn’t want an above average hitter with an above average walk-rate and above average power? And that is the type of hitter than Rafael Palmeiro was for the balance of his career.
But none of that is ever going to matter to the BBWAA because Palmeiro got busted when a urinalysis came back positive for steroids.
Was it the Ballpark in Arlington or the short walls at Camden Yards that played perfectly to the kind of swing that Palmeiro had? Or was it the anabolic cocktails that he was taking? We will never know. But we will always know this: From Palmeiro’s rookie season on, he never posted an OPS+ below 108, and that came in the final two seasons of his career. He wasn’t the best defender despite his fabled Gold Glove season in 1999. But with a bat in his hand, Rafael Palmeiro had few equals during his 20-year baseball career. Very few equals.
22. Sammy Sosa, 134 votes out of 208 (Does he belong in the Hall of Fame? 68 yes, 64 no, 2 N/A), written by Mauricio Rubio of Cubs Den and Baseball Prospectus:
When baseball was taken from me in my youth by a confusing labor dispute my passion for the game waned and I experimented with other sports. I wandered in the football and soccer territories but was called home by Sammy Sosa and 1998. We’ve learned a lot about what was behind those home run chases. The luster is gone but I do remember Sosa in a warmer light than most. His 609 HR total and career slash line of .273/.344/.534 isn’t as impressive as it seemed 20 years ago but those numbers still speak to a player who was great at his peak, even if the numbers were augmented by playing conditions (probable) and chemicals (likely).
Sosa is a polarizing figure whose greatness is overshadowed by what went on during his career, but I feel that history will be kinder to him in the long run. It’s irresponsible to pretend that he didn’t happen and we should make peace with his place in baseball history.
23. Luis Tiant, 133 votes out of 208, (Does he belong in the Hall of Fame? 85 yes, 42 no, 6 N/A), written by Andrew Martin of Baseball Historian:
Tiant is an interesting case. Although he had 229 wins, a 3.30 ERA and 2,416 strikeouts, he comes across as more of an accumulator because of his 19-year career. Make no mistake about it though, because he was a dominant pitcher.
A severe shoulder injury abbreviated his 1970 and 1971 seasons and caused him to reinvent himself in his prime, which prevented him from padding his already impressive resume.
The right hander’s record is one of contradictions. He won 20 or more games four times, led the league in ERA twice, and totaled an impressive 187 complete games and 49 shutouts. His career WAR of 66.1 is 40th all-time among pitchers according to BaseballReference.com. On the other hand, he made just three All-Star teams and never finished higher than fourth in Cy Young voting—both things Hall of Fame pundits typically hold in high regard.
Bert Blyleven (career ERA+ of 118), who was a similar accumulator and took 14 years of steadily increasing vote totals to finally get inducted, is a reason for Tiant (career ERA+ of 114) to have hope. However, since Tiant fell off the ballot in 2002, his fate rests in the hands of the Veterans Committee.
24. (Tie) Bobby Grich, 126 votes out of 208, (Does he belong in the Hall of Fame? 97 yes, 28 no, 1 N/A), written by Diane Firstman of Value Over Replacement Grit:
Robert Anthony Grich was a first-round draft pick of the Orioles in 1967 and played shortstop during his time in the minors before settling in at second in Baltimore in 1973 after the O’s traded away Davey Johnson.
Grich was a confident soul. Writer Phil Jackman recounted one day in 1970, Frank Robinson came by when Grich was talking about hitting and remarked: “What does a rookie like you know about hitting?” Grich replied to Robinson: “Tell you something, pal. I’ll be hitting for 10 years around here after you’re gone.”
1972 was the Grich’s first full season in the big leagues, and he compiled a 127 OPS+ (.278/.358/.415) while being named an All-Star and receiving a few down-ballot MVP votes. He quickly established himself as an excellent fielder, with good range, soft hands, a good arm, and skill turning the double play. He won four consecutive Gold Gloves from 1973-1976 and in 1973 he set an all-time major league fielding record with a .995 fielding percentage (he broke that record in 1985, with a .997). For his career he out-performed his peers in Range Factor (5.70 to 5.40 per 9 innings) and fielding percentage (.984 to .979).
He left the Orioles via free agency after 1976 and spent the next ten years with the Angels, logging a 124 OPS+, three All-Star appearances, two years with MVP votes, and a Silver Slugger award in the strike-shortened 1981 season. Despite all of his regular season success, he never played in a World Series. He himself batted a mere .182/.247/.318 in 24 post-season games.
How should we think of Bobby Grich now? Well of the top 10 second baseman in Jay Jaffe’s JAWS Hall of Fame metric, only Grich is missing from Cooperstown. His WAR, WAR7 (7 best seasons) and JAWS scores are all above the average of the enshrinees, and the WAR7 and JAWS scores are better than current “missing from the Hall” darling Lou Whitaker.
24. (Tie) Kenny Lofton, 126 votes out of 208 (Does he belong in the Hall of Fame? 75 yes, 45 no, 6 N/A), written by Lewie Pollis, freelance writer for ESPN.com:
[Lofton is third from left. Photo from 1980 Senior League teammate Tony Puente.]
You don’t need me to tell you that Kenny Lofton was a six-time All-Star who won four Gold Gloves. It doesn’t take a third party to point out that the Hall of Stats has Lofton as the sixth-best center fielder in MLB history. And I hope it is obvious that Lofton’s falling off the Hall of Fame ballot in his first year of eligibility is one of the biggest mistakes the BBWAA has ever made.
But the stats don’t tell you that, for a baseball fan growing up in Cleveland, Lofton’s infectious energy came to define the great Indians teams of the 1990’s. With all due respect to fans of the many other teams he played for later in his career, those outside Northeast Ohio might not know what a joy it was to watch him flying across the dirt to steal a base or leaping into — or over — the wall to make a jaw-dropping catch.
I still look at Lofton with the same sense of childlike wonder that I did when my dad would take me to Jacobs Field as a kid. And I know I’m not alone.
26. Ted Simmons, 123 votes out of 208 (Does he belong in the Hall of Fame? 97 yes, 22 no, 4 N/A):
Former Hall of Fame senior research associate Bill Deane wrote for this project last year:
As a teenager in the mid-1970s, I’d hear people debating about who was the best catcher in baseball: Johnny Bench, Carlton Fisk, or Thurman Munson? I’d say, “What about Ted Simmons? The guy hit .332 with 100 RBI!” I’d get only puzzled looks from people who were barely aware that St. Louis had a team. That exemplified Simmons’s problems in getting attention throughout his career: He played in media-Siberias and was overshadowed by two contemporary HOF catchers. But consider their average HR-RBI-AVG stats from 1971-80: Bench (27-93-.263), Fisk (16-57-.285), Simmons (17-90-.301). Simba was also unjustly regarded as a poor defensive catcher; I tackle this legend at length in my book, Baseball Myths. (Editor’s note: Page 375 of The New Bill James Historical Baseball Abstract notes: ‘Bill Deane has studied the records at great length, and demonstrated that Simmons threw out an above-average percentage of opposing base stealers in his prime seasons.’) Ted Simmons retired as the all-time leader in hits and doubles among catchers, and ranked second in RBI behind only Yogi Berra. Only Ivan Rodriguez has surpassed him in those categories since. Yet, Simmons was dropped from the BBWAA HOF ballot after one try, then waited 16 years to be snubbed by the Veterans’ Committee. His next try is this December. Simmons was one of the ten best all-around catchers in baseball history. He deserves serious consideration for Cooperstown.
27. (Tie) Keith Hernandez, 122 votes out of 208 (Does he belong in the Hall of Fame? 58 yes, 56 no, 8 N/A), written by Howard Megdal of Capital New York:
Usually, the list of players who aren’t in the Hall of Fame is filled with those who excelled, but cannot be called the best at anything. (Leaving the tiresome steroids arguments aside, that is.) Or if they managed to reach the absolute peak at some part of baseball, it’s a remarkably narrow one, and mitigated by other failings in their game. Lenny Harris and pinch-hitting, or Pat Tabler and bases-loaded situations come to mind.
But Keith Hernandez is the finest defensive first baseman I’ve ever seen, and I suspect will ever see. He came along just before defensive metrics allowed the baseball world to more completely factor this incredibly aspect of his game into total value, so it became almost a trivialized fact you’d find about him on the back of a Topps card: “Keith enjoys fishing, hunting, and playing first base as well as anyone, ever.”
Those lucky enough to have seen baseball when Vic Power or Gil Hodges or, when he was on the level, Hal Chase played it might disagree. But I’ve seen many first basemen since Hernandez-no one comes close.
We have no advanced defensive metrics from Hernandez’s time, though. So we are left with this fact, along with an offensive game that isn’t a blight upon his overall record, like Power’s or a man on the other side of the high brick wall to entry, Bill Mazeroski.
He was an astonishingly graceful hitter, with an offensive game notable for its breadth. Hernandez won an MVP in 1979, a year he hit .344 with 48 doubles, both league-leading marks. A year later, his .408 on-base percentage led the league as well. He recorded nine double-digit home run seasons, hitting 15 at age 23, 18 at age 33. He had a pair of top-ten NL finishes in triples. He walked 100 times one season, led the league in walks another season, and his team won the World Series both times. |
Pharmacodynamic aspects of peptide administration biological response modifiers.
Cytokines, growth factors and other recombinant proteins have been one of the most rapidly growing areas of pharmaceuticals. Further, the development of these bio-engineered drugs is occurring at an astonishing pace with rapid preclinical and clinical development and licensing by regulatory agencies. In addition, the availability of the gene sequences and rational drug design technologies have resulted in a rapid development of engineered genes, proteins and peptidomimetics. In contrast to traditional pharmacophores, which are developed based on the identification of the maximum tolerated dose (MTD), most recombinant proteins have abnormal biodistributions, and pharmacodynamic and pharmacokinetic attributes. Within this chapter, representative cytokines including interferon-alpha (IFN-alpha), IFN-gamma and interleukin-2 are used to discuss the pharmacodynamic aspects of protein/peptide administration that are important in the development of these drugs. This includes the conceptual need for chronic immunoaugmentation for optimal therapeutic activity; the need to consider the pharmacokinetics of administration to optimize drug delivery and the nonlinear dose response relationship, which can result in a bell shaped dose response. Furthermore, these therapeutics have maximal potential in an adjuvant protocol and their development in combination with high-dose chemotherapy and stem cell rescue is discussed. The strategies for combination chemotherapy and immunotherapy, while holding great promise, require close attention to the pharmacodynamics of protein administration in order to impact on failure free and overall survival. |
Outstanding location with unlimited potential! This area is quickly developing into commercial opportunity at the highway intersection upgrade. Great visibility & easy access for a convenience store, fast food restaurant, etc, with the added benefit of getting paid $1000 annually on billboard advertising currently on property. 2 add'l tracts available for a total of 13.594 Acres. |
Photo illustration by Lisa Larson-Walker. Photo by Tang Ming Tung/Getty Images.
Every time you open Facebook, one of the world’s most influential, controversial, and misunderstood algorithms springs into action. It scans and collects everything posted in the past week by each of your friends, everyone you follow, each group you belong to, and every Facebook page you’ve liked. For the average Facebook user, that’s more than 1,500 posts. If you have several hundred friends, it could be as many as 10,000. Then, according to a closely guarded and constantly shifting formula, Facebook’s news feed algorithm ranks them all, in what it believes to be the precise order of how likely you are to find each post worthwhile. Most users will only ever see the top few hundred.
Will Oremus Will Oremus is Slate’s senior technology writer. Email him at will.oremus@slate.com or follow him on Twitter.
No one outside Facebook knows for sure how it does this, and no one inside the company will tell you. And yet the results of this automated ranking process shape the social lives and reading habits of more than 1 billion daily active users—one-fifth of the world’s adult population. The algorithm’s viral power has turned the media industry upside down, propelling startups like BuzzFeed and Vox to national prominence while 100-year-old newspapers wither and die. It fueled the stratospheric rise of billion-dollar companies like Zynga and LivingSocial—only to suck the helium from them a year or two later with a few adjustments to its code, leaving behind empty-pocketed investors and laid-off workers. Facebook’s news feed algorithm can be tweaked to make us happy or sad; it can expose us to new and challenging ideas or insulate us in ideological bubbles.
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And yet, for all its power, Facebook’s news feed algorithm is surprisingly inelegant, maddeningly mercurial, and stubbornly opaque. It remains as likely as not to serve us posts we find trivial, irritating, misleading, or just plain boring. And Facebook knows it. Over the past several months, the social network has been running a test in which it shows some users the top post in their news feed alongside one other, lower-ranked post, asking them to pick the one they’d prefer to read. The result? The algorithm’s rankings correspond to the user’s preferences “sometimes,” Facebook acknowledges, declining to get more specific. When they don’t match up, the company says, that points to “an area for improvement.”
“Sometimes” isn’t the success rate you might expect for such a vaunted and feared bit of code. The news feed algorithm’s outsize influence has given rise to a strand of criticism that treats it as if it possessed a mind of its own—as if it were some runic form of intelligence, loosed on the world to pursue ends beyond the ken of human understanding. At a time when Facebook and other Silicon Valley giants increasingly filter our choices and guide our decisions through machine-learning software, when tech titans like Elon Musk and scientific laureates like Stephen Hawking are warning of the existential threat posed by A.I., the word itself—algorithm—has begun to take on an eerie affect. Algorithms, in the popular imagination, are mysterious, powerful entities that stand for all the ways technology and modernity both serve our every desire and threaten the values we hold dear.
A panel of news feed testers has become Facebook’s equivalent of the Nielsen family.
The reality of Facebook’s algorithm is somewhat less fantastical, but no less fascinating. I had a rare chance recently to spend time with Facebook’s news feed team at their Menlo Park, California, headquarters and see what it actually looks like when they make one of those infamous, market-moving “tweaks” to the algorithm—why they do it, how they do it, and how they decide whether it worked. A glimpse into its inner workings sheds light not only on the mechanisms of Facebook’s news feed, but on the limitations of machine learning, the pitfalls of data-driven decision making, and the moves Facebook is increasingly making to collect and address feedback from individual human users, including a growing panel of testers that are becoming Facebook’s equivalent of the Nielsen family.
Facebook’s algorithm, I learned, isn’t flawed because of some glitch in the system. It’s flawed because, unlike the perfectly realized, sentient algorithms of our sci-fi fever dreams, the intelligence behind Facebook’s software is fundamentally human. Humans decide what data goes into it, what it can do with that data, and what they want to come out the other end. When the algorithm errs, humans are to blame. When it evolves, it’s because a bunch of humans read a bunch of spreadsheets, held a bunch of meetings, ran a bunch of tests, and decided to make it better. And if it does keep getting better? That’ll be because another group of humans keeps telling them about all the ways it’s falling short: us.
When I arrive at Facebook’s sprawling, Frank Gehry–designed office in Menlo Park, I’m met by a lanky 37-year-old man whose boyish countenance shifts quickly between an earnest smile and an expression of intense focus. Tom Alison is director of engineering for the news feed; he’s in charge of the humans who are in charge of the algorithm.
Alison steers me through a maze of cubicles and open minikitchens toward a small conference room, where he promises to demystify the Facebook algorithm’s true nature. On the way there, I realize I need to use the bathroom and ask for directions. An involuntary grimace crosses his face before he apologizes, smiles, and says, “I’ll walk you there.” At first I think it’s because he doesn’t want me to get lost. But when I emerge from the bathroom, he’s still standing right outside, and it occurs to me that he’s not allowed to leave me unattended.
Photo by Christophe Wu/Facebook
For the same reason—Facebook’s fierce protection of trade secrets—Alison cannot tell me much about the actual code that composes the news feed algorithm. He can, however, tell me what it does, and why—and why it’s always changing. He starts, as engineers often do, at the whiteboard.
“When you study computer science, one of the first algorithms you learn is a sorting algorithm,” Alison says. He scribbles a list of positive integers in dry erase:
4, 1, 3, 2, 5
The simple task at hand: devise an algorithm to sort these numbers into ascending order. “Human beings know how to do this,” Alison says. “We just kind of do it in our heads.”
Computers, however, must be told precisely how. That requires an algorithm: a set of concrete instructions by which a given problem may be solved. The algorithm Alison shows me is called “bubble sort,” and it works like this:
For each number in the set, starting with the first one, compare it to the number that follows, and see if they’re in the desired order. If not, reverse them. Repeat steps 1 and 2 until you’re able to proceed through the set from start to end without reversing any numbers.
The virtue of bubble sort is its simplicity. The downside: If your data set is large, it’s computationally inefficient and time-consuming. Facebook, for obvious reasons, does not use bubble sort. It does use a sorting algorithm to order the set of all posts that could appear in your news feed when you open the app. But that’s the trivial part—a minor subalgorithm within the master algorithm. The nontrivial part is assigning all those posts a numerical value in the first place. That, in short, is the job of the news feed ranking team: to devise a system capable of assigning any given Facebook post a “relevancy score” specific to any given Facebook user.
That’s a hard problem, because what’s relevant to you—a post from your childhood friend or from a celebrity you follow—might be utterly irrelevant to me. For that, Alison explains, Facebook uses a different kind of algorithm, called a prediction algorithm. (Facebook’s news feed algorithm, like Google’s search algorithm or Netflix’s recommendation algorithm, is really a sprawling complex of software made up of smaller algorithms.)
“Let’s say I ask you to pick the winner of a future basketball game, Bulls vs. Lakers,” Alison begins. “Bulls,” I blurt. Alison laughs, but then he nods vigorously. My brain has taken his input and produced an immediate verbal output, perhaps according to some impish algorithm of its own. (The human mind’s algorithms are far more sophisticated than anything Silicon Valley has yet devised, but they’re also heavily reliant on heuristics and notoriously prone to folly.)
Random guessing is fine when you’ve got nothing to lose, Alison says. But let’s say there was a lot of money riding on my basketball predictions, and I was making them millions of times a day. I’d need a more systematic approach. “You’re probably going to start by looking at historical data,” he says. “You’re going to look at the win-loss record of each team, the records of the individual players, who’s injured, who’s on a streak.” Maybe you’ll take into account environmental factors: Who’s the home team? Is one squad playing on short rest, or after a cross-country flight? Your prediction algorithm might incorporate all of these factors and more. If it’s good, it will not only predict the game’s winner, but tell you its degree of confidence in the result.
That’s analogous to what Facebook’s news feed algorithm does when it tries to predict whether you’ll like a given post. I ask Alison how many variables—”features,” in machine-learning lingo—Facebook’s algorithm takes into account. “Hundreds,” he says.
It doesn’t just predict whether you’ll actually hit the like button on a post based on your past behavior. It also predicts whether you’ll click, comment, share, or hide it, or even mark it as spam. It will predict each of these outcomes, and others, with a certain degree of confidence, then combine them all to produce a single relevancy score that’s specific to both you and that post. Once every possible post in your feed has received its relevancy score, the sorting algorithm can put them in the order that you’ll see them on the screen. The post you see at the top of your feed, then, has been chosen over thousands of others as the one most likely to make you laugh, cry, smile, click, like, share, or comment.
What if people “like” posts that they don’t really like?
Yet no matter how meticulously you construct an algorithm, there are always going to be data to which you aren’t privy: the coaches’ game plans, how Derrick Rose’s knee is feeling that day, whether the ball is properly inflated. In short, the game isn’t played by data. It’s played by people. And people are too complex for any algorithm to model.
Facebook’s prediction algorithm faces still another complication, this one a little more epistemological. The relevancy score is meant to be analogous to the likelihood that the Bulls will win the game. That’s a discrete outcome that’s fully measurable: They either win or they don’t. Facebook’s ranking algorithm used to try to predict a similarly measurable outcome: whether you’d interact in some way with the post in question. Interactions, the humans behind Facebook’s news feed figured, are a good indicator that a given post has struck a chord. They also happen to be the fuel that drives the Facebook economy: clicks, likes, shares, and comments are what make posts go viral, turn individual users into communities, and drive traffic to the advertisers that Facebook relies on for revenue.
But those interactions are only a rough proxy for what Facebook users actually want. What if people “like” posts that they don’t really like, or click on stories that turn out to be unsatisfying? The result could be a news feed that optimizes for virality, rather than quality—one that feeds users a steady diet of candy, leaving them dizzy and a little nauseated, liking things left and right but gradually growing to hate the whole silly game. How do you optimize against that?
It was late 2013, and Facebook was the hottest company in the world. The social network had blown past 1 billion users and gone public at a valuation of more than $100 billion. It had spent the past year building a revamped mobile app that quickly surpassed Google Search and Google Maps as the nation’s most popular. No longer just a way to keep in touch with friends, Facebook had become, in effect, the global newspaper of the 21st century: an up-to-the-minute feed of news, entertainment, and personal updates from friends and loved ones, automatically tailored to the specific interests of each individual user.
Inside the company, the people in charge of the news feed were thrilled with the growth. But while users’ engagement was skyrocketing, it wasn’t clear whether their overall satisfaction with Facebook was keeping pace. People were liking more things on Facebook than ever. But were they liking Facebook less?
To understand how that question arose, you have to rewind to 2006. Facebook—which was originally little more than a massive compendium of profile pages and groups, something like Myspace—built the news feed in that year as a hub for updates about your friends’ activities on the site. Users bristled at the idea that their status updates, profile picture changes, and flirtatious notes on one another’s pages would be blasted into the feeds of all of their friends, but Facebook pressed on.
Even then, not everything your friends did made it into your news feed. To avoid overwhelming people with hundreds of updates every day, Facebook built a crude algorithm to filter them based on how likely they were to be of interest. With no real way to measure that—the like button came three years later—the company’s engineers simply made assumptions based on their own intuition. Early criteria for inclusion of a post in your news feed included how recent it was and how many of your friends it mentioned. Over time, the team tried tweaking those assumptions and testing how the changes affected the amount of time users spent on the site. But with no way to assess which sorts of posts were delighting people and which were boring, offending, or confusing them, the engineers were essentially throwing darts.
Photo by Christophe Wu/Facebook
The like button wasn’t just a new way for users to interact on the site. It was a way for Facebook to enlist its users in solving the problem of how best to filter their own news feeds. That users didn’t realize they were doing this was perhaps the most ingenious part. If Facebook had told users they had to rank and review their friends’ posts to help the company determine how many other people should see them, we would have found the process tedious and distracting. Facebook’s news feed algorithm was one of the first to surreptitiously enlist users in personalizing their experience—and influencing everyone else’s.
Suddenly the algorithm had a way to identify the most popular posts—and make them go “viral,” a term previously applied to things that were communicated from person to person, rather that broadcast algorithmically to a mass audience. Yet Facebook employees weren’t the only ones who could see what it took for a given post to go viral. Publishers, advertisers, hoaxsters, and even individual users began to glean the elements that viral posts tended to have in common—the features that seemed to trigger reflexive likes from large numbers of friends, followers, and even random strangers. Many began to tailor their posts to get as many likes as possible. Social-media consultants sprung up to advise people on how to game Facebook’s algorithm: the right words to use, the right time to post, the right blend of words and pictures. “LIKE THIS,” a feel-good post would implore, and people would do it, even if they didn’t really care that much about the post. It wasn’t long before Facebook users’ feeds began to feel eerily similar: all filled with content that was engineered to go viral, much of it mawkish or patronizing. Drowned out were substance, nuance, sadness, and anything that provoked thought or emotions beyond a simple thumbs-up.
Engagement metrics were up—way up—but was this really what the news feed should be optimizing for? The question preoccupied Chris Cox, an early Facebook employee and the news feed’s intellectual architect. “Looking at likes, clicks, comments, and shares is one way of determining what people are interested in,” Cox, 33, tells me via email. (He’s now Facebook’s chief product officer.) “But we knew there were places where this was imperfect. For example, you may read a tragic post that you don’t want to click like, comment on, or share, but if we asked you, you would say that it really mattered to you to have read it. A couple of years ago, we knew we needed to look at more than just likes and clicks to improve how News Feed worked for these kinds of cases.”
An algorithm can optimize for a given outcome, but it can’t tell you what that outcome should be. Only humans can do that. Cox and the other humans behind Facebook’s news feed decided that their ultimate goal would be to show people all the posts that really matter to them and none of the ones that don’t. They knew that might mean sacrificing some short-term engagement—and maybe revenue—in the name of user satisfaction. With Facebook raking in money, and founder and CEO Mark Zuckerberg controlling a majority of the voting shares, the company had the rare luxury to optimize for long-term value. But that still left the question of how exactly to do it.
Media organizations have historically defined what matters to their audience through their own editorial judgment. Press them on what makes a story worthwhile, and they’ll appeal to values such as truth, newsworthiness, and public interest. But Cox and his colleagues at Facebook have taken pains to avoid putting their own editorial stamp on the news feed. Instead, their working definition of what matters to any given Facebook user is just this: what he or she would rank at the top of their feeds given the choice. “The perfect way to solve this problem would be to ask everyone which stories they wanted to see and which they didn’t, but that’s not possible or practical,” Cox says. Instead, Facebook decided to ask some people which stories they wanted to see and which they didn’t. There were about 1,000 of those people, and until recently, most of them lived in Knoxville, Tennessee. Now they’re everywhere.
Adam Mosseri, Facebook’s 32-year-old director of product for news feed, is Alison’s less technical counterpart—a “fuzzie” rather than a “techie,” in Silicon Valley parlance. He traffics in problems and generalities, where Alison deals in solutions and specifics. He’s the news feed’s resident philosopher.
The push to humanize the news feed’s inputs and outputs began under Mosseri’s predecessor, Will Cathcart. (I wrote about several of those innovations here.) Cathcart started by gathering more subtle forms of behavioral data: not just whether someone clicked, but how long he spent reading a story once he clicked on it; not just whether he liked it, but whether he liked it before or after reading. For instance: Liking a post before you’ve read it, Facebook learned, corresponds much more weakly to your actual sentiment than liking it afterward.
After taking the reins in late 2013, Mosseri’s big initiative was to set up what Facebook calls its “feed quality panel.” It began in summer 2014 as a group of several hundred people in Knoxville whom the company paid to come in to an office every day and provide continual, detailed feedback on what they saw in their news feeds. (Their location was, Facebook says, a “historical accident” that grew out of a pilot project in which the company partnered with an unnamed third-party subcontractor.) Mosseri and his team didn’t just study their behavior. They also asked them questions to try to get at why they liked or didn’t like a given post, how much they liked it, and what they would have preferred to see instead. “They actually write a little paragraph about every story in their news feed,” notes Greg Marra, product manager for the news feed ranking team. (This is the group that’s becoming Facebook’s equivalent of Nielsen families.)
“The question was, ‘What might we be missing?’ ” Mosseri says. “‘Do we have any blind spots?’” For instance, he adds, “We know there are some things you see in your feed that you loved and you were excited about, but you didn’t actually interact with.” Without a way to measure that, the algorithm would devalue such posts in favor of others that lend themselves more naturally to likes and clicks. But what signal could Facebook use to capture that information?
Photo by Christophe Wu/Facebook
Mosseri deputized product manager Max Eulenstein and user experience researcher Lauren Scissors to oversee the feed quality panel and ask it just those sorts of questions. For instance, Eulenstein used the panel to test the hypothesis that the time a user spends looking at a story in her news feed might be a good indicator that she likes it, even if she didn’t actually click like. “We speculated that it might be, but you could think of reasons why it wouldn’t be, too,” Eulenstein tells me. “It might be that there are scary or shocking stories that you stare at, but don’t want to see.” The feed quality panelists’ ratings allowed Eulenstein and Scissors to not only confirm their hunch, but to examine the subtleties in the correlation, and to begin to quantify it. “It’s not as simple as, ‘5 seconds is good, 2 seconds is bad,’ ” Eulenstein explains. “It has more to do with the amount of time you spend on a story relative to the other stories in your news feed.” The research also revealed the need to control for the speed of users’ Internet connections, which can make it seem like they’re spending a long time on a given story when they’re actually just waiting for the page to load. Out of that research emerged a tweak that Facebook revealed in June, in which the algorithm boosted the rankings of stories that users spent more time viewing in their feeds.
Within months, Mosseri and his team had grown so reliant on the panel’s feedback that they took it nationwide, paying a demographically representative sample of people around the country to rate and review their Facebook feeds on a daily basis from their own homes. By late summer 2015, Facebook disbanded the Knoxville group and began to expand the feed quality panel overseas. Mosseri’s instinct was right: The news feed algorithm had blind spots that Facebook’s data scientists couldn’t have identified on their own. It took a different kind of data—qualitative human feedback—to begin to fill them in.
Crucial as the feed quality panel has become to Facebook’s algorithm, the company has grown increasingly aware that no single source of data can tell it everything. It has responded by developing a sort of checks-and-balances system in which every news feed tweak must undergo a battery of tests among different types of audiences, and be judged on a variety of different metrics.
That balancing act is the task of the small team of news feed ranking engineers, data scientists, and product managers who come to work every day in Menlo Park. They’re people like Sami Tas, a software engineer whose job is to translate the news feed ranking team’s proposed changes into language that a computer can understand. This afternoon, as I look over his shoulder, he’s walking me through a problem that might seem so small as to be trivial. It is exactly the sort of small problem, however, that Facebook now considers critical.
Most of the time, when people see a story they don’t care about in their news feed, they scroll right past it. Some stories irk them enough that they’re moved to click on the little drop-down menu at the top right of the post and select “Hide post.” Facebook’s algorithm considers that a strong negative signal and endeavors to show them fewer posts like that in the future.
Not everyone uses Facebook the same way, however. Facebook’s data scientists were aware that a small proportion of users—5 percent—were doing 85 percent of the hiding. When Facebook dug deeper, it found that a small subset of those 5 percent were hiding almost every story they saw—even ones they had liked and commented on. For these “superhiders,” it turned out, hiding a story didn’t mean they disliked it; it was simply their way of marking the post “read,” like archiving a message in Gmail.
Yet their actions were biasing the data that Facebook relied on to rank stories. Intricate as it is, the news feed algorithm does not attempt to individually model each user’s behavior. It treats your likes as identical in value to mine, and the same is true of our hides. For the superhiders, however, the ranking team decided to make an exception. Tas was tasked with tweaking the code to identify this small group of people and to discount the negative value of their hides.
Photo by Christophe Wu/Facebook
That might sound like a simple fix. But the algorithm is so precious to Facebook that every tweak to the code must be tested—first in an offline simulation, then among a tiny group of Facebook employees, then on a small fraction of all Facebook users—before it goes live. At each step, the company collects data on the change’s effect on metrics ranging from user engagement to time spent on the site to ad revenue to page-load time. Diagnostic tools are set up to detect an abnormally large change on any one of these crucial metrics in real time, setting off a sort of internal alarm that automatically notifies key members of the news feed team.
Once a change like Tas’ has been tested on each of these audiences, he’ll present the resulting data at one of the news feed team’s weekly “ranking meetings” and field a volley questions from Mosseri, Allison, Marra, and his other colleagues as to its effect on various metrics. If the team is satisfied that the change is a positive one, free of unintended consequences, the engineers in charge of the code on the iOS, Android, and Web teams will gradually roll it out to the public at large.
Even then, Facebook can’t be sure that the change won’t have some subtle, longer-term effect that it had failed to anticipate. To guard against this, it maintains a “holdout group”—a small proportion of users who don’t see the change for weeks or months after the rest of us.
To speak of Facebook’s news feed algorithm in the singular, then, can be misleading. It isn’t just that the algorithm is really a collection of hundreds of smaller algorithms solving the smaller problems that make up the larger problem of what stories to show people. It’s that, thanks to all the tests and holdout groups, there are more than a dozen different versions of that master algorithm running in the world at any given time. Tas’ “hide stories” tweak was announced July 31, and his post about it on Facebook’s “News Feed FYI” blog passed largely unnoticed by the public at large. Presumably, however, the superhiders of the world are now marginally more satisfied with their news feeds, and thus more likely to keep using Facebook, sharing stories with friends, and viewing the ads that keep the company in business.
Facebook’s feed quality panel has given the company’s news feed team richer, more human data than it ever had before. Tas and the rest of the ranking team are growing more skillful at finding and fixing the algorithm’s blind spots. But there is one other group of humans that Facebook is turning to more and more as it tries to keep the news feed relevant: ordinary users like you and me.
The survey that Facebook has been running over the past six months—asking a subset of users to choose their favorite among two side-by-side posts—is an attempt to gather the same sort of data from a much wider sample than is possible through the feed quality panel. But the increasing involvement of ordinary users isn’t only on the input side of the equation. Over the past two years, Facebook has been giving users more power to control their news feeds’ output as well.
The algorithm is still the driving force behind the ranking of posts in your feed. But Facebook is increasingly giving users the ability to fine-tune their own feeds—a level of control it had long resisted as onerous and unnecessary. Facebook has spent seven years working on improving its ranking algorithm, Mosseri says. It has machine-learning wizards developing logistic regressions to interpret how users’ past behavior predicts what posts they’re likely to engage with in the future. “We could spend 10 more years—and we will—trying to improve those [machine-learning techniques],” Mosseri says. “But you can get a lot of value right now just by simply asking someone: ‘What do you want to see? What do you not want to see? Which friends do you always want to see at the top of your feed?’ ”
The age of the algorithm is not over, but there has been a change in velocity.
Those are now questions that Facebook allows every user to answer for herself. You can now “unfollow” a friend whose posts you no longer want to see, “see less” of a certain kind of story, and designate your favorite friends and pages as “see first,” so that their posts will appear at the top of your feed every time you log in. How to do all of these things is not immediately obvious to the casual user: You have to click a tiny gray down arrow in the top right corner of a post to see those options. Most people never do. But as the limitations of the fully automated feed have grown clearer, Facebook has grown more comfortable highlighting these options via occasional pop-up reminders with links to explanations and help pages. It is also testing new ways for users to interact with the news feed, including alternate, topic-based news feeds and new buttons to convey reactions other than like.
The shift is partly a defensive one. The greatest challenges to Facebook’s dominance in recent years—the upstarts that threaten to do to Facebook what Facebook did to Myspace—have eschewed this sort of data-driven approach altogether. Instagram, which Facebook acquired in 2012 in part to quell the threat posed by its fast-growing popularity, simply shows you every photo from every person you follow in chronological order. Snapchat has eclipsed Facebook as teens’ social network of choice by eschewing virality and automated filtering in favor of more intimate forms of digital interaction.
Facebook is not the only data-driven company to run up against the limits of algorithmic optimization in recent years. Netflix’s famous movie-recommendation engine has come to rely heavily on humans who are paid to watch movies all day and classify them by genre. To counterbalance the influence of Amazon’s automated A/B tests, CEO Jeff Bezos places outsize importance on the specific complaints of individual users and maintains a public email address for that very purpose. It would be premature to declare the age of the algorithm over before it really began, but there has been a change in velocity. Facebook’s Mosseri, for his part, rejects the buzzword “data-driven” in reference to decision making; he prefers “data-informed.”
Photo by Christophe Wu/Facebook
Facebook’s news feed ranking team believes the change in its approach is paying off. “As we continue to improve news feed based on what people tell us, we are seeing that we’re getting better at ranking people’s news feeds; our ranking is getting closer to how people would rank stories in their feeds themselves,” says Scissors, the user experience researcher who helps to ovesee the feed quality panel.
There’s a potential downside, however, to giving users this sort of control: What if they’re mistaken, as humans often are, about what they really want to see? What if Facebook’s database of our online behaviors really did know us better, at least in some ways, than we knew ourselves? Could giving people the news feed they say they want actually make it less addictive than it was before? |
Q:
os x creating desktop app to show rtsp stream
I'm new on OS X.
I've never programmed in Objective C or Swift.
I want to create a desktop app with the following features:
Read a rtsp stream from a DVR and show the video on a window (Up to 64 images). I know how to do this with VLC WebPlugin.
Need to be sure that I'm using hardware acceleration. I have a Mac Pro.
My question
Which is the best combination on software (vlc, avplayer, c++, swift) for better performing?
I've been trying to develop this app with swift, objective c, QT 5 and I always get the same error:
FigByteFlumeCustomURLOpen signalled err=-12936 (kFigByteFlumeError_BadState) (no provider) at /SourceCache/CoreMedia/CoreMedia-1562.240/Prototypes/FigHTTP/FigByteFlumeCustomURL.c line 1486
A:
One option is to use QtAV if you already experienced in Qt5:
QtAV. A multimedia playback framework based on Qt + FFmpeg. Cross platform. High performace. Easy to use and develop
GitHub - wang-bin/QtAV
|
Georgetown University advisor Jeff Bernstein resigned from his post on Monday after he faced a backlash online for wishing a sexual assault upon conservative commentator Allie Stuckey.
Bernstein, an advisor for Georgetown’s Master of Science in Foreign Service program, resigned on Monday after facing a blowback for his unusual comments to conservative commentator Allie Stuckey. “Wishing you a #metoo moment,” he said in a tweet to the conservative commentator over the weekend. “Maybe then you won’t be so insensitive.”
Bernstein’s tweet came in response to a Stuckey tweet in which she argued that the #MeToo movement is a “symptom of a broken world.” She later clarified the tweet, saying that she was arguing “that we live in a broken (sinful) world, and sexual assault and harassment is symptomatic of that brokenness.”
Georgetown University issue a statement on Monday, announcing that Bernstein would be stepping down from his role as an advisor as a result of his tweet.
The Master of Science in Foreign Service (MSFS) program at Georgetown University is deeply committed to fostering the role of women in international affairs and promoting respectful dialogue and debate on the critical issues facing our world. Encouraging, threatening or condoning violence and harassment against another person, in any form and on any format, is deeply inconsistent with the values of the program, our school and our university. We appreciate Mr. Bernstein’s efforts to apologize for recent comments deeply inconsistent with our values and mission and have accepted his resignation from the MSFS Board of Advisors. MSFS will continue its dedication to preparing women and men for leadership roles in global affairs.
I really appreciate Georgetown's statement. https://t.co/svy9fMNsDj — Allie Beth Stuckey (@conservmillen) January 15, 2018
Stuckey tweeted that she “appreciate(d)” Georgetown’s statement. She also suggested that Bernstein sent her a private apology note, calling it a “sincere apology.” |
Anesthesia
Three small incisions will be made in the abdomen. A
laparoscope
(small tool with a camera on the end) will be passed through an incision. Gas will be blown into the abdomen to make it easier for the doctor to see. Other tools will be inserted into the incisions. The camera will send images to a video screen. These images will be used to find and remove the appendix.
The appendix will be detached from surrounding tissue. Any bleeding from the blood vessels will be stopped. The appendix will then be tied off and cut out. The incisions will be closed with stitches or staples.
This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.
To send comments or feedback to our Editorial Team regarding the content please email us at healthlibrarysupport@ebsco.com. Our Health Library Support team will respond to your email request within 2 business days. |
Touhou is a phenomenon. Despite niche appeal, this long-running series of bullet hell shmups has grown into an enormous shared franchise in Japan. It’s an indie scene unto itself, enabled by creator Zun giving his blessing to people making and selling fan works. Touhou boasts twice-yearly conventions dense with cosplayers, multiple official comic lines and fan-made works including music, anime, and games spanning every genre, including boozy RTSs and even football RPGs. And yet, it’s still an almost impenetrable mystery to those standing on the outside.
That barrier has become a lot easier to traverse yesterday, as Touhou 16: Hidden Star In Four Seasons has arrived on Steam, accompanied by a three-level free demo, and a comprehensive – albeit unofficial – localization patch.
Update: The full release of the game came with a little more DRM than anticipated. The Touhou translation crew are attempting to work around it. Please wait warmly until it is ready.
Update Again: Well, that was fast. The translation patch is fully compatible with the Steam version of the game now.
While there have been many opportunities in the past to import these games from Japan, and I know of at least one fan-game to get official blessing for an international console release, this is the first time the long-running series has been available via a major global storefront, although Touhou 14 got a similar release on Playism back in the day. Despite being a Japanese language only release, the Steam version is fully compatible with the community-made English patch made months ago for the original retail release of the game. Series creator Zun has stated that he has more faith in his fans to handle localisation than a third-party company, so an official translation seems unlikely at this point.
Set in the strange parallel world of Gensokyo, much of the Touhou series revolves around shrine-maiden Reimu Hakurei and her quest to avoid doing any work. She’d rather just hang out with friends, drink, sleep in the shade and count her shrine donations, but unfortunately living in a magical realm full of fairies, spirits, monsters, vampires and more means that incidents happen from time to time, and nobody is going to calm down until someone sets things straight. This time round, all four seasons seem to be happening simultaneously in different locations around Gensokyo, so it’s off to the skies to shoot at fairies until someone explains what’s going on.
This adds a little wrinkle to the usual Touhou action. You’ve got your usual movement, shooting and a screen-clearing smartbomb, but clearing enemies and ‘grazing’ enemy bullets (have your character’s sprite touch them, but not the central hitbox) will increase the Season gauge. Hitting the Season Release button will create a bullet-eating temporary safe zone, and also give you a hefty slab of points if you manage to absorb a lot of a bosses attack. Beyond that, this is as straightforward as Touhou gets, and a solid enough introduction to the series.
As mentioned, the enormous shared dream that is Touhou extends far beyond any officially released game. Due to the often-commercial nature of Touhou fan-works, it’s hard to get hold of them outside of Japan in any legal capacity, but it’s worth being on the lookout for the Koumajou Densetsu series, transplanting the Touhou cast into a super-polished Castlevania tribute replete with some astoundingly good gothic interpretations of the characters, all backed up by an official (if slightly patchy) English translation.
There are also some professional-quality animated shorts, treating the setting as if it were a long-running TV anime series, and even a series of Touhou fighting games developed by Twilight Frontier that are counted by Zun as series canon, making them numbered releases along with the mainline games. The latest of these is rumored to be headed to Steam as well. Good news, as they’re genuinely unique games, mixing shmup elements into the fighting game genre, and where the story mode plays out more like an arcade boss-rush than a traditional series of bouts. Until then, we’ve got Touhou 16.
Touhou 16: Hidden Star In Four Seasons is out now on Steam for £11.39/€15/$15, and if you want to play it in English, just grab the patch here. There’s a three-level demo on the storefront as well, and is compatible with the same translation patch. |
Final Fantasy XIV: Stormblood pre-orders now open
Square Enix has announced that pre-orders for Final Fantasy XIV: Stormblood are now open. The second expansion to Square Enix's MMORPG is set to launch on June 20th on PS4, PC and Mac in the UK, and a Collector's Edition of the game will be available alongside the regular boxed versions. The Mac edition is digital only.
The Collector's Edition of the game currently costs 179.99 for both PS4 and PC on the EU Square Enix Store and will include a special Stormblood art box, a Stormblood art book, a cloth map of Eorzea, a Stormblood logo sticker, a Zenos yae Galvus figurine statue and three exclusive in-game items, the Syldra Mount, Wind-up Bartz Minion and Chicken Knife.
There will also be a 44.99 digital PC Collector's Edition available, but this version of the game will only include the three in-game items mentioned above. The standard version, meanwhile, will cost 39.99 on PS4 and 29.99 on PC and Mac.
Regardless of which edition of the game customers buy, there will be a variety of pre-order items available for all versions of the game. These include Early Access to the game servers ahead of the game's official launch, a Wind-up Red Mage Minion and Ala Mhigan Earrings. PS4 buyers will also earn themselves an exclusive PS4 theme and avatar.
In this second expansion of Final Fantasy XIV, players will have a whole new chapter of the game to explore. The level cap will be raised from 60 to 70, new jobs will become available opening up new ways of play, and new areas will be available to explore with its new swimming and diving mechanics. A fourth residential area will also come into effect, and new high-level raids will be waiting to challenge players further down the line.
Final Fantasy XIV currently has more than six million players across the world, and more Stormblood details are due to be announced next month at Square Enix's European Fan Festival event. |
Q:
Returning a collection with Ajax Request
I have the following in my view:
<ul id="statements">
<% foreach (var s in Model.Statements)
{ %>
<%Html.RenderPartial("StatementControl", s); %>
<% } %>
</ul>
Now I want to use Ajax to return a new Statements object when user clicks on one of several links:
<ul id="statementChoices">
<li>group1<li>
<li>group2<li>
<li>group3<li>
<ul>
If I use Ajax form how do I tell RenderPartial to render the new collection? How do I go about this? What about using JQUery here?
A:
Check out my blog. I've posted about this a few times.
http://www.jarrettmeyer.com/search?q=mvc
Generally, I'd wrap the whole thing that gets refreshed in a <div> and return a partial result from a controller.
|
t k?
36*k - 3102
Differentiate 200*n*u - 369*n - 14*u + 9370 with respect to n.
200*u - 369
Find the third derivative of -1599*g**5 - 297*g**4 - 2*g**2 - g - 61677 wrt g.
-95940*g**2 - 7128*g
What is the first derivative of 21108*a**4*z - 5*a**3*z**3 + 365987*z**3 wrt a?
84432*a**3*z - 15*a**2*z**3
What is the third derivative of -5194*v**6 + 4*v**5 - 355971*v**2?
-623280*v**3 + 240*v**2
Find the second derivative of a**3*x**2 + 11*a**3*x + 787*a**3 + 561302*a**2*x**2 + 12*a*x wrt x.
2*a**3 + 1122604*a**2
Find the second derivative of 8*r**3*t**2*x + 184*r**3*t*x - 14*r**3*x + 3*r**2*t**2*x - 2*r**2*t - 6*r*t - 4721*t**2 + 2*t*x + 2 wrt t.
16*r**3*x + 6*r**2*x - 9442
Find the second derivative of 12165*l**2 + 3688*l.
24330
Differentiate -5*k*y**2 - k*y - 11733*k - 2*y**2 - 16*y - 2 wrt y.
-10*k*y - k - 4*y - 16
What is the third derivative of 310240*q**5 + 557*q**2 + 18*q + 23 wrt q?
18614400*q**2
Find the second derivative of -2317124*p**2 + 2*p - 951255 wrt p.
-4634248
What is the second derivative of 1247568*m**5 + 7767*m + 13 wrt m?
24951360*m**3
What is the third derivative of 2429549*q**5 - 4*q**2 + 161788*q?
145772940*q**2
What is the first derivative of -54426*f**2 - 16581?
-108852*f
What is the second derivative of -21*i**2*o**2 - 131097*i**2*o + 3641*i*o**2 + o wrt o?
-42*i**2 + 7282*i
What is the second derivative of -226*d**2*z**2 - d**2*z + 40*d**2 - 2*d*z - 8*d + 1358*z**2 wrt d?
-452*z**2 - 2*z + 80
Find the third derivative of -201290*t**3 + 91245*t**2 wrt t.
-1207740
What is the third derivative of -b*l**3 + 2*b*l**2*u + 6042643*l**3*u - 660700*l*u wrt l?
-6*b + 36255858*u
What is the third derivative of -f**6 + 45*f**5 - 321*f**3 + 676*f**2 - 5*f - 1?
-120*f**3 + 2700*f**2 - 1926
Differentiate -193*j**2*o + 21*j*o**2 - 22*o**2 - o + 198 with respect to j.
-386*j*o + 21*o**2
What is the third derivative of -12*b**2*j*y**3 + b**2*j - 62*b**2*y**2 + 3*b*j*y**3 + b*j + 783*j*y**2 - 1713*y**4 wrt y?
-72*b**2*j + 18*b*j - 41112*y
Find the second derivative of -3*j*w**3 - 8640*j*w**2 - 12*j*w - 58*j - 3*w**3 - 40*w - 1 wrt w.
-18*j*w - 17280*j - 18*w
Find the third derivative of -7*x**5 + 36985*x**4 - 1446959*x**2 wrt x.
-420*x**2 + 887640*x
Find the third derivative of 162*f**2*w**5 - 4*f**2*w**2 - f**2 + 2*f*n*w**2 - f*w**2 + 133*n*w**3 - 45*n*w**2 wrt w.
9720*f**2*w**2 + 798*n
Find the second derivative of -321*m**4 - 34*m**2 + 2*m + 2159.
-3852*m**2 - 68
What is the second derivative of -105*c*i**2*x + 4786*c*i**2 + 3460*c*i*x - 71*c*x + 1 wrt i?
-210*c*x + 9572*c
What is the first derivative of 2611*q**3 - 7*q + 806523?
7833*q**2 - 7
Differentiate 4352321*a + 34341.
4352321
What is the second derivative of -h**4 + 7*h**3 + 2465*h**2 - 24292*h?
-12*h**2 + 42*h + 4930
What is the second derivative of -2*i**2*j**3 + 2*i**2*j + 47*i*j**3 + 4354*j**3 - 472679*j wrt j?
-12*i**2*j + 282*i*j + 26124*j
Find the third derivative of 408*a**4*l + 17*a**4 - a**2*l + 2542*a*l wrt a.
9792*a*l + 408*a
What is the second derivative of 107321*u**2 + 40546*u?
214642
What is the second derivative of -5*k**4 + 154*k**3 + 27*k**2 - 141254*k wrt k?
-60*k**2 + 924*k + 54
What is the second derivative of -939*a**3 + 21*a**2 - 15758*a wrt a?
-5634*a + 42
Find the first derivative of 2*u**4 - 3001*u**3 - u**2 + 3*u - 155765 wrt u.
8*u**3 - 9003*u**2 - 2*u + 3
Differentiate -199803*q*r + 215668*q with respect to r.
-199803*q
Find the third derivative of -29763*k**4*r**2 + 4*k**2*r**2 + 2*r**2 - 480 wrt k.
-714312*k*r**2
Find the third derivative of 700321*i**6 + 80*i**2 - 219 wrt i.
84038520*i**3
Find the third derivative of -131*y**5 + 178*y**3 - 116*y**2 + 44.
-7860*y**2 + 1068
Find the first derivative of 1202403*j - 992782.
1202403
What is the second derivative of 1619094*y**5 + 3103362*y wrt y?
32381880*y**3
Differentiate -5*o*p*z**3 + 11604*o*p*z - o*z**3 - 5273*o*z**2 + 2*o*z + 2*p with respect to p.
-5*o*z**3 + 11604*o*z + 2
Find the first derivative of -5335*b**3*p + 1978445*b**3 - 106*p**4 wrt p.
-5335*b**3 - 424*p**3
What is the second derivative of -1396*i**3 - 13*i**2 - 2883*i?
-8376*i - 26
Find the second derivative of 283*u**3 + 75*u**2 + 128515*u.
1698*u + 150
Differentiate -182469*a**3 - 56740 with respect to a.
-547407*a**2
What is the second derivative of -71170*k**2*o + 2*k*o - 2784*o wrt k?
-142340*o
What is the third derivative of -1734775*c**3 + 1503037*c**2 wrt c?
-10408650
What is the first derivative of -489*h*m**3*o**2 + 2*h*m**3 - 2*h*m**2 + 559*m*o**2 - 1580779 wrt o?
-978*h*m**3*o + 1118*m*o
Find the first derivative of -335590*s - 380753.
-335590
What is the third derivative of -7*a**3*y**3 - 166*a**3*y + 2*a**2*y**3 + 90510*a*y**3 + 2*y**3 wrt a?
-42*y**3 - 996*y
What is the second derivative of -706570*d**2*t - 1250*d*t - 2*d + 38*t - 1 wrt d?
-1413140*t
Differentiate 3*o**3*y + 10*o**3 - 815*o**2 + 17*o*y**4 + o - 867*y**4 wrt y.
3*o**3 + 68*o*y**3 - 3468*y**3
Find the second derivative of 2*k**2*z**2 + 19*k**2 + k - 5670*z**3 + 2*z - 189 wrt z.
4*k**2 - 34020*z
What is the second derivative of -1634186*b**2 - 1514*b + 358?
-3268372
Find the third derivative of 4908*o**6*v + 154*o**6 + 2*o**2 - 61708*o*v wrt o.
588960*o**3*v + 18480*o**3
What is the derivative of 29615*k*m**3 + 71*m**3 + m**2 - 32*m wrt k?
29615*m**3
What is the first derivative of -5*l**4 - 14*l**3 - 7*l**2 + 40*l + 86225 wrt l?
-20*l**3 - 42*l**2 - 14*l + 40
What is the second derivative of 2*i**2*r**3*u - 100*i**2*r**2*u - 107*i**2*u + i*r**2 + i*r*u + 2*i*u - r**3 - 17628*u wrt i?
4*r**3*u - 200*r**2*u - 214*u
Find the second derivative of -2*l**4 - l**3*u + 2079*l**2 - 4*l*u - 13*l + 114*u + 2 wrt l.
-24*l**2 - 6*l*u + 4158
What is the third derivative of 681*s**4 + 15*s**3*u - 101*s**2*u - s - 59*u wrt s?
16344*s + 90*u
What is the third derivative of 7*v**4*y**3 + 372271*v**4*y - 2113*v**2*y**2 + 2*v*y**3 - 8*v*y + 17*y**3 wrt v?
168*v*y**3 + 8934504*v*y
What is the third derivative of -125732*d**4 - 108421*d**2 wrt d?
-3017568*d
What is the third derivative of 32900*u**4 + 4*u**3 + 280*u**2 + u + 67?
789600*u + 24
What is the second derivative of -83343*k**3 + 59388*k?
-500058*k
What is the second derivative of 5*g**5 + 238*g**2 - 16*g - 198?
100*g**3 + 476
What is the second derivative of -9*q**2*t*v**3 + 10*q**2*t - 22*q**2*v**2 - 3*q*t*v**3 - 33*q*v**3 - 50*t*v wrt q?
-18*t*v**3 + 20*t - 44*v**2
Find the third derivative of -34331*p**4 + 4*p**2 + 2557*p.
-823944*p
What is the second derivative of -2*m**5 + 1188969*m**3*v**2 - 4*m*v**2 + 213*m*v + 33*m + v**2 + 2 wrt m?
-40*m**3 + 7133814*m*v**2
What is the third derivative of -61581*p*q**3*s**3 - 3*p*q**3 - 2*p*q**2*s**3 - 2*p*q**2 - 5863*p*s**3 + p*s**2 + 2*q**3*s + 2*q*s**3 - 5 wrt q?
-369486*p*s**3 - 18*p + 12*s
Find the second derivative of 2965671*f**3*i**2 + 3*f**3 - 37*f**2*i + 2*f*i + 4*f + 5*i wrt i.
5931342*f**3
What is the third derivative of -907*y**6 - 2*y**5 - 14415*y**2?
-108840*y**3 - 120*y**2
Find the second derivative of -364868*n*o**2 + 9*n*o - 32*n - 116*o wrt o.
-729736*n
What is the third derivative of 29823*m**3*r - 2*m**2*r + 38588*r wrt m?
178938*r
What is the second derivative of -5*c*l**3 + 6*c*l**2 - 58*c*l - 59*c - 26*l**3 + 3*l wrt l?
-30*c*l + 12*c - 156*l
Find the third derivative of 6347*r**6 - 89664*r**2 wrt r.
761640*r**3
Find the third derivative of 16*g**3*x**3 - 6*g**3 - 2*g**2*x**3 + g + 88*x**3 - 1107*x**2 + 2 wrt x.
96*g**3 - 12*g**2 + 528
Differentiate 2124*a**2*k**2 - a**2 - 5887*a - 2*k**2 wrt k.
4248*a**2*k - 4*k
What is the third derivative of 63509*m**3*y - 7*m**2*y - 4*m**2 - 2*m - 32*y wrt m?
381054*y
What is the third derivative of -964122*i**4 - 232*i**2 - 40*i wrt i?
-23138928*i
What is the derivative of -37459*h*u**3 - 2*h*u - 102539*h wrt u?
-112377*h*u**2 - 2*h
What is the third derivative of -194242*g**6*o + 10*g**2 - 5433*g*o wrt g?
-23309040*g**3*o
What is the derivative of -581654*l - 284469?
-581654
Find the second derivative of 825809*k**2 - 784*k - 373.
1651618
What is the third derivative of -10*t**5 + 4422*t**4 + 2*t**3 - 44994*t**2?
-600*t**2 + 106128*t + 12
Find the second derivative of -496*j*w**3 + 43409*j*w + 4*w**5 + 2*w**4 wrt w.
-2976*j*w + 80*w**3 + 24*w**2
Find the second derivative of 3*b**3 - 2012*b**2 - 8354*b.
18 |
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Earlier this month, Nevada Rep. Susie Lee joined Democratic colleagues to introduce a resolution opposing efforts to ban transgender people from serving in the Armed Forces.
It was a response to President Trump’s call to reverse an Obama administration policy that, for the first time ever, allowed trans service members to disclose their identity.
Thursday Lee met with representatives from Gender Justice Nevada, the Gay and Lesbian Community Center of Southern Nevada and the ACLU of Nevada for a roundtable discussion about attacks on the LGBT community, HIV prevention, sex workers rights and access to health care, and the transgender military ban.
The Supreme Court decided in 5-4 decision in January to allow Trump to implement the ban while challenges still make their way through the courts.
Frankie Perez, who came out as transgender while serving in the United States Air Force, still doesn’t understand the opposition to transgender service. Research has found allowing trans service members has no significant impact on cost or readiness.
“When (my unit) had training in Georgia, we were in tents and had male and female latrines and showers,” he said. “We only had to make small adjustments. There was no need to build a new facility. There was no cost involved. There wasn’t anything extra.”
Perez added that any money spent on hormone therapy has been significantly less than what the military spends on erectile dysfunction medication.
The Trump administration’s actions notwithstanding, Lee is hoping for bipartisan support for other LGBT issues, including increased HIV treatment funding.
To Lee’s surprise, at his State of the Union speech,Trump announced an ambitious goal to end HIV within 10 years. “He hasn’t introduced any legislation yet,” she added. “I’ll be looking out for it.”
Lee added that one of the top issues Democrats have focused on is reining in prescription drug prices, which could overlap in efforts to reduce HIV by making medications more affordable.
Gary Costa, executive director of Golden Rainbow, said a lot of the federal dollars geared toward prevention have gone away. “There is a lack of dollars to educate the new communities of people who weren’t even alive during the 80s and 90s.” he said. “It’s primarily impacted communities of color.”
Echoing Costa, Andre Wade, the state director of the LGBT rights organization Silver State Equality, added there not only needs to be a push to develop an outreach plan specifically for people of color — who are often most vulnerable — but also an effort to recruit people of color to do that outreach. “We know there is a problem,” he said. “We know through years of research there is intervention that works. We need dollars to have them in place.”
As a member of the House Committee on Education and Labor, Lee is also looking at what needs the LGBT community has when it comes to education resources. ”Recently (the Department of Education) has admitted that they’ve refused to respond to civil rights complaints when they are filed by transgender students,” she said.
Like many in the room, Tristan Torres told Lee about experiences being a trans student within Clark County School District. “I’ve had multiple issues,” he said. “It wasn’t necessarily the students that were the biggest problem. It was the faculty.”
Though others talked about some of the issues within the school district — some briefly rehashed recent decisions to develop policies for gender diverse students — none had heard of specific complaints being filed to the Department of Education.
When Lee asked openly what concerns her office was missing, Allie Goard told her to look into issues plaguing sex workers. “They are a marginalized community who need a voice,” she says.
Goard pointed to Stop Enabling Sex Traffickers Act and Fight Online Sex Trafficking Act, two federal bills signed into law in 2018, Those opposed to the legislation contended it conflates consensual sex work with human trafficking. Goard added these bills hurts sex workers who relied on online “cam shows” as a way to make money.
“I’m speaking from an intersectionality standpoint,” she added. Trans women who can’t find jobs who used to earn income from cam shows “are now forced out on the street to work,” Goard said, “and that’s why you’re seeing these increased levels of violence, especially with trans women of color.”
While it wasn’t talked about during the roundtable, Lee said in an interview after the meeting that one of the priorities being discussed in the House was legislation to protect LGBT people from employment discrimination.
“I think we are going to move pretty quickly on that,” she added.
Though she didn’t know what traction it would get in the Senate, she hoped people could get behind equality. |
Syrian Refugees
Sabah at home in the Bekaa Valley. Sabah, who has diabetes, was home when a neighbor’s house was bombed. Several toes were amputated after a glass wound that has never healed: “I haven't walked in two years." |
Can football season get here already? Because Iowa State and Iowa fans each have even more reasons to be jacked.
The latest fist-pump moment is the unprecedented double ranking of both the Cyclones and the Hawkeyes in the preseason USA TODAY Amway Coaches' Poll, which was released late Thursday morning.
Kirk Ferentz's squad debuts at 19th in the poll, while Matt Campbell's bunch comes in at No. 24.
It's the first time the Cyclones have been ranked in the preseason poll, and the first honor for the Hawkeyes since 2016.
Clemson, the defending national champion, will enter the campaign with the top ranking. It is the first preseason No. 1 ranking for the Tigers in the history of the coaches poll.
Clemson received 59 of 65 first-place votes, with the remaining six all going to second-ranked Alabama. This is the first time since 2010 that only two teams received first-place votes in the preseason.
The rest of the teams in the top five are also the same as those who started last season there, though the order is slightly different. Georgia will open at No. 3, followed by No. 4 Oklahoma and No. 5 Ohio State. It is the first time since 1992 that the preseason top five has been made up by the same teams in consecutive seasons.
MORE ON IOWA: Chad Leistikow's Big Ten championship checklist
MORE ON IOWA STATE: Randy Peterson's observations from media day
The Hawkeyes are picked second in the Big Ten Conference's West Division in the annual Cleveland.com preseason media poll, sharing 14 first-place votes with favored Nebraska.
Iowa State was chosen third in the Big 12 Conference preseason poll, behind league stalwarts Texas and Oklahoma.
The two schools could make more history Aug. 19 when The Associated Press' preseason rankings are released. Iowa State has been ranked in that early poll just once, in 1978. Iowa has 23 preseason top-25 rankings in its history, most recently in 2016.
The annual Cy-Hawk game is scheduled for 3 p.m. Sept. 14. And as long as neither side has an uncharacteristic slip-up in the first couple of weeks, you can expect the hype for the rivalry game to be unprecedented as well.
Bring it on.
FULL AMWAY COACHES' POLL TOP 25
Clemson (59 first-place votes), 1619 points Alabama (6), 1566 Georgia, 1447 Oklahoma, 1415 Ohio State, 1368 LSU, 1218 Michigan, 1155 Florida, 1103 Notre Dame, 1100 Texas, 1038 Texas A&M, 893 Washington, 834 Oregon, 787 Penn State, 699 Utah, 642 Auburn, 606 Wisconsin, 436 (tie) Central Florida, 436 (tie) Iowa, 343 Michigan State, 313 Washington State, 274 Syracuse, 227 Stanford, 200 Iowa State, 169 Northwestern, 161
Others receiving votes: Nebraska 152; Boise State 118; Mississippi State 111; Miami 94; Army 91; Kentucky 79; Virginia Tech 64; Texas Christian 63; Southern California 47; Utah State 32; Fresno State 32; Virginia 30; Cincinnati 25; West Virginia 24; Memphis 24; Oklahoma State 20; South Carolina 15; NC State 12; Duke 10; Boston College 5; Florida State 4; Baylor 4; Appalachian State 4; North Texas 3; Houston 3; UCLA 2; Temple 2; Arizona State 2; Troy 1; Tennessee 1; Mississippi 1; Minnesota 1. |
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Shutdown Windows when pwd-protected screensaver is active...
Hi. I have an API question.
I'm using ExitWindowsEx function to shutdown Windows (usually Win2K). It is working fine, it shutsdown, restarts, etc. If a screensaver is active and password protected though, it does not work at all.
Is there a way to "persuade" Win2K to shutdown even if a password-protected screensaver is active?
I dont have a definate answer for ya unfortunately, but I wonder if it is possible to somehow find the threadID of the screensaver and kill it. I can remember a few years ago fooling around with a program called Sub7 (by mobman) which could do this remotely but that was very very naughty!!!
It is indeed a naughty solution but i don't believe it will solve my problem. I'm using Win2K and it is most probable that the screensaver "tells" the system to lock itself so killing the ss will not unlock the system. This might work on a Win98 system.
Originally posted by Illuvatan
you're trying to shutdown windows while the workstation is locked isn't it ?
windows 2000 has no password protected screensavers, windows locks the workstation and then starts the screensaver.
Yes, that's what i'm trying to do... I know about all the things you mention here.
And I don't know any way to unlock a workstation without entering a password.
Maybe you could try using the shutdown.exe windows has.
Windows has no such exe AFAIK. Perhaps you are talking about a third-party utility. In any case, do you know of any utility which will shutdown the system, even if it has been locked?
* The Perfect Platform for Game Developers: Android
Developing rich, high performance Android games from the ground up is a daunting task. Intel has provided Android developers with a number of tools that can be leveraged by Android game developers.
* The Best Reasons to Target Windows 8
Learn some of the best reasons why you should seriously consider bringing your Android mobile development expertise to bear on the Windows 8 platform. |
Here's Your First Look At The Tess Holliday x Penningtons Collection
There’s no denying that Tess Holliday is a polarizing figure, gathering supporters and detractors with every Instagram post. Recently named one of the “30 Most Interesting People on the Internet” by Time, the model and activist is challenging societal norms left and right with her unapologetic self-acceptance. And if her 1.1 million followers are any indication, it’s clear she’s made an impact. With that much power behind her, it’s no surprise that she’s taking a dip in the designer pond, releasing Tess Holliday x Mblm,a year-long collaboration with Canadian retailer Penningtons.
Similar to how Target is angling its WhoWhatWear collaboration, Penningtons will offer several new Holliday-designed styles each month, providing a revolving door of items. By delivering fresh options monthly, chances are, you’re bound to find an affordable must-have (and have a better chance of snagging a style you’re longing for).
The first offering is filled with casual-chic pieces that could easily translate from office to out; perfect for those who need a wardrobe of double-duty items. “It's all about having a few statement pieces, but mostly your basic everyday pieces that are staples in your wardrobe,” Holliday told Refinery29. “I call it ‘effortless,’ because that's what I really wanted for the line. Something you know will work and make you feel good and requires little effort.”
Regarding her biggest challenges, Holliday explained: “Remembering that not everyone had my design esthetic. Not everyone loves my kind of style, but with that being said, my style is so eclectic! I tried to keep everyone in mind and give options for women each month that allowed them to show off or cover up as much as they wanted. There are bodysuits, crop tops, and sheer items; but there are also sweaters, maxi dresses, and other pieces for those that don't love showing it all off.” And with prices ringing in under $100, chances are you’ll be able to regularly refresh your closet without breaking the bank.
With that idea in mind, we’re preparing our wallets and wardrobes for the monthly drop. Click through to see the shoppable pieces we can’t wait to get our hands on. |
1. Introduction {#sec1-molecules-23-01827}
===============
Although tablets and capsules are the most popular types of pharmaceutical dosage forms, different oral liquid formulations (syrups, herbal extracts, suspensions, emulsions, etc.) still have specific therapeutic indications, mainly in paediatrics. Flavouring is a crucial part of these formulations because patient compliance is highly dependent on the taste of the product. Usually they contain high amount of sweet carbohydrates (glycose, fructose, maltitol, xylitol, sorbitol, etc.), which can be metabolized by different microorganisms, thus the product can be easily contaminated \[[@B1-molecules-23-01827]\]. It must be noted, that these liquid preparations are opened and closed multiple times during their life-time and each application increases the possibility of contamination. In order to avoid it, an appropriate amount of preservatives must be used, which can kill or inhibit the growth of bacteria, fungi and other unicellular. The exact mechanism of action of preservatives is unclear in some cases, but as the cell membrane is the only common subcellular component in these microbes, they mostly distort the structure of the membrane resulting in several consequences \[[@B2-molecules-23-01827]\]. Their cytotoxicity is mostly based on these effects as well \[[@B3-molecules-23-01827]\].
One of the most widely used group of pharmaceutical preservatives is the parabens. They are derivatives of 4-hydroxybenzoic acid in the form of its carboxylic esters. The most commonly used parabens ([Figure 1](#molecules-23-01827-f001){ref-type="fig"}) are methyl paraben (MP) (E218), ethyl paraben (EP) (E214), propyl paraben (PP) (E216), butyl paraben (BP), heptyl paraben and their respective sodium salts. The longer the alkyl chain, the lower the solubility in water is. Hence, some co-solvent such as ethanol is usually required to increase their solubility and it must also be noted, that the sodium salts are less frequent in different formulations. Generally, they are considered as synthetic compounds, but in the recent years many natural sources were found \[[@B4-molecules-23-01827],[@B5-molecules-23-01827],[@B6-molecules-23-01827]\]. They are preferred in the pharmaceutical and cosmetic industries, because of their odourless and tasteless characteristics, great chemical stability over a wide range of pH values and a broad spectrum of antimicrobial activity \[[@B7-molecules-23-01827]\].
The esters of 4-hydroxybenzoic acid also have certain well-known risks. In the case of topical application, contact dermatitis is a well-known problem \[[@B8-molecules-23-01827],[@B9-molecules-23-01827]\] however, the latest results are controversial, describing a low occurrence of allergic reactions caused by parabens \[[@B10-molecules-23-01827],[@B11-molecules-23-01827]\] or a severe influence on sensitization \[[@B12-molecules-23-01827]\]. Recent studies have indicated the carcinogenic effect of parabens, as they interfere with oestrogen receptors \[[@B13-molecules-23-01827],[@B14-molecules-23-01827]\]. Furthermore, in vivo evidence suggests that urine paraben levels can be associated with menstrual cycle problems \[[@B15-molecules-23-01827]\]. They are able to penetrate through the skin from cosmetic products \[[@B16-molecules-23-01827],[@B17-molecules-23-01827]\]. Their direct cytotoxic behaviour has been reported on corneal epithelial cells \[[@B18-molecules-23-01827]\], on dermal fibroblasts \[[@B19-molecules-23-01827]\] and on liver cells \[[@B20-molecules-23-01827]\]. Paraben exposure is not only restricted to the users of cosmetics \[[@B21-molecules-23-01827]\], as they can pass through the placenta \[[@B22-molecules-23-01827]\] and can be measured in the milk of lactating mothers \[[@B23-molecules-23-01827]\]. These results suggest a decline in the use of these 4-hydroxybenzoic acid derivatives in oral and topical formulations during the next few years.
An oral, liquid pharmaceutical preparation contains many excipients, which is the reason why cytotoxicity tests of each chemical by itself is not enough to gain a comprehensive view of the biocompatibility profile of the product. There are only few studies on how the biocompatibility of an excipient is influenced if other components are present in the test systems. However, in order to get authorized by governmental authorities, the whole product cannot be toxic, but positive interactions might decrease the appropriate concentration of additives i.e., the quantity of preservatives may also be reduced. However, serious cytotoxicity values may be measured, if the excipients can potentiate their harmful effects \[[@B24-molecules-23-01827]\]. As the cytotoxic effects of surface-active agents are well-known \[[@B25-molecules-23-01827]\], they might have synergetic antimicrobial activity with preservatives. Different co-solvent mixtures can have different biocompatibility profiles and might modify the toxicity of preservatives, increasing their effect on the cell membranes by creating a better chemical environment at the site of action \[[@B24-molecules-23-01827]\].
In this study, our objective was to investigate the cytotoxicity and antimicrobial properties on Caco-2 cells and on various pathogenic microorganisms of different 4-hydroxybenzoic acid derivatives alone and in two complex co-solvent systems to explore interferences between the preservatives and the component of the co-solvent systems. Caco-2 cells are widely applied as an in vitro model of human gastrointestinal transport and mainly used as a monolayer rather than individual cells, however several assays are performed prior to reach complete integrity, such as end point or non-invasive cell viability assays (MTT assay, LDH test, RT-CES, etc.) \[[@B26-molecules-23-01827]\]. In our antimicrobial experiments, our test solutions were tested on clinically relevant pathogens: *S. aureus* as a Gram-positive facultative anaerobe, *E. coli* and *P. aeruginosa* as a Gram-negative aerobes and *C. albicans* as the most common fungal pathogen and *C. parapsilosis* and *C. glabrata* as the top *Candida* species opportunistic pathogens different from *C. albicans* \[[@B27-molecules-23-01827]\].
The formulations of the investigated systems contain a co-solvent and a surface-active agent. The first formulation (S1) consisted of 30% (*v*/*v*) glycerol and 0.002% (*v*/*v*) Polysorbate 20. The surfactant of the second formulation (S2) was 0.5% (*v*/*v*) Capryol PGMC™ and the parabens in the form of their 10 (*w*/*w*)% solutions, dissolved in 70% (*v*/*v*) ethanol. [Table 1](#molecules-23-01827-t001){ref-type="table"} and [Table 2](#molecules-23-01827-t002){ref-type="table"} summarize the composition of every solution used in our experiments. The experimental design is presented in [Figure 2](#molecules-23-01827-f002){ref-type="fig"}.
Test solutions were prepared in situ, 10 min before the inoculation for antimicrobial investigations. Caco-2 cells were incubated for 30 min with the test solutions, then these solutions were removed and the MTT-solution was added for a 3 h long reaction. The converted formazan crystals were dissolved in appropriate solvents after the unreacted MTT was removed. Absorbance was measured at two different wavelengths and the cell viability was calculated. After seeding the bacterial and fungal cells in appropriate concentrations into 96-well microplates, a 24 h long incubation was started. Optical density was measured at two wavelengths at the end of the incubation period.
2. Results {#sec2-molecules-23-01827}
==========
2.1. Cytotoxicity Tests {#sec2dot1-molecules-23-01827}
-----------------------
### 2.1.1. Cytotoxicity of Parabens {#sec2dot1dot1-molecules-23-01827}
In order to mimic the dilution of samples in the gastrointestinal tract, the cytotoxicity of parabens was measured in tenfold, hundredfold and thousand-fold dilutions ([Figure 3](#molecules-23-01827-f003){ref-type="fig"}). The samples were diluted by PBS. At 0.2 (*w*/*w*)% butyl and ethyl paraben had significantly higher cytotoxicity than methyl and ethyl paraben, which had similar toxicity patterns. There was a linear relationship between the cytotoxicity and the dilution ratio of different paraben derivatives. The more concentrated samples decreased the cell viability and resulted in significant cytotoxicity. The higher the ratio of dilution of parabens, the better the cell viability of the Caco-2 cell line was.
### 2.1.2. Cytotoxicity of Solvents {#sec2dot1dot2-molecules-23-01827}
Ethanol and glycerol were tested in different concentrations diluted with phosphate buffered saline (PBS) for cytotoxicity experiments. As it can be seen on [Figure 4](#molecules-23-01827-f004){ref-type="fig"} and [Figure 5](#molecules-23-01827-f005){ref-type="fig"}, the cell viability decreased in a concentration dependent manner in the case of these solvents. The IC~50~ (the inhibitory concentration value, where the 50% cell viability was measured by an MTT test) of glycerol was 45 (*v*/*v*)%. In our complex systems, the concentrations of glycerol were 30 (*v*/*v*)%, 3 (*v*/*v*)%, 0.3 (*v*/*v*)%, 0.03 (*v*/*v*)% which were lower than this inhibitory concentration.
The concentrations of ethanol (1.75 (*v*/*v*)%, 1.4 (*v*/*v*)%, 0.14 (*v*/*v*)%, 0.014 (*v*/*v*)%) in complex systems were applied for cytotoxicity and antimicrobial tests. Based on this cytotoxicity test, the IC~50~ value cannot be determined in these concentration ranges. The cell viability slightly decreased according to the concentration, but the highest concentration (1.75 (*v*/*v*)%) decreased the cell viability significantly (80 ± 1.7%).
### 2.1.3. Cytotoxicity of Formulated Systems {#sec2dot1dot3-molecules-23-01827}
The cytotoxicity of S1 can be seen in [Figure 6](#molecules-23-01827-f006){ref-type="fig"}. The formulated control was highly toxic, and the cell viability was less than 50% compared to the untreated control at the original concentration. MP had the highest survivability from all esters, the second was EP. The results of the two longer parabens were not significantly different from each other at the tested concentrations. Moreover, the methyl paraben was not significantly different from the formulated control, but at the original concentration and at tenfold dilution, along with ethyl paraben, these derivatives were different from the longer ones. All statistical differences between the test solutions diminished at hundredfold and thousand-fold dilutions.
In the case of S2 ([Figure 7](#molecules-23-01827-f007){ref-type="fig"}), BP had the highest cell viability at the original concentration, while the other parabens caused nearly total cell death. The tenfold dilution showed another ranking: propyl and ethyl paraben matched the results of the formulated control, while BP had slightly worse cell viability and MP was also significantly more toxic than the formulated control. After further dilution, all esters, except BP caused 100% cell viability.
2.2. Antimicrobial Tests {#sec2dot2-molecules-23-01827}
------------------------
### 2.2.1. Antifungal Tests {#sec2dot2dot1-molecules-23-01827}
In order to test the antimicrobial properties of parabens, three different concentrations were used. Cell viability was expressed as a percent of the absorbance of the positive control in the case of every species, respectively. The critical 50% cell viability threshold was presented with a line in each figure. Above this value a certain compound is considered ineffective in the case of antimicrobial activity, while below this line it has an inhibitory effect. We also formulated a control solution for every paraben to control their normal antimicrobial effects, without any additives.
In the case of *C. albicans*, ([Figure 8](#molecules-23-01827-f008){ref-type="fig"}) there was no significant difference between formulated and non-formulated parabens, both the control solutions and the S1 and S2 solutions resulted in the same results. However, S1-PP, S1-BP and S2-EP had higher cell viability values than their controls, the formulations decreased the effectiveness of the parabens. There was no difference between the longer and the shorter esters.
The investigation of *C. parapsilosis* ([Figure 9](#molecules-23-01827-f009){ref-type="fig"}) showed a high cell viability gap between the control parabens and the formulations. The control solutions totally eradicated the fungal cells, however, both formulations slightly increased their survivability. The increase of dissolved paraben did not reduce this gap, but even further weakened the antimicrobial effect of the parabens. At the highest concentration, the S1-PP no longer had inhibitory effect at all.
*C. glabrata* was also sensitive to both the control and the formulated solutions ([Figure 10](#molecules-23-01827-f010){ref-type="fig"}), but the results of S1 were worse than S2 or the control. This lack of effectiveness increased with the growing concentration.
### 2.2.2. Antibacterial Tests {#sec2dot2dot2-molecules-23-01827}
*S. aureus* ([Figure 11](#molecules-23-01827-f011){ref-type="fig"}) was not sensitive to the control solutions, and increasing doses of MP, EP and PP did not decrease the cell viability. Meanwhile, the ethanolic solution of BP and S1 proved to be highly effective. S2 containing Capryol PGMC™ apart from ethanol was also effective, with the exception of the formulated MP, which only passed the 50% limit at 1.5 (*w*/*w*)%.
*E. coli* ([Figure 12](#molecules-23-01827-f012){ref-type="fig"}) had resistance against EP and BP, except for the S1, which was very effective against it. The addition of a surface-active agent in S2 could increase the antimicrobial properties of BP and PP as they showed greater inhibitory effect than the normal ethanolic solutions. S1 showed higher efficacy than the other solutions.
*P. aeruginosa* ([Figure 13](#molecules-23-01827-f013){ref-type="fig"}) showed the widest spectrum of resistance. The ethanolic EP, PP and BP could not inhibit its growth at all, like PP and BP in S2. The presence of Capryol PGMC™ was also advantageous for the EP and BP, their effectiveness was highly increased, but they still could not reach a 50% inhibitory rate. All derivatives formulated in S1 were totally effective in every concentration, and methyl paraben was also effective at the highest dose in S2 and the control ethanolic solutions.
3. Discussion {#sec3-molecules-23-01827}
=============
The microbial stability of any oral pharmaceutical product until its expiry date is essential regardless if the product was contaminated during its application. However, the use of preservatives is a cheap way to protect any product, there are authorized drugs on the market with ineffective microbial protection \[[@B28-molecules-23-01827]\]. In our study, we formulated two different co-solvent systems:
S1 which contained 30% (*v*/*v*) glycerol and 0.002% (*v*/*v*) Polysorbate 20 (HLB value: 16.7) and S2 which contained 0.5% (*v*/*v*) Capryol PGMC™ (HLB value: 5) and parabens in the form of their 70% (*v*/*v*) ethanolic solutions \[[@B25-molecules-23-01827]\].
The basis of selection was to use one co-solvent, different surfactants with high and moderate HLB values and preservatives (parabens) in our investigations, because these excipients are officially widely applied in liquid, oral pharmaceutical formulations. In order to comply with EMEA guidelines, these authorized excipients were used in safe concentrations \[[@B29-molecules-23-01827]\]. The cytotoxicity of ethanol and glycerin as co-solvents were also tested on Caco-2 cell line and their cytocompatible concentrations were determined. The safe 0.5 (*v*/*v*)% ethanol concentration was controlled in OTC products for children \[[@B30-molecules-23-01827]\]. We applied ethanol as co-solvent in 1.75 (*v*/*v*)%, 1.4 (*v*/*v*)%, 0.14 (*v*/*v*)%, 0.014 (*v*/*v*)% concentration range and these concentrations proved to be cytocompatible on Caco-2 cells. Ethanol can increase the solubility of several drugs, such as COX-2 inhibitors even at low concentration and it showed cytotoxic properties at 10% (*v*/*v*) on Caco-2 cells \[[@B31-molecules-23-01827],[@B32-molecules-23-01827]\].
The effective glycerol concentration for enhancing the solubility of different active pharmaceutical ingredients (APIs) was proved from 20% (*v*/*v*) \[[@B33-molecules-23-01827]\]. The concentration of glycerol of our complex systems was used from 30 (*v*/*v*)%, 3 (*v*/*v*)%, 0.3 (*v*/*v*)%, to 0.03 (*v*/*v*)% which were lower than the inhibitory concentration.
The selection of Polysorbate 20 and Capryol PGMC based on our previous experiments \[[@B25-molecules-23-01827]\]. It was found that the safe concentration range of Polysorbate 20 was 0.002 (*v*/*v*)%, 0.0002 (*v*/*v*)%, 0.00002 (*v*/*v*)% and 0.000002 (*v*/*v*)%. The HLB value of Polysorbate 20 is high and effective solubilizing properties can be presented. Surfactant with lower HLB value was Capryol PGMC and cytocompatible concentration range (0.5 (*v*/*v*)%, 0.05 (*v*/*v*)%, 0.005 (*v*/*v*)%, 0.0005 (*v*/*v*)%) was confirmed in our study.
Based on our experimental design, we tested two complex formulations containing different parabens to evaluate their cytotoxic and antimicrobial interference and to investigate how these materials influence the safety and efficacy of parabens on human cells, bacteria and fungi---*E. coli*, *P. aeruginosa*, *S. aureus*, *C. albicans*, *C. parapsilosis*, *C. glabrata*. The antimicrobial stability can depend on the formulation and the different excipients used in the product. Ribes et al. have found that the antimicrobial effect of cinnamon leaf essential oil can be heavily enhanced by a nanoemulsion of emulsifying agents \[[@B34-molecules-23-01827]\]. Han et al. also investigated the effects of preservatives and they found that there are multiple preservatives which influence the stability of Diprivan^®^ injection (an intravenous anaesthetic emulsion) in an undesirable way \[[@B35-molecules-23-01827]\].
As it was found, S1 and S2 complex systems had significant concentration dependent cytotoxic effect on Caco-2 cells. In the in vitro Caco-2 cell line investigations, our systems were diluted with phosphate buffered saline (PBS). We prepared our solutions 10 minutes before the starting point of the incubations of Caco-2 cells to prevent any accelerated hydrolysis caused by the other excipients as the transesterification of parabens by Caco-2 cells after long incubation times was reported \[[@B36-molecules-23-01827]\], the incubation time was minimized in our MTT-test in order to avoid any significant conversion. Our experiment was supported by the results of Tomankova et al., because they showed that parabens were chemically stable, and they only converted by spontaneous hydrolysis in aqueous solutions after months of storage \[[@B37-molecules-23-01827]\].
It was found that in our test systems the relative toxicity of parabens was different in these two formulated systems, and the ranking of toxicity was not general. The parabens alone, presented the ranking of BP \> PP \> EP \> MP as butyl paraben was the most toxic. In most scientific studies, such as the publication of Dagher et al., it was reported that the cytotoxicity increased with the length of alkyl chains as well \[[@B38-molecules-23-01827]\]. They investigated that MP was the least toxic on MCF7 breast cancer cells, while the cytotoxicity of more lipophilic parabens (BP and benzyl paraben) eventually increased. While the S1 had identical results, in S2, the other excipients could modify the ranking, BP at the highest concentration was the safest paraben.
In S1, in the presence of glycerol and Polysorbate 20, MP was the least toxic compound, while the other parabens with longer alkyl chains had similar curves and reached nearly total cell death at 0.2 (*w*/*w*)%. At tenfold dilution, the cell viability value of MP was significantly higher than the other parabens, but at that concentration, EP became distinguishable from the more lipophilic derivatives. The more diluted solutions showed no toxicity at all. In S1, the low cell viability values can be explained by the increased osmotic pressure of glycerol which has already been proved on human cells \[[@B39-molecules-23-01827]\]. The Polysorbate 20, which was found to have an IC~50~ value of 0.004% (*v*/*v*) can easily distort the cell membrane \[[@B25-molecules-23-01827]\]. On A549 human lung cancer cells and HUVECs even a very minimal concentration of Polysorbate 20 caused nearly total cell death \[[@B40-molecules-23-01827]\]. Polysorbate is known to increase the transport of certain drug molecules through cell membranes by a membrane component solubilization mechanism \[[@B41-molecules-23-01827]\]. It was supposed that this dual effect---the osmotic stress and the distortion of the cell membrane---was responsible for the dramatically low cell viability of Caco-2 cells. This may well mean that when a pharmaceutical product has a high osmotic pressure or contains a surfactant with high HLB value, the cytotoxicity must be reconsidered, because these excipients can enhance the toxicity of each other in a synergetic way.
In S2, in the presence of ethanol and Capryol PGMC™, the results were controversial. At the original concentration, BP was the least toxic compound, but at tenfold dilution, it was not statistically distinguishable from MP, while these two were significantly different from both the control, and the other esters. The formulated control of the second system had lower cell viability than, the control of the first system. The parabens alone still showed the same ranking as the S1, it can be assumed, that the surfactant with low HLB value were responsible for the lower toxicity of BP.
In the case of the antimicrobial tests, our systems were tested on clinically relevant pathogens which can represent a variety of possible contaminating agents. However, the exact mechanism of action of parabens is unknown, and there are various papers describing different pathways. Bredin et al. found that on *E. coli*, PP had similar potassium efflux-creating effects as polymyxin. The site of action was the porin channels, as their specific blockers could protect the bacteria from damage \[[@B42-molecules-23-01827]\]. It was also reported that they could distort the structure of the cell membrane \[[@B43-molecules-23-01827]\]. It was also a menacing result, as parabens showed higher affinity to distort phospholipids in mammalian cell membranes than bacterial ones. A general theory of action, is that like other weak acids used as preservatives (sorbates, benzoates, propionates, etc.) 4-hydroxybenzoic acid at acidic pH penetrates the cells in a nonionized way and in the cytosol, it dissolves and the resulting H^+^ act as the main metabolic disruptive force \[[@B44-molecules-23-01827]\]. According to Thong et al., MP had no direct dependence on the pH, for *A. sulphureus* and *P. viridicatum*, nevertheless, it was able to drastically decrease the production of ochratoxin A for both species \[[@B45-molecules-23-01827]\]. Er et al. reported similar results, where the difference between the inhibition on the growth and the biofilm formation at pH 6 and pH 7 on *Salmonella* strains was not significant \[[@B46-molecules-23-01827]\]. A possible way of resistance to parabens can be the hydrolysis of esters by enzymatic activity \[[@B47-molecules-23-01827]\].
As for the antibacterial results, it can be said that inhibitory potential of parabens differed greatly. While *E. coli*, a Gram-negative bacterium showed resistance towards PP and BP, another Gram-negative strain, *P. aureginosa*, had nearly total resistance towards all parabens, and only the highest dose of MP could effectively inhibit it. The S1 formulation was very effective against both species, even the formulated control, and without any additional paraben could eradicate the microbes. This is greatly advantageous, as the resistance of *P. aeruginosa* towards many disinfectants in known \[[@B48-molecules-23-01827]\]. Formulation S2 which only contained an additional surface-active agent, could not drastically increase the effect of parabens, and only a small decrease of cell viability could be measured. The formulated control of S2 had no effect on *P. aeruginosa*, but was effective against *E. coli*, as this bacterium was overall more sensitive to the parabens. The only Gram-positive bacterium, *S. aureus,* was resistant to MP, EP and PP and susceptible only to BP. S1 caused total cell death and the presence of Capryol PGMC™ could effectively increase the effect of the shorter esters. It can be stated that Gram-positive and negative strains have different sensitivity towards surface-active agents and as the results indicate, the Gram-positive species are more vulnerable to them, supposedly due to their different cell wall structure. Smaoui et al., found that 1% (*w*/*w*) MP had limited effect on *S. aureus*, which correlates with our results \[[@B49-molecules-23-01827]\]. The controversial susceptibility to the different parabens means, that for the tested bacteria, there was no linear relationship between the length of alkyl chain and the antimicrobial effect as it was stated in literature \[[@B50-molecules-23-01827]\], but rather every ester must be tested against a given microbe in a solution that has the composition of the final pharmaceutical product.
The cell wall of *Candida* species is different from its bacterial counterparts, it is not a rigid structure, but a more flexible outer layer of the cells, capable of structural changes \[[@B51-molecules-23-01827]\]. The cell wall of *C. albicans* and *C. glabrata* are relatively well described. They are similar, the main reported difference being their adhesin-like proteins, which are mostly important for the pathogenicity and mask them from the immune system \[[@B52-molecules-23-01827]\]. However, the cell wall of *C. parapsilosis* is not described precisely, but it also has similar attributes that of the *C. albicans* \[[@B53-molecules-23-01827]\]. Despite this, *C. parapsilosis* was the most resistant of all the tested yeasts, and the only one where the 50% cell viability threshold was reached, in case of the highest concentration of PP formulated in the first system. *C. parapsilosis* was also sensitive to ethanolic solutions of parabens, but both S1 and S2 had less effect on it as cell viability was always above 20% for the formulated systems. For *C. glabrata* and *C. albicans*, there was a small, but persistent gap between the formulated and the non-formulated test solutions. At the same time, it could be noted, that in most scenarios MP was as effective as the longer parabens which correlates well with the broad range study of Matos et al. \[[@B54-molecules-23-01827]\]. On all fungi, but mostly on *C. parapsilosis*, a very interesting pattern could be seen: the control samples, which only consists of the given ester, ethanol and PBS had better inhibition effect than the formulated systems. Nor a high amount of glycerol---and the osmotic pressure of it---nor the two surfactant, could enhance the effect of parabens, on the contrary, they increased the survivability of the fungi. The exact mechanism is poorly understood and needs further investigation. Also, for the tested fungi, no linear relationship was found between the length of alkyl chain and the antimicrobial activity, as stated in previous results \[[@B55-molecules-23-01827]\].
Generally, the S1 totally eradicated all bacteria, so they were less resistant to the dual effect of osmotic pressure and solubilization, while S2 had limited effects on them. The fungi were mostly sensitive to the parabens, but both formulations proved to be less effective on them, than the ethanolic solutions of parabens. The two systems presented similar patterns of cytotoxicity on human cells, but as it was seen on the bacteria and the fungi, but the length of the paraben alone is not informative to to predict the cytotoxic and antimicrobial properties.
4. Materials and Methods {#sec4-molecules-23-01827}
========================
4.1. Materials {#sec4dot1-molecules-23-01827}
--------------
Methyl 4-hydroxybenzoate and glycerol were purchased from Hungaropharma (Budapest, Hungary). Ethyl 4-hydroxybenzoate was obtained from Acros Organics (Geel, Belgium), propyl 4-hydroxybenzoate from Alfa Aesar (Karlsruhe, Germany), butyl 4-hydroxybenzoate from TCI (Zwijndrecht, Belgium). Capryol PGMC™ was a kind gift from Gattefossé (Lyon, France). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Dulbecco's Modified Eagle's Medium (DMEM), phosphate buffered saline (PBS), Trypsin-EDTA, Heat-inactivated fetal bovine serum (FBS), L-glutamine, non-essential amino acids solution, gentamycin, RPMI-1640 broth with L-glutamine and Mueller-Hinton broth were purchased from Sigma-Aldrich (Budapest, Hungary). Non-essential amino acids solution and penicillin-streptomycin mix were obtained from VWR (Debrecen, Hungary), L-glutamine and GlutaMax™ supplement was from Thermo Fisher (Budapest, Hungary).
4.2. Cell Culture {#sec4dot2-molecules-23-01827}
-----------------
Caco-2 cell line was obtained from the European Collection of Cell Cultures (ECACC, Salisbury, United Kingdom). Cells were grown in plastic cell culture flasks in Dulbecco's Modified Eagle's Medium, supplemented with 3.7 g/L NaHCO~3~, 10% (*v*/*v*) heat-inactivated fetal bovine serum (FBS), 1% (*v*/*v*) non-essential amino acids solution, 1% (*v*/*v*) L-glutamine, 100 IU/mL penicillin, and 100 µg/mL streptomycin at 37 °C in an atmosphere of 5% CO~2~. The cells were routinely maintained by regular passaging and glutamine was supplemented by GlutaMax™. The cells used for cytotoxic experiments were between passage numbers 20 and 40.
4.3. Cytotoxicity Tests {#sec4dot3-molecules-23-01827}
-----------------------
The cytotoxic effects of the various solutions were evaluated using the 3-(4,5-dimethylthiazol-2-yl))-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity method. Caco-2 cells in complete medium were seeded on 96-well plate at a final density of 10.000 cells/well. After 7 days, the medium was removed, and the cells were incubated for 30 min with the test solutions. All test solutions were prepared 10 min before the start of incubation. The samples were removed, and a 5 mg/mL MTT solution (MTT salt solved in PBS) was added to each well. The plates were incubated for 3 h, then the MTT solution was removed and 0.1 mL of a solution of isopropanol---1 M hydrochloride acid (25:1) was added to dissolve the formed formazan crystals. The absorbance was measured at 570 nm against a 690 nm reference with a Thermo-Fisher Multiskan Go (Thermo Fisher, Budapest, Hungary) microplate reader. Cell viability was expressed as a percent of the cell viability of the untreated control cells, which were incubated with PBS for 30 min.
4.4. Antimicrobial Tests {#sec4dot4-molecules-23-01827}
------------------------
Antibacterial and antifungal susceptibility testing was performed using standard broth microdilution method in accordance with the recent EUCAST protocols (E.Dis 5.1, E.Def 7.3.1) against *Pseudomonas aeruginosa* (ATCC^®^ 27853™), *Escherichia coli* (ATCC^®^ 25922™), *Staphylococcus aureus* (ATCC^®^ 43300™), *Candida albicans* (ATCC^®^ 10231™), *C. parapsilosis* (ATCC^®^ 22019™) and *C. glabrata* (ATCC^®^ 90030™) \[[@B56-molecules-23-01827],[@B57-molecules-23-01827]\]. Briefly, the broth microdilution assays were performed using 96-well standard microtitre plates, where the given concentrations of the tested compounds are prepared in RPMI-1640 and Mueller-Hinton medium for fungal species and bacteria, respectively. All test solutions were prepared 10 min before the start of incubation. The final volume of each well contained 100 µL from the tested compounds and 100 µL fungal or bacterial inoculum. The inoculum size was 2 × 10^3^ cells/mL and 5 × 10^5^ CFU/mL for Candida species and bacteria species, respectively. Plates were incubated for 24 h at 37 °C. After the incubation period, the absorbance was measured by a Thermo-Fisher Multiskan Go (Thermo Fisher) microplate reader at 492 nm and 600 nm for fungal species and bacterial species, respectively. Prominent inhibition was determined based on turbidity as at least 50% growth reduction compared with the compound-free control. Percent change in turbidity was calculated on the basis of absorbance (A) as 100% × (A~well~ − A~background~)/(A~compound-free\ well~ − A~background~). The background was measured from the microbe-free well.
4.5. Statistical Analysis {#sec4dot5-molecules-23-01827}
-------------------------
All data were analysed using GraphPad Prism (version 6; GraphPad Software, Inc., La Jolla, CA, USA). In case of MTT-assay results, the data was presented as means ± SEM. Each cell viability value represents the mean of twelve independent, parallel wells, with the highest and lowest absorbance values were excluded when calculating the mean. After that, at each concentration, the means of different solutions where compared with one-way ANOVA test followed by Tukey's test when all solutions were compared to each other ([Table 3](#molecules-23-01827-t003){ref-type="table"}).
Previously, all data group were analysed with Shapiro-Wilk test for Gaussian distribution and Bartlett's test for equal variances. In each case we used significance level *p* \< 0.05. In case of antimicrobial tests the results of four parallel, independent wells were represented as means ± SEM.
5. Conclusions {#sec5-molecules-23-01827}
==============
Different test systems containing parabens as preservatives were formulated (S1: glycerol and polysorbate 20; S2: ethanol and Capryol PGMC™) to observe any kind of correlation between the cytotoxicity and microbial inhibitory potential of parabens. The cytocompatibility and antimicrobial activity of parabens depends on the length of alkyl chains, the chemical environment and the targeted cells. The IC~50~ values of different parabens can be modified by other excipients. Co-solvents (glycerol, ethanol) and surfactants (Polysorbate 20 and Capryol PGMC) can modify the cytotoxicity and antimicrobial activity of different parabens. The mechanism of these connections may be different, because surfactants may solubilize membrane components and disrupted the membrane integrity, while co-solvents resulted in the damage of mitochondria in the cells. It can be concluded that in vitro data are not necessarily predictive, but complemented with in vivo experiments could be informative.
The project was financed by the Gedeon Richter's Talentum Foundation (1103 Budapest, Gyömrői street 19-21). The published work was also supported by EFOP-3.6.1-16-2016-00022 and EFOP-3.6.3-VEKOP-16-2017-00009.
**Sample Availability:** Not available.
I.B. and D.N. designed the experiment. D.N., M.M., N.P. and Á.P. carried out the cytotoxicity experiments. F.N. and R.K. made the antimicrobial tests. P.F., Z.U., F.F., J.V. and I.B. evaluated the data. D.N. carried out the statistical analysis. All authors read and approved the final manuscript.
The authors declare no conflict of interest.
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{#molecules-23-01827-f010}
{#molecules-23-01827-f011}
{#molecules-23-01827-f012}
{#molecules-23-01827-f013}
molecules-23-01827-t001_Table 1
######
Composition of test solutions for cytotoxicity tests.
Component S1 S2
-------------------- ---------------------------------------------------------------------- --------------------------------------------------------------
**Paraben** 0.2 *w*/*w*%, 0.02 *w*/*w*%, 0.002 *w*/*w*%, 0.0002 *w*/*w*%
**Glycerol** 30 *v*/*v*%, 3 *v*/*v*%, 0.3 *v*/*v*%, 0.03 *v*/*v*% \-
**Polysorbate 20** 0.002 *v*/*v*%, 0.0002 *v*/*v*%, 0.00002 *v*/*v*%, 0.000002 *v*/*v*% \-
**Capryol PGMC™** \- 0.5 *v*/*v*%, 0.05 *v*/*v*%, 0.005 *v*/*v*%, 0.0005 *v*/*v*%
**Ethanol** \- 1.4 *v*/*v*%, 0.14 *v*/*v*%, 0.014 *v*/*v*%, 0.0014 *v*/*v*%
**PBS** solvent, used for tenfold, hundredfold, thousand-fold dilution
molecules-23-01827-t002_Table 2
######
Composition of test solutions for antimicrobial tests.
Component S1 S2 Control
-------------------------- -------------------------------------------- -------------------------------------------- --------------------------------------------
**Paraben** 0.1 *w*/*w*%, 0.15 *w*/*w*%, 0.25 *w*/*w*%
**Glycerol** 30 *v*/*v*% \- \-
**Polysorbate 20** 0.002 *v*/*v*% \- \-
**Capryol PGMC™** \- 0.5 *v*/*v*% \-
**Ethanol** \- 0.7 *v*/*v*%, 1.05 *v*/*v*%, 1.75 *v*/*v*% 0.7 *v*/*v*%, 1.05 *v*/*v*%, 1.75 *v*/*v*%
**RPMI-1640** solvent for antifungal tests
**Mueller-Hinton broth** solvent for antibacterial tests
molecules-23-01827-t003_Table 3
######
Result of Tukey\'s multiple comparison test performed on the results of Caco-2 cells. FC: formulated control, Methyl: formulated methyl-paraben, Ethyl: formulated ethyl-paraben, Propyl: formulated propyl-paraben, Butyl: formulated butyl-paraben. \* *p* \< 0.05; \*\* *p* \< 0.01; \*\*\* *p* \< 0.001, \*\*\*\* *p* \< 0.0001.
ANOVA Followed by Tukey's Multiple Comparisons Test Level of Significance
----------------------------------------------------- -----------------------
Parabens alone, 0.2% Methyl vs. Ethyl ns
Parabens alone, 0.2% Methyl vs. Propyl \*\*
Parabens alone, 0.2% Methyl vs. Butyl \*\*\*\*
Parabens alone, 0.2% Ethyl vs. Propyl \*\*
Parabens alone, 0.2% Ethyl vs. Butyl \*\*\*\*
Parabens alone, 0.2% Propyl vs. Butyl ns
Parabens alone, 0.02% Methyl vs. Ethyl ns
Parabens alone, 0.02% Methyl vs. Propyl \*\*
Parabens alone, 0.02% Methyl vs. Butyl \*
Parabens alone, 0.02% Ethyl vs. Propyl \*
Parabens alone, 0.02% Ethyl vs. Butyl ns
Parabens alone, 0.02% Propyl vs. butyl ns
Parabens alone, lower concentrations all are insignificant
S1, 0.2% Formulated control vs. Methyl \*
S1, 0.2% FC vs. Ethyl \*\*\*\*
S1, 0.2% FC vs. Propyl \*\*\*\*
S1, 0.2% FC vs. Butyl \*\*\*\*
S1, 0.2% Methyl vs. Ethyl \*\*\*\*
S1, 0.2% Methyl vs. Propyl \*\*\*\*
S1, 0.2% Methyl vs. Butyl \*\*\*\*
S1, 0.2% Ethyl vs. Propyl ns
S1, 0.2% Ethyl vs. Butyl ns
S1, 0.2% Propyl vs. Butyl ns
S1, 0.02% FC vs. Methyl \*
S1, 0.02% FC vs. Ethyl \*\*\*\*
S1, 0.02% FC vs. Propyl \*\*\*\*
S1, 0.02% FC vs. Butyl \*\*\*\*
S1, 0.02% Methyl vs. Ethyl \*\*\*\*
S1, 0.02% Methyl vs. Propyl \*\*\*\*
S1, 0.02% Methyl vs. Butyl \*\*\*\*
S1, 0.02% Ethyl vs. Propyl \*\*\*
S1, 0.02% Ethyl vs. Butyl \*\*\*
S1, 0.02% Propyl vs. Butyl ns
S1 lower concentrations all are insignificant
S2, 0.2% Formulated control vs. Methyl \*\*\*\*
S2, 0.2% FC vs. Ethyl \*\*\*\*
S2, 0.2% FC vs. Propyl \*\*\*\*
S2, 0.2% FC vs. Butyl \*\*\*\*
S2, 0.2% Methyl vs. Ethyl ns
S2, 0.2% Methyl vs. Propyl ns
S2, 0.2% Methyl vs. Butyl \*\*
S2, 0.2% Ethyl vs. Propyl ns
S2, 0.2% Ethyl vs. Butyl \*\*
S2, 0.2% Propyl vs. Butyl \*\*
S2, 0.02% FC vs. Methyl \*
S2, 0.02% FC vs. Ethyl ns
S2, 0.02% FC vs. Propyl ns
S2, 0.02% FC vs. Butyl \*\*
S2, 0.02% Methyl vs. Ethyl \*
S2, 0.02% Methyl vs. Propyl \*
S2, 0.02% Methyl vs. Butyl ns
S2, 0.02% Ethyl vs. Propyl ns
S2, 0.02% Ethyl vs. Butyl \*
S2, 0.02% Propyl vs. Butyl \*
S2 lower concentrations all are insignificant
|
J Am Heart Assoc. 2019;8:e012731 DOI: 10.1161/JAHA.119.012731.31215339
Abnormal heart development is a key feature contributing to the cardiac defects of congenital heart diseases, which are the most common birth defects in humans, occurring in 1% to 5% of newborns.[1](#jah34211-bib-0001){ref-type="ref"}, [2](#jah34211-bib-0002){ref-type="ref"}, [3](#jah34211-bib-0003){ref-type="ref"}, [4](#jah34211-bib-0004){ref-type="ref"} Revealing the cellular, genetic, and molecular mechanisms that govern normal heart development will provide key information necessary for the development of effective clinical applications to prevent or treat congenital heart diseases.
The heart is the first organ formed in mammals and is essential for embryo survival.[5](#jah34211-bib-0005){ref-type="ref"}, [6](#jah34211-bib-0006){ref-type="ref"}, [7](#jah34211-bib-0007){ref-type="ref"}, [8](#jah34211-bib-0008){ref-type="ref"}, [9](#jah34211-bib-0009){ref-type="ref"}, [10](#jah34211-bib-0010){ref-type="ref"} Cardiogenesis involves a series of complicated and precisely controlled processes (Figure [1](#jah34211-fig-0001){ref-type="fig"}). During gastrulation in mice, the cardiac progenitor cells enter the primitive streak and assimilate to constitute the primary heart field in the anterior splanchnic mesoderm at embryonic day 6.5 (E6.5). Cardiogenic mesodermal cells then coalesce to form a cardiac crescent at E7.5.[11](#jah34211-bib-0011){ref-type="ref"}, [12](#jah34211-bib-0012){ref-type="ref"} These cells move toward the ventral midline and form the linear heart tube at E8.0. At this stage, another group of cardiac precursor cells from the second heart field join the primitive heart tube from the pharyngeal mesoderm and dorsal mesocardium.[10](#jah34211-bib-0010){ref-type="ref"}, [11](#jah34211-bib-0011){ref-type="ref"}, [12](#jah34211-bib-0012){ref-type="ref"}, [13](#jah34211-bib-0013){ref-type="ref"}, [14](#jah34211-bib-0014){ref-type="ref"}, [15](#jah34211-bib-0015){ref-type="ref"}, [16](#jah34211-bib-0016){ref-type="ref"} Shortly thereafter, the linear heart undergoes rightward looping to bring the future inflow chambers (atria) to the top of the outflow chambers (ventricles). At E9.5, a heart with 4 primordial chambers is formed, and cardiac precursor cells from the second heart field continue to join the hearts from both arterial and venous poles until E11.5.[10](#jah34211-bib-0010){ref-type="ref"}, [11](#jah34211-bib-0011){ref-type="ref"}, [12](#jah34211-bib-0012){ref-type="ref"}, [13](#jah34211-bib-0013){ref-type="ref"}, [14](#jah34211-bib-0014){ref-type="ref"}, [15](#jah34211-bib-0015){ref-type="ref"}, [16](#jah34211-bib-0016){ref-type="ref"} Cells derived from the primary heart field give rise to the left ventricle and parts of the atria, whereas cells derived from the second heart field generate the right ventricle, outflow tract (OFT) and main parts of the atria.[10](#jah34211-bib-0010){ref-type="ref"}, [11](#jah34211-bib-0011){ref-type="ref"}, [12](#jah34211-bib-0012){ref-type="ref"}, [13](#jah34211-bib-0013){ref-type="ref"}, [14](#jah34211-bib-0014){ref-type="ref"}, [15](#jah34211-bib-0015){ref-type="ref"}, [16](#jah34211-bib-0016){ref-type="ref"} From E11.5 to E18.5, embryonic hearts undergo complicated maturation and remodeling processes including myocardial wall trabeculation and compaction, septation between chambers, septation of the OFT, valvulogenesis, formation of coronary vessels, and formation of the conduction system. In mice, nearly all cardiomyocytes withdraw from the cell cycle and undergo maturation during the first 2 weeks after birth.[17](#jah34211-bib-0017){ref-type="ref"}, [18](#jah34211-bib-0018){ref-type="ref"}, [19](#jah34211-bib-0019){ref-type="ref"} In contrast to the hyperplastic growth observed in embryos, postnatal cardiac growth primarily relies on hypertrophic growth.[17](#jah34211-bib-0017){ref-type="ref"}, [18](#jah34211-bib-0018){ref-type="ref"}, [19](#jah34211-bib-0019){ref-type="ref"} The major processes of cardiogenesis are highly conserved between rodent and human; therefore, mice and rats serve as power model systems to study human heart development.[20](#jah34211-bib-0020){ref-type="ref"}
{#jah34211-fig-0001}
Accumulated evidence suggests that mitochondria are critical for embryonic heart development in mammals, in addition to their well‐established roles in postnatal hearts. Impaired mitochondrial activities in embryonic hearts may lead to severe cardiomyopathy and embryonic/neonatal lethality in animal models and human patients.[21](#jah34211-bib-0021){ref-type="ref"}, [22](#jah34211-bib-0022){ref-type="ref"}, [23](#jah34211-bib-0023){ref-type="ref"}, [24](#jah34211-bib-0024){ref-type="ref"}, [25](#jah34211-bib-0025){ref-type="ref"}, [26](#jah34211-bib-0026){ref-type="ref"}, [27](#jah34211-bib-0027){ref-type="ref"}, [28](#jah34211-bib-0028){ref-type="ref"}, [29](#jah34211-bib-0029){ref-type="ref"}, [30](#jah34211-bib-0030){ref-type="ref"}, [31](#jah34211-bib-0031){ref-type="ref"}, [32](#jah34211-bib-0032){ref-type="ref"}, [33](#jah34211-bib-0033){ref-type="ref"} This review will summarize recent knowledge regarding the regulatory roles of mitochondria during embryonic and early postnatal heart development in mammals.
Mitochondrial Structure and Function {#jah34211-sec-0002}
====================================
Mitochondria arose ≈2 billion years ago through engulfment of α‐proteobacteria by precursors of modern eukaryotic cells and have evolved to become a vital organelle with multiple activities in eukaryotes.[34](#jah34211-bib-0034){ref-type="ref"}, [35](#jah34211-bib-0035){ref-type="ref"}, [36](#jah34211-bib-0036){ref-type="ref"}, [37](#jah34211-bib-0037){ref-type="ref"}, [38](#jah34211-bib-0038){ref-type="ref"} Mitochondria are composed of 2 lipid bilayer membranes (ie, the relatively permeable outer membrane and the much less permeable, highly folded inner membrane) and 2 aqueous spaces (ie, the intermembrane space and the matrix)[39](#jah34211-bib-0039){ref-type="ref"}, [40](#jah34211-bib-0040){ref-type="ref"} (Figure [2](#jah34211-fig-0002){ref-type="fig"}). The outer membrane serves as the boundary between the cytoplasm and mitochondria. It contains multiple receptors to mediate communication between mitochondria and other organelles.[41](#jah34211-bib-0041){ref-type="ref"}, [42](#jah34211-bib-0042){ref-type="ref"} The inner membrane is folded into cristae protruding into the matrix and thus has a much larger surface area than the outer membrane.[38](#jah34211-bib-0038){ref-type="ref"} The oxidative phosphorylation (OXPHOS) complexes, complexes I to V, are located on the inner membrane and mediate electron transportation to generate ATP.[43](#jah34211-bib-0043){ref-type="ref"}, [44](#jah34211-bib-0044){ref-type="ref"} The mitochondrial permeability transition pore (mPTP) contains both inner and outer membrane components, and its exact biomolecular configuration has not been finally determined.[45](#jah34211-bib-0045){ref-type="ref"} Under normal conditions, this pore is closed to maintain proper membrane integrity. When open, it allows passage of molecules \<1.5 kDa.[46](#jah34211-bib-0046){ref-type="ref"} The intermembrane space between the inner and outer membranes contains cytochrome c, which is essential for transporting electrons and inducing apoptosis.[47](#jah34211-bib-0047){ref-type="ref"}, [48](#jah34211-bib-0048){ref-type="ref"} The mitochondrial matrix is the space inside the inner membrane. It contains the mitochondrial DNA (mtDNA), ribosomes, enzymes, and ions and is the location of the tricarboxylic acid cycle.[49](#jah34211-bib-0049){ref-type="ref"}, [50](#jah34211-bib-0050){ref-type="ref"}
{#jah34211-fig-0002}
At the cellular level, mitochondria form dynamic networks with morphologies varying with cell types,[51](#jah34211-bib-0051){ref-type="ref"} for example, a highly ordered lattice in adult cardiac cells and a more irregular tubular arrangement in neonatal cardiomyocytes.[52](#jah34211-bib-0052){ref-type="ref"}, [53](#jah34211-bib-0053){ref-type="ref"}, [54](#jah34211-bib-0054){ref-type="ref"} Functionally, mitochondria play a pivotal role in regulating cellular functions (eg, energy production) and signaling molecules (eg, reactive oxygen species \[ROS\] and Ca^2+^).[55](#jah34211-bib-0055){ref-type="ref"}, [56](#jah34211-bib-0056){ref-type="ref"}
In adult cardiomyocytes, mitochondria are the major cellular powerhouse and produce \>95% of the cell\'s energy in the form of ATP. Once the substrates (eg, glucose and fatty acids) enter the cell, they are sequentially oxidized to produce acetyl coenzyme A, which drives the tricarboxylic acid cycle to produce the reducing equivalents NADH (Nicotinamide Adenine Dinucleotide‐Hydrogen) and FADH~2~ (Flavin Adenine Dinucleotide‐2 Hydrogen) in the mitochondrial matrix. NADH and FADH~2~ are oxidized by NADH dehydrogenase (complex I) and succinate dehydrogenase (complex II), respectively, in the inner membrane, driving the electron transport chain (ETC; complex I--IV) to establish the proton‐motive force. In the last step of OXPHOS, the energy derived from the proton‐motive force is utilized by F~1~F~O~ ATP synthase (complex V) to convert ADP and inorganic phosphate to ATP.
In addition to energy production, mitochondria are the major site of ROS production.[57](#jah34211-bib-0057){ref-type="ref"}, [58](#jah34211-bib-0058){ref-type="ref"}, [59](#jah34211-bib-0059){ref-type="ref"}, [60](#jah34211-bib-0060){ref-type="ref"} In vitro studies have shown that up to 2% of electrons flowing through the ETC are partially reduced to form superoxide anion ($O_{2}^{-}$),[61](#jah34211-bib-0061){ref-type="ref"} likely at complexes I, II, and III.[57](#jah34211-bib-0057){ref-type="ref"}, [58](#jah34211-bib-0058){ref-type="ref"} Superoxide is rapidly dismutated by superoxide dismutase (eg, MnSOD (manganese superoxide dismutase) and CuZnSOD (copper‐zinc superoxide dismutase)) to form H~2~O~2~ (hydrogen peroxide), which is further reduced to H~2~O by various antioxidant enzymes such as catalase, glutathione peroxidase, and peroxiredoxins.[62](#jah34211-bib-0062){ref-type="ref"}, [63](#jah34211-bib-0063){ref-type="ref"}, [64](#jah34211-bib-0064){ref-type="ref"}, [65](#jah34211-bib-0065){ref-type="ref"}, [66](#jah34211-bib-0066){ref-type="ref"}, [67](#jah34211-bib-0067){ref-type="ref"} As natural byproducts of oxygen metabolism, ROS signaling molecules regulate a variety of oxygen‐sensing machineries, including gene expression.[68](#jah34211-bib-0068){ref-type="ref"}, [69](#jah34211-bib-0069){ref-type="ref"}, [70](#jah34211-bib-0070){ref-type="ref"} However, excessive ROSs are toxic and can oxidize large molecules such as proteins, DNA, and lipids, which can lead to oxidative damage.[57](#jah34211-bib-0057){ref-type="ref"}, [64](#jah34211-bib-0064){ref-type="ref"}, [71](#jah34211-bib-0071){ref-type="ref"} In addition, oxidative stress can promote the pathological opening of the mPTP, causing mitochondrial swelling, membrane rupture, and cell death.[72](#jah34211-bib-0072){ref-type="ref"}, [73](#jah34211-bib-0073){ref-type="ref"}, [74](#jah34211-bib-0074){ref-type="ref"}, [75](#jah34211-bib-0075){ref-type="ref"} ROS overload also can deplete the intracellular redox pool,[76](#jah34211-bib-0076){ref-type="ref"} impairing cellular Ca^2+^ handling,[77](#jah34211-bib-0077){ref-type="ref"} ion channel activity, and ROS‐mediated redox signaling pathways.[78](#jah34211-bib-0078){ref-type="ref"}, [79](#jah34211-bib-0079){ref-type="ref"}, [80](#jah34211-bib-0080){ref-type="ref"}, [81](#jah34211-bib-0081){ref-type="ref"}
In cardiomyocytes, Ca^2+^ homeostasis is maintained by various Ca^2+^ channels and exchangers in the sarcolemma and subcellular membranes, including the L‐type Ca^2+^ channel, the Na^+^/Ca^2+^ exchanger, RyR (ryanodine receptor), and SERCA (sarcoplasmic reticulum Ca^2+^ ATPase). Recent studies suggest that Ca^2+^ dynamics also may be shaped by mitochondria,[82](#jah34211-bib-0082){ref-type="ref"}, [83](#jah34211-bib-0083){ref-type="ref"}, [84](#jah34211-bib-0084){ref-type="ref"} either directly by inner membrane Ca^2+^ transport or indirectly by ROS‐mediated signaling pathways. The mitochondrial Ca^2+^ uniporter is the primary route for Ca^2+^ entry into the mitochondrial matrix,[85](#jah34211-bib-0085){ref-type="ref"} and RyR1 has been proposed as an alternative Ca^2+^ uptake mechanism.[86](#jah34211-bib-0086){ref-type="ref"} Evidence suggests that mitochondrial Ca^2+^ uptake channels are located at the proximate side of sarcoplasmic reticulum Ca^2+^ release sites (ie, RyRs),[87](#jah34211-bib-0087){ref-type="ref"}, [88](#jah34211-bib-0088){ref-type="ref"} facilitating rapid mitochondrial Ca^2+^ uptake and ATP production in response to increased workload. The extrusion of Ca^2+^ from the mitochondria is mediated by a mitochondrial Na^+^/Ca^2+^ exchanger,[89](#jah34211-bib-0089){ref-type="ref"} which is much slower compared with the mitochondrial Ca^2+^ uniporter. The transient mPTP opening also may be associated with mitochondrial Ca^2+^ release.[90](#jah34211-bib-0090){ref-type="ref"} Under pathological conditions, mitochondria can affect Ca^2+^ handling by releasing ROS close to redox‐sensitive ion transporters involved in cytoplasmic Ca^2+^ handling, such as the L‐type Ca^2+^ channel,[91](#jah34211-bib-0091){ref-type="ref"} RyRs,[80](#jah34211-bib-0080){ref-type="ref"}, [92](#jah34211-bib-0092){ref-type="ref"} and SERCA.[93](#jah34211-bib-0093){ref-type="ref"} Thus, mitochondria play a multifactorial role in regulating Ca^2+^ homeostasis and signaling in cardiomyocytes.[94](#jah34211-bib-0094){ref-type="ref"}
Mitochondria in mature cardiomyocytes are different from those found in other tissue and cell types. Mitochondria are significantly more abundant in hearts than in skeletal muscle, brain, kidney, and liver.[95](#jah34211-bib-0095){ref-type="ref"} Consistent with these observations, the ratio of mtDNA to nuclear DNA in hearts is also significantly higher than in other tissues.[96](#jah34211-bib-0096){ref-type="ref"} Transmission electron microscopy reveals that mitochondria in striated muscles (skeletal and cardiac muscles) appear to be located within membranous compartments along the myofiber.[95](#jah34211-bib-0095){ref-type="ref"} In contrast, mitochondria are more perinuclear in liver cells and more dispersed throughout the cytosol in brain. In addition to the differences in abundance and morphology, mitochondria from different tissues can utilize different fuel to generate ATP. For example, cardiac mitochondria primarily use fatty acid as fuel, whereas most other organs use glucose as the major energy substrate.[96](#jah34211-bib-0096){ref-type="ref"}
Maturation of Cardiac Mitochondria in Mammalian Embryos {#jah34211-sec-0003}
=======================================================
In this section we summarize the process of mitochondrial maturation at different stages of mammalian heart development. Little is known regarding mitochondria in cardiac precursor cells. Between E6.5 and E8.5 in mice, the whole embryo is under low‐oxygen conditions; therefore, aerobic glycolysis presumably serves as the primary source of ATP for cardiac precursor cells.[97](#jah34211-bib-0097){ref-type="ref"}, [98](#jah34211-bib-0098){ref-type="ref"} At E8.5 in mouse embryos or E10 in rat embryos, some mitochondria can be observed in cardiomyocytes through transmission electron microscopy; however, these mitochondria are considered "very immature" (class 1; Figure [3](#jah34211-fig-0003){ref-type="fig"}).[24](#jah34211-bib-0024){ref-type="ref"}, [32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} They contain few cristae and no expanded matrix. At E9.5 in mice and E11 in rats, the number of mitochondria in cardiomyocytes is increased and cristae can be clearly observed within mitochondria.[24](#jah34211-bib-0024){ref-type="ref"}, [32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} At this stage most mitochondria are still Class 1. At E10.5 in mice and E12 in rats, the number of cristae in cardiac mitochondria is increased compared with earlier stages. Some mitochondria contain tubular cristae, which form connections to the periphery. The matrix in these mitochondria is slightly expanded. This type of mitochondria is considered "immature" (class 2).[24](#jah34211-bib-0024){ref-type="ref"}, [32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} In class 1 and 2 mitochondria, ETC activity and ATP generation are not coupled, although OXPHOS complexes can be detected in the inner membrane of mitochondria.[24](#jah34211-bib-0024){ref-type="ref"}, [32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} Cardiomyocytes primarily acquire ATP through anaerobic glycolysis (Figure [4](#jah34211-fig-0004){ref-type="fig"}). At E11.5 in mouse embryonic hearts, OXPHOS complexes begin to assemble into highly efficient respirasomes (supercomplexes) and ETC activity and ATP generation are coupled.[100](#jah34211-bib-0100){ref-type="ref"} Initiation of ETC activity coincides with the activation of complex I,[100](#jah34211-bib-0100){ref-type="ref"} suggesting that complex I activation is critical for initiation of electron transportation along the OXPHOS complexes. Unfortunately, no ultrastructural examination of mitochondria at this stage has been published. In rodent hearts corresponding to E12.5 and E13.5 of mouse embryos, most cardiac mitochondria become "almost mature" (class 3), with structures resembling the mature mitochondria (class 4) observed in postnatal and adult heart tissues.[32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} Class 3 mitochondria contain many tubular cristae that are connected with the periphery.[32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} Their matrices are highly compacted with occasional "voids" observed in transmission electron microscopy images. More respirasomes can be observed on the inner membranes of mitochondria. By E13.5 the mitochondria are functionally matured and their mPTPs are closed.[32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} Electron transportation and OXPHOS activities in E13.5 cardiac mitochondria are indistinguishable from those in adult mitochondria.[32](#jah34211-bib-0032){ref-type="ref"}, [99](#jah34211-bib-0099){ref-type="ref"} At this stage, embryonic cardiomyocytes acquire ATP through both anaerobic glycolysis and OXPHOS.[101](#jah34211-bib-0101){ref-type="ref"}, [102](#jah34211-bib-0102){ref-type="ref"} By the end of gestation in prenatal and newborn hearts, ≈44% of total ATP is generated through anaerobic glycolysis; production of the remaining ATP relies on OXPHOS (Figure [4](#jah34211-fig-0004){ref-type="fig"}).[101](#jah34211-bib-0101){ref-type="ref"}, [103](#jah34211-bib-0103){ref-type="ref"}
{#jah34211-fig-0003}
{ref-type="ref"} E indicates embryonic day; OXPHOS, oxidative phosphorylation.](JAH3-8-e012731-g004){#jah34211-fig-0004}
It is a common misconception that aerobic metabolism in hearts becomes critical only after birth. The metabolic shift from anaerobic glycolysis to aerobic metabolism already occurs during the mid‐ to late‐gestation stages in mammalian hearts. By the end of gestation, the generation of \>50% of ATP relies on OXPHOS in prenatal hearts (Figure [4](#jah34211-fig-0004){ref-type="fig"}).[101](#jah34211-bib-0101){ref-type="ref"}, [103](#jah34211-bib-0103){ref-type="ref"} This embryonic metabolic shift, originally proposed by Baker and Ebert,[21](#jah34211-bib-0021){ref-type="ref"} can serve at least 2 major purposes. First, the normal assembly of respiratory complexes in embryonic hearts is necessary to prepare hearts to undergo the fetal to neonatal metabolic shift after birth. Second, OXPHOS provides \>50% of ATP in fetal hearts to support their pumping activity.[21](#jah34211-bib-0021){ref-type="ref"}, [98](#jah34211-bib-0098){ref-type="ref"}, [101](#jah34211-bib-0101){ref-type="ref"}, [104](#jah34211-bib-0104){ref-type="ref"} Defective OXPHOS in embryonic hearts leads to severe heart defects and embryonic or neonatal lethality in mouse models and human patients.[21](#jah34211-bib-0021){ref-type="ref"}, [22](#jah34211-bib-0022){ref-type="ref"}, [23](#jah34211-bib-0023){ref-type="ref"}, [24](#jah34211-bib-0024){ref-type="ref"}, [25](#jah34211-bib-0025){ref-type="ref"}, [26](#jah34211-bib-0026){ref-type="ref"}, [27](#jah34211-bib-0027){ref-type="ref"}, [28](#jah34211-bib-0028){ref-type="ref"}, [29](#jah34211-bib-0029){ref-type="ref"}, [30](#jah34211-bib-0030){ref-type="ref"}, [31](#jah34211-bib-0031){ref-type="ref"} This "embryonic" metabolic shift remains poorly studied in the literature.
Mitochondrial Biogenic Surge During the Fetal/Neonatal Metabolic Shift and Potential Roles of Mitochondria in Regulating Neonatal Cardiomyocyte Maturation {#jah34211-sec-0004}
==========================================================================================================================================================
After birth, the cardiac environment shifts from hypoxia in embryos (10--30 mm Hg oxygen) to normoxia (80--100 mm Hg oxygen).[98](#jah34211-bib-0098){ref-type="ref"}, [105](#jah34211-bib-0105){ref-type="ref"} Neonatal hearts undergo the well‐defined fetal/neonatal metabolic shift through which the primary source of ATP generation transitions from glycolysis to fatty acid β‐oxidation.[98](#jah34211-bib-0098){ref-type="ref"}, [101](#jah34211-bib-0101){ref-type="ref"}, [105](#jah34211-bib-0105){ref-type="ref"} By postnatal day 21 (P21), nearly 80% of ATP is generated through fatty acid β‐oxidation in cardiomyocytes (Figure [4](#jah34211-fig-0004){ref-type="fig"}).[98](#jah34211-bib-0098){ref-type="ref"}, [101](#jah34211-bib-0101){ref-type="ref"} Compared with glycolysis, fatty acid β‐oxidation is much more efficient with respect to ATP generation; therefore, the fetal/neonatal metabolic shift is essential for cardiomyocytes to fulfill the increased cardiac workload during this period.[98](#jah34211-bib-0098){ref-type="ref"}, [101](#jah34211-bib-0101){ref-type="ref"} Accompanying this metabolic shift, the mitochondrial biogenic surge occurs in cardiomyocytes soon after birth.[106](#jah34211-bib-0106){ref-type="ref"} For example, the mtDNA copy number increases by ≈1.5‐fold at P1 and by ≈5.0‐fold at P21 compared with fetal hearts in rats.[107](#jah34211-bib-0107){ref-type="ref"}
The essential functions of mitochondria in neonatal and infant hearts can be clearly demonstrated through studies of *Tfam* (transcription factor A, mitochondrial) in mice. TFAM is a DNA‐binding protein that is required for replication and transcription of the mitochondrial genome.[108](#jah34211-bib-0108){ref-type="ref"}, [109](#jah34211-bib-0109){ref-type="ref"}, [110](#jah34211-bib-0110){ref-type="ref"} Inactivation of *Tfam* in muscle cells at the perinatal stage uses *MCK* (muscle creatine kinase)--*Cre* reduced expression of TFAM in cardiac and skeletal muscle cells at E18.5, as determined from Western analysis.[111](#jah34211-bib-0111){ref-type="ref"} The steady‐state level of mitochondrial transcripts in these mutant hearts between P20 and P30 was ≈30% of the control level, suggesting that the function of TFAM was efficiently inactivated at this stage.[111](#jah34211-bib-0111){ref-type="ref"} Deletion of *Tfam* by *MCK*‐*Cre* caused deficiency in the respiratory chain, blockage of atrioventricular heart conduction, dilated cardiomyopathy, and animal lethality between P15 and P35.[111](#jah34211-bib-0111){ref-type="ref"} Knocking out *Tfam* using another muscle Cre line, *MCK‐Nls‐Cre*, reduced mtDNA to ≈25% of the control level at P14 and allowed mutant animals to survive 10 to 12 weeks after birth.[112](#jah34211-bib-0112){ref-type="ref"} In these mutant hearts, respiration was severely impaired and a fetal gene expression program was activated between 4 and 9 weeks after birth.[112](#jah34211-bib-0112){ref-type="ref"} Reactivation of the fetal gene expression program is a well‐recognized phenotype of cardiac diseases.[113](#jah34211-bib-0113){ref-type="ref"}, [114](#jah34211-bib-0114){ref-type="ref"} The studies described, in which *Tfam* was deleted, clearly show that mitochondria are required for normal cardiac postnatal development. Whether cardiomyocyte maturation was impaired in these mutant mice was not reported.[111](#jah34211-bib-0111){ref-type="ref"}, [112](#jah34211-bib-0112){ref-type="ref"}
A classical study[115](#jah34211-bib-0115){ref-type="ref"} published a decade ago strongly supported the idea that mitochondrial biogenesis and the perinatal biogenic surge are required for postnatal cardiomyocyte maturation. PGC‐1α (PPARG \[peroxisome proliferator‐activated receptor γ\] coactivator 1α; encoded by *Ppargc1a* \[PPARG coactivator 1α\]) and its homolog PGC‐1β (encoded by *Ppargc1b*) play a central role in regulating mitochondrial biogenesis and maturation.[24](#jah34211-bib-0024){ref-type="ref"}, [115](#jah34211-bib-0115){ref-type="ref"}, [116](#jah34211-bib-0116){ref-type="ref"}, [117](#jah34211-bib-0117){ref-type="ref"} To understand the role of *Ppargc1a* and *Ppargc1b* during heart development, *Ppargc1b* was specifically inactivated in fetal hearts using *Myh6* (*Myosin heavy chain 6)‐Cre* on the *Ppargc1a*‐deficient (*Ppargc1a* ^*−/−*^) background (*Ppargc1a* ^*−/−*^ *;Ppargc1b* ^*loxp/loxp*^ *;Myh6‐Cre*).[115](#jah34211-bib-0115){ref-type="ref"} At P0.5, expression of *Ppargc1b* mRNA in *Ppargc1a* ^*−/‐*^ *;Ppargc1b* ^*loxp/loxp*^ *;Myh6* mice was reduced to \<5% of the control level.[115](#jah34211-bib-0115){ref-type="ref"} Double inactivation of *Ppargc1a* and *Ppargc1b* in mouse fetal hearts decreased mitochondrial volume density and arrested mitochondrial biogenesis and maturation at the perinatal stage.[115](#jah34211-bib-0115){ref-type="ref"} Double‐knockout (DKO) animals survived to P0 and died during the first week after birth because of heart failure. Heart size and activity in DKO animals was significantly decreased compared with controls. Molecular examination showed that the expression of fetal cardiac genes (including *Nppa* (natriuretic peptide A) and *Nppb* (natriuretic peptide B)) remained high, whereas the expression of the adult sarcomeric isoform, *Myh6*, was reduced within neonatal DKO hearts.[115](#jah34211-bib-0115){ref-type="ref"} These data collectively suggest that blocking mitochondrial biogenesis at the perinatal stage impairs cardiomyocyte maturation.
The conclusion from the study described above is challenged by a recent study in which *Tfam* was specifically inactivated in neonatal hearts using an adeno‐associated viral system, AAV9‐*cTnt‐Cre* (Cre driven by the cardiac Troponin T promoter in the AAV9 vector).[31](#jah34211-bib-0031){ref-type="ref"} Mice at P0 were treated with either high‐ or low‐dose AAV9‐*cTnt‐Cre* virus, resulting in ≈55% and ≈30% Cre‐mediated recombination in cardiomyocytes, respectively. Four weeks after injection with low‐dose AAV9‐*cTnt‐Cre*, expression of TFAM was undetectable in isolated cardiomyocytes.[31](#jah34211-bib-0031){ref-type="ref"} Mutant mice displayed mitochondrial dysfunction leading to dilated cardiomyopathy.[31](#jah34211-bib-0031){ref-type="ref"} However, cardiomyocyte maturation did not appear to be impaired, as judged from the development of transverse tubules, sarcomere organization, physiological hypertrophy of cardiomyocytes, and switching of sarcomeric isoform expression.[31](#jah34211-bib-0031){ref-type="ref"} Consequently, the authors concluded that normal mitochondrial function is not essential for postnatal cardiomyocyte maturation.
It remains unclear how to reconcile these opposing opinions. Other than the simple explanation that the difference is due to the different mouse genetic backgrounds used by the 2 groups, we propose 6 possible explanations. First, most *Ppargc1a* and *Ppargc1b* DKO mice die within the first week after birth, and the cardiomyocyte maturation defect was evaluated by examining the expression of 3 marker genes (*Nppa*,*Nppb*, and *Myh6*) at P0.5.[115](#jah34211-bib-0115){ref-type="ref"} The early postnatal lethality of these mice precludes the detailed examination of cardiomyocyte maturation using multiple complementary experiments at later stages, as performed by another group.[31](#jah34211-bib-0031){ref-type="ref"} It is thus unclear to what degree the cardiomyocytes are immature and whether maturation is completely blocked or simply delayed at the neonatal stage in *Ppargc1a* and *Ppargc1b* DKO mice. A second, alternative possibility is that PGC‐1α and PGC‐1β have broader activities in mitochondrial biogenesis through regulating nuclear encoded mitochondrial genes,[24](#jah34211-bib-0024){ref-type="ref"} whereas *Tfam* only regulates mtDNA‐encoded genes.[108](#jah34211-bib-0108){ref-type="ref"}, [109](#jah34211-bib-0109){ref-type="ref"}, [110](#jah34211-bib-0110){ref-type="ref"} This could explain why the phenotype caused by DKO of *Ppargc1a* and *Ppargc1b* is stronger than knocking out *Tfam*. Third, PGC‐1α and PGC‐1β may exert certain unidentified mitochondrial‐unrelated activities to promote cardiomyocyte maturation. Therefore, the observed defect in cardiomyocyte maturation is not directly caused by mitochondrial dysfunction in the DKO hearts. Fourth, in the *Tfam* knockout study, the AAV9‐*Cre* virus was injected into P0 *Tfam* ^*loxp/loxp*^ mice. Considerable time is required to allow the cardiomyocytes to express CRE, to knockout *Tfam*, and to deplete the expressed *Tfam* mRNA and protein. It is possible that neonatal cardiomyocytes have already begun the maturation program before the expression of *Tfam* is efficiently inactivated in these cells and that once the program is initiated, it no longer relies on mitochondrial biogenesis. Fifth, related to the fourth explanation, *Tfam* was inactivated using AAV9‐*Cre* virus,[31](#jah34211-bib-0031){ref-type="ref"} whereas *Ppargc1b* was inactivated using the *Myh6‐Cre* transgenic line.[115](#jah34211-bib-0115){ref-type="ref"} A high dose of virus led ≈55% of cardiomyocytes to express the reporter; however, the efficiency of inactivation of *Tfam* expression was not examined directly.[115](#jah34211-bib-0115){ref-type="ref"} Thus, we cannot exclude the possibility that the failure to observe the maturation defect in AAV9‐*Cre;Tfam* ^*loxp/loxp*^ mice is due to incomplete deletion of *Tfam*. The sixth possibility would be that the embryonic metabolic shift is required for the postnatal heart to undergo the neonatal metabolic shift and maturation. In this scenario, inactivation of *Ppargc1a* and *Ppargc1b* in embryonic hearts impairs the embryonic metabolic shift, which in turn causes maturation defects in postnatal hearts. In contrast, AAV9‐*Cre*--mediated deletion of *Tfam* occurred postnatally, and the embryonic metabolic shift was not affected in these mice. Future studies are warranted to solve this important issue regarding the relationship between mitochondrial functions and postnatal heart maturation.
Role of ROS in Heart Development {#jah34211-sec-0005}
================================
ROS is a physiological byproduct of ETC electron flow, and its production can be increased or uncontrolled if ETC electron flow is compromised.[57](#jah34211-bib-0057){ref-type="ref"}, [58](#jah34211-bib-0058){ref-type="ref"}, [59](#jah34211-bib-0059){ref-type="ref"}, [60](#jah34211-bib-0060){ref-type="ref"} In addition, ROS can be generated through cell membrane--bound NADPH oxidase complexes.[118](#jah34211-bib-0118){ref-type="ref"} Recent studies have indicated that ROS may act as signaling molecules.[119](#jah34211-bib-0119){ref-type="ref"} Using embryonic stem cells as a model system, a high level of ROS increased the percentage of beating cardiomyocytes in embryoid bodies.[118](#jah34211-bib-0118){ref-type="ref"} ROS may stimulate cardiomyocyte differentiation through multiple signaling pathways including JNK, ERK1/2, p38, Ca^2+^ and BMP.[118](#jah34211-bib-0118){ref-type="ref"}, [120](#jah34211-bib-0120){ref-type="ref"} However, a role for ROS in cardiac precursor cells has not been demonstrated through in vivo genetic studies.
ROS levels remain high in mouse E9.5 cardiomyocytes and decrease as embryos age.[32](#jah34211-bib-0032){ref-type="ref"}, [118](#jah34211-bib-0118){ref-type="ref"}, [121](#jah34211-bib-0121){ref-type="ref"} The reduction in ROS levels in later stage embryos stimulates cardiomyocyte maturation, based on studies of mPTP.[32](#jah34211-bib-0032){ref-type="ref"}, [121](#jah34211-bib-0121){ref-type="ref"} Located on the mitochondrial inner membrane, mPTP is closed in matured cardiomyocytes under physiological conditions. In mouse embryonic hearts, mPTP is open until E9.5 and closes between E9.5 and E13.5.[32](#jah34211-bib-0032){ref-type="ref"} Closure of mPTP not only increases the mitochondrial membrane potential (Δψm) to promote OXPHOS (aerobic respiration) but also decreases ROS levels in embryonic cardiomyocytes.[32](#jah34211-bib-0032){ref-type="ref"} The forced closure of mPTP using a pharmacological reagent (cyclosporin A) or deletion of *Ppid* (peptidylprolyl isomerase D; *CyP‐D* \[cyclophilin D\]), which is required for mPTP opening, led to prematuration of both mitochondria and cardiomyocytes at E9.5.[32](#jah34211-bib-0032){ref-type="ref"} Treatment of E9.5 cardiomyocytes with an antioxidant (Trolox, Hoffmann‐La Roche Inc) stimulated, and treatment with a stable oxidant (tertiary butyl hydroperoxide) inhibited, cardiomyocyte differentiation, regardless of whether mPTP was open or closed.[32](#jah34211-bib-0032){ref-type="ref"} Collectively, these data support the idea that closure of mPTP acts upstream of redox signaling and reduces ROS levels in embryonic cardiomyocytes, which stimulates their maturation.[32](#jah34211-bib-0032){ref-type="ref"}
In addition to regulating cardiomyocyte differentiation and maturation, ROS may regulate cardiomyocyte proliferation. The treatment of cardiomyocytes derived from embryonic stem cells or mouse neonatal hearts with 100 nmol/L H~2~O~2~ significantly enhanced their proliferation.[120](#jah34211-bib-0120){ref-type="ref"}, [122](#jah34211-bib-0122){ref-type="ref"} H~2~O~2~ treatment increased nuclear localization of cyclin D1, reduced the expression of p27^Kip1^ (a negative cell cycle regulator), and enhanced phosphorylation of retinoblastoma in cultured myocardial cells.[120](#jah34211-bib-0120){ref-type="ref"}
Abnormally high ROS levels due to mitochondrial dysfunction in embryonic hearts may lead to severe inborn cardiomyopathy. For example, embryonic heart inactivation of *Tfam* led to mitochondrial dysfunction, elevated ROS products, reduced cardiomyocyte proliferation, and embryonic lethality.[31](#jah34211-bib-0031){ref-type="ref"} Furthermore, inhibition of ROS or the DNA damage response pathway using MitoTEMPO (Santa Cruz Biotechnology) or MK‐1755 (a WEE1 \[WEE1 G2 checkpoint kinase\] kinase inhibitor) rescued the cell proliferation defect observed in cultured fetal cardiomyocytes in which *Tfam* was deleted.[31](#jah34211-bib-0031){ref-type="ref"}
Taken together, ROSs exert complex activities during cardiogenesis, and their activities are stage dependent. Increased ROS levels stimulate cardiomyocyte differentiation from precursor cells. At later stages, reduction of ROS levels through closure of mPTP is required for normal maturation of cardiomyocytes. In addition, ROS can promote cardiomyocyte proliferation, according to evidence from in vitro cell culture analysis. Mitochondrial dysfunction in fetal hearts elevates ROS species, which triggers the DNA damage pathway to block cardiomyocyte proliferation.
Role of Apoptosis in OFT Remodeling {#jah34211-sec-0006}
===================================
In addition to their role as the cellular powerhouse, it is well established that mitochondria play key roles in controlling cell apoptosis (programmed cell death).[123](#jah34211-bib-0123){ref-type="ref"}, [124](#jah34211-bib-0124){ref-type="ref"}, [125](#jah34211-bib-0125){ref-type="ref"} In contrast to necrosis, which is caused by acute cellular injury, apoptosis is a precisely controlled process that regulates multiple processes during embryonic development.[126](#jah34211-bib-0126){ref-type="ref"}, [127](#jah34211-bib-0127){ref-type="ref"}, [128](#jah34211-bib-0128){ref-type="ref"} In apoptotic cells, the death signal activates the proapoptotic protein BAX (BCL‐2--associated X protein) and BAK (BCL2‐antagonist/killer 1), which then associate with the mitochondrial outer membrane to form pores.[123](#jah34211-bib-0123){ref-type="ref"}, [124](#jah34211-bib-0124){ref-type="ref"}, [125](#jah34211-bib-0125){ref-type="ref"} The pore alters the outer membrane potential and releases cytochrome c from the intermembrane space to the mitochondrial cytosol, where it interacts with APAF‐1 (apoptotic protease activating factor 1) to form the apoptosome.[123](#jah34211-bib-0123){ref-type="ref"}, [124](#jah34211-bib-0124){ref-type="ref"}, [125](#jah34211-bib-0125){ref-type="ref"} Apoptosomes activate the caspase cascade to induce cell death.[123](#jah34211-bib-0123){ref-type="ref"}, [124](#jah34211-bib-0124){ref-type="ref"}, [125](#jah34211-bib-0125){ref-type="ref"} In addition to cytochrome c, mitochondria may also release SMAC (second mitochondrial‐derived activator of caspases) to activate caspases.[124](#jah34211-bib-0124){ref-type="ref"}, [125](#jah34211-bib-0125){ref-type="ref"}, [129](#jah34211-bib-0129){ref-type="ref"}
During heart development, apoptosis serves as the driving force for OFT shortening and remodeling. Watanabe et al initially reported that, in chicken embryos, OFT shortening and rotation occurs through cardiomyocyte apoptosis in the proximal OFT region.[130](#jah34211-bib-0130){ref-type="ref"} Pharmacologically blocking apoptosis in *ex ovo* chicken cultures resulted in an abnormally long infundibulum. In some embryo cultures, the OFT failed to rotate, leading to the double‐outlet‐right‐ventricle defect.[131](#jah34211-bib-0131){ref-type="ref"} The function of cardiomyocyte apoptosis in the OFT appears to be evolutionarily conserved from chicken to mammals. In mouse embryonic hearts, apoptosis in the proximal OFT region can be observed initially at E12.5, peaks at E13.5 to E14.5, and declines thereafter.[132](#jah34211-bib-0132){ref-type="ref"} The stages of apoptosis in the OFT region correlate well with the shortening period of the OFT.[132](#jah34211-bib-0132){ref-type="ref"} In addition to the OFT region, apoptosis can be detected in the ventricle and endocardial cells, suggesting that it may also be involved in ventricular morphogenesis.[131](#jah34211-bib-0131){ref-type="ref"}
Considering the well‐established role of mitochondria in apoptosis, we speculate that apoptosis during OFT remodeling is mitochondria dependent; however, we cannot exclude the involvement of mitochondria‐independent mechanisms. Further studies are required to reveal the signal that initiates cell death in the OFT and to understand exactly which apoptotic pathway is used to regulate OFT remodeling.
Regulation of Heart Development by Mitochondrial Fission and Fusion {#jah34211-sec-0007}
===================================================================
Mitochondria are highly dynamic organelles with constantly changing morphologies in response to altered inter‐ and intracellular environments.[133](#jah34211-bib-0133){ref-type="ref"}, [134](#jah34211-bib-0134){ref-type="ref"}, [135](#jah34211-bib-0135){ref-type="ref"}, [136](#jah34211-bib-0136){ref-type="ref"} The mitochondrial tubular network is regulated by fusion and fission. Reducing or blocking mitochondrial fusion (or overfission) leads to the fragmentation of mitochondria and the loss of mtDNA, whereas reducing or blocking fission (or overfusion) results in enlargement of mitochondria and overly interconnected tubules.[38](#jah34211-bib-0038){ref-type="ref"}, [137](#jah34211-bib-0137){ref-type="ref"}, [138](#jah34211-bib-0138){ref-type="ref"}, [139](#jah34211-bib-0139){ref-type="ref"}
Regulators of mitochondrial fission and fusion are GTPases and belong to the dynamin family.[136](#jah34211-bib-0136){ref-type="ref"}, [140](#jah34211-bib-0140){ref-type="ref"} MFN1 (mitofusin 1) and MFN2 are the GTPases that act on the mitochondrial outer membrane to promote fusion. Systematic knockout and rescue experiments have revealed that MFN1 and MFN2 possess partially overlapping functions in regulating mitochondrial morphology.[141](#jah34211-bib-0141){ref-type="ref"}, [142](#jah34211-bib-0142){ref-type="ref"} To reveal their potential functions during heart development, *Mfn1* and *Mfn2* were simultaneously inactivated in embryonic hearts using the *Nkx2.5‐Cre* line,[143](#jah34211-bib-0143){ref-type="ref"}, [144](#jah34211-bib-0144){ref-type="ref"} which inactivates target genes in the early cardiac crescent at E7.5.[145](#jah34211-bib-0145){ref-type="ref"} *Mfn1/Mfn2* cardiac DKO mice die between E9.5 and E15.5. Double‐mutant hearts displayed severe hypocellular defects in their myocardial wall at E13.5.[143](#jah34211-bib-0143){ref-type="ref"} Expression of multiple cardiac differentiation markers was impaired by deletion of the 2 genes at E9.5. Further mechanistic studies using embryonic stem cells as the model system suggested that blocking mitochondrial fusion decreases the capacity of Ca^2+^ to enter mitochondria and increases the Ca^2+^ concentration in the cytoplasm. Consequently, calcineurin activity is upregulated, which increases Notch signaling and impairs cardiomyocyte differentiation.[143](#jah34211-bib-0143){ref-type="ref"} The studies on double deletion of *Mfn1* and *Mfn2* using *Nkx2.5‐Cre* thus provided definitive evidence to support the essential role of mitochondrial fusion during cardiomyocyte differentiation.[143](#jah34211-bib-0143){ref-type="ref"}, [144](#jah34211-bib-0144){ref-type="ref"}
Cardiac functions of *Mfn1* and *Mfn2* have also been examined using another Cre line, *Myh6‐Cre*, which inactivates target genes at midgestation.[146](#jah34211-bib-0146){ref-type="ref"} The transcripts of both genes were efficiently reduced at E15.5 in DKO mice; however, no cardiac phenotype was observed in these mice from E15.5 to P0, suggesting that mitochondrial fusion is not essential for heart development from midgestation to birth.[146](#jah34211-bib-0146){ref-type="ref"} Starting from P7, many DKO mice start to display dilated cardiomyopathy, and they all die before P16, supporting the essential role of mitochondrial fusion in postnatal cardiac development. Therefore, the results from *Nkx2.5‐Cre* and *Myh6‐Cre* lines have revealed that mitochondrial fusion is critical for heart development at different stages.
The DRP1 (Dynamin Related Protein 1) GTPase acts on the outer membrane of mitochondria to promote fission.[38](#jah34211-bib-0038){ref-type="ref"}, [137](#jah34211-bib-0137){ref-type="ref"}, [138](#jah34211-bib-0138){ref-type="ref"}, [147](#jah34211-bib-0147){ref-type="ref"} The potential role of *Drp1* during mouse heart development has been studied using 2 different Cre drivers to knockout *Drp1* in embryonic hearts. Inactivation of *Drp1* using the *Myh6‐Cre* line reduced the expression of DRP1 to 50% of the control level at P1, and the activity of the left ventricle in mutants was reduced at this stage according to echocardiographic analyses.[148](#jah34211-bib-0148){ref-type="ref"} However, it is unclear whether the reduced activity of the left ventricle in mutant hearts began during the fetal stage. At P7, the mutant animals displayed multiple cardiac defects, including reduced heart rate, abnormal patterns of electrocardiography and reduced left ventricle contraction. The sizes of mitochondria were abnormally enlarged in cardiomyocytes with *Drp1* deleted, and OXPHOS was also impaired.[148](#jah34211-bib-0148){ref-type="ref"} All mutant mice died between P9 and P11. In another study, *Drp1* was inactivated by a muscle cell Cre line, *MCK*‐*Cre*.[149](#jah34211-bib-0149){ref-type="ref"} Reduced expression of DRP1 was not observed until P1 in mutant hearts. Mice with *Drp1* inactivated using *MCK‐Cre* died between P7 and P10, which was slightly earlier than observed with mice in which the *Myh6‐Cre* line was used. Mutant mice at P7 showed dilated cardiomyopathy, disorganized myofibrils, impaired mitochondrial respiration, and reduced hypertrophic growth of postnatal hearts.[149](#jah34211-bib-0149){ref-type="ref"} Collectively, the 2 complementary studies support the essential role of mitochondrial fission in regulating early postnatal heart development and function. Whether mitochondrial fission also regulates embryonic heart development, as mitochondrial fusion does, will need to be addressed using Cre lines acting at earlier stages in embryonic hearts.
It should be noted that in addition to the canonical activities, MFN1, MFN2, and DRP1 also exhibit noncanonical functions.[150](#jah34211-bib-0150){ref-type="ref"} MFN1/2 tethers mitochondria to the endoplasmic reticulum or the sarcoplasmic reticulum to form contact sites, which are important for mitochondrial Ca^2+^ uptake and bioenergetics.[151](#jah34211-bib-0151){ref-type="ref"}, [152](#jah34211-bib-0152){ref-type="ref"}, [153](#jah34211-bib-0153){ref-type="ref"} In addition, MFN2 is involved in mitophagy, which will be discussed next. The noncanonical activities of DRP1 include regulating mPTP opening, respiration, mitophagy, and cell death.[154](#jah34211-bib-0154){ref-type="ref"}, [155](#jah34211-bib-0155){ref-type="ref"}, [156](#jah34211-bib-0156){ref-type="ref"} Therefore, the phenotypes observed in *Mfn1, Mfn2*, and *Drp1* knockout hearts are likely caused by the combined defects of multiple aspects of mitochondrial activities rather than solely by impaired mitochondrial fusion or fission.
Regulation of the Perinatal Metabolic Shift by Mitophagy in Mouse Hearts {#jah34211-sec-0008}
========================================================================
Mitophagy refers to the selective degradation of mitochondria by autophagy, a process that can be induced through both Parkin‐dependent and Parkin‐independent pathways.[157](#jah34211-bib-0157){ref-type="ref"}, [158](#jah34211-bib-0158){ref-type="ref"} A previous elegant study provided strong evidence to support the critical role of Parkin‐dependent mitophagy in regulating the perinatal metabolic shift in mouse hearts.[159](#jah34211-bib-0159){ref-type="ref"} The MFN2 T111A/S442A (MFN2 AA) mutation inhibits mitochondrial Parkin localization and thus blocks Parkin‐dependent mitophagy. However, this mutation does not affect mitochondrial fusion or Parkin‐independent mitophagy induced by starvation.[159](#jah34211-bib-0159){ref-type="ref"} Ectopic expression of MFN2 AA in neonatal cardiomyocytes led to cardiac dilation, impaired contraction, pulmonary congestion, and eventually heart failure.[159](#jah34211-bib-0159){ref-type="ref"} All mutant animals died 7 to 8 weeks after birth. Conversely, ectopic expression of a comparable level of wild‐type MFN2 in neonatal hearts did not result in any overt defects. MFN2 AA mitochondria retained fetal mitochondrial morphology, failed to undergo maturation, and exhibited impaired functionality.[159](#jah34211-bib-0159){ref-type="ref"} Furthermore, high‐throughput RNA‐sequencing examination showed that perinatal cardiac expression of MFN2 AA blocked metabolic gene reprogramming in postnatal hearts,[159](#jah34211-bib-0159){ref-type="ref"} suggesting that Parkin‐dependent mitophagy is required for perinatal mitochondrial maturation at both the morphological and gene expression levels. A mismatch between mitochondrial programming and the substrate availability was proposed as the major cause for the juvenile cardiomyopathy observed in mice with cardiac ectopic expression of MFN2 AA.[159](#jah34211-bib-0159){ref-type="ref"}
Conclusion {#jah34211-sec-0009}
==========
Accumulated evidence has established that mitochondria not only serve as the cellular powerhouse enabling the heart to beat but also play a critical role in regulating embryonic and neonatal heart development in mammals (Figure [5](#jah34211-fig-0005){ref-type="fig"}). In [Table](#jah34211-tbl-0001){ref-type="table"}, we summarize the roles of genes important for mitochondrial morphology and function during mammalian cardiogenesis that are discussed in this review. Revealing the role of mitochondria in heart development and the underlying mechanisms will provide crucial clues to the development of novel clinical applications aimed at treating cardiomyopathies caused by mitochondrial dysfunction in infants.
{#jah34211-fig-0005}
######
Functions of Genes Important for Mitochondrial Morphology/Activity During Cardiogenesis
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Names of Gene Genetic Manipulation Methods Defects in Mutants
--------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
*Drp1* 1\. *Myh6‐Cre*, inactivation of target genes in fetal hearts\ Lethality between P9 and P11. Reduced heart rate, abnormal patterns of electrocardiography, and reduced left ventricle activity at P7. Enlarged mitochondria in cardiomyocytes. Impaired OXPHOS.[148](#jah34211-bib-0148){ref-type="ref"}\
2. *MCK‐Cre*, perinatal inactivation of target genes in cardiac and skeleton muscle cells Lethality between P7 and P10. Dilated cardiomyopathy, disorganized myofibrils, impaired mitochondrial respiration, and reduced hypertrophic growth at P7.[149](#jah34211-bib-0149){ref-type="ref"}
*Mfn1* and *Mfn2* 1\. *Nkx2.5‐Cre*, cardiac precursor cells\ Lethality between E9.5 and E15.5. Severe hypocellular defects in the myocardial wall at E13.5.[143](#jah34211-bib-0143){ref-type="ref"}\
2. *Myh6‐Cre*, inactivation of target genes in fetal hearts Lethality before P16. Dilated cardiomyopathy at P7.[146](#jah34211-bib-0146){ref-type="ref"}
*Mfn2* (T111A/S442A) Transgenic expression of *Mfn2(T111A/S442A)* in neonatal hearts, only affects mitophagy Lethality 7 to 8 wks after birth. Impaired mitophagy. Cardiac dilation, impaired contraction, pulmonary congestion, and eventually heart failure.[159](#jah34211-bib-0159){ref-type="ref"}
*Ppargc1a* and *Ppargc1b* *Myh6‐Cre* inactivation of *Ppargc1b* on the *Ppargc1a^−/−^* background (*Ppargc1a^−/−^; Ppargc1b* ^*loxp/loxp*^ *; Myh6‐Cre*), inactivation of target genes in fetal hearts Lethality during the first week after birth. Heart failure, reduced heart size and activities. Impaired neonatal cardiomyocyte maturation.[115](#jah34211-bib-0115){ref-type="ref"}
*Tfam* 1\. *MCK‐Cre*, perinatal inactivation of target genes in cardiac and skeleton muscle cells\ Deficiency in the respiratory chain, blockage of atrioventricular heart conduction, dilated cardiomyopathy and animal lethality between P15 and P35.[111](#jah34211-bib-0111){ref-type="ref"}\
2. *MCK‐Nls‐Cre*, perinatal inactivation of target genes in cardiac and skeleton muscle cells. CRE activity weaker than *MCK‐Cre*\ Survive to 10 to 12 weeks after birth. Deficiency in respiration. Reactivation of a fetal gene expression program between 4 and 9 weeks after birth.[112](#jah34211-bib-0112){ref-type="ref"}\
3. AAV9*‐cTnt‐Cre*, neonatal injection Dilated cardiomyopathy. No defect in postnatal cardiomyocyte maturation.[31](#jah34211-bib-0031){ref-type="ref"}
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John Wiley & Sons, Ltd
Sources of Funding {#jah34211-sec-0011}
==================
Research in the authors' laboratory is supported by R01 (R01HL095783) and American Heart Association (17GRNT33410623) grants awarded to Jiao.
Disclosures {#jah34211-sec-0012}
===========
None.
We would like to acknowledge the many valuable contributions of our colleagues but regret that, due to the limited scope of this review article, all studies could not be cited. We thank the members of the Jiao laboratory for their comments and suggestions for the article.
|
Metal-Free Directed Diastereoselective C2,C3-Cyclopropanation of Substituted Indoles with Diazoesters.
A metal-free directed C2,C3-cyclopropanation of suitably substituted indoles with α-diazo esters has been accomplished for the diastereoselective synthesis of cyclopropane-fused indolines in good yield. This method works well with a wide range of differently substituted α-diazo esters as well as indole derivatives and shown excellent compatibility for diverse directing group like pyridyl, pyrimidyl, acyl, and urea derivatives. Furthermore, the preliminary mechanistic investigation revealed the importance of directing group for the developed transformation. |
Digital round-up: Inaugural Charity Film Awards launched
Plus: New animation film from Aardman for Remember A Charity Week and GirlGuiding launches new website
Entries are now open for the inaugural Charity Film Awards, set up to recognise the best films and videos that have been created for or on behalf of registered charities within the UK.
The awards are split into six categories; five are for films under five minutes in length and are based on each charity’s turnover for the latest financial year, and a final category for videos of more than five minutes, including documentaries.
Simon Burton, founder of the Charity Film Awards, said: "In the digital age, charities abilities to create video content and share it to communicate their stories and messages is powerful and essential. Video in all its forms is a crucial part of the modern charity's marketing toolkit. We want to celebrate the very best examples of the art."
Remember A Charity Week 2016 encourages people to consider leaving charitable gifts in their wills. A record number of legacy donors have been reported this year, with more than 37,000 wills including gifts to charity in 2015.
Remember A Charity is also asking the nation to reflect on the wisdom passed between the generations. As part of the campaign, Aardman Animations, creator of Wallace and Gromit, has released a new short film voiced by the Barnsley poet and broadcaster Ian McMillan, with contributions from charity supporters across the UK, including Eamonn Holmes and Rufus Hound.
The new device-responsive site consolidates previous sub-sites into one online hub and features examples of the impact guiding has on girls’ lives as well as the impact girls make in their communities and beyond through youth social action. The charity says the website will also act as a platform for girls’ views to be heard on the challenges they face and the change they are making.
Becky Hewitt, communications director at Girlguiding, said: "We want to enable girls to participate in guiding digitally as well as face to face to build on the fantastic opportunities we offer girls to have fun, build their confidence and develop their interests in a safe, girl-only space. Our new site is just the first step." |
Bipolar membranes have been prepared for a variety of uses including, for example, for improving desalination processes, as analogs to certain biological membranes, and for the production of acid and base from salt. The latter process has great potential usefulness since it allows the production of commercially important acids and bases from neutral salts, e.g., NaCl may be converted to HCl and NaOH. The potential for carrying out this type of conversion by means of bipolar membranes, the process known as electrodialytic water splitting, has not yet been realized as an industrial process primarily due to insufficient membrane life, stability and electrical properties of bipolar membranes which should have the following properties:
(1) sufficient mechanical strength PA1 (2) ability to operate at high current density PA1 (3) high permselectivity PA1 (4) low potential drop PA1 (5) stable properties
Additionally the bipolar membrane should be easily fabricated and have reproducible properties. Many preparations of bipolar membranes are reported in the literature. For example in U.S. Pat. No. 2,829,095, bipolar membranes are disclosed as being prepared by adhering two membranes consisting of oppositely charged ion exchange resins in an inert matrix bonded together either by fusion with heat and pressure or by use of a polyethyleneimine-epichlorohydrin paste. Anion and cation membranes have also been fused together as disclosed in U.S. Pat. No. 3,372,101 and British Pat. No. 1,038,777 by means of heat and pressure to give bipolar membranes. Additionally the application of an anionic polyelectrolyte paste to a cationic membrane which is then cured to yield a bipolar membrane has been described. Further, the preparation of bipolar membranes from a single sheet of material by selective functionalization of one side to cation or anion membrane followed by functionalization of the other side to the opposite type of membrane is disclosed for example in U.S. Pat. No. 3,654,125, and the formation of bipolar membranes in situ by passing a direct current through anion or cation membranes in contact with finely divided ion exchange resin slurries of charge opposite to that of the membrane is disclosed in published U.S. Patent Application No. 435,791, filed Jan. 23, 1974 (PB 230409) National Technical Information Service. In spite of such prior disclosures most membranes available up to the present time have been deficient in one or more of the properties desirable for bipolar membranes to be used for the process of electrodialytic water splitting on a practical level. It is thus seen that a need exists for a bipolar membrane of improved stability, high permselectivity and low potential drop.
In U.S. Pat. No. 4,116,889 (F. P. Chlanda, L. T. C. Lee and K. J. Liu) there is disclosed a method of preparing cast bipolar membranes by applying a second layer or coating of a cation exchange resin in a matrix polymer upon an anionic first layer preformed from a mixture of polyvinylidene fluoride, polyvinyl benzyl chloride solvent and multifunctional amine at least one of which is tertiary, mixed together in the proper proportions.
The subject matter of this application is also related to subject matter disclosed in U.S. Pat. No. 4,024,403 (G. J. Dege and K. J. Liu) entitled "Single Film, High Performance Bipolar Membrane" issued on May 17, 1977 and in U.S. Pat. No. 4,057,481 (L. T. C. Lee, G. J. Dege and K. J. Liu) issued on Nov. 8, 1977 entitled "High Performance, Quality Controlled Bipolar Membrane" and U.S. Pat. No. 4,083,768 (L. T. C. Lee and K. J. Liu) issued on Apr. 11, 1978, entitled "Preparation of High Performance Polyelectrolyte Membrane." |
NBA 2K14: Breaking Down Biggest Gameplay Takeaways Post-Release
In our constantly evolving culture, the honeymoon phase of a sports video game release lasts about the lifespan of a Mayfly. If a release isn't satisfactory, it will be discarded to gather dust or even sold on the secondary market, whereupon the consumer will use his or her earnings to purchase the next game, which invariably came out 0.6 seconds after the disappointing acquisition.
Luckily, the NBA 2K series has rarely delved into the disappointment well. Released in the busiest time of the year for sports gaming developers, the NBA 2K series has been nothing short of a yearly success. I mean, there may be no better compliment to the series as a whole than it being so far ahead of EA Sports' NBA Live that the company had to cancel the series for nearly a half-decade to catch up.
NBA 2K14, which was released on Oct. 1, follows in its predecessor's footsteps. Equipped with a Metacritic score of 87 (on a scale of 1-100), the game has gotten rave reviews from critics and fans alike.
Now, if you ask those reviewers what their favorite aspect of the game is, they'll probably come up with a bevy of answers. Association mode. Path to Greatness. My Career. The return of Crew mode. All of those things help make NBA 2K14 a worthy addition to this growing monolith.
But ask those same people what keeps them coming back, you'll invariably get the same answer: gameplay. NBA 2K drove NBA Live back to the drawing board not by beating it in the depth of its game modes but by the depth and understanding of the sport 2K's trying to recreate.
The game has been out a week now, and I have some thoughts on how the gameplay works in this year's release. Spoiler alert: kudos, 2K Sports. With that in mind, here's a quick breakdown of the biggest takeaways from the game thus far.
Don't Expect Athleticism to Rule the Day
When playing sports video games, we all sign a silent social contract that acknowledges the medium's pseudo-realism. It's that way in all games, of course. But sports gaming developers strive for a completely different level of accurate representation. When you die in Call of Duty, the game doesn't just, like, end for good and become completely unplayable.
In sports games, a majority of the same rules still apply. You still can foul out, get injured, etc., and each of those in-game traits are supposed to follow a line similar to that of real life.
Majority, though, is the operative word. You're still playing a video game. It's impossible to create actual reality, and thus there are some stretches of the truth we've come to live with. In Madden, it's long been known that speed is king; you'd much rather be scampering past folks with Chris Johnson than, say, Arian Foster. These are the most minor exploitable traits in a game, ones that everyone notices but no one complains about because, well, just because we're not all angry message board dwellers.
2K Sports
The most "exploitable" trait in the NBA 2K series has always been anyone with a three-point jumper and athleticism. Many an online game has been won by dropping 40 points with J.R. Smith, and last year Bradley Beal became one of my favorite building blocks in Association mode for that very reason. If you can shoot a three, it draws defensive respect and makes it far easier to blow past the initial line of defense to the rim—exactly as it is in real life. But slightly ratcheted up for a video game, wing players with bounce became nearly unstoppable.
2K Sports
Until NBA 2K14, that is. One of the subtle differences in this iteration is a slightly more deliberate pace. Players aren't able to cover as much ground as quickly. Coming cross-court for steals that stretch the bounds of even video game truth has been eliminated.
This was done mostly to improve on spacing and make defense a more fun experience—mission accomplished, by the way—but has also had a trickle-down effect on our once-beloved exploitable players. Their quick first steps and unabated drives to the rim are a thing mostly of the past, with defensive AI understanding where to rotate on the floor and the increased proliferation of blocks near the rim making things more difficult.
Don't get me wrong, it's still better to roll with athletic players than a group of 30-somethings. Just remember that skill is slowly creeping up on athleticism in the video game world.
Do Yourself a Favor—Run Some Plays
2K Sports
Speaking of subtle changes, hopefully you all have gotten used to the different controls by now. (Or just changed them back, but whatever. We're not talking to you right now, Mr. I Don't Like Change.)
The folks at 2K Sports decided to switch a few things up this year. The shot stick is now activated by holding in the right stick—for what it's worth, I'll be using Xbox 360 as a controller reference—rather than a combination of the left trigger and right stick. Alley-oops no longer force you to combine X and A, but rather X and the left trigger.
The change that's most noteworthy—at least for my money—has been the alteration of the play-calling system. As someone who rarely takes time to read instruction manuals (OK, never reads instruction manuals), I was three games deep into playing online before I realized engaging in pick-and-rolls now begins with the B button. I tried holding in the LB, tapping it, bringing up drop-down menus after pressing it. Everything.
Twas flabbergasting. Pick-and-rolls are the bread and butter of any good offense, NBA or video game. So being unable to access that play—which, again, could have very easily been found by taking a look inside the book—proved frustrating.
But in that frustration came a gem: The new, revamped plays that feel like they came out a real coaching playbook. These options were here in the past, mind you. You could run sets like the Spurs' weak-side motion in the past, but getting to that play too often felt like running through minefields of encrypted code that made it not worth using.
2K Sports
In NBA 2K14, the initial LB option runs a "smart play." That play will depend on team and situation, and its on-court implementation has been superb. Those who don't know the X's and O's of NBA basketball will have the play walked through for them via on-screen commands and icons on where to take the user-controlled player, and those who are well-versed will have a field day by basking in the realism.
Run properly, the plays are also deadly effective. The deeper you get into the game, you begin figuring out which plays work best for which teams and can even begin moving away from the "smart play" option accordingly. Even if it proves too difficult in a game situation to keep things steadied, running real-life plays is a great opportunity to leave the mundanities of isolations and constant PNRs behind.
Stray Thoughts
2K Sports
Get Yourself a Big Man: It will probably be addressed at some point with a patch, but the ease of blocking a shot under the basket could be tuned down. The developers made an admirable effort in addressing the complaints of NBA 2K13, where it was impossible to block dunks and nearly impossible to take down shots at the basket. Just a half-step too far here, especially when you're getting chase-down stuffs from the likes of Steve Nash. Nowhere near a deal-breaker, though.
Time Your Shots: In keeping with the game's improved realism, the developers have also made knocking down shots a bit more difficult. I've found that in previous years gamers could get away with being a couple ticks too early or too late without being punished. Not so with NBA 2K14. Plenty of B-rated free throws and closely timed shots will clank off the rim this year, which makes getting an open look even more important.
Do Not Play Anyone Using the Miami Heat Online: For obvious reasons. (LeBron is that good.) |
If untreated, acute elevations in intracranial pressure (ICP) due to hydrocephalus, brain injury, stroke, or mass lesions can result in permanent neurologic impairment or death. Hydrocephalus, the most common pediatric neurosurgical condition in the world, has been well studied as a model for understanding the impact of elevated ICP. The visual disturbances and diplopia associated with hydrocephalus were first described by Hippocrates in approximately 400 B.C. (Aronyk, Neurosurg Clin N Am. 1993; 4(4):599-609). Papilledema, or swelling of the optic disc, and its association with elevated ICP was described by Albrecht von Graefe in 1860 (Pearce, European neurology 2009; 61(4):244-249). In the post-radiographic era, acute and chronic pathology of the optic nerve and disc (cranial nerve II), and of ocular motility (cranial nerves III, IV and VI) are well characterized in hydrocephalic children (Dennis et al., Arch Neurol. October 1981; 38(10):607-615; Zeiner et al., Childs Nerv Syst. 1985; 1(2):115-122 and Altintas et al., Graefe's archive for clinical and experimental ophthalmology=Albrecht von Graefes Archiv fur klinische and experimentelle Ophthalmologie. 2005; 243(12):1213-1217). Visual fields may be impaired in treated hydrocephalus (Zeiner et al., Childs Nerv Syst. 1985; 1(2):115-122), and there is increased latency in light-flash evoked responses in acutely hydrocephalic children relative to their post treatment state (Sjostrom et al., Childs Nerv Syst. 1995; 11(7):381-387). Clinically apparent disruption of ocular motility may precede computed tomography (CT) findings in some acute hydrocephalics (Tzekov et al., Pediatric Neurosurgery 1991; 17(6):317-320 and Chou et al., Neurosurgery Clinics of North America 1999; 10(4):587-608).
Several potential mechanisms may contribute to cranial nerve dysfunction due to hydrocephalus. The optic nerve (II) is most frequently analyzed because it can be visualized directly with ophthalmoscopy, and indirectly with ultrasound. Edema of the optic nerve appears earlier than ocular fundus changes, and resolves after treatment of elevated ICP (Gangemi et al., Neurochirurgia 1987; 30(2):53-55). Fluctuating elevated neural pressure leads to impaired axonal transport along the optic nerve after as little as 30 minutes in a rabbit model (Balaratnasingam et al., Brain Research 2011; 1417:67-76). Axoplasmic flow stasis and intraneuronal ischemia may occur in the optic nerve exposed to chronically elevated ICP (Lee et al., Current Neurology and Neuroscience Reports. Feb. 23, 2012).
At present, the diagnosis of elevated intracranial pressure relies on history, physical exam, radiographic imaging, and possibly direct invasive assessment of the subarachnoid space or structures contiguous with it via cannulated needle tap of a shunt or monitoring device placement. Chemical dilatation of the pupil to assess for papilledema may be unpleasant for the examinee, relies on the experience of the examiner and obfuscates further examination of the pupillary reflex. Papilledema is not always a sensitive marker for hydrocephalus, and in one study was present in as few as 14% of patients with a shunt malfunction (Nazir et al., J Aapos 2009; 13(1):63-66) consistent with the relatively short intracranial course of II relative to cranial nerves III and IV. Compartmentalization of subarachnoid spaces is hypothesized to explain why papilledema may be present in a patient without elevated ICP, and not occur in patients with elevated ICP (Killer et al., Clinical & Experimental Ophthalmology 2009; 37(5):444-447).
Automated eye movement tracking has been used for marketing and advertising research, the development of assistive devices for immobile individuals, and for video games. Calibration of the device requires the subject to have relatively intact ocular motility that implies function of cranial nerves II (optic), III (oculomotor), IV (trochlear) and VI (abducens) and their associated nuclei as well as sufficient cerebral function to enable cognition and volition for calibration. Calibrated eye movement tracking has been utilized to detect cognitive impairment secondary to axonal shearing after mild traumatic brain injury (Lee et al., Brain research. 2011; 1399:59-65; Contreras et al., Brain Research 2011; 1398:55-63 and Maruta et al., The Journal of Head Trauma Rehabilitation 2010; 25(4):293-305).
Others have successfully demonstrated the clinical applications of eye movement data (Lee et al., Brain Research. 2011; 1399:59-65; Contreras et al., Brain Research 2011; 1398:55-63; Maruta et al., The Journal of Head Trauma Rehabilitation 2010; 25(4):293-305). Trojano et al., J Neurol 2012; (published online; ahead of print) recently described uncalibrated eye movement measurements in a population of minimally conscious and persistently vegetative patients. They report data from 11 healthy control subjects evaluating chronic disorders of consciousness, not acute changes in intracranial pressure. They sample eye movements at 60 Hz rather than 500 Hz, effectively reducing the power of their data 100-fold, and they report differences in on-target and off-target fixations between the groups without spatially calibrated data. Moreover, they use static stimuli moving in a quasi-periodic way.
All publications, patent applications, patents and other reference material mentioned are incorporated by reference in their entirety. In addition, the materials, methods and examples are only illustrative and are not intended to be limiting. The citation of references herein is not to be construed as an admission that the references are prior art to the present invention. |
Andrew Yang has managed to outlast some of the early Democratic presidential frontrunners. Maybe that’s because, while his policy ideas are a bit goofy, he’s still a likable guy. While a lot of other celebs are throwing their lots in with Elizabeth Warren and Bernie Sanders, Yang’s managed to get comedian Dave Chappelle to join the Yang Gang:
.@AndrewYang campaign announces that Dave Chappelle has officially endorsed Yang for president. Chappelle: “I’m Yang Gang!” pic.twitter.com/UN2NQoCWxx — Pat Ward (@WardDPatrick) January 14, 2020
And Yang’s pretty pleased about it:
Thank you @DaveChappelle and welcome to the #yanggang. You are the best. Let’s do this for our kids. ?? pic.twitter.com/HGznFG00kr — Andrew Yang? (@AndrewYang) January 14, 2020
With their powers combined, who knows what can happen?
I'm not super surprised by this and I'm not sure why https://t.co/4LyXsPIdIU — Jerrod A. Laber (@JerrodALaber) January 14, 2020
Well, for one thing, like Andrew Yang, Dave Chappelle regularly defies expectations. And then there’s this:
Because he is a rare candidate with a sense of humor? https://t.co/Ewo2BYPJdP — Jim Antle (@jimantle) January 14, 2020
True story. |
Frédéric Swarts
Frédéric Swarts (2 September 1866 – 6 September 1940) was a Belgian chemist who prepared the first chlorofluorocarbon, CF2Cl2 (Freon-12) as well as several other related compounds. He was a professor in the civil engineering at the University of Ghent. In addition to his work on organofluorine chemistry, he authored the textbook "Cours de Chimie Organique." He was a son of Theodore Swarts (chemist, *1839 Antwerpen; †1911 Kortenberg, Belgium) and a colleague of Leo Baekeland.
References
Category:Belgian inventors
Category:Belgian chemists
Category:1866 births
Category:1940 deaths
Category:Ghent University faculty |
.PhotoDetailBody-spinner,
.PhotoDetailBody-error {
position: absolute;
left: 50%;
top: 50%;
transform: translate(-50%, -50%);
}
|
Awarded for top essay
Wednesday, March 2, 2011
Piscitelli
Angela Piscitelli, second year cadet in the JROTC program at the Panther Valley High School received an award for her essay in the top ten out of 15,800 entries in the Annual 2nd Brigade Essay contest. She was presented with a certificate and coin at the annual inspection program held at the high school. |
Akin Fernandez, the owner of the Bitcoin startup Azteco, thinks that Bitcoin Unlimited is “100 percent anti-Bitcoin.” His comments come in the wake of the ongoing scaling impasse which has bedeviled the ecosystem.
He explains what convinced him to come to that conclusion:
"If someone came to your country and said, 'We are going to break up your government and take over the running of this country...because we have more money than all of you put together. We do not care what you want or think, just obey us, or you are free to go anywhere' you would say that that is "Anti-human" wouldn't you?"
BU will fail
However, Fernandez is quite sure the plans of those who are behind Bitcoin Unlimited will not succeed. "If Bitcoin forks, it will be unfortunate but Core supporters will win," he asserted. "Core has world-class developers in a team that is unique. It is not possible to replicate the Core team or their innovation."
Besides, he believes if Bitcoin splits, the altcoin "Bitcoin Unlimited" will have a different code base that cannot accept Core's new software and immediately they will start to diverge and fall behind in features and security.
"The ill effects have already started with Bitcoin Unlimited, who have just closed their source and are releasing binary only versions," the Software Engineer added. He strongly believes BU is now not only hiding how their client works, as auditable source helps keep their users safe but they are in violation of the open source licenses of libraries used to build their altcoin client.
Hijacking the network
Then again Fernandez thinks that not only is the altcoin Bitcoin Unlimited violating the software licenses they agreed to but they are violating the "gentleman's agreement of Bitcoin," by launching an aggressive client onto the network in an attempt to hijack it.
"He is also of the opinion that exchanges will not list BU as Bitcoin but businesses are signaling that they want nothing to do with this as he puts it, “destructive, selfish, suicidal anti-Bitcoin coup attempt” and their decision is being made easier by the bugs in BU."
"The BU dev team has taken on a very difficult task that only a handful of men on earth can handle properly and they have run into many quality control problems,” Fernandez say.
According to him, observers have poured over the last published BU source code to identify problems and rumor has it that there are critical flaws that are deliberately baked into their implementation that will make Bitcoin Unlimited unstable, unpredictable and dangerous. The Bitcoin entrepreneur thinks BU is a disaster waiting to happen on every level.
Wasteful but useful
On the whole cul-de-sac, Fernandez's view is that it is wasteful, stressful and painful but they serve a useful purpose.
He states:
"Anti-Bitcoin saboteurs are exposed, liars are identified and the steady hands that give consistent good advice, rigorously tested software and solid stewardship are appreciated."
Subsequently, he praised Bitcoin Core and said without their exemplary work, Bitcoin would have been a disaster. He declares:
"It's also clear that a great deal of patience and software innovation is going to be required in the coming years from the companies relied on the reference client and clients that imp lint e to protocol. There is a lot of very risky hard work to be done and shenanigans like Bitcoin Unlimited are unproductive." |
A 30-year-old man who allegedly tried to rob a Southeast Portland bar with a sawed-off shotgun early this morning got far more than he bargained for when he ran into an employee who goes by the nickname "Stub."
Instead of leaving with cash, the man was hauled off in an ambulance.
Police say he was shot by Ormand "Stub" Fentress, a 57-year-old no-nonsense employee who took action when the suspect started threatening patrons with his weapon even after he'd chased off a bartender and taken cash from the bar's till.
His wife said Fentress' mother nicknamed him "Stub" as a child because he was stubborn.
"He doesn't look at himself as a hero," said Chris Fentress. "He doesn't like any attention. I just talked with him a while ago. He's doing fine. He saw a problem and took care of it. That's his nature."
The incident began about 12:45 a.m. when a man walked into the Mt. Scott Pub, located at 72nd Avenue and Woodstock Boulevard, the Portland Police Bureau reported.
The suspect demanded money from the bartender, who ran to a back room. The man chased the bartender, then returned to the bar, opened the till and started pulling out cash, police said.
When the man continued to threaten patrons with the weapon, Fentress pulled a gun from the bar and fired multiple shots at the suspect's lower body, police said. The suspect was hit and fell to the floor. Fentress then held the suspect at gunpoint until police arrived.
Police said the suspect, who has not yet been charged, was taken to an area hospital with non-life threatening injuries. Police said his name will be released when he is arrested and booked into jail.
Police are continuing to investigate the shooting and said the bar patrons and employees are cooperating.
–Tom Hallman Jr.
|
XG IOS SDK ReleaseNote
===================
VERSION 3.0.1
-------------------------------------------
1. 新增LBS位置上报接口
2. 新增角标设置接口
3. 修复Xcode8.x打包问题
VERSION 3.0.0
-------------------------------------------
1. 代码全面优化，简化接口、改善接口扩展性，精简了SDK的体积
2. 自动兼容iOS系统版本变更
3. 新增统计用户推送权限的关闭情况
VERSION 2.6.0
-------------------------------------------
* 调整注册接口
VERSION 2.5.0
-------------------------------------------
* 修改接口，去掉无用API
* 增加静默推送以及推送样式
VERSION 2.4.9
-------------------------------------------
* 提高sdk稳定性
VERSION 2.4.8
-------------------------------------------
* 增加ipv6支持
VERSION 2.4.7
-------------------------------------------
* 加入客户端识别机制,减少重复推送发生的概率
VERSION 2.4.6
-------------------------------------------
* 完善回调调用机制,现在大多数情况下都会调用回调
VERSION 2.4.5
-------------------------------------------
* 用XCode7.1重新编译
* 提供XCode6.4兼容包
VERSION 2.4.4
-------------------------------------------
* 提高SDK弱网下的稳定性
VERSION 2.4.3
-------------------------------------------
* 修复setTag不回调的问题
VERSION 2.4.2
-------------------------------------------
* 增加XCode7 bitcode支持
VERSION 2.4.0
-------------------------------------------
* 优化网络连接
* 解决已知的内存泄露问题
VERSION 2.3.2
-------------------------------------------
* 修复由于bundle id命名导致启动时crash的bug
VERSION 2.3
-------------------------------------------
* 增加MD5函数调用前对AppKey的nil判断
* 和XG共享deviceToken
VERSION 2.2
-------------------------------------------
* 增加iOS8的支持。
* 增加渠道，游戏大区上报。
* 增加registerDeviceStr接口
VERSION 2.1.1
-------------------------------------------
* 优化注销逻辑
* 增加registerDeviceStr接口
VERSION 2.1.0
-------------------------------------------
* 增加对arm64的优化支持
* 增加若干接口的回调函数
* 注册的逻辑优化
* 注意:个别函数名替换"Location"为"Local"
VERSION 2.0.1
-------------------------------------------
* 修改SDK特性,增加对预定义标签的支持
* 删除了一些无用的文件
VERSION 2.0.0
-------------------------------------------
* 增加本地推送功能
* 提高SDK的稳定性
VERSION 1.0.3
-------------------------------------------
* 增加别名功能
VERSION 1.0.2
-------------------------------------------
* 切换到全新后台接口
* SDK代码全面优化
VERSION 1.0.1
-------------------------------------------
* 实现和XG兼容
VERSION 1.0.0
-------------------------------------------
* 初始版本
|
Photochemical reduction of CO₂ using TiO₂: effects of organic adsorbates on TiO₂ and deposition of Pd onto TiO₂.
Reduction of CO(2) using semiconductors as photocatalysts has recently attracted a great deal of attention again. The effects of organic adsorbates on semiconductors on the photocatalytic products are noteworthy. On untreated TiO(2) (P-25) particles a considerable number of organic molecules such as acetic acid were adsorbed. Although irradiation of an aqueous suspension of this TiO(2) resulted in the formation of a significant amount of CH(4) as a major product, it was strongly suggested that its formation mainly proceeded via the photo-Kolbe reaction of acetic acid. Using TiO(2) treated by calcination and washing procedures for removal of the organic adsorbates, CO was photocatalytically generated as a major product, along with a very small amount of CH(4), from an aqueous suspension under a CO(2) atmosphere. In contrast, by using Pd (>0.5 wt %) deposited on TiO(2) (Pd-TiO(2)) on which organic adsorbates were not detected, CH(4) was the main product, but CO formation was drastically reduced compared with that on the pretreated TiO(2). Experimental data, including isotope labeling, indicated that CO(2) and CO(3)(2-) are the main carbon sources of the CH(4) formation, which proceeds on the Pd site of Pd-TiO(2). Prolonged irradiation caused deactivation of the photocatalysis of Pd-TiO(2) because of the partial oxidation of the deposited Pd to PdO. |
Q:
How to increase md-tab size in angular-material?
I want to increase my tab width like shown in below image,but not sure how to do this in angular-material.
Please help
A:
You can check all options for md-tabs in the official doc md-tabs doc.
md-stretch-tabs mobile desktop
auto stretched ---
always stretched stretched
never --- ---
<md-tabs md-stretch-tabs="always">
<md-tab label="Tab #1"></md-tab>
<md-tab label="Tab #2"></md-tab>
<md-tab label="Tab #3"></md-tab>
</md-tabs>
In Angular Material version 6.0.1
<mat-tab-group mat-stretch-tabs="always">
<mat-tab label="Tab 1">Content 1</mat-tab>
<mat-tab label="Tab 2">Content 2</mat-tab>
</mat-tab-group>
|
Q:
Grid rows disappear on custom tab
Against the Project Task screen I have added a new tab with a grid on it.
I have created a custom table which holds a projectid and a taskid against it which I I use to filter my PXSelect against the graph extension.
When I switch to the tab the rows display there correctly then after a second they disappear? It like the Current.TaskId and Current.ProjectId loose there values or something. Please help
Heres how I set it up
My Graph Extension
public class ProjectTaskEntryExt : PXGraphExtension<ProjectTaskEntry>
{
public PXSelect<UsrMAXXTaskEmployees,
Where<UsrMAXXTaskEmployees.projectID, Equal<Current<PMTask.projectID>>,
And<UsrMAXXTaskEmployees.taskID, Equal<Current<PMTask.taskID>>>>> BudgetEmployees;
#region Event Handlers
protected void UsrMAXXTaskEmployees_RowInserting(PXCache cache, PXRowInsertingEventArgs e, PXRowInserting InvokeBaseHandler)
{
if (InvokeBaseHandler != null)
InvokeBaseHandler(cache, e);
var row = (UsrMAXXTaskEmployees)e.Row;
if (row != null)
{
row.ProjectID = Base.Task.Current.ProjectID;
row.TaskID = Base.Task.Current.TaskID;
}
}
public override void Initialize()
{
base.Initialize();
}
#endregion
}
Here is my Custom dac for the table
public class UsrMAXXTaskEmployees : IBqlTable
{
#region Selected
public abstract class selected : IBqlField
{ }
[PXBool]
[PXUIField(DisplayName = "Selected")]
public virtual bool? Selected { get; set; }
#endregion
#region ID
public abstract class iD : PX.Data.IBqlField
{
}
protected int? _ID;
[PXDBIdentity(IsKey = true)]
[PXUIField(Enabled = false)]
public virtual int? ID
{
get
{
return this._ID;
}
set
{
this._ID = value;
}
}
#endregion
#region EmployeeID
public abstract class employeeId : PX.Data.IBqlField
{
}
protected String _EmployeeId;
[PXDBString()]
[PXUIField(DisplayName = "Employee")]
[PXSelector(
typeof(Search<PX.Objects.EP.EPEmployee.acctCD>),
typeof(PX.Objects.EP.EPEmployee.acctCD),
typeof(PX.Objects.EP.EPEmployee.acctName),
DescriptionField = typeof(PX.Objects.EP.EPEmployee.acctName))]
public virtual String EmployeeId
{
get
{
return this._EmployeeId;
}
set
{
this._EmployeeId = value;
}
}
#endregion
#region StartDate
public abstract class startDate : PX.Data.IBqlField
{
}
protected DateTime? _StartDate;
[PXDBDate()]
[PXDefault(typeof(AccessInfo.businessDate))]
[PXUIField(DisplayName = "Start Date")]
public virtual DateTime? StartDate
{
get
{
return this._StartDate;
}
set
{
this._StartDate = value;
}
}
#endregion
#region EndDate
public abstract class endDate : PX.Data.IBqlField
{
}
protected DateTime? _EndDate;
[PXDBDate()]
[PXUIField(DisplayName = "End Date")]
public virtual DateTime? EndDate
{
get
{
return this._EndDate;
}
set
{
this._EndDate = value;
}
}
#endregion
#region ProjectID
public abstract class projectID : PX.Data.IBqlField
{
}
protected int? _ProjectID;
[PXDBInt()]
[PXDBDefault(typeof(PX.Objects.PM.PMProject.contractID))]
[PXUIField(DisplayName = "Project")]
public virtual int? ProjectID
{
get
{
return this._ProjectID;
}
set
{
this._ProjectID = value;
}
}
#endregion
#region TaskID
public abstract class taskID : PX.Data.IBqlField
{
}
protected int? _TaskID;
[PXDBInt()]
[PXDefault(0)]
[PXUIField(DisplayName = "Task")]
public virtual int? TaskID
{
get
{
return this._TaskID;
}
set
{
this._TaskID = value;
}
}
#endregion
}
A:
Please check if AutoSize is enabled for your grid and SkinID is set to DetailsInTab:
<px:PXGrid ID="gridNS" runat="server" SkinID="DetailsInTab" Width="100%" Height="150px" Caption="Mailings" AdjustPageSize="Auto" AllowPaging="True" DataSourceID="ds">
<AutoSize Enabled="True" />
<AutoCallBack Target="gridNR" Command="Refresh" />
<Levels>
<px:PXGridLevel DataMember=“NotificationSources" DataKeyNames="SourceID,SetupID">
<Columns>
...
</Columns>
</px:PXGridLevel>
</Levels>
</px:PXGrid>
|
The Hindu religion is REALLY big on their cows. I wouldn't expect them to get angry about it, but then again, you never know. Still, the Hindus are usually pretty good about this kind of thing. Thicker skin than most.
I dunno, maybe they got a message from some "cows rights" group or something... Microsoft really wants to appeal in India so they're not going to do anything that could potentially hurt their chances.
From I theory I heard on Digg, Microsoft decided to cut their losses. By not releasing the game, they won't lose money in manufacturing, distribution etc. if it ends up banned or boycotted later. Sensible market decision, but more like a nod to piracy amirite.
So, I got the game Tuesday and it is great. It's not "the same," but I was expecting that. Yet, at the same time, it feels like Fallout. I think it's a very natural progression of the series and had Black Isle not gone under, I could see them making this game.
I guess I should start by comparing it to Oblivion, since that was the big pre-release mantra of many original gamers. The Oblivion influence is there, but this IS Fallout. You can definitely tell the same company made both games, much like you can tell BioWare made KotOR and Jade Empire.
The menus in Fallout 3 are similar to Oblivion, and you will see (and hear) Baurus walking around, but the character diversity is better. Actually, it's probably just that there are less characters running around than in Oblivion, what with humanity barely around and all. The world is similar in that you are giving a map that you can pick a direction and just run and explore, which you could do in the original games by using your map and seeing the "travel lines" until you came across something, but in Fallout 3, you just manually run. Fast Travel is in the game once you discover an area of interest, however.
Combat works well in Fallout 3, although the turn based system is gone. The game plays like a First Person Shooter, until you use you V.A.T.S. The V.A.T.S. is awesome. You pick your target, and when you bring up V.A.T.S., you are given the old Fallout targeting system. You can target the mobs head, left arm, right arm, left leg, right leg, and whatever weapon they are carrying, but if you want the best chance to hit, you can also target their torso. The cool thing is that if you target anything other than the torso, there's a chance the limb will get blown off or in the case of the head, explode.
The really cool thing happens after you select your target and click accept. The camera switches to a slow motion cinematic view. It will show you different angles of the fight from behind you to behind the mob to, my personal favourite, a closeup of my character's face, gleefully smiling as rounds are pumped into the enemy!
All in all, I find the combat system to be a good balance between the faster FPS type combat and the old Turn Based combat of the the originals.
The old Fallout mobs are back. While running around, I came across a Deathclaw. I was torn between "OH CRAP! THE DEATHCLAW IS GOING TO EAT ME!" and "YES! THIS IS AWESOME! A DEATHCLAW!" It was strange mix of fear and nostalgic excitement.
Voice acting is very good in the game. Ron Perlman returns with a new "War. War never changes." speech. Then you meet your Dad, who is voiced by Liam Neeson. Yep, Liam Neeson. The only other actor I picked out was Malcolm McDowell, who voiced The President. This seems a good time to mention a cool new function of your Pip Boy. It has a radio. You can turn it on and listen to The President giving patriotic speeches about rebuilding the American government and conquering the Wasteland as you play. There's also another radio station you can listen to and probably should because the two stations have different beliefs about what's best for the Wasteland. Both stations also play music between speeches by their respective host. Oh, and while not necessary, you can also pick up clues about the main quest through the radio. You're leaving the Vault is big news, and people are talking.
Anyway, I could go on for a while, but it's hard to think what to say without giving away spoilers. Overall, I like the game. It's fun and feels like it was done right. There are some things that perhaps could have been done better, but all in all, the atmosphere of the game works. One of my favourite early moments was picking up a Leather Armour. It's a small thing, perhaps, but it looks exactly like the Leather Armour from the originals, just in 3D and much more detailed.
And with that, I'm off to kill some more Super Mutants! The Wasteland calls!
I pretty much agree with Bob Lion. It seems like that everything that was wrong with Oblivion was "fixed" in this game. No more two dimensional characters, a lot better writing and voice acting, quests that can be solved in more than one or two ways... It definitely feels more like the first two Fallouts (graphic, combat, and controls notwithstanding) than Oblivion, which is a very good thing indeed. I'll have to play some more before I make any final judgments, though.
Quote:
Have you tried using any Oblivion mods in the game? Im thinking about trying it. I just have to actually put the files where they go and turn on the game...
Even though the game's using the same engine as Oblivion, the content is different; I doubt any Oblivion mods will actually work. The only "mods" from Oblivion that I'm using is some .ini tweaks and in-game console commands (like changing the game's timescale). Those work because they are more Gamebryo engine than Oblivion related.
I disagree with it being more Falloutish then Oblivionish ^^ Both me and my friend played thourgh the begining then when we went outside the vault and started exploring we went into a raider base. After being in there for like a minute we both looked on eachother and said "This feels like Oblivion". Well i haven't played so long yet, but im not too impressed yet.
I think the random bases feels way to much like the dungeons in Oblivion, and i really don't think it belong to the Fallout universe to have raider bases evrywhere, i mean in whole Fallout 1 & 2 we encoutered like three raider bases and they were story bases. It would be alot better if they did it like STALKER where the raiders actually move around the world (Well maybe they do, but i havent encounterd any yet in the way im thinking)
And i really wondering about the removal of traits, was it to much of a hassle to have start traits like in 1 & 2 ? Where they to similar to perks for Bethseda to bother make them ?
But overall the game is pretty funny, but not like the old Fallout games, i have the feel of playing Oblivion with guns and alittle better dialougs. But like i said, i havent played for to long so my opinion may change when i get more into the main story.
I would recommend that you start with Fallout 1 then 2, because they are so much better then Fallout 3 probaly ever will be (Yes, im a hardcore Fallout fan, since Fallout2 top my list of best games ever)
I disagree with it being more Falloutish then Oblivionish ^^ Both me and my friend played thourgh the begining then when we went outside the vault and I think the random bases feels way to much like the dungeons in Oblivion, and i really don't think it belong to the Fallout universe to have raider bases evrywhere, i mean in whole Fallout 1 & 2 we encoutered like three raider bases and they were story bases. It would be alot better if they did it like STALKER where the raiders actually move around the world (Well maybe they do, but i havent encounterd any yet in the way im thinking)
It's definitely similar in many aspects (similar graphic and gameplay), but writing and atmosphere isn't one of them, IMO. But each to their own. It's purely a matter of opinion.
I agree about the raiders, though I must say that it doesn't bother me that much; I never expected this game to be just like the first two Fallouts anyway. In fact, I chose not to compare it to the first two Fallouts at all. This helps me get over some annoyances... if I don't consider it to be a sequel, but rather a game set in the Fallout universe.
It would be nice if they could release a construction set. That way I would be able to get rid of all of the annoyances pretty fast.
Quote:
Originally Posted by Lance Monance
EDIT: Ok, that gamebanshee article.. is that true? Quest are worse than Oblivion's?
As far as I can tell, that's definitely not true. I think the one who wrote that review never played or enjoyed the first two Fallouts, but liked Oblivion.
all this comparisons to Oblivion, i think, is just utter nonsense. IMHO, this game is its own game pure and simple. yes, you can tell its from the same developer, but i really don't see the point in sweating out little details like "the lighting is similar" or "it feels like they scattered Oblivion dungeons everywhere". if you go in comparing it to Oblivion, then that's all you'll see. if you go in to just play the game, i know you'll have a lot of fun because i'm having a lot of fun.
yes, i notice similarities between the two games, but the main reason is that i pay attention to a lot of technical nuances. that comes from being a detail-oriented programmer and not from a desire to pick the game apart trying to find every last similarity to other games.
so far, i'm having a lot of fun, but for the moment, my character is struggling a bit because he can't seem to find enough ammo....
How would you rate it compared to other good RPGs you've played, say Kotor, BG2, PS:T, the Witcher, ME, Motb, vampire 2, .. (assuming you have played any of those )
I can't really. I hold all of those in high regard, so I don't really consider one better than the other. They all have their strengths and weaknesses (more of the former, though), and I've enjoyed them all one way or another.
all this comparisons to Oblivion, i think, is just utter nonsense. IMHO, this game is its own game pure and simple. yes, you can tell its from the same developer, but i really don't see the point in sweating out little details like "the lighting is similar" or "it feels like they scattered Oblivion dungeons everywhere". if you go in comparing it to Oblivion, then that's all you'll see. if you go in to just play the game, i know you'll have a lot of fun because i'm having a lot of fun.
yes, i notice similarities between the two games, but the main reason is that i pay attention to a lot of technical nuances. that comes from being a detail-oriented programmer and not from a desire to pick the game apart trying to find every last similarity to other games.
so far, i'm having a lot of fun, but for the moment, my character is struggling a bit because he can't seem to find enough ammo....
Yeah, opinions is a bitch, aint they ?
@Lance: Well like i said, Fallout 2 atleast top my list of best games i played, and i played all those you listed there. And i think all the games you listed also is very good, Kotor, PS:T, BG2 are atleast very high up on my same list. And like SpaceAlex said, they all have there strength and weakness, like i don't think there is a game that even can come close to match PS:T story and dialougs, but it's still aint my favorite RPG
hehe, i keep getting myself into situations where i'm fighting outnumbered and outgunned. those moments can be frustrating at times, but its also rather rewarding when i'm the last man standing.
at least i solved the problem of not having enough ammo. i will say this about this game: stealth works pretty darn good. i just wish that you had some cool takedown animations whenever you sneak up behind someone and knife'em real good.
If anyone's having problems with LIVE or just wants to improve performance and how fast the game will load, renaming Fallout3.exe.cat to something else will cause the game to skip loading the LIVE dll.
edit: just finished the game and was completely meh'd by the ending i got.
"No, Mama. You can bet your sweet ass and half a titty whoever put that hit on you already got the cops in their back pocket." ~Black Dynamite
A tough question to answer. I just started playing two days ago. To me, it "feels" more like Fallout than Oblivion. Besides the obvious wasteland setting, the Pip Boy and S.P.E.C.I.A.L. system are familiar aspects to its predecessors. The real-time combat and camera angle system much more akin to Oblivion, though the optional V.A.T.S. targeting system does use some of the better aspects of the old Fallout system. The dialog system seems to combine the best of both games using skill-based and perk-based dialog options combined with full voice-overs. The jibber-jabber dialog of NPCs in the background seems to have a better repertoire than I remember Oblivion having.
So far I'd say Fallout 3 has its own flavor distinct from F1/F2 and Oblivion. If you liked the earlier Fallouts and Oblivion, I think it's safe to assume you'll enjoy the game play of Fallout 3.
As far as I can tell, you can play each of the Fallouts separately without missing much. Sure there will be references that will have deeper meaning if you played the earlier game(s), but nothing to stop you from enjoying the individual games on their own. F3 takes place on the east coat while F1 and F2 take place on the west coast, very near yours truly as a matter of fact.
You can get the gist of the backstory from wikipedia and also, for those who don't have F1 or F2, you can play them for free by signing up with Gametap. Since you're an old fogie like me, I have confidence you'll enjoy the charm of the old isometric POV and dialogs, so feel free to play in any order you like.
If you want to go into further details about the series, there's also a Fallout Wiki.
The only thing that is tempting me to buy F3 is, well, mods. There's quite a few out already, and many of them try to inject the original Fallout "feel" into F3. However, the only thing stopping from getting F3 is that it's been in the hands of Bethesda, so I'm expecting cheese galore with the voice acting.
The first two fallouts take place on the west coast, Fallout 3 takes place on the east coast and quite a bit of time has passed as well, so anything from the first two that you need to know is told to you in Fallout 3. Playing the first two will get you "into" the world of Fallout, which is honestly a really well put together, amazing world. So you should seek the experience from the first two, but don't let not having played them keep you from just firing up 3. I do highly recommend playing Fallout 1 before 2 though as they do tie together.
About Fallout 3 though... I may be the odd man out, but I really didn't think Oblivion was so amazing. It had some good graphics, and the size of the world was a pretty big wow factor for me, but once I started getting my own houses, killing things, etc., etc. I just had a hard time holding onto the core storyline. It was like the immensity of the world kept dragging me from it. Fallout 3 doesn't quite play out that way for me, which is why I love it.
Fallout 3's main quest is pretty straightforward, its all about your dad. I won't throw in any spoilers here, so don't worry. The quest takes you to several places where you learn about more quests and options that can help you become a better wastelander. The really nice thing is that despite the fact you might get sidetracked trying to help some slaves rebuild lincoln's memorial or you're debating blowing up that nuke the town was built around, many times the dialogue with people will lead you back to the main quest, fortunately not in an annoying way.
The world is truly free roam. If you run afoul of a couple deathclaws cause you went into the wrong cave, or an enclave patrol stumbles across you, well needless to say if you're not ready for it, it won't take long for you to find out. The world moves beyond you, there are roaming patrols, creatures move from area to area, its really pretty dynamic. The game does have a linearity to it though that will be hard to escape. For instance in DC, I felt many times like the rubble in my way should have been easily scaleable, but the designers felt otherwise and I was forced into one of the very many subway systems to get to the next area I wanted to go to, which leads to some frustration sometimes. Also, there are occasions in combat where things can get pretty hot and heavy, and the game really shines there, cars exploding around you, blood flying on your screen, sounds are dulled from the shockwave and you're trying to gun down that super mutie with a gatling gun. Very exciting.
The dialogue was really well written and the actors mentioned above did a great job, particularly McDowell. The side quests are excellent as well, very well thought out for the Fallout world though occasionally a bit predictable, which fortunately the game uses for some comedic moments. A radio dish has been broken and ironically another dish can be found, you get pegged to go get it, and the dialogue reflects that irony well with humour about "Let me guess, you want me to get that for you?" The game achieves a realism through dialogue because your character can be any number of different personalities.
Anyway, there are some bugs in the game that are pretty hard to get around, but there is a thread on the bethsoft forums that is the official thread for fixing game breaking bugs as best we can, many solutions for people have been found there if they're having problems. I personally never really hit any problems that were not my own comps fault, but thats just me. I've played the game from start to finish, and like some others, felt the ending was forced on me, and am somewhat disappointed by it, but such is life, it was still half decent and I'm working on my next playthrough to experience a different ending. This game isn't to be missed though, they obviously put a lot of hard work into it. The overall feeling is that they created this with alot of care and thought as well as respect for the first two games and made it into something new, which I'm ok with. Definitely check it out though as its an experience not to be missed.
Bethesda has announced forthcoming downloadable content for Fallout 3 for both Xbox 360 and PC versions. First up however is the PC exclusive game editor that will allow Fallout 3 players to create their own quests and content. Called the G.E.C.K., short for Garden of Eden Creation Kit, PC gamers will be able to create new creatures, weapons, quests, etc. sometime in December. Then starting in January, both PC and Xbox 360 players will get new content: Operation Anchorage, followed by The Pit in February, and Broken Steel in March.
While the new editor will be a free download it's not real clear to me that the in-game content will be free downloads. My guess is they won't be but will likely need to be purchased via Games for Windows Live or Xbox Live.
Want to battle against cancer and other chronic diseases? Join Team LFN!
I suppose a performance hit is to be expected given that the new textures are in 2048x2048...personally, I didn't tried the pack but I am not sure that the new textures are really an improvement (it was certainly a lot of work for the modder though ). From the screenies published here (in French but you don't need to understand to see the screenshots) tiling seems more visible to me and I can't say that I am very fond of all those rocks...to each its own I guess...to me pure "photo-realistic" textures != automatical improvement .
OK so I just got through my first run of Fallout 3. About the ending.... what the hell? I mean.... what the hell? Even Oblivion's ending was better then that and Oblivion's ending was crap.
I thought the same thing my first time through.
spoiler:
Thought it was going to be like Oblivion where I could continue on my merry way, but…
I've competed 4 times through now on the 360 and I’m now on my first play through with the PC version of Fallout 3. Still need to go through at least twice on the 360 to get the evil, neutral and the slave quest achievements. FWIW I actually like Fallout 3’s ending now, well at least the good ending (as I have not seen the others).
OK so I just got through my first run of Fallout 3. About the ending.... what the hell? I mean.... what the hell? Even Oblivion's ending was better then that and Oblivion's ending was crap.
Yea, that's really my only problem with the game. The ending is horrible. The rest of the game was fun, but then you hit the brick wall of the ending.
Which, speaking of brick walls, is the other problem with the ending. It felt too abrupt, like there should be more game. On my first playthrough, I decided to work on the main quest some more, then go back and do some more of Moira's stuff, but then BAM! The end.
I kind of had a feeling when Sarah Lyons said "Are you ready, we won't be coming back for a while," or whatever her exact line was, but I was in disbelief that I really was at the ending that soon... the lead up wasn't natural.
So, my second playthrough, I just went to Megaton and talked to Moriarty. Then, I just went and explored, avoiding all the places and people I knew would move the story along until I was ready.
I wanted more of the Fallout/Fallout 2 epilogue narration, recapping how my various actions affected others in various areas of the game and what became of them. Instead there was just a couple variations on the main quest's outcome. I mean, that let me down way more than the ending of the main quest. |
class User < ApplicationRecord
attr_accessor :remember_token
validates :name, presence: true, length: { maximum: 50 }
VALID_EMAIL_REGEX = /\A[\w+\-.]+@[a-z\d\-.]+\.[a-z]+\z/i
validates :email, presence: true, length: { maximum: 255 },
format: { with: VALID_EMAIL_REGEX },
uniqueness: { case_sensitive: false }
has_secure_password
validates :password, presence: true,
length: { minimum: 6 }, allow_nil: true
def User.digest(string)
cost = ActiveModel::SecurePassword.min_cost ? BCrypt::Engine::MIN_COST :
BCrypt::Engine.cost
BCrypt::Password.create(string, cost: cost)
end
def User.new_token
SecureRandom.urlsafe_base64
end
def remember
self.remember_token = User.new_token
self.update_attribute(:remember_digest,
User.digest(remember_token))
end
def forget
self.update_attribute(:remember_digest, nil)
end
# 渡されたトークンがダイジェストと一致したらtrueを返す
def authenticated?(remember_token)
return false if remember_digest.nil?
BCrypt::Password.new(self.remember_digest).is_password?(remember_token)
end
end
|
This project focuses on the design aspects of multicontract cochlear implants concentrating on the factors that affect their ability to be removed and replaced, possibly with dimensionally different implants. The new designs must cause minimal mechanical trauma and foreign body reaction in middle and inner ear structures. It is anticipated that this will include improvements in surface materials, electrode geometries and implant fixation techniques as compared with presently existing electrode arrays. Evaluation will be in non-deaf animal models of the developing child. The decision to use a non-deaf model is based on the fact that hair cells are sensitive indicators of disturbances of cochlear structure and function. Also, in deaf models with implanted electrode arrays, cochlear damage produced by inducing deafness complicates the interpretation of damage caused by the implant itself. |
Today I am going to take full advantage of my own rules and relax with just pictures of what we had for breakfast. It was Idlis with Meddu Vada, Hotel Sambar and chutney, though it was made as well, it's missing in the picture. For a long time, hubby dear has been after me to replace the blog picture with new ones. I have even included that theme in the next BM.
I was surprised that though we make idlis every week, I never thought I should replace them. I am still yet to do it. The basic Idli post has lot of details, tips and discussions with readers. I have been planning to do a step by step post as well, which will be up soon. So then I might come out with the new pictures. This post, however is not about the recipe, rather the memories associated with this wonderful staple to all South Indian families.
South Indian Breakfast
Growing up, I have always professed dislike to this dish, simply to spite my brother. As an eight year old kid, I was bored to death for want of somebody to fight up. I came up with this brilliant idea to pick up a fight with my older brother, who is too sweet and calm for my own good. He was and still is a person, who never raises his voice, unless and until, trust me, is really really provoked to the core. And that happens very rarely too. All my growing up years, I tried my best to do it at every opportunity. If he likes a dish, I made it a point to dislike it, and made things tough for Amma. Plus somehow pick up a fight. To my dismay it never used to happen.
So it was like this, he never touches Idlis, I love it. He likes Ven Pongal and I won't touch it. The list was quite long. For a long time I never tasted Okra stir fry because he loved it. You are reading a person, who had such a dull as a dishwasher childhood, always with imagined fights with siblings. I envied my friends who fought with their siblings and lapped on their stories and wished I had the same.
Of course I grew out of my childhood antics and accepted that I had to live with a brother who was too kind to believe. We miss him whenever we make his favorite dishes, which happens to be almost on everyday basis. He still doesn't like Idlis much, though my sil says he eats because his kids like it.
And my Chinnu has many of his food habits and Amma gushes each time she talks about Chinnu's likes and dislikes and how much he resembles his uncle. The scene is quite comically most times. While Konda, Peddu loves to eat Idlis, Chinnu will not even come close. Same goes to anything to do with breads. He has not even tasted a bit of bread. While first two loves pizzas, burgers, Chinnu will not even touch with a barge! And on top demands that I make something special for him alone as others are having their favorite! That something special always happens to be Maggi.
I always love to eat it mashed and mixed with Amma's Podi this way all crumbled as Upma or completely mashed and mixed with Sambar! You know the quote right, 2 idlis with a bucket Sambar, we keep that true..
I hope you enjoyed reading this as much as I enjoyed writing it. It's been a while since I rambled and never thought a simple dish like an Idli can get me on so much!
This day next week, Konda will be starting her school. So it's only another week for us to be laid back and enjoying our summer holidays. We will be rushing out to begin a whole new year at school!
That reminds me of my own Summer vacations, how I used to begin each year with loads of Enid Blyton, Famous Five, Nancy Drew books, later to be replaced by Frederick Forsyth, Robin Cook, M&Bs and more serious literary works. I tried my best to get Konda interested in the huge collection I have accumulated over years, she is unable to cross past Tinkle. Of course I can read Tinkle even now, but just saying!
It's been a great fantastic two weeks of Blogging Marathon. And I am left with nostalgic thoughts of ending this session today. We will be beginning a new season of Blogging Marathon next week, which is set to be more exciting as before, if not more! |
On girls:"Whatever I thought might hold me back, I avoided. I crossed girls off my list—except as tools for my sexual needs."
Girls continued"I had no difficulty getting girls. I'd been introduced to sex with almost no hangups. The older bodybuilders at the gym had started including me in their parties. It was easy for me. These guys always saw to it that I had a girl. "Here, Arnold, this one's for you." Girls became sex objects. I saw the other bodybuilders using them in this way and I thought it was all right. We talked about the pitfalls of romantic situations, serious ones, how it could take away from your training. Naturally, I agreed with them. They were my idols."
Arnold talking about his Ego @ 19 years old:"There was a funny period I went through which began about the time I was nineteen. I'd become fully developed physically, weighing between 240 and 250 pounds. I'd begun to get a lot of notoriety and I started feeling superior to everyone. I think that when you're almost up to the top, but not quite there, it's easy to be carried away with what you imagine to be your own importance. I was pretty ego-oriented anyway. I already felt I was better than anyone else. I felt as if I were a Superman or something. That was my attitude: macho. I was strong and I walked the streets feeling and acting tough. If someone made the slightest remark or gave me trouble I would hit them over the head.I was aggressive and rude. I'd go into a beer hall where we ate dinner after training and start a fight for no reason at all. It was a bad time. Now, looking back on it, I'm embarrassed. I was nothing more than a punk, a big bully throwing my weight around.I had fights almost every day. It might be in the train station with an Italian or a Greek. Or it might be in front of a girl, just to show off what kind of a man I was. I made a lot of trouble, got in scrapes with the police, drove crazily, collected handfuls of speeding tickets—they were all connected with my need to emphasize my masculinity, my superior size and strength."
Arnold on training beyond failure & Shocking the muscles"Every bodybuilder in Munich
wanted to train with Arnold. They thought I knew some secret.We got into forced reps, real torture routines where wepushed ourselves beyond the point of pain. We ate enormous meals. After each workout we would go to the beer hall and devour a whole chicken each and mugs of beer. That was our dinner.
In the actual training routines I was trying to be more creative than I'd ever been, putting my imagination into play in an attempt to figure out how I could go beyond everyone else. If someone could get a 21-inch arm, I would blow mine up to 22 inches. Arnold, I asked myself over and over, "What can you do to be special and different?" I finally arrived at the idea of shocking the muscles. If you do ten sets of bench presses or any other exercise regularly for a
year, the muscles gradually get used to ten sets of bench presses and the growth slows down. So once a week I took a training partner and drove out intothe country with the weights. We limited ourselves to one exercise for a particular body part. I remember for the first day we carried 250 pounds out into the forest and did squats for three hours straight. I began by doing twenty repetitions with 250 pounds; then my partner did whatever he could. Then it was my turn again. We ended up doing something like fifty-five sets of squats each. The last hour seemed endless. But it worked. Our thighs pumped up like balloons.
That first day we gave our thigh muscles such a shock that
we couldn't walk right for a week. We barely could crawl. Our
legs had never experienced anything as tough as those fifty-five
sets. And each of us put something like an eighth or a quarter of
an inch on our thighs; they just blew up, they had no chance to
survive except to grow.
We made it a regular thing. We brought girls out there to cook.
We made a fire outdoors and turned the whole thing into a little
contest. We worked hard but we had a good time. After the
muscle-shocking sessions we drank wine and beer and got drunk
and carried on like the old-time weight lifters back in the 1800s
or early 1900s. Sometimes it became pure insanity. We'd grab up
the weights again, but we were weaker because of the beer, and
the weights would fall back over our heads. Or we'd get themdown on our chests and wouldn't be able to press them on up
from there and someone would have to lift them off for us. It was
a great time. We cooked shish kebab, sat around the fire, and
made love.We got into this trip that we were gladiators, male
animals. We swam naked out in nature, had all this food, wine
and women; we ate like animals and acted like animals. We got
off on it so much it became a weekly routine—eating fresh meat and drinking wine and exercising.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10.
Legend. The most famous scene from Pumping Iron, "It's like I'm cumming day & night!"
"Imitate the action of the tiger; Stiffen the sinews, summon up the blood"
"To hell with circumstances; I create opportunities."
"If you always put limits on everything you do, physical or anything else, it will spread into your work and into your life. There are no limits. There are only plateaus, and you must not stay there, you must go beyond them."
***No Fap Crew(as of 11/10/2012)***
---Challenge:365 Days of No Fap -- Day 10. |
[Retrospective study of acute myelogenous leukemia in 83 elderly patients: clinical and biological characteristics].
In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients. |
DDT-related compounds bound to the nonextractable particulate matter in sediments of the Teltow Canal, Germany.
Sediment samples of the Teltow Canal (Berlin, Germany) were analyzed with respect to extractable and nonextractable organic compounds. The study focused on the identification and quantitation of bound 2,2-bis(chlorophenyl)-1,1,1-trichlorethane (DDT) residues in order to obtain further information about the fate of DDT-derived compounds within the particulate matter of the aquatic environment. Various chemical degradation techniques and a complementary online pyrolysis-GC/MS method were applied to the pre-extracted sediment residues. Generally, the distribution of the bound DDT-related compounds was found to differ distinctly from the substances distribution within the extractable fraction. The main metabolite of the anaerobic degradation pathway (2,2-bis(chlorophenyl)-1,1-dichlorethane, DDD) is most abundant in the sediment extracts but occurred only in insignificant concentrations in the degradation products of all procedures applied. The most abundant DDT-metabolites released after the degradation procedures were 4,4'-DBP, 4,4'-DDA, and 4,4'-DDM. In addition, 4,4'-DDM was detected at rather high concentrations by pyrolytic analysis. The results imply a weak association to the nonextractable particulate matter based on noncovalent interactions for the observed DDT-related contaminants. The release of these compounds was initiated by the modification and degradation of the organic macromolecular matrix as well as of the inorganic material. Furthermore, numerous methoxychlor-related compounds were detected not only in the extracts but also in parts of the hydrolysis products. |
Q:
Join tables on columns of composite foreign / primary key in a query
CREATE TABLE subscription (
magazine_id bigint,
user_id bigint,
PRIMARY KEY (magazine_id, user_id)
);
CREATE TABLE delivery (
magazine_id bigint,
user_id bigint,
FOREIGN KEY (subscription) REFERENCES subscription (magazine_id, user_id)
);
What is a good way to query for deliveries given a particular subscription? Is there a way to assign a column name to PRIMARY KEY (magazine_id, user_id) and the corresponding foreign key so that I can query like this:
SELECT *
FROM subscription
JOIN delivery ON (delivery.subscription_fk = delivery.subscription_pk);
Note: I can write something like this:
SELECT *
FROM subscription
JOIN delivery ON (delivery.magazine_id = subscription.magazine_id
AND delivery.user_id = subscription.user_id);
However, I am under the impression that there is a less verbose way to achieve this.
A:
There is a NATURAL JOIN:
SELECT *
FROM subscription
NATURAL JOIN delivery;
Quoting the manual on SELECT:
NATURAL
NATURAL is shorthand for a USING list that mentions all columns in the two tables that have the same names.
It would work for your test setup, but it's not strictly doing what you ask for. The connection is based on all columns sharing the same name. Foreign keys are not considered. The cases where NATURAL JOIN is a good idea are few and far between.
Simplify code / less verbose
For starters, you could use table aliases and you don't need parentheses around the join conditions with ON (unlike with USING):
SELECT *
FROM subscription s
JOIN delivery d ON d.magazine_id = s.magazine_id
AND d.user_id = s.user_id;
Since column names in the join conditions are identical, you can further simplify with USING:
SELECT *
FROM subscription s
JOIN delivery d USING (magazine_id, user_id);
There is no syntax variant making joins based on foreign key constraints automatically. You would have to query the system catalogs and build the SQL dynamically.
|
Skeptics are winning: “the carbon market is dead”
The collapse of the Man-Made Myth continues apace. You may not read headlines as such (at least not in major dailies) but all the signs are there.
People who we never would have imagined speaking against the Big Scare Campaign are now doing so. Key glaciers are not melting and corals are happy. Governments won’t tell you it’s over, but they are behaving that way (the Australian one excepted, due to an election fluke that gave the Greens the balance of power). The Catholic Herald headlined it: Is the ‘anthropogenic global warming’ consensus on the point of collapse?
Mini update: The carbon market is being referred to as “dead”. Johannes Teyssen, chief executive of Germany’s EON, urged policymakers to make fixes. “Let’s talk real: the ETS is bust, it’s dead,” Mr Teyssen said in Brussels this week, adding: “I don’t know a single person in the world that would invest a dime based on ETS signals.” [full story: Financial Times]. Point Carbon analysts have downgraded the forecast price of carbon credits for the second time in two months as the carbon market continues to slide. What was estimated to be 12 Euros, has fallen to 9 euros for 2012, and 8 euro’s for 2013. It’s a long way below $23, set by our Australian “free-market-lovin’-Labor-Party”. (If only they knew what a free market was.)
The best known environmentalist in the German Social Democratic Party announced he had become a skeptic (see FOCUS and read about his new book). It doesn’t get much more damning than this. Fritz Vahrenholt was a chemistry professor and a leftie politician, and, could it be any more poignant… also headed up the renewable energy division of Germany’s second largest utility company. CEO of a wind farm for goodness sake. H/t to Keith and many many others.
The Cold Sun: Why the Climate Disaster Won’t Happen, is making waves in Germany where people don’t critize climate-change science much and where His book,is making waves in Germany where people don’t critize climate-change science much and where solar and wind power are major industries. I hear from a friend in Europe that this book is very much “hot stuff” in Germany. Thanks Stefan.
Thanks to the GWPF I also know that Australia will probably be the last-man-standing on the deck of the burning ship called “Climate Change”. Everywhere else around the world, the only people who aren’t abandoning ship are those who never climbed aboard. Subsidies to all new wind and solar plants were outright suspended in Spain last week, which was not just bad, but described as “one of the biggest blows ever to the sector. ” The changes are predicted to kill off much of the investment in renewables there. The people selling solar power in Greece were also told the government could not afford to pay their rates, and didn’t really want more of that kind of power right now either, thanks. The U.K. government joined the rush to abandon renewables and promised to cut subsidies for solar energy (see Bloomberg). Meanwhile 101 Tory ministers in the UK government declared they want to toss the wind-farm subsidies out the window. If Julia Gillard wants to lead the way in this market she could start by buying up the solar plants, and drilling their ground for shale gas.
Why now: The perfect storm?
Skeptics have been hammering away at this for years. The mainstream media won’t publish any skeptical science, not even a comparison of land or ocean temperatures against the model predictions (how “technical” is that?). But thanks to the Internet, people found out anyway — it just took a bit longer. The weather is cold or wet. The witchdoctors claim that this is what they predicted, and it’s due to global warming, but the crowd are not that dumb (and again, the Internet — their bad predictions are there for all to see). The money ran out. Ten years later, people have noticed. Shale gas.
Dr Benny Peiser of the Global Warming Policy Foundation says: “Shale gas is the big game changer because it has previously been argued that fossil fuels are near to running out. There could now be enough gas for 200 or 300 years”. –-Adrian Lee, Daily Express, 25 January 2012
It’s a global thing, Barack Obama is also “discovering” shale.
President Barack Obama pushed drilling for gas in shale rock and support for cleaner energy sources to boost the economy in his final State of the Union address before facing U.S. voters in November. He also pledged more oil drilling. Bloomberg, 25 January 2012
The evidence is killing even the pet-scare-lines
Somewhere, some bright spark realized that coral reefs like warm water, and in areas where corals were growing at the edge or outside the tropics, what ho, but the corals liked it when the water got warmer. (And someone needed a study to know that? Or did they just need a research grant?) Where oceans have warmed the most (because they were the coolest to start with) the corals just got happier and happier. Where the temperatures warmed the most — the corals increased their growth rate the fastest…
Over the last seven years or so the Himalayan glaciers stopped losing ice. The Guardian. [NASA] h/t [Watts Up] Only a few years ago they were saying those glaciers would be gone.
The world is rediscovering those derided “extremists”
When all is said and done, they turned out to be more mainstream than anyone knew…
We Are Winning the Debate and Greens Don’t Like It
Source: UK Express
Lord Lawson, who was Margaret Thatcher’s Chancellor from 1983 to 1989 and an MP for 28 years, is not the only one to have suffered for his views on climate change. Anyone who dares to challenge the often zealous green lobby is apparently fair game.
Entertainer and mathematician Johnny Ball has been vilified for opposing the commonly held view about global warming.
He says: “For daring to take this contrarian view I’ve lost bookings, had talks cancelled and been the subject of a sinister internet campaign that only came to an end following the intervention of the police.”
Environmental campaigner David Bellamy also claims he has been victimised for taking an alternative position. He has said: “The sad fact is that since I said I didn’t believe human beings caused global warming I’ve not been allowed to make a TV programme. The idiot fringe has accused me of being like a Holocaust denier.”
Even the Greenie groups at the leading edge know they need to move on, and call it something else…
Rio+20 or the Earth Summit, that it risks ending up as all talk and little action. In an attempt to avoid too much confrontation, the conference will focus not on climate change but on sustainable development. –Deborah Zabarenko and Nina Chestney, Reuters, 24 January 2012
General hat-tip to the excellent GWPF
———
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Noise-level estimation of time series using coarse-grained entropy.
We present a method of noise-level estimation that is valid even for high noise levels. The method makes use of the functional dependence of coarse-grained correlation entropy K2(epsilon ) on the threshold parameter epsilon. We show that the function K2(epsilon ) depends, in a characteristic way, on the noise standard deviation sigma. It follows that observing K2 (epsilon ) one can estimate the noise level sigma. Although the theory has been developed for the Gaussian noise added to the observed variable we have checked numerically that the method is also valid for the uniform noise distribution and for the case of Langevin equation corresponding to the dynamical noise. We have verified the validity of our method by applying it to estimate the noise level in several chaotic systems and in the Chua electronic circuit contaminated by noise. |
Mosques Need Better Social Safety Nets
Zarqa Nawaz
Creator of hit television series Little Mosque on the Prairie and author of best selling comedic memoir Laughing all the Way to the Mosque.
ADVERTISEMENT
A few years ago, on Little Mosque on the Prairie, we had an episode entitled The Convert. Marlon comes to a mosque open house and decides to become Muslim. Everyone's excited at first and welcomes him with open arms. And then Marlon gets a bit too extreme about his newfound faith. He starts to wear robes and begins to berate everyone for being lax Muslims. Even Baber, the ultra-conservative can't dodge criticism from Marlon about not forcing his daughter to wear a hijab. Everyone realizes that Marlon's a little unhinged so they conspire to get rid of him by behaving like lecherous Muslims, which for us involves eating pork and drinking alcohol while dressing up like Hugh Hefner and Mr. T. They're successful and Marlon leaves. I thought it was funny. It was based on my experience with convertisis, a cycle a lot of new Muslims go through when they enter the community for the first time.
But now with two converts who have tragically killed members of our military personnel, it's no longer humorous. It's very real. Kicking out converts may not be the answer.
Our mosques are set up so kids can read the Qur'an in Arabic and learn about the stories of the prophets, and yes my kids hate going which I think is a universal for all faiths. Back in my day as a mosque-hating child, we had extremely few converts and they were our heroes, giving lectures during fundraising dinners about Why I Became Muslim -- always the perennial favourite. With the advent of social media and a global awareness of international politics, the landscape of the average mosque has changed.
These days we're finding people, both Muslim and non-Muslim, coming to the mosque suffering from a host of social issues: criminal history, poverty, mental illness, elder neglect, drug abuse, and domestic violence to name a few.
Mosques are set up for Muslims to come and perform the five daily communal prayers, and usually can just afford the salary of the imam and pay basic utility bills. We depend on volunteers to teach on the weekend school. I would love it if our humble mosque in Regina, Saskatchewan could also afford a social worker, a psychiatrist, a drug addictions counselor, a shelter for victims of abuse and a food bank among its services. But this is beyond the budget of most mosques. And given the extra level of scrutiny that the community is under, unstable individuals are quickly reported to the RCMP and told never to return.
Michael Zehaf-Bibeau was kicked out of his mosque in Burnaby, British Columbia. The Muslim community had to change the locks to make sure he wasn't able to come back and sleep in their premises. And I don't blame them. They weren't in any position to give him the support he so desperately needed.
Muslims are justifiably worried that we'll be implicated in the crimes of these individuals. But Michael Zehaf-Bibeau was still a human being looking for support from both his Muslim and non-Muslim communities. And although we'll never know the truth, it seems he eventually found his support on the Internet, which preys on the marginalized in our society.
People want moderate Muslims to speak out and decry radicalization. And they do, but tweets and press releases are not always the answer because they don't solve a very real societal problem. There are unwell people out there who need our help. And they are increasingly showing up in our mosques.
What we actually need are Muslim social support associations set up to work with mosque communities to get first responders to deal with people in crisis. We can't get to everyone. It's not possible. Lone wolves will always be among us. But we have to start somewhere and some Muslim communities have already begun.
The Edmonton Muslim community has done an admirable job with help from the city of Edmonton, by setting up IFSSA, the Islamic Family and Social Services Association. They are an excellent role model for Canadian Muslim communities to emulate.
What am I going to do as a Canadian of Muslim faith to help prevent this type of senseless tragedy from happening again? I'm going to find out what funding there in my city of Regina, Saskatchewan and work with existing agencies to make sure there is a Muslim-based social safety net in place for vulnerable people who come to my mosque.
We all need to work together to make sure that Canada remains safe. The Marlons and Michaels of our world should always be treated with compassion and never be left to fend for themselves. |
Stereoisomers in clinical oncology: why it is important to know what the right and left hands are doing.
In the past few years it has become clear that the individual stereoisomers, especially the enantiomers, of a biologically active chiral molecule may differ in potency, pharmacological action, metabolism, toxicity, plasma disposition and urine excretion kinetics. The situation exists in all classes of therapeutically active agents including chiral agents used in clinical oncology. Chiral anticancer agents which exist as a pair of enantiomers are commonly administered as racemic (50:50) mixtures of the two isomers. The possibility exists that only one of the enantiomers possesses the desired pharmacological activity while the other is responsible for part or all of the observed toxicity. The toxicity due to the non-efficacious isomer may be the difference between a clinically useful anticancer drug and one which is too toxic to use. The chiral compounds used in standard and experimental cancer chemotherapy include leucovorin, ifosfamide and verapamil. Only one stereoisomer of leucovorin, (6S)-leucovorin is active and data suggests that the administration of just the single isomer may enhance the activity of the agent as well as improve therapeutic monitoring. Both enantiomers of verapamil, (R)-verapamil and (S)-verapamil, are active in reversing adriamycin resistance in some tumor lines. The standard clinical formulation of verapamil is a mixture of the two isomers and cannot be used in clinical treatment of resistant disease due to the cardiotoxicity of the (S)-isomer. (S)-verapamil is the active calcium channel blocking agent while (R)-verapamil has no effect in this area. Thus, an effective anticancer drug would be (R)-verapamil. Data also exists which suggests that the use of a single isomer of ifosfamide may reduce dose limiting CNS toxicity. The existence of stereoisomeric forms of a chemical has been a recognized fact for almost 150 years. However, the clinical consequences of symmetry and asymmetry are only just beginning to be considered. Within the three-dimensional structures of the human body lie tremendous potentials for differential drug actions and, perhaps, new keys to the treatment of cancer and other diseases. The next few years should see the end to the two-dimensional clinical pharmacology we are accustomed to and the growth of stereochemical clinical pharmacology; where we always know what the right and left hands are doing. |
Q:
Tomcat 7 + Annotations in log4j-api-2.11.1.jar
I get this exception from tomcat upon startup of the war file:
Unable to process Jar entry [META-INF/versions/9/module-info.class] from Jar [jar:file:/C:/tomcat/apache-tomcat-7.0.61/webapps/monitormonitor/WEB-INF/lib/log4j-api-2.11.1.jar!/] for annotations
org.apache.tomcat.util.bcel.classfile.ClassFormatException: Invalid byte tag in
constant pool: 19
at org.apache.tomcat.util.bcel.classfile.Constant.readConstant(Constant.java:97)
I tried to switch the log4j to an older version in the pom.xml, but failed, it still scans log4j-api-2.11.1.jar.
I added metadata-complete="true" to the tomcats web.xml but this didn't change the error.
I read other pages on stackoverflow, but it didn't resolve my problem:
Tomcat 7 and Java 8 compatibility issue
Invalid byte tag in constant pool: 19 error message
The latter seems to have a good answer, but I don't understand how to exclude files from annotation scanning, and I also do not know how excluding files affects the functionality of the web application.
Please find attached my pom.xml. It includes some of my attempts to fix this in a commented out version.
<?xml version="1.0" encoding="UTF-8"?>
<project xmlns="http://maven.apache.org/POM/4.0.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
xsi:schemaLocation="http://maven.apache.org/POM/4.0.0 http://maven.apache.org/xsd/maven-4.0.0.xsd">
<modelVersion>4.0.0</modelVersion>
<parent>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-parent</artifactId>
<version>2.1.2.RELEASE</version>
<relativePath/> <!-- lookup parent from repository -->
</parent>
<groupId>com.xxx</groupId>
<artifactId>monitormonitor</artifactId>
<version>0.0.1-SNAPSHOT</version>
<name>monitormonitor</name>
<description>Web Service Monitoring project for Spring Boot</description>
<properties>
<java.version>1.8</java.version>
</properties>
<packaging>war</packaging>
<dependencies>
<!-- added recent version of icu4j and log4j for invalid byte tag error -->
<!-- https://mvnrepository.com/artifact/org.apache.logging.log4j/log4j-core -->
<dependency>
<groupId>org.apache.logging.log4j</groupId>
<artifactId>log4j-core</artifactId>
<!-- changed version vs. ClassFormatException: Invalid byte tag in constant pool: 19 -->
<!--<version>2.11.1</version>-->
<version>2.7</version>
<!--<scope>provided</scope>-->
</dependency>
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-jdbc</artifactId>
</dependency>
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-mail</artifactId>
</dependency>
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-web</artifactId>
<scope>provided</scope><!-- changed -->
</dependency>
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-devtools</artifactId>
<scope>runtime</scope>
</dependency>
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-test</artifactId>
<scope>test</scope>
</dependency>
<dependency>
<groupId>org.springframework</groupId>
<artifactId>spring-context-support</artifactId>
</dependency>
<!-- duplicate
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-mail</artifactId>
</dependency>
-->
<!--
<dependency>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-starter-tomcat</artifactId>
<scope>provided</scope>
</dependency>
-->
<!-- added recent version of icu4j and log4j for invalid byte tag error -->
<!-- https://mvnrepository.com/artifact/com.ibm.icu/icu4j -->
<!--<dependency>
<groupId>com.ibm.icu</groupId>
<artifactId>icu4j</artifactId>
<version>63.1</version>
</dependency>
-->
<!-- added this dependency vs. ClassFormatException: Invalid byte tag in constant pool: 19 -->
<!-- https://mvnrepository.com/artifact/org.aspectj/aspectjtools -->
<!-- <dependency>
<groupId>org.aspectj</groupId>
<artifactId>aspectjtools</artifactId>
<version>1.9.1</version>
</dependency>
-->
<!-- https://mvnrepository.com/artifact/org.aspectj/aspectjweaver -->
<!-- <dependency>
<groupId>org.aspectj</groupId>
<artifactId>aspectjweaver</artifactId>
<version>1.9.1</version>
</dependency>
-->
</dependencies>
<build>
<plugins>
<plugin>
<groupId>org.springframework.boot</groupId>
<artifactId>spring-boot-maven-plugin</artifactId>
</plugin>
</plugins>
</build>
</project>
I would prefer a solution where I don't have to upgrade the tomcat.
My tomcat version is apache-tomcat-7.0.61.
A:
Downgrading the right log4j package seems to have solved the problem:
<dependency>
<groupId>org.apache.logging.log4j</groupId>
<artifactId>log4j-api</artifactId>
<!-- changed version vs. ClassFormatException: Invalid byte tag in constant pool: 19 -->
<!--<version>2.11.1</version>-->
<version>2.7</version>
<!--<scope>provided</scope>-->
</dependency>
The spring boot app still doesn't start up properly, but that is a different issue.
|
WTO Blows Tradewinds Between Taiwan and
China
China's widely heralded entry into the World Trade Organization last week eclipsed Taiwan's own admission to the multilateral organization. Yet there are high hopes about increased trade between the two, and whispers of greater trade may even hasten reunification of China and Taiwan, which the former regards as a breakaway province.
Already, Taiwanese companies have invested an estimated $60 billion or so in the mainland -- in garment and shoe companies, and in some electronics assembly. Yet they've needed to invest through offshore vehicles. Ahead of last week's talks in Qatar, Taiwan lifted restrictions on direct investment in China, including a $30 million cap on investments, and Taiwanese banks are now allowed to move money to and from Mainland banks. Removal of the investment cap also lets Taiwanese companies make big tech investments, which require bigger cash outlays.
Taiwan's market has sprung higher of late, with the Taiwan Weighted index up sharply since its October 3 low. The MSCI Taiwan index advanced 11% in October. So far this year, the Taiex is down nearly 10% in dollar terms, while China "B" shares are up 70% plus. Meanwhile, China will eliminate quotas, cut duties, and lift its own investment caps and other restrictions.
Taiwan's lifting of investment limitations wasn't simply preparation for WTO, under which it would need to boost trade with China. The island nation also recognizes China's competitive advantages, including a huge domestic market and a cheap, stable labor force from which it can export to the rest of the globe. Foreign direct investment in China, now running at around $60 billion annually, is expected to jump to $75 billion or so within a couple of years.
Says Hong Lu, the chief executive of Alameda, California-based
UTStarcom,
which sells telecommunications switches and equipment to service providers in China and Taiwan: "WTO is great news for us. There has to be more trade between the two! And now that both are in WTO, there's good potential, maybe as soon as next year, that we'll have things like direct air links between Taiwan and China."
Lu continues: "In China, it will allow other investors to invest in operators, like
Verizon
and so forth. More cash will be available for operators, and they will buy more equipment." And part of the increased competition means China will also relax restrictions on UTStarcom's own operations. As recently as last year, UTStarcom couldn't sell equipment to providers in larger cities, and Lu expects that to change.
And with Taiwan, says Lu, "It's good news. There has to be more trade!"
Says Albert King, the lead manager of
Taiwan Fund
: The idea of reunification "becomes more real."
Make no mistake, it won't all be sweet. Some worry that China, an exporting powerhouse, will create tough times for its neighbors. Says Warren Bailey, a management professor at Cornell University and an Asia expert: "Once China gets into the WTO, it will generate 50%-75% of all complaints. It will be a big mess."
For the past year, with China's WTO accession imminent, the rest of Asia has been shuddering. Japan, for example, is expected to benefit if it invests quickly and swiftly moves production offshore. China, of course, is expected to lure the largest share of foreign investment.
China is a rare bright spot of growth in the world just now, and restructuring is likely to shave that growth. Nobody has quantified just how bad things will be. Yet Joe Quinlan, the global economist at Morgan Stanley Dean Witter, notes that the flood of foreign investment will create jobs.
Yet Taiwan still faces a number of thorny problems. The country is undergoing a massive recession. What's more, President Chen Shui-Bian, leader of the ruling Democratic Progressive Party, still remains opposed to negotiating on any points of the "One-China" platform that China insists Taiwan accept. He'd like an economic alliance, while maintaining the political status quo. Taiwan, incidentally, enters WTO as a "customs territory" of China, just as Hong Kong, another "customs territory" is also a full member of WTO.
That's why so many believe that WTO accession for both countries will only worsen the cross-Strait tensions. Yadong Liu, managing director at Medley Global Advisors, says that "there are very high expectations that WTO accession by both will resolve some of the political issues in the Strait relations or help Taiwan to get around some of them to advance economic relations. But I think there is less truth than people realize."
To a large degree, says Liu, hopes of increased trade are "hyped up by the Taipei government" to put pressure on Mainland China. "They want to say that WTO is about trade, and whatever barriers there are, you should lower them. If we can, we should resolve political issues, but if we can't, we should shelve them and start trading. Of course, that's not what Beijing wants." Still, Liu adds, Chinese President Jiang Zemin has just one year left in office, and wants to leave a legacy. Says Liu: "If he can get Taipei to sign up on this one China concept, his legacy will be that he's locked China into agreement."
Lack of a political agreement, says Liu, could lead to discrimination against Taiwanese companies. And Taiwan, he suspects, may start pressuring other WTO members to put pressure on Beijing. "They'll say, we are both members, but we can't trade and accuse Beijing of violating the WTO agreement. With all these political problems, it's hard to imagine any major strides in economic and trade ties. You will hear more complaints about China from Taiwan."
Yet clearly, economic links between the two have prospered even as the political relationship deteriorated. Albert King of the Taiwan Fund is keeping a close watch on the coming yearend legislative elections to see if political leaders will take steps to improve the political relationship as a way of bolstering the economic ties. Says King: "The DPP and its management of the economic crisis have really alienated voters. People want a more liberal environment to invest and do business with China. After WTO, China will attract a lot of capital. China will be less dependent on Taiwan capital. But Taiwan becomes even more dependent on China as an important market. Beijing will just sit and wait. Politicians are really ignorant of the economic quandary." The best solution, says King, is a consensus on the "One Country" issue.
King and his comanager, Pedro Tai, think Taiwan's trading range will be little changed in coming months, owing to softness in global demand, weak U.S. corporate profits, high real interest rates, and continued concerns about bad loans in Taiwan's financial institutions. Yet demand is clearly getting better in some key sectors, including wireless and networking-related products, video conferencing, PCs, games, and so on. Foreigners continue to plow money into Taiwan, even as domestic investors remain wary. They're betting heavily on electronics, PC and peripherals, but are underexposed to semiconductors. (Not so tough to do, given that chips make up an enormous proportion of Taiwan's indexes.) Among their largest positions are
Mediatek,
which makes CD-ROMs and chipsets and is a former subsidiary of United Microelectronics, the world's second-largest chip foundry,
Taiwan Semiconductor Manufacturing,
and
Faraday Technology,
another maker of integrated circuits.
Says Fang Zheng, a China specialist for J.P. Morgan Fleming Asset Management: "Politically we don't expect reunification will happen tomorrow or in the near future. What we're focusing on is economic integration. At some point will it be one big economy? It's already there. The risk premium attached to Taiwan stocks will come down."
Zheng is investing in WTO through what he calls "T" shares: Taiwanese companies with more than 50% of assets in the mainland. Incidentally, these make up about a third of Taiwan's listed universe. They're cheap, he notes, and Taiwan companies have better corporate governance, product leadership, accounting, and flexible manufacturing capability than their mainland counterparts.
This copy is for your personal, non-commercial use only. Distribution and use of this material are governed by our Subscriber Agreement and by copyright law. For non-personal use or to order multiple copies, please contact Dow Jones Reprints at 1-800-843-0008 or visit www.djreprints.com. |
Today, we are announcing that Peter Chernin, our President and
COO, will not be renewing his employment contract. Peter will be
taking up the opportunity to start a new motion picture and
television production venture with Fox.
Attached is the press release.
Many of us who have worked with Peter over his 20 years with the
company can attest to his leadership, his diligence, and his
wisdom. I can also testify to Peter’s friendship, dedication, and
honesty. He has been a close colleague and an ally to me for many
years.
While Peter has distinguished himself at News Corp, he has also,
increasingly and tirelessly, circled the globe in support of
Malaria No More, which has achieved nothing short of remarkable
results. Let us all wish him the best of luck, and the
greatest success, as he embarks on this new chapter of his
career, both as a professional and as a role model for an
executive who gives back.
As you all know the downturn we are operating in is more severe
and global than anything we have seen before. No company is
immune to its effects. I want to take this opportunity, today, to
write to you about how we will manage such an important
leadership transition, and why I am convinced that today our
company is not only well-positioned financially and
competitively, but is on the cusp of a new phase of growth.
Remember, we began priming ourselves for a weakening economy over
a year ago. We have managed expenses and capital expenditure
prudently, and strengthened our balance sheet. Following the
partial sale of NDS, we will have over five billion dollars in
cash, and this year we should exceed $3.5 billion in adjusted
operating income.
In the past, we have met downturns with vigor, often departing
from the herd. We have emerged much stronger.
Achieving our ambitions will require change and renewal. So
throughout 2009, I will continue to work closely with all of our
companies to make sure that we are organized and resourced in the
best way to take advantage of this extraordinary point in time.
We will press our advantages and invest in our great
franchises. And, of course, we will keep our eyes on big
prizes, some of which may arise only once in a generation.
Across News Corp. we have a broad and deep reservoir of extremely
able executives.
Over the years we have accomplished great things. People
understand, and have acknowledged, our entrepreneurial spirit as
well as our doggedness; our willingness to take risks, our
contrarian investment style; and our commitment to long-term
development and shareholder value.
Many of you have told me how hungry you are to work more closely
across our companies. Many of us have been frustrated by the
things that can get in the way of that. From systems that don’t
talk to each other to incentives that struggle to capture the
opportunity and aspiration of our total group. These
obstacles are obvious to us all. There will be a streamlined
management structure between our Los Angeles based business units
and the rest of the company. Peter and I will be
communicating more on this over the next few months. For the time
being, of course, the talented executive team at the Fox Group
will continue to report to Peter.
Now is also an ideal opportunity to streamline and enhance many
of the corporate and administrative functions of the
business. There will be cost savings as a result, but the
more important aim is to be leaner so that we can better leverage
our collective talent and expertise. For instance, and
beginning immediately, H.R. functions throughout all our units
will report to Beryl Cook in New York as well as their division
heads. Beryl reports directly to me.
We have worked hard to develop and advance the best among us. The
renewal of great companies begins within themselves.
Pursuing an edge through superior talent is a priority.
This will be a key focus for us in 2009.
In the coming months, I will be reaching out to you with new
questions, and with new plans.
We are in the midst of a phase of history in which nations will
be redefined and their futures fundamentally altered. Many
people will be under extreme pressure and many companies mortally
wounded. Our competitors will be sorely tempted to
take the easy beat, to reduce quality in the search for immediate
dividends.
Let me be very clear about our company: where others might step
back from their commitment to their viewers, their users, readers
and customers – we will renew ours.
The direction of the business now and over the next few years
will define the character of our company for decades.
We have always thrived on change and challenge. This was
true when we began building a newspaper business in Australia.
Just as it was when we created BSkyB and developed a fourth US
network, the Fox Network, when conventional wisdom dictated that
there was room for only three players. It was true when we
launched Star, now the leading network in India, and the Fox News
Network and Sky Italia.
The best things we have done, and there are many examples, have
defied conventional wisdom, often in the teeth of fierce
opposition and near universal disbelief in our
capabilities.
Over the past 12 months I have spent time with you in India and
China, in Italy and the UK and many other countries. We have
brought Dow Jones into the fold, extended our influence in
Europe, and been at the center of reporting the arrival of a new
American president and the impact of the global financial crisis.
We’ve told extraordinary stories, in theaters around the world
and on page and screen from Mumbai to Malibu.
Our own international reach is a profound strength. We have
intelligent, creative and highly motivated colleagues around the
world who are ambitious for themselves, for their countries, for
our customers and for our company. The result is that where
others simply seek distribution, we are building durable
businesses at scale. We are also creating large franchises
in marketplaces that will grow at a faster pace in the coming
years and, increasingly, our businesses are based on direct
customer relationships..
We must always be acutely aware of our responsibility to
shareholders, and to create real value for them. This is entirely
consistent with, and in many cases inseparable from, the enormous
social value we have created over the decades. We provide
information and entertainment to billions, enabling them to
improve their lives and those of their families. There is
genuine value in the values of our company – these are values
that are even more important in a world confronting so much
today
We believe in communities. The very idea of community is broad,
and encompasses interests that cross national, ethnic and
demographic borders. We are all members of many different
communities, whether it be of people who are passionate about
Hollywood films, or care about living in a healthy environment,
or use a local jobs website, or trade commodities in Chicago and
London, relish soccer whether in China or Nigeria. These
communities are our communities, as they read, evaluate and
create everyday
That is why, most of all, I believe in the community that is our
company.
I wanted to let you know that I have decided to leave News
Corporation when my contract expires on June 30th.
This is not a decision that came easily, but after more than 12
years in my current job, 20 years at Newscorp, and 30 years of
corporate life, I am ready for new entrepreneurial
challenges. I would not be making this difficult decision
if I were not confident in the superb management team we have at
Fox and in the visionary leadership of Rupert Murdoch. I
have worked closely with Rupert every day, and I know he shares
my belief that Fox executives are the best in the business.
I want to thank Rupert for his remarkable support, encouragement
and friendship over the years. No company in our industry
can match News Corporation's track record of creating
opportunities for employees and there is no better example of
that than the opportunities Rupert has given me over the
years.
I also want to thank all of you for the privilege of working side
by side with such a talented and deeply principled group of
colleagues. I am not only deeply proud of your
achievements, but even prouder of the character and integrity of
the company.
Over the next several months, Rupert and I will work closely to
make sure this is a smooth transition for everyone. Thank
you for the dedication and enthusiasm that you have always shown
and I know will continue to show as the company moves forward to
even greater heights. |
Q:
checkbox checked event trigger multiple time wpf mvvm
I got checkbox column in DataGrid that populating realtime download percentage in particular row, filtered by caseRefNo. i need to add checkbox changed event to perform some action. i used InvokeCommandAction to add the action to checkbox.
I realize that when i click the checkbox for the first time, It is ok and trigger only one time. but there are two times triggered when i click second time on the same checkbox.For third time clicking the same checkbox, it triggered four time. quite scary and difficult to figure it out.
here is my viewmodel code
public class DataGridDownloadViewModel:BindableBase
{
public ObservableCollection<tblTransaction> TransList { get; private set; }
public DispatcherTimer dispatchTimer = new DispatcherTimer();
public CollectionView TransView { get; private set; }
public DelegateCommand<object> CheckCommand { get; set; }
private String _UpdatePer;
public String UpdatePercentage
{
get { return _UpdatePer; }
set { SetProperty(ref _UpdatePer, value); }
}
private string _caseId;
public string CaseID
{
get { return _caseId; }
set { SetProperty(ref _caseId, value); }
}
private string _isChecked;
public string isChecked
{
get { return _isChecked; }
set { SetProperty(ref _isChecked, value); }
}
private bool CanExecute(object args)
{
return true;
}
private void CheckBoxChecker(object args)
{
//Should Work Here
// Totally not coming to this function
CheckBox chk = (CheckBox)args;
string thichintae = chk.Name.ToString();
Console.WriteLine(thichintae);
}
public DataGridDownloadViewModel(List<tblTransaction> model)
{
CheckCommand = new DelegateCommand<object>(CheckBoxChecker, CanExecute);
dispatchTimer.Interval = TimeSpan.FromMilliseconds(3000);
dispatchTimer.Tick += dispatchTimer_Tick;
BackGroundThread bgT = Application.Current.Resources["BackGroundThread"] as BackGroundThread;
bgT.GetPercentChanged += (ss, ee) =>
{
UpdatePercentage = bgT.local_percentage.ToString();
};
bgT.GetCaseID += (ss, ee) =>
{
CaseID = bgT.local_caseRef;
};
TransList =new ObservableCollection<tblTransaction>(model);
TransView = GetTransCollectionView(TransList);
TransView.Filter = OnFilterTrans;
var tokenSource = new CancellationTokenSource();
var token = tokenSource.Token;
var cancellationTokenSource = new CancellationTokenSource();
dispatchTimer.Start();
}
private void dispatchTimer_Tick(object sender, EventArgs e)
{
UpdateDataGrid();
}
public void UpdateDataGrid()
{
foreach (tblTransaction tran in TransList)
{
if (tran.caseRefNo == CaseID)
{
tran.incValue = int.Parse(UpdatePercentage);
}
else
{
tran.incValue = tran.incValue;
}
}
TransView.Refresh();
}
bool OnFilterTrans(object item)
{
var trans = (tblTransaction)item;
return true;
}
public CollectionView GetTransCollectionView(ObservableCollection<tblTransaction> tranList)
{
return (CollectionView)CollectionViewSource.GetDefaultView(tranList);
}
}
this is XAML for above view model.
<Window x:Class="EmployeeManager.View.DataGridDownload"
xmlns="http://schemas.microsoft.com/winfx/2006/xaml/presentation"
xmlns:x="http://schemas.microsoft.com/winfx/2006/xaml"
xmlns:i="http://schemas.microsoft.com/expression/2010/interactivity"
xmlns:ei="http://schemas.microsoft.com/expression/2010/interactions"
Title="DataGridDownload" Height="600" Width="790">
<Grid>
<DataGrid HorizontalAlignment="Left" ItemsSource="{Binding TransView}" AutoGenerateColumns="False" Margin="10,62,0,0" VerticalAlignment="Top" Height="497" Width="762">
<DataGrid.Columns>
<DataGridTextColumn Header="caseRefNo" Binding="{Binding caseRefNo}" />
<DataGridTextColumn Header="subjMatr" Binding="{Binding subjMatr}" />
<DataGridTextColumn Header="Download %" Binding="{Binding incValue}" />
<DataGridTemplateColumn>
<DataGridTemplateColumn.CellTemplate>
<DataTemplate>
<CheckBox Name="abcdef"
Content="Please Select" IsChecked="{Binding Path=IsSelected, Mode=TwoWay, UpdateSourceTrigger=PropertyChanged}">
<i:Interaction.Triggers>
<i:EventTrigger EventName="Checked">
<i:InvokeCommandAction CommandParameter="{Binding ElementName=abcdef}" Command="{Binding DataContext.CheckCommand, RelativeSource={RelativeSource FindAncestor, AncestorType=DataGrid}}" />
</i:EventTrigger>
</i:Interaction.Triggers>
</CheckBox>
</DataTemplate>
</DataGridTemplateColumn.CellTemplate>
</DataGridTemplateColumn>
<DataGridTemplateColumn>
<DataGridTemplateColumn.CellTemplate>
<DataTemplate>
<Label Content="{Binding incValue,UpdateSourceTrigger=PropertyChanged}" Background="Red" Foreground="White" />
</DataTemplate>
</DataGridTemplateColumn.CellTemplate>
</DataGridTemplateColumn>
</DataGrid.Columns>
</DataGrid>
<Label Content="{Binding UpdatePercentage}" HorizontalAlignment="Left" Background="Blue" Foreground="White" Margin="10,10,0,0" VerticalAlignment="Top" Width="338" Height="30">
</Label>
<Button Content="Button" HorizontalAlignment="Left" Margin="672,20,0,0" VerticalAlignment="Top" Width="75"/>
</Grid>
</Window>
Here is my model
public class tblTransaction
{
public string caseRefNo { get;set;}
public string subjMatr { get; set; }
public int incValue { get; set; }
public DateTime? longTime { get; set; }
public bool IsSelected { get; set; }
}
This is picture of my form
Is it because of DispatcherTimer ? All suggestion are welcome.
df
A:
I think I left a comment in your previous question saying that wrapping your collection to CollectionView is quite smelly.
Anyway, the TransView.Refresh(); is causing the problem in your code.
TransView.Refresh will trigger the "Checked" event for each checked checkbox. The refresh basically asking the wpf engine re-populate all the data to your CollectionView and in turn, each checked checkbox will fire the checked event all over again.
Try setting dispatchTimer.Interval to a much shorter time e.g. 300. You should be able to see the "tick" in checkbox keep flicking becoz of the TransView.Refresh.
For real, I have no idea why you don't just bind your TransList to your DataGrid and called BeginInvoke on UpdateDataGrid method.
To demo how ObservableCollection works
I used the ObservableCollection to re-wrote some part of your code. At least make things better fall in line with MVVM model.
public abstract class ViewModelBase : INotifyPropertyChanged
{
public event PropertyChangedEventHandler PropertyChanged;
[NotifyPropertyChangedInvocator]
protected virtual void OnPropertyChanged([CallerMemberName] string propertyName = null)
{
var handler = PropertyChanged;
if (handler != null) handler(this, new PropertyChangedEventArgs(propertyName));
}
}
public class MainViewModel : ViewModelBase
{
public ObservableCollection<TblTransaction> TransList { get; private set; }
public DispatcherTimer DispatchTimer = new DispatcherTimer();
public MainViewModel()
{
var model = new ObservableCollection<TblTransaction>();
for (int i = 0; i < 5; i++)
{
model.Add(new TblTransaction { CaseRefNo = i.ToString(), IncValue = i, LongTime = DateTime.Now, SubjMatr = i.ToString() });
if (i == 3)
model[i].IsSelected = true;
}
DispatchTimer.Interval = TimeSpan.FromMilliseconds(200);
DispatchTimer.Tick += dispatchTimer_Tick;
TransList = model;
DispatchTimer.Start();
}
private void dispatchTimer_Tick(object sender, EventArgs e)
{
UpdateDataGrid();
}
public void UpdateDataGrid()
{
var ran = new Random();
foreach (var tran in TransList)
tran.IncValue = ran.Next(0, 100);
}
}
public class TblTransaction : ViewModelBase
{
private string caseRefNo;
private string subjMatr;
private int incValue;
private DateTime? longTime;
private bool isSelected;
public DelegateCommand<object> CheckCommand { get; set; }
public TblTransaction()
{
CheckCommand = new DelegateCommand<object>(CheckBoxChecker, (p) => true);
}
private void CheckBoxChecker(object args)
{
//Should Work Here
// Totally not coming to this function
//CheckBox chk = (CheckBox)args;
//string thichintae = chk.Name;
Console.WriteLine(args);
}
public string CaseRefNo
{
get { return caseRefNo; }
set
{
caseRefNo = value;
OnPropertyChanged();
}
}
public string SubjMatr
{
get { return subjMatr; }
set
{
subjMatr = value;
OnPropertyChanged();
}
}
public int IncValue
{
get { return incValue; }
set
{
incValue = value;
OnPropertyChanged();
}
}
public DateTime? LongTime
{
get { return longTime; }
set
{
longTime = value;
OnPropertyChanged();
}
}
public bool IsSelected
{
get { return isSelected; }
set
{
isSelected = value;
OnPropertyChanged();
}
}
}
<Window x:Class="WpfTestProj.MainWindow"
xmlns="http://schemas.microsoft.com/winfx/2006/xaml/presentation"
xmlns:x="http://schemas.microsoft.com/winfx/2006/xaml"
xmlns:mc="http://schemas.openxmlformats.org/markup-compatibility/2006"
xmlns:d="http://schemas.microsoft.com/expression/blend/2008"
xmlns:local="clr-namespace:WpfTestProj"
xmlns:interact="clr-namespace:System.Windows.Interactivity;assembly=System.Windows.Interactivity"
mc:Ignorable="d"
d:DataContext="{d:DesignInstance Type=local:MainViewModel, IsDesignTimeCreatable=False}"
Title="MainWindow" Height="350" Width="525">
<Grid>
<DataGrid HorizontalAlignment="Left" ItemsSource="{Binding TransList}" AutoGenerateColumns="False" Margin="10,62,0,0" VerticalAlignment="Top" Height="497" Width="762">
<DataGrid.Columns>
<DataGridTextColumn Header="caseRefNo" Binding="{Binding CaseRefNo}" />
<DataGridTextColumn Header="subjMatr" Binding="{Binding SubjMatr}" />
<DataGridTextColumn Header="Download %" Binding="{Binding IncValue}" />
<DataGridTemplateColumn>
<DataGridTemplateColumn.CellTemplate>
<DataTemplate>
<CheckBox
Content="Please Select" IsChecked="{Binding Path=IsSelected, Mode=TwoWay, UpdateSourceTrigger=PropertyChanged}">
<interact:Interaction.Triggers>
<interact:EventTrigger EventName="Checked">
<interact:InvokeCommandAction CommandParameter="{Binding Path=CaseRefNo}" Command="{Binding Path=CheckCommand}" />
</interact:EventTrigger>
</interact:Interaction.Triggers>
</CheckBox>
</DataTemplate>
</DataGridTemplateColumn.CellTemplate>
</DataGridTemplateColumn>
<DataGridTemplateColumn>
<DataGridTemplateColumn.CellTemplate>
<DataTemplate>
<Label Content="{Binding IncValue, UpdateSourceTrigger=PropertyChanged}" Background="Red" Foreground="White" />
</DataTemplate>
</DataGridTemplateColumn.CellTemplate>
</DataGridTemplateColumn>
</DataGrid.Columns>
</DataGrid>
<Button Content="Button" HorizontalAlignment="Left" Margin="672,20,0,0" VerticalAlignment="Top" Width="75"/>
</Grid>
|
Anesthetic technique and postoperative outcome in preterm infants undergoing PDA closure.
To describe the various anesthetic techniques used for surgical closure of PDA in premature infants at the Montreal Children's Hospital and assess their impact on postoperative outcome. The charts of all preterms who underwent PDA ligation during a 21-month period were reviewed for preoperative status, intraoperative anesthetic management and postoperative outcome. We determined the associations between independent variables and two postoperative outcome variables: unstable postoperative respiratory course (UPRC) and hypotension. The mean weight at surgery of the 33 infants was 1.031±0.29 kg. All infants, but one, received intraoperative opioids. Eight patients presented UPRC. Mean fentanyl doses were 5.3±2.6 mcg kg(-1) for patients with UPRC vs 22.6±16.6 mcg kg(-1) for patients without UPRC (P=0.004). Applying the receiver-operator characteristic curve (ROC), 10.5 mcg kg(-1) of fentanyl was established as the dose that discriminated and identified patients who experienced UPRC. The postnatal and postmenstrual age of the patient, birthweight, current weight, ventilator settings preoperatively, previous courses of indomethacin, sex and preoperative creatinine, were not correlated with the dose of fentanyl equivalent used. Logistic regression did not show a relationship between any of the previously mentioned factors and receiving a fentanyl equivalent of >10.5 mcg kg(-1). The only factor associated with the total fentanyl equivalent dose (as a continuous variable) or receiving <10.5 mcg kg(-1) (as a dichotomous variable) was the identity of the anesthetist involved, P<0.001. We conclude that the use of at least 10.5 mcg kg(-1) of fentanyl equivalent as a component of the anesthetic regimen for surgical closure of a PDA in premature infants, avoids an unstable postoperative respiratory course. |
Igor Kochetkov
Igor Victorovich Kochetkov (born 13 May 1970) is a Russian gay rights activist who heads the Russian LGBT Network.
Kochetkov has been active in the opposition to the 2013 Russian law that bans promotion of homosexuality to minors. He has blamed the law for legitimizing and increasing violence against gays.
In September 2013, Kochetkov along with other Russian human rights activists met with US President Barack Obama in St. Petersburg.
Along with Alexey Davydov he was named one of the world's 100 top thinkers in 2013 by the magazine Foreign Policy "for fighting Russia's state-sponsered homophobia".
Kochetkov was along with Frank Mugisha, Sunil Babu Pant and ILGA nominated for the 2014 Nobel Peace Prize by Norwegian Labour Parliamentarians Anette Trettebergstuen and Håkon Haugli.
References
Category:1970 births
Category:Living people
Category:Gay men
Category:LGBT rights activists from Russia
Category:LGBT people from Russia |
09:51
While Brexit machinations continue at Westminster, Thursday at Holyrood sees the first parliamentary vote on the SNP’s budget, with cross-party negotiations ongoing to muster enough support to pass the SNP minority government’s plans. While the SNP have previously relied upon the Scottish Greens, this year a row over council funding means their support is still wavering.
Indeed, the Scotsman is reporting this morning that Nicola Sturgeon has warned her party to prepare for a possible Scottish election if the Holyrood government fails to pass its budget today. According to the Scotsman, during a meeting of the SNP group at Westminster attended by Sturgeon on Monday, she warned her MPs that they should prepare for a snap Holyrood election if the SNP government fails to get its budget through. This adds to speculation that Sturgeon may seek a fresh mandate from the electorate to secure another referendum on independence, as she prepares to reveal her plans in the coming weeks.
The Scottish Green’s Andy Wightman was on BBC Radio Scotland this morning insisting that his party were not being “obstructive”. Although they have the promise of legislation by the end of this parliament and a green light for a local tourist tax, the sticking point remains their call for a hefty increase in spending on local government this year. It’s going to be a long day at Holyrood. |
Death of a sibling: five sisters, five stories.
The sudden, unexpected death of a child is likely to have profound and enduring implications for surviving siblings. In this article, stories from five sisters are presented to demonstrate how children's experiences of and responses to the death of a sibling can vary greatly, even within the same family. Each child creates his or her own reality, and this "unique" definition of reality influences the child's behavior. Giving children a chance to "tell their stories" may help nurses and other professionals to understand the meanings and values that are guiding how children respond following the unexpected death of a sibling. |
Scalp stratum corneum histamine levels: novel sampling method reveals association with itch resolution in dandruff/seborrhoeic dermatitis treatment.
Dandruff and seborrhoeic dermatitis are accompanied by bothersome itch. We have established a novel non-invasive methodology to sample histamine levels in the stratum corneum in order to facilitate an understanding of pruritogenesis in this condition. Histamine levels were assessed in two groups of subjects with dandruff before and after 3 weeks of treatment with a commercial potentiated zinc pyrithione shampoo. A comparative population without dandruff was also studied. Itch self-perception was quantified on a visual analogue scale. The histamine level in subjects with dandruff was more than twice that in those who did not have dandruff. Under conditions known to resolve flaking symptoms, the shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. This reduction in histamine was accompanied by a highly significant reduction in the perception of itch intensity. These findings suggest an association between the subjective perception of itch in the scalp and the level of histamine in the skin. |
Signal-transducing GTP-binding proteins of mammalian heart and lungs.
Signal-transducing GTP-binding Proteins of Mammalian Heart and Lungs. Journal of Molecular and Cellular Cardiology (1989) 21 (Suppl I) 91-95. Three distinct G-proteins have been found in mammalian heart sarcolemma: Gi (alpha i = 40 kDa, beta = 36 kDa, and lambda less than 14 kDa), Gp (alpha p = 23 kDa, beta = 36 kDa, and lambda less than 14 kDa), and Gs (alpha s = 42 kDa). ADP-ribosylation of sarcolemmal alpha i by pertussis toxin (PT) or preincubation of sarcolemma with protein kinase C and PMA resulted in increased adenylate cyclase activity and blockade of GTP-dependent inhibition by carbachol whereas the GTP-dependent activating effect of isoproterenol on the adenylate cyclase was preserved. ADP-ribosylation of alpha i in sarcolemma by endogenous NADP-sensitive ADP-ribosyltransferase abolished the PT-induced ADP-ribosylation of alpha i. Gpp (NH)p attenuated the PT-induced ADP-ribosylation of alpha i and promoted the cholera toxin (CT)-induced ADP-ribosylation of alpha s. The CT-induced alpha s ADP-ribosylation was enhanced in the presence of heart cytosol. Soluble Gi- and Gs-proteins were identified in lung cytosol. The 40 kDa alpha i in membrane and soluble fractions was ADP-ribosylated by PT, while the soluble 42 kDa alpha s was ADP-ribosylated by CT in lung tissue. The ADP-ribosylation of soluble alpha i by PT-suppressed guanyl nucleotide binding to Gi. The apparent molecular mass of partially purified soluble Gi was 75 kDa. |
Faculty Council
The College of Information Systems and Technology Faculty Council is comprised of six faculty members who have extensive professional experience and are considered subject matter experts in their respective fields. Our Faculty Council advises on conceptual frameworks, assists in the design of new programs, reviews curricula and recommends updates. Members also assist in the assessment of program outcomes and conduct research, as needed, for the College.
Information Systems and Technology faculty council members:
Phyllis Chasser, PhD (Florida)
Bob Goddard, PhD (Idaho)
Jessica Keyes, PhD (New Jersey)
Steve Mohan, DCS (Colorado)
Stephen Trask, MScBA (Colorado)
Charlie vonUrff, PhD (Nevada)
Your journey begins here
Fill out a request form in your desired area of study, and an enrollment representative can help you start your journey toward success. |
This invention relates to computer systems for simulating physical processes, e.g., fluid flow.
The conventional approach to simulating high Reynolds number flow has been to generate discretized solutions of the Navier-Stokes differential equations, in which high-precision floating point arithmetic operations are performed at each of many discrete spatial locations on variables representing the macroscopic physical quantities (e.g., density, temperature, flow velocity). The fastest and most powerful computers available are used, and yet very limited and inexact results have been achieved. To keep run times manageable, very coarse grid resolutions are used, and even at those coarse resolutions there are unacceptable errors in the solutions due to accumulated round off errors inherent in performing successive floating point arithmetic operations.
There has long been an effort to replace the differential equation approach with what is generally known as lattice gas (or cellular) automata, in which the macroscopic-level simulation provided by solving the Navier-Stokes equations is replaced by a microscopic-level model that performs operations on particles moving between sites on a lattice. The goal has long been to find a microscopic-level model of particle interactions and movement that would produce the correct macroscopic results (i.e., variations in density, temperature, etc. as prescribed by the Navier Stokes equations).
The traditional lattice gas simulation assumes a limited number of particles at each lattice site, with the particles being represented by a short vector of bits. Each bit represents a particle moving in a particular direction. For example, one bit in the vector might represent the presence (when set to 1) or absence (when set to 0) of a particle moving along a particular direction. Such a vector might have six bits, with, for example, the values 110000 indicating two particles moving in opposite directions along the X axis, and no particles moving along the Y and Z axes. A set of collision rules governs the behavior of collisions between particles at each site (e.g., a 110000 vector might become a 001100 vector, indicating that a collision between the two particles moving along the X axis produced two particles moving away along the Y axis). The rules are implemented by supplying the state vector to a lookup table, which performs a permutation on the bits (e.g., transforming the 110000 to 001100). Particles are then moved to adjoining sites (e.g., the two particles moving along the Y axis would be moved to neighboring sites to the left and right along the Y axis).
Molvig et al. taught an improved lattice gas technique in which, among other things, many more bits were added to the state vector at each lattice site (e.g., 54 bits for subsonic flow) to provide variation in particle energy and movement direction, and collision rules involving subsets of the full state vector were employed. Molvig et al PCT/US91/04930; Molvig et al., "Removing the Discreteness Artifacts in 3D Lattice-Gas Fluids", Proceedings of the Workshop on Discrete Kinetic Theory, Lattice Gas Dynamics, and Foundations of Hydrodynamics, World Scientific Publishing Co., Pte., Ltd., Singapore (1989); Molvig et al., "Multi-species Lattice-Gas Automata for Realistic Fluid Dynamics", Springer Proceedings in Physics, Vol. 46, Cellular Automata and Modeling of Complex Physical Systems, Springer-Verlag Berlin, Heidelberg (1990) (all hereby incorporated by reference). These improvements and others taught by Molvig et al. produced the first practical lattice-gas computer system. Discreteness artifacts that had made earlier lattice gas models inaccurate at modeling fluid flow were eliminated.
At higher Reynolds numbers, flow at the surface of an object forms a turbulent boundary layer, which is a thin region of complex flow. Simulating flow within such a boundary layer is not currently practical, even with the improved lattice gas techniques taught by Molvig et al. in the publications referenced above. Prior lattice gas simulations, including the above referenced improved simulations of Molvig et al., have modeled the particle-boundary interactions using what could be termed a "bounce back" technique, in which a particle colliding with the boundary returns a particle with the same energy but in the opposite direction. This correctly produces a zero velocity at the surface of solid objects, but the simulation does not accurately model the boundary layer flow, particularly when the boundary layer is turbulent. |
Russellville Public Works Director Morgan Barrett told the City Council during Thursday night's regular meeting he will bring an updated version of the city's five-year Capital Improvement Plan for review next month.
The council will also review in February an amended zoning ordinance. City Planner Jim von Tungeln told aldermen Thursday night the amendments should update about 90 percent of the city's ordinances pertaining to zoning, and will be available for public review on the city's Web site (russellvillearkansas.org).
Council members will also take another look at amendments to the city's ordinance regarding its personnel policy manual. Alderman Robert Wiley said Barrett will provide a shorter version.
After a resident spoke during a public hearing on an ordinance to vacate the north 10 feet of East "E" Street, block 80, lots 9-12 of the J.L. Shinn Addition, the council approved reading the ordinance one time by a short description, but failed to garner enough votes for passage. Wiley, Faye Abernathy and Bill Eaton voted against the ordinance, while Freddie Harris abstained, saying she would like additional time to analyze the situation.
Mayor Tyrone Williamson, answering a question from Barrett, said it would be brought back to next month's meeting.
n Appropriation of $5,000 for animal control donations and $8,500 for animal control improvements.
All members were present, including Wiley, Abernathy, Eaton, Harris, Scott Sanders, Randal Croucy, Phil Carruth and Cliff Kirchner. Also attending were City Clerk Kathy Collins and City Attorney Trey Smith.
The council's agenda preparation and Finance Committee meeting is scheduled for 5:30 p.m. Feb. 6. The next regular meeting is slated for 6 p.m. Feb. 15. |
For a "European renewal" built on three pillars: freedom, protection and progress
In an open letter published in newspapers across the European Union's 28 Member States, the President of the Republic has set out his vision for Europe, with three months to go until the elections of the European Parliament.
With the European elections approaching, the President of the Republic wished to directly address all European citizens in the newspapers of all the European Union's Member States, for "never, since the Second World War, has Europe been as essential. Yet never has Europe been in so much danger."
Brexit is a symptom of that: everywhere in Europe, an anger is brewing to which we have a duty to respond, without falling into the trap of resignation or the status quo.
To address this anger, the President of the Republic outlines the vision of a European renewal built on three pillars – freedom, protection and progress – setting out concrete proposals for each.
Defending our freedom
Create a European Agency for the Protection of Democracies, to protect the Member States' election processes against cyber-attacks and manipulation.
Ban the funding of European political parties by foreign powers, by strengthening existing European legislation.
Protecting our continent
Rethink the Schengen area, so that those who participate in it comply with obligations of responsibility (stringent border controls) and solidarity (a single asylum policy with common acceptance and refusal rules), under the authority of a European Council for Internal Security.
Establish a European treaty on defence and security, with an ambitious list of pledges in terms of defence spending or operational solidarity in the event of attack, and a European Security Council bringing together the most ambitious States.
Guarantee fair competition, by reforming our trade and competition policies to bring about leading European stakeholders, protect our standards (environmental for example) and ensure genuine reciprocity.
Recovering the spirit of progress
Introduce a "social shield" to guarantee the same pay in the same workplace and a minimum wage appropriate to each country.
Empower the EU to spearhead new technological breakthroughs: the next multi-year financial framework must make it possible to increase funding for artificial intelligence and the European Innovation Council; the EU must also lead the way in terms of regulation, by putting in place European supervision of the tech giants, in the same way as for banks (prompt penalties for unfair competition, transparent algorithms, etc.). |
The difficulty with known sockets resides in the fact that they do not take into account the imperatives of radius of curvature of the input cable which is connected to the rear of the socket.
In order to clarify the specification, accompanying FIG. 1 shows all the existing possibilities for routing the input cable on a socket 1 of known type. This socket 1 may be supplied by a cable which is routed either in projecting tubings 2, 3 whence it can arrive from the right or from the left, or from the rear in flush-mounted tubings 4, 5, or from above in a column 6, or from below in a bracket 6A.
No risks should be taken, at the point of connection of the cable on the rear of the socket 1, of breaking this cable or at least of tearing its screen. To that end, a standard exists, whereby the radius of curvature given to the cable in a bend must never be less than 8 times the outer diameter of this cable.
In addition, the depth of the routing tubing should be taken into account. For a conventional tubing with a depth of 40 mm, the radius of curvature of the cable can, finally, not be less than 30 mm.
Of course, the wires emerging from the end of the cable may be bent and connected to the so-called I.D.C.'s, or insulation displacement contacts, which are found, generally aligned in two parallel rows, at the rear of the socket. Although it is acceptable to bend these wires at 90 degrees, it is, on the contrary, inacceptable to bend them to more than 90 degrees, and therefore even less so to 180 degrees.
It follows that, with these known devices, it is impossible to connect socket 1 cables arriving in diametrally opposite directions, with the result that the installation must finally be adapted accordingly, this considerably restricting the latitude of concept of such an installation.
It is an object of the invention to overcome this drawback. |
Effect of unusual guanosine nucleotides on the activities of some Escherichia coli cellular enzymes.
Unusual guanosine nucleotides guanosine 5'-diphosphate 3'-diphosphate (ppGpp, also known as MSI) and guanosine 5'-diphosphate 3'-monophosphate (ppGp, also known as MSIII) accumulate to high concentrations in wild-type cells of Escherichia coli during amino acid starvation. We reported here that both nucleotides strongly inhibit the activity of enzymes IMP dehydrogenase and adenylosuccinate synthetase, the first enzymes of the guanylate and adenylate biosynthetic pathways. In both cases, ppGP (MSII) is a stronger inhibitor than ppGpp (MSI). On the other hand, these two nucleotides exhibited opposite effects on the activity of phosphoenolpyruvate carboxylase, the enzyme that utilizes phosphoenolpyruvate. At their respective physiological concentrations, the activity of phosphoenolpyruvate carboxylase is activated by ppGpp and inhibited by ppGp. |
Introduction {#sec1_1}
============
The Brain Attack Coalition (BAC) defined the requirements for the establishment of primary stroke centers in 2000 and comprehensive stroke centers (CSCs) in 2005 \[[@B1],[@B2]\]. Subsequently, many hospital systems within the United States have established CSCs. In late 2011, the Kennedy Health System (Camden and Gloucester Counties, N.J., USA) initiated a CSC at one of its three campuses. This CSC is a referral center for all three hospitals within its health system as well as for the local community. This CSC is also a joint venture with a regional academic medical center (Thomas Jefferson University, Philadelphia, Pa., USA). Neurologists employed by the hospital and telemedicine stroke neurologists based at the academic center provide vascular neurology coverage. Endovascular stroke therapy (EST) is carried out by two interventional neurosurgeons with joint appointments at both the hospital system and the academic center. The purpose of this article is to review the outcomes of patients who received EST at a new CSC and look at trends in outcomes over time. In the literature, we could not identify any normative data on the initiation phase of a CSC in the United States. Our contribution is to help define expected progress during such a start-up phase and the utilization of EST during that period.
Our hypothesis was that over time, outcomes improve as the system for providing EST evolves in terms of personnel, equipment, and protocols. Our data showed that there was a statistically significant increase in good outcomes from year 1 to year 2. There were also trends towards decreased mortality, decreased complications, and increased revascularization over time. Furthermore, improved revascularization and decreased NIH stroke scale (NIHSS) scores were significantly associated with decreased mortality and improved outcomes.
Methods {#sec1_2}
=======
A retrospective chart review was conducted on patients admitted to the CSC with the diagnosis of acute ischemic stroke and treated with EST from January 2012 (start of the CSC) through December 2013. Demographic data was collected along with outcome and treatment data including method of revascularization, thrombolysis in cerebral infarction (TICI) score \[[@B3],[@B4]\], and NIHSS score as established by the National Institute of Neurological Disorders and Stroke (NINDS). Data is divided into year 1 (January to December 2012) and year 2 (January to December 2013). For parametric data, significance testing was performed with a two-tailed Student t test, assuming equal variances using Excel 2011 (Microsoft, Inc., Redmond, Wash., USA). For nonparametric data, Fisher\'s exact test for 2 × 2 contingency tables and one-way analysis of variance (ANOVA) testing was performed with SPSS (IBM, Inc., Armonk, N.Y., USA).
Demographic Data {#sec2_1}
----------------
For each patient, several stroke risk factors were recorded including age, history of prior stroke, hypertension, hyperlipidemia, atrial fibrillation, and smoking. Hypertension was defined as a previous history of hypertension as reported by the patient or family or an admission systolic blood pressure \>180 mm Hg. Hyperlipidemia was recorded if the patient reported a history of hyperlipidemia or had total cholesterol \>200 mg/dl on initial laboratory screening. Atrial fibrillation was recorded if the patient or family reported a history of atrial fibrillation or electrocardiography documented atrial fibrillation on admission.
Selection for EST {#sec2_2}
-----------------
The selection process for EST is described below; the process was not altered during the entire study period. Acute stroke patients were initially evaluated in the emergency department (ED) of one of the three hospitals in the system by an ED physician. A noncontrast head computed tomography (CT) scan was obtained, and a neurology consultation was requested. If the in-house neurologist was unavailable, a university-based neurologist conducted a telemedicine stroke consult. Standard criteria for administering intravenous recombinant tissue plasminogen activator (IV rt-PA) (Activase; Genentech, South San Francisco, Calif., USA) were used \[[@B5]\]. If the patient was ineligible for IV rt-PA administration based on standard criteria or failed to improve after 1 h of IV rt-PA administration, a CT perfusion scan of the brain and a CT angiogram of the brain and the neck were performed. In multiple studies, CT perfusion of the brain has been noted to be valuable in defining penumbra versus core infarct and avoiding posttreatment hemorrhage \[[@B6]\]. If, in those studies, a major perfusion deficit without an accompanying area of decreased blood volume (ischemic penumbra) was identified, a review of the CT angiogram was undertaken to identify a corresponding occluded vessel \[[@B7]\]. If such a vessel was identified, the patient was deemed a candidate for EST unless the decreased blood volume on perfusion imaging exceeded one third of the corresponding middle cerebral artery (MCA) territory. For posterior circulation ischemia, the decision to proceed with EST was based on whether there was major vessel occlusion on CT angiography, major neurological deficit, and significant penumbra on CT perfusion. Door-to-needle (DTN) time was the time from ED arrival to delivery of IV rt-PA for the patients who were able to receive the medication. Door-to-intervention (DTI) time was the time from ED arrival to procedure start time in the interventional suite. Procedure length was the time from procedure start to recorded procedure end time (catheters and sheaths removed from patient).
Interventional Methods and Outcomes {#sec2_3}
-----------------------------------
General endotracheal anesthesia was used for all interventions. Electroencephalography, somatosensory evoked potentials, and brainstem auditory evoked responses were recorded during the procedures. Arterial access was obtained through the common femoral artery. A large bore sheath (7 or 8 Fr) was placed. Diagnostic angiography was first performed to confirm an arterial occlusion. Next, a guide catheter was brought up close to the skull base or into the petrous carotid. Depending on the operator\'s preference, either thromboaspiration or mechanical retrieval (stentriever) was used. Thromboaspiration was performed with the Penumbra system (Penumbra Inc., Alameda, Calif., USA) using the standard technique. Mechanical retrieval based on a stentriever was done with either the Solitaire FR (ev3 Neurovascular, Irvine, Calif., USA) or the Trevo Pro (Stryker Neurovascular, Fremont, Calif., USA). In two cases, emergent carotid angioplasty and stenting were performed following EST; a Viatrac balloon, Rx Acculink carotid stent and Emboshield NAV6 embolic protection device were used (Abbott Laboratories, Abbott Park, Ill., USA). At the operator\'s discretion, small doses (2-5 mg) of either rt-PA and/or abciximab (2-5 mg) (Reopro; Eli Lilly and Co., Indianapolis, Ind., USA) were administered intra-arterially through the catheter during some EST procedures. In no case was intra-arterial (IA) medication the sole treatment.
NIHSS scores were calculated on admission and 24 h after treatment. The degree of revascularization was assessed using the TICI scale as originally described by Higashida et al. \[[@B4]\]. Disability at the time of discharge was measured based on the modified Rankin Scale (mRS) \[[@B8]\].
Results {#sec1_3}
=======
Demographic Data {#sec2_4}
----------------
The entire Kennedy Memorial Hospital system receives approximately 145,000 emergency room visits per year. Hospital records indicate that during the 2-year period, 1,644 patients were admitted to the hospital system with a diagnosis of stroke or transient ischemic attack. Of these, 91 (5.5%) received IV rt-PA. Nineteen patients (1.1%) were identified for EST treatment during the analysis period; however, 1 patient was transferred to the academic center when the biplane fluoroscopy equipment malfunctioned at the beginning of the procedure and could not be immediately repaired. This patient was excluded from the analysis.
The average age of the patient population was 74.6 years. During the first year, the average age was 78.3, and 66.1 years in the second year. This difference was statistically significant although selection criteria did not change from year 1 to year 2. In total, 7 male and 11 female patients were treated. The mean NIHSS score prior to intervention in year 1 was 19, and in year 2, it was 14 (p = 0.16). Hypertension, hyperlipidemia, and atrial fibrillation were highly represented among the patient population, while smoking and history of prior stroke were not (table [1](#T1){ref-type="table"}).
In both year 1 and year 2, approximately half of the patients received IV rt-PA prior to intervention (table [1](#T1){ref-type="table"}). In order to be candidates for EST, these patients continued to have a significant deficit after 1 h of IV rt-PA administration. CT perfusion and CT angiography were also required to demonstrate an ischemic penumbra and a vessel occlusion. Other reasons for referral for EST in both year 1 and year 2 included: age \>80 years (2 patients), unknown time of onset of symptoms ('wake-up strokes') (5 patients), \>4.5 h from symptom onset (1 patient), and recent gastrointestinal hemorrhage (1 patient). For both year 1 and year 2, the majority of patients had MCA occlusions (year 1, 90%; year 2, 100%). The proportion of left ('dominant') hemisphere occlusions was not significantly different between year 1 and year 2 (0.7 vs. 0.43, p = 0.35).
Outcome Data {#sec2_5}
------------
The proportion of patients receiving EST with a good outcome (defined as mRS at discharge ≤2) was significantly higher in year 2 compared to year 1 (p = 0.05; table [2](#T2){ref-type="table"}). There were also trends towards other outcome improvements in year 2 compared to year 1, but these did not reach statistical significance (table [2](#T2){ref-type="table"}). For example, the 30-day mortality rate fell from 36 to 14% from year 1 to year 2 (p = 0.6), while the rate of complete revascularization (TICI score = 3) improved from year 1 to year 2 (absolute increase 30%, p = 0.33). The mean improvement in the NIHSS score 24 h after the procedure was similar over the two periods (year 1, score 5; year 2, score 6) (table [3](#T3){ref-type="table"}).
With data from both year 1 and year 2, one-way ANOVA testing was performed to analyze the relationship between several variables (age, DTI time, NIHSS score change, and procedure length) and 30-day mortality (table [4](#T4){ref-type="table"}). A similar analysis was done between those variables and the TICI score (TICI score ≥2b) (table [4](#T4){ref-type="table"}). Notably, NIHSS score improvement was significantly associated with decreased 30-day mortality (p = 0.008). We found a statistically significant trend between 30-day mortality and increasing age (p = 0.06) as well as between DTI time and mortality (p = 0.09). The other variables were not significantly associated with 30-day mortality. A TICI score ≥2b was significantly associated with improvement in NIHSS score (p = 0.01). This result is similar to recent reports \[[@B9]\].
Process Data {#sec2_6}
------------
For the patients receiving IV rt-PA, the average DTN time for administration of IV rt-PA decreased from year 1 to year 2 by approximately 20 min or 36% (p = 0.03; table [3](#T3){ref-type="table"}). The DTI time decreased from year 1 to year 2 but was not significantly different. Procedure length only slightly decreased from year 1 to year 2 (p = 0.51). In both years, approximately three quarters of procedures were done with stentrievers and about 40% used IA medications (table [2](#T2){ref-type="table"}). Three procedural complications were identified in year 1 and one in year 2. In year 1, there was one case of femoral artery dissection in an elderly patient with severe peripheral atherosclerotic disease. There were two intracerebral hemorrhages within 24 h of treatment and one case of ventilator-dependent respiratory failure requiring prolonged intubation and conversion to tracheostomy. Although the complication rate decreased from year 1 to year 2, the decrease was not statistically significant.
Discussion {#sec1_4}
==========
CSC Requirements {#sec2_7}
----------------
In 2000, the BAC established guidelines for a primary stroke center \[[@B1],[@B10]\], and in 2005, further requirements for a CSC were outlined \[[@B2]\]. Since 2005, many academic and community medical centers have sought to establish CSCs. Retrospective analysis has suggested that patient outcomes are improved when stroke care is organized into such centers \[[@B11],[@B12],[@B13],[@B14]\]. For example, Kim et al. \[[@B15]\] calculated a 28% reduction in 30-day mortality after establishment of a CSC. Currently, there is a need to define expected progress during the initiation of a CSC and examine the benefits of EST. The aim of the present research is to address this need.
Recent Randomized Clinical Trials {#sec2_8}
---------------------------------
Several recent clinical trials have purported to show the limited efficacy of EST for acute ischemic stroke \[[@B16],[@B17],[@B18]\]. These results created a great deal of discussion and re-evaluation of endovascular therapy protocols \[[@B19]\]. While some have suggested a moratorium of EST for stroke \[[@B20]\], finer analysis of the data suggests that certain patients may benefit from this therapy \[[@B19],[@B21],[@B22]\]. A number of authors have noted flaws in those trials including outdated treatment modalities, poor patient selection algorithms, and inadequate data analysis \[[@B23]\]. Our center has continued to offer EST because our selection criteria differ from those of the reported trials. We select patients based on two necessary criteria: (1) imaging evidence of significant ischemic penumbra and a vessel occlusion of CT angiography, and (2) ineligibility for IV rt-PA or failure to improve after 1 h of IV rt-PA. In addition, the prospective, randomized trials published in 2013 suggested that EST has a safety profile similar to IV rt-PA \[[@B16],[@B17],[@B18]\].
Outcome Improvements {#sec2_9}
--------------------
At our CSC, we found that there was a statistically significant improvement in the number of independent patients at discharge (mRS ≤2) following EST in year 2 compared to year 1. In addition, there were trends towards decreased mortality, decreased complications, and increased revascularization. Despite identical selection criteria, the patients in year 2 were slightly younger which may confound the results since our separate analysis has shown that older age is negatively correlated with a good outcome following EST. Others have shown a similar relationship between age and poor outcome \[[@B24],[@B25]\]. Nevertheless, our data suggests that improvement in a number of outcome metrics (e.g. TICI score, change in NIHSS score, and complication rates) also occurred from year 1 to year 2, not all of which are likely due to the age variation in the patient population. Overall, for both years, approximately 40% of patients improved following EST. This result is similar to previous reports \[[@B26],[@B27]\].
Process and Technical Improvements {#sec2_10}
----------------------------------
Our data suggests that there are improvements over time in the delivery of EST. In our series, there was a decrease in mortality and morbidity from year 1 to year 2 as well as an increase in excellent revascularization (TICI score = 3), but these did not reach statistical significance. Although many individual improvements did not reach statistical significance, it is likely that the aggregate effect of these changes led to the statistically significant improvement in discharge status (mRS score ≤2).
We did observe statistically significant decreases in DTN time (p = 0.03) from year 1 to year 2. There were also trends towards decreased DTI time and procedure length from year 1 to year 2. In their study of stentriever use, Eesa et al. \[[@B28]\] have also shown procedural improvements over time. In our ANOVA analysis, increasing DTI time is associated with increased mortality suggesting that accelerating delivery of care in these complex systems is of value.
In summary, the initiation phase of a CSC is associated with significant improvements in outcome over time. These improvements may be attributed to increasing technical ability as well as to decreasing time in delivery of effective therapy. Furthermore, shorter time to intervention and successful revascularization are associated with improved outcomes.
Disclosure Statement {#sec1_5}
====================
The authors have no conflicts of interest to disclose.
The authors would like to thank Eileen Gallagher, RN, for her assistance with data collection and Robert H. Rosenwasser, MD, for his helpful suggestions and editorial advice.
######
Demographic data for acute stroke patients treated with EST in year 1 and year 2 at a new CSC
Year 1 Year 2 p
------------------ ----------- ---------- ------
Mean age, years 78.4 66.1 0.03
Min.-max. 63--89 34--88
Mean NIHSS score 19 14 0.16
Min.-max. 8--25 6--21
Male/female 3/8 4/3 0.33
\% prior stroke 0 (0/11) 14 (1/7) 0.39
\% smoker 9 (1/11) 29 (2/7) 0.53
\% HL 64 (7/11) 85 (6/7) 0.60
\% Afib 45 (5/11) 28 (2/7) 0.64
\% HTN 82 (9/11) 71 (5/7) 1.00
\% IV rt-PA 55 (6/11) 57 (4/7) 1.00
Mean NIHSS score = Mean NIHSS score on admission; Min.-max. = minimum to maximum values; % Afib = percentage of patients with atrial fibrillation; % HL = percentage of patients with hyperlipidemia; % HTN = percentage of patients with hypertension; % IV rt-PA = percentage of patients who had received IV rt-PA prior to ET. p values are based on Fisher\'s exact test (see Methods section).
######
Comparison of outcome and procedure data on acute stroke patients treated with EST at a new CSC in year 1 and year 2 (Fisher\'s exact test)
Year 1 Year 2 p
--------------------------- ------------ ----------- ------
\% discharge mRS score ≤2 9 (1/11) 57 (4/7) 0.05
%TICI score 3 27 (3/11) 57 (4/7) 0.33
\% 30-day mortality 36 (4/11) 14 (1/7) 0.60
\% MCA 90 (10/11) 100 (7/7) 1.00
\% complication 27 (3/11) 14 (1/7) 1.00
\% stentriever 73 (8/11) 85 (6/7) 1.00
\% TICI score ≥2b 64 (7/11) 71 (5/7) 1.00
\% IA medications 36 (4/11) 43 (3/7) 1.00
The fraction in parentheses is the number of patients with characteristics over the total. % discharge mRS score ≤2 = percentage of patients at discharge who had an mRS score ≤2 (independent); % TICI score 3 = percentage of patients with complete revascularization on the TICI scale; % MCA = percentage of patients with an MCA occlusion on angiography; % complication = percentage of patients who had a procedural complication; % stentreiver = percentage of patients treated with a stentriever as the primary endovascular device; % TICI ≥2b score = percentage of patients with a revascularization score on the TICI scale of 2b or higher; % IA medications = percentage of patients that received IA rt-PA or abciximab as an adjunct to their procedure. p values are based on Fisher\'s exact test.
######
Comparison of procedure and outcome variables from year 1 and year 2 at a new CSC
Year 1 Year 2 p
---------------------------- ------------ --------- ------
Mean DTN, min 57.5 36.3 0.03
Min.-max. 54--121 35--37
Mean discharge mRS score 4.4 2.8 0.18
Min.-max. 2--6 1--6
Mean DTI, min 157 136 0.40
Min.-max. 70--222 72--201
Mean procedure length, min 135 117 0.51
Min.-max. 49--234 50--217
Mean Δ NIHSS score 5 6 0.88
Δ NIHSS range (--13)--21 0--14
Mean Δ NIHSS score = Average decrease in NIHSS following the procedure at 24 h after the procedure. The p value is based on significance testing as described in the text. Min.-max. = minimum to maximum values.
######
Results of the one-way ANOVA on pooled data from year 1 and year 2
Variable 1 Variable 2 p
-------------------------- ------------------ ------
Δ NIHSS score 30-day mortality 0.01
Age 30-day mortality 0.06
DTI time 30-day mortality 0.09
Procedure length 30-day mortality 0.12
Preoperative NIHSS score 30-day mortality 0.50
Δ NIHSS score TICI score \>2b 0.01
DTI time TICI score \>2b 0.14
Procedure length TICI score \>2b 0.32
Age TICI score \>2b 0.72
Preoperative NIHSS score TICI score \>2b 0.76
Δ NIHSS score = Change in NIHSS score 24 h following the procedure. 30-day mortality and TICI score ≥2b are categorical variables.
|
Solar panels and wind farms churn out energy around midday and at night when demand lulls.
This forces utilities to discard it in favor of more predictable oil and coal plants and more controllable natural gas “peaker” plants.
2) Technology
Alphabet Inc.’s project named Malta, is working on a molten salt storage system. The system consists of two tanks that are filled with salt, and two are filled with antifreeze or a hydrocarbon liquid. The system takes in energy in the form of electricity and turns it into separate streams of hot and cold air.
The hot air heats up the salt, while the cold air cools the antifreeze. By the flip of a switch the process can be reversed and hot and cold air rush toward each other, creating powerful gusts that spin a turbine and spit out electricity when the grid needs it.
Salt maintains its temperature well, so the system can store energy for many hours, and even days, depending on how insulated the tanks are. |
Awesome Board/Bags
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Finish is too slick
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I love the design, quality, and the speed of delivery. The only problem I have is after the bags land on the board, they slide to the bottom. They are not staying on the board. I have to figure out how to make either the bags or the board more abrasive to prevent them from sliding.
Better Than Expected
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We ordered Board with our company logo on them; they are better than expected! Sturdy frame construction and the Logo is Perfect! We are so pleased with how these turned out- this will be great for our company marketing.
one of the greatest boards I've seen!
nice art work!
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great style of custom art work. A couple nicks on the top and sides.
Fabulous Product, Great Price
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Product Description
This is the real deal! Completely customize your boards with whatever you want! Your custom set will include two high quality, heavy-duty 24”x48” tournament grade cornhole boards with folding legs and 8 bags of your choice. The boards can literally be customized with whatever you desire. Provide us with your own details, or just send us your logo and let us design a set for you! All custom designed boards require your approve before we begin building them. That means we’ll send you some mockups to look at before starting.
To produce the best results, please send us the highest quality files you have available. Preferably, EPS, AI, or scalable PDF files.
We also have digital Illustrator and Photoshop templates if you would like to submit your own design. Once the design is finalized, it will be less than two weeks before we get you out there throwing bags and having fun on your new customized boards! |
HOW TO MANAGE STRESS, PART II
You cannot avoid all stress situations because some of them need to be addressed, however you can alter these situations, and this involves changing the way you operate in your everyday life. First, you need to express your feelings; if someone or something is bothering you, reveal your concerns in a respectful and open way because if you do not, stress will build and the situation will remain the same.
Accept compromise; when you want someone to change his or her behavior, you also should be willing to bend a little so that both of you can find a middle ground.
You need to be more assertive; deal with your problems and do not take the backseat in your own life, for example if you have to study for an exam, do not be shy to tell your chatty friend that you only have five minutes to talk.
You need to manage your time well, as bad time management can lead to a lot of stress; plan ahead and do not overextend yourself so that you can alter the stress amount you are under. Sometimes you need to change yourself, if you cannot change the stressor; you can get your sense of control by altering your attitude and expectations.
Try to have a more positive perspective with the stressful situations; instead of fuming about a traffic jam, consider it an opportunity to pause, enjoy some time alone and listen to radio.
Look at the big picture; when you face a stressful situation, ask yourself “will it matter in the long run? Is it worthy of getting upset?” if the answer is no, focus on something else and spare yourself the time and energy. If you are a perfectionist, you need to adjust your standards because perfectionism can cause you a big amount of stress that can be avoided. |
<?php
declare(strict_types=1);
namespace Shlinkio\Shlink\Core;
use Doctrine\DBAL\Types\Types;
use Doctrine\ORM\Mapping\Builder\ClassMetadataBuilder;
use Doctrine\ORM\Mapping\ClassMetadata;
use Shlinkio\Shlink\Common\Doctrine\Type\ChronosDateTimeType;
return static function (ClassMetadata $metadata, array $emConfig): void {
$builder = new ClassMetadataBuilder($metadata);
$builder->setTable(determineTableName('short_urls', $emConfig))
->setCustomRepositoryClass(Repository\ShortUrlRepository::class);
$builder->createField('id', Types::BIGINT)
->columnName('id')
->makePrimaryKey()
->generatedValue('IDENTITY')
->option('unsigned', true)
->build();
$builder->createField('longUrl', Types::STRING)
->columnName('original_url')
->length(2048)
->build();
$builder->createField('shortCode', Types::STRING)
->columnName('short_code')
->length(255)
->build();
$builder->createField('dateCreated', ChronosDateTimeType::CHRONOS_DATETIME)
->columnName('date_created')
->build();
$builder->createField('validSince', ChronosDateTimeType::CHRONOS_DATETIME)
->columnName('valid_since')
->nullable()
->build();
$builder->createField('validUntil', ChronosDateTimeType::CHRONOS_DATETIME)
->columnName('valid_until')
->nullable()
->build();
$builder->createField('maxVisits', Types::INTEGER)
->columnName('max_visits')
->nullable()
->build();
$builder->createOneToMany('visits', Entity\Visit::class)
->mappedBy('shortUrl')
->fetchExtraLazy()
->build();
$builder->createManyToMany('tags', Entity\Tag::class)
->setJoinTable(determineTableName('short_urls_in_tags', $emConfig))
->addInverseJoinColumn('tag_id', 'id', true, false, 'CASCADE')
->addJoinColumn('short_url_id', 'id', true, false, 'CASCADE')
->setOrderBy(['name' => 'ASC'])
->build();
$builder->createManyToOne('domain', Entity\Domain::class)
->addJoinColumn('domain_id', 'id', true, false, 'RESTRICT')
->cascadePersist()
->build();
$builder->addUniqueConstraint(['short_code', 'domain_id'], 'unique_short_code_plus_domain');
};
|
Bhalla rallies Hoboken Dems to elect Stack as the next HCDO chairman
Hoboken Mayor Ravi Bhalla rallied members of the local Democratic Committee to elect state Senator (D-33)/Union City Mayor Brian Stack as the next chairman of the Hudson County Democratic Organization at a private meeting last night.
“As long as I’ve known or been in Hudson County, we’ve only had one county executive: County Executive [Tom] DeGise, whose a wonderful person. But as you all know, in Hoboken, we give a lot more than we get back from the county, in terms of out county taxes,” Bhalla said.
“There are a lot of issues where we just do not get our fair share of the pie: we subsidize a lot of the streets and roads, the parks, the jail, the courthouse and we pay the highest percentage of taxes.”
The new mayor continued that Hoboken has continually held the line on municipal taxes, only to see a noticeable increase on the county level.
As a result, Bhalla said it’s about time to “finally have a seat at the table” in county government, with the first step in that process being electing Stack at the head of the HCDO in June.
Bhalla was quick to back Stack and Jersey City Mayor Steven Fulop’s plan to oust DeGise next year, despite the fact they have yet to select a candidate.
While DeGise made it clear on our live show last week that he’s furious with Fulop, he also had a few choice words for Stack and Bhalla.
Assemblywoman Annette Chaparro (D-33), one of Stack’s legislative running mates, is expectedly on board with making a change at the county level, making it a point that they never intended to start a civil war.
“I think that we all know that Hudson County needs to change things up, especially for Hoboken, and I think this is the man [Stack] that’s gonna get it done for us and we are not looking for a fight, we just wanted a change,” she explained.
“That’s what it was, and to declare a war, before it even started, just tells you that they are nervous because they know we are really gonna make a change.”
DeGise also told us that he can’t envision a scenario where he drops his re-election bid, which is being spearheaded by state Senator (D-32)/North Bergen Mayor Nick Sacco and U.S. Rep. Albio Sires (D-8).
Hoboken 3rd Ward Councilman Mike Russo added that this isn’t about a political scrap, it’s about the residents of the county getting the services they need.
“Senator Stack will be the first one to tell you that this isn’t about him: this is about all of you. It’s about all of the constituents that he represents and we represent. This is not just about the chairmanship of the Democratic party in Hudson County,” Russo said.
“This is about getting each and every person in the City of Hoboken, and throughout the county, involved so that we can make the changes that we all would like to see.”
Addressing the room of about 30 people, Stack admitted he got involved in the Hoboken Democratic Committee races last year because “outside influence,” clearly referencing Team Sacco, tried to get involved.
“I didn’t think it was right, with the games that were being played at the time, so I got involved,” he said.
If elected HCDO chair, Stack says he’s going to make being a committee representative matter again, the way it did when he was a kid growing up in Union City.
“I feel, that as the chairman of the party, I would make the committee person matter again. What I mean by that, is when I was a kid growing up in Union City, and I had family who lived in Hoboken and Jersey City, the committee person really meant something,” Stack recalled.
“Not just once a year when you’re on the ballot and you’ve gotta pull for the entire column because you’re the ones that book.”
Stack also leveled that when someone like Bhalla meets with the HCDO, Assembly or Senate delegation, that look at the voter tallies from the last election cycle to determine what sort of political clout they have.
“There was a time when presidential candidates made Hudson County a must stop. The Democratic candidates would make it a must stop location. That’s been lost because the county is disorganized. There’s a lot of people that are not coming out to vote,” noting that this has been the trend for about 20 years.
While Stack and Sacco are at odds again, with things likely to get worse before they get better, the Union City power broker is almost a certainty to succeed former Assembly Speaker Vincent Prieto as the next HCDO chair.
DeGise told Hudson County View last week that he doesn’t think anyone will challenge Stack for the county position this summer.
The event, hosted at Carpe Diem, was a success for Bhalla, with about 60 members of the HDC – although many of them did not attend – committing their June vote to Stack.
Unlike Councilwoman Giattino Councilman Russo is, was and always will be a Democrat.
The betrayal of the Hoboken Democrats by Councilwoman Fisher in the age of Trump who was backed a Republican for Hoboken Mayor Giattino while head of the Hoboken Democratic Committee so enraged the members of HDC they want her gone but she refuses to call a meetings they can not vote to get rid of her.
Now Giattino may have committed a ethics violation by accepting gifts from a politically connected law firm to help change Hoboken’s rules to give two of her campaign workers Board appointments.
City officials are not permitted by law to accept gifts of $25 or greater. The Council vp accepted a very expensive gift of legal work from Saccos lawyer pal which they used to justify changing municipal law for 2 patronage appointments. This is political corruption.
Making out in the tree of corruption! There’s no room on this limb Nancy. You’ll break it, get off. Hoboken is our piggy bank. We don’t do $25 or $1200 palm card deals for political operative work. Ravi is a deal-making money mastermind! Law firms around NJ love him!
What was the name of the guy a while back who claimed he was a some sort of a reformer and then made a deal to get on the sewerage board with a nod from Russo and everyone said it was because he wanted taxpayers to pay for his medical insurance ?
We dun nee no stinking ethics in Hoboken. Ravi & Russo are the Boss of Bosses. No deal goes down in Hoboken without our blessing. You best kick up to us. Nancy is our new Hoboken411! Don’t mess with us or will have her make up all kinds of BS on you while we clean up the moolah! We love Hoboken and the $$$$$!
The only change for Hoboken will be higher taxes. Then Russo and Ravi will do more dirty deals for themselves. Does Russo have to split any zoning fees earned with Ravi’s law firm? They specialize in land use. Someone tell Solomon Dwek, he and his friends are welcome back in Hoboken again.
Nancy, you keep makin up dat stuff about Jen, Peter and Tiffanie. That’s good political operative lying you’re doing. Leave the Hoboken dirty deals to us. SSSHHH, we don’t talk nuthin about it. Ravi and me, we got a whole lot of money to make in Hoboken. He’s a full member and we love the new PILOT and all the deals we’re gonna do! Show me the money Ravi! He’s the best mayor since Peter Cammarano.
The first rule of any Ravi-Russo deal is, we don’t talk about any Ravi-Russo deal. That goes double for a Russo-Stack deal and three times for a Ravi-Stack deal. Shaddup your face moron! This is bidness $$$.
Nancy, who are you now accusing of a crime? Bet you won’t sign your name to another of your latest scurrilous attacks. Coward.
If Ravi got picked up by the Feds tomorrow you would immediately make up something about Jen, Peter or Tiffanie per usual. Fakes news is what you live for and you’re absolutely pathetic.
Every news revelation on HCV or MSV about Ravi Bhalla’s latest ethical challenges is met with you scurrying here in a panicked state lashing out at everyone and anyone trying to distract from the issue.
Didn’t get my pledge pin for the meeting in the back room at Carpe Diem. Is it too late? How can I get in on the one-party, one-candidate action? Is Ravi the only one getting a deal? Russo has to get a deal? What kind of deal does Hoboken get? The one that begins “shafted!” Screw that.
Does Nancy think everyone is dumb as a brick like her or anywhere as crazy?
It’s called LEGISLATION. Changing part of an appointment process to a board is less different then in 2009 when Dawn Zimmer advocated to move the entire zoning board appointments from mayor to the City Council.
You’re going to need better lies Nancy if you hope to distract from the big stories about Ravi’s shady employment contract and getting into bed with Hoboken’s Crown Prince of Corruption.
Wait until the mayor sues your crybaby fake news blogging a$$ for accusing him of taking bribes. Paid crybaby fake news blog boy has no idea who I am… just one of many who think hes a nut. can dish it out but cant take it.
Bhalla complains that Hoboken is not getting fair share. This is a result of the real estate assessments not being performed across all cities in the County. While complaining on this issue, Bhalla has done NOTHING to estimate the expected reduction in Hoboken’s share of County taxes due to the reval of Jersey City properties.
Will Bhalla’s firm get a contract with Union City? Oh wait, I forgot — Balla’s firm already had a contract with Union City! So we should try this again because they “want a change”? No thanks!
Stack and Bhalla are looking for change, but its more of the same. And who is that with Bhalla? Mike Russo? Remember when “reform” correctly called Russo out for what he is — a seedling of a corrupt former mayor? Let’s forget that though, because it’s now politically convenient.
Senator/Mayor Stack (what should we call you since you have two jobs) guess what, nobody cares about you in Hoboken, and two-job Bhalla has 32% of the electorate and most of them voted for him because they thought he was being bullied by a flier he sent out about himself.
I see unlimited sales commissions in Ravi’s future in Hudson County. How much does he have to cut Mike Russo in for? Does Russo need an agent? Is there a lawyer on the Dem Committee available to help these two mensches out? Oy vey, what Dawn Zimmer gave Hoboken. Thanks Dawn!
Are the “real men of Hoboken” supporting the Sacco team? That would be terrible news for Senator Stack and Mayor Fulop. Especially if their sister group, the “real women of the Hoboken City Council” follow suit.
Seems like Mayor Sacco and his pal Joey were not in attendance. And the story about Mayor Zimmer not returning contributions to people who requested refunds turned out to be just one if the many lies told by Roman as part of his wildly successful effort to sabotage Jen Giattino’s campaign.
Ravi bots can pile on the lies and try any distraction they want. You sold a fuggazy in Ravi. He lied to the Hoboken people and did a shady law firm deal. Now he’s in bed with Michael Russo. You people suck hard. Own it.
BobMc – Will the anti-Bhalla City Council members now try to get Mayor Sacco’s politically connected law firm some Hoboken taxpayer money in return for their free legal work to help reward Giattino’s two campaign workers ?
Todays daily obsessive sick attack on Jen Giattino is really troubling. These City Hall assaults on council members by their paid political blogger are gone too far, if it were me- someone would be facing a HUGE lawsuit. Maybe for some it’s a second…
Wait until the mayor sues your crybaby fake news blogging a$$ for accusing him of taking bribes. Paid crybaby fake news blog boy has no idea who I am… youd be surprised how many people think youre nuts.
Tom Degise has been screwing the Hoboken taxpayers for years. Maybe a County Executive sponsored by Stack will merely just screw up. Won’t make much of a difference. Hoboken is Hudson County’s ATM machine.
I did not sign a pledge card and there were not 60 people in the room to sign pledge cards as has been mentioned elsewhere. What is this Animal House? Is sneaky backstabbing Phil Cohen the new Niedermayer? Pledge pins sound very Putinesque don’t you think?
Hi HR. Do you agree with your idiot sidekick’s characterization of the two of you as “the real men of Hoboken?” Or are you tired of having what’s left of you credibility be further damaged by your association with him?
Also, you avoided taking a position on the future of our county leadership in your post. Do you support or oppose having an alternative ti Tom Degise’s re-election? Or are you waiting to see which way the wind blows?
Do you agree with Ravi’s second job LindaStan? How about a third “job” with a Republican law firm? A fourth? How much money can a mayor make off the office of mayor with outside “employment” contracts? Did you help cut a Ravi-Russo PILOT deal? What deals has the Ravi-Russo Team cut to date? Hoboken is just dying to know.
I fly solo. No sidekicks. Do you think Ravi’s contract to get commissions trading off his office of Mayor for personal profit represents the zenith of governmental ethics? I sure as heck don’t.
Zimmer may have been numerically challenged and had limited bandwidth at times but would have never signed up for a contract where she profited off of government contracts. She at least had standards of ethics. Now the only person she trusted has done what Cammarano only dreamed of doing which is sell out a Hoboken to the highest bidder.
Looks like some of Ravi”s most ardent and robotic followers are following NG him into the ethical abyss on the Democratic Committee just to settle political scores. Now are they not only saying this unethical contract is ok but it’s ok to hop in bed with the Clown Prince of Corruption Mike Russo.
So “Sibilitis” lied when he referred to you and Roman Brice as “the real men of Hoboken?” If so I apologize for believing that you you shared that particular delusion with him.
Do you support a competitive primary for county executive or do you believe Tom DeGise should simply be coronated by the unanimous consent of the party Bosses? That is the topic of this thread. As a Democratic committeeman and executive committee member your opinion on that issue, is of public concern. That’s why I have now asked you the question twice and am interested in hearing your answer which you have so far failed to provide.
I am not going to respond to your childish rants about masculinity. If you want to engage in that nonsense I suggest you go to GA where the harried hermit engages in the petty politics of personal destruction paid for by Ravi Bhalla who politically is the most divisive mayor in recent history. It’s a shame to because minus the corrupt contract where he profits personally from the Mayor’s office under color of official right and the political paranoia he does seem to be much more decisive than dithering Dawn with her craven misanthropic shadowy sidekick Starinlaw Grossfart.
Of course there should be a competetitive primary for County Executive.There has not been one in a while. Remember I once ran for Freeholder knowing I had no chance in hell of winning being outspent 20-1 but got 25% of the vote on a shoe string budget. Thus I have proven record of wanting choice.
Let’s see who steps up and decides to run. Hopefully they won’t be as inept as a prior Freeholder candidate who ran on the line, had the Mayor’s endorsement, spent a ton of money, and got walloped by Romano. He also got fewer votes than I did. We don’t want losers like that running for sure.
Whether it’s Degise, Sacco, Stack, Roque, or even Turner the county players view Hoboken as their personal piggy bank. Ravi is just following the Hudson model with contract deal.
I don’t expect much to change but a real challenge to Degise would be a start.
Why didn’t Deigise help fund Washington Street? Did demure distracted Dawn not have the courage to ask for her fair share? What would The Shadow say? The Shadow knows. The Shadow knows. Lol.
So let’s be real. There were fewer than 30 people in the room last night at Carpe Diem. Inflating the number is necessary in order to deal with the two inflated egos in the room: Stack and Bhalla.
It makes me laugh reading about how Stack feels that Hoboken is being cheated by the County! Does he really care about Hoboken? Has anyone noticed the decline in State funding coming into Hoboken since Stack became the State Senator? Each year fewer and fewer dollars have been returned to Hoboken while Union City keeps raking it in. The State is paying for only a small portion of the Washington Street Project when, in fact, it should be paying the lion’s share. Just last week I read that Hoboken Schools will receive zero additional dollars next year while Union City gets a whopping $9 milliion more.
Of Course Ravi will support anything Stack wants because Ravi had a nice contract with Union City when he was needy. It’s payback time and Ravi is paying back with our votes.
Ravi also knows that the only way he can get a turnout is to make a deal with Russo. Boy, the reformer really knows how to sell his soul!
As far a DeGise goes, he did restore a sense of trust in the Office of County Exec after the Bobby J scandal. Maybe he’s a bit too honest for the power brokers in Jersey City, Union City and Hoboken.
Can’t believe Stan , Ravi and Russo are all together
Quite a little trio that is certainly a match made in HUDCOland
As a matter of fact there hasn’t been such unity since Staci and Russo all joined forces against Zimmer, Lenz and Pinchevsky in the 4th Ward
Ravi doesn’t mind, he was trying to make deals with Russo even before he joined Mello and Zimmer in the original park reformers initiatives
Ravi was begging Mason, then Cammarano and not until they told him no did he come to Zimmer and 4 years later saw his popularity tumble to 3rd place on Zimmer’s slate
Mr 32%
More palm cards please
Extra for the new family member with Ravi and Russo at the top
Send the checks ASAP
Before the next election cycle- Sybil needs some money for new yoga pants
Are you referring to the park group Lenz and Soares tried to infiltrate and manipulate even though they didn’t give a damn about parks? In the immortal words of Michael Lenz “I don’t really care about parks but I can’t get to 50% +1 without the people who do so I support parks.”
The same Michael Lenz who reportedly struck a back room deal with Michael Russo putting his pal Tony Soares on the NHSA board (when he was already ZBA chair) in exchange for putting Russo’s choice on the HHA? The rumor was that it was all about trying to get Tony health benefits on the public dime, but it didn’t work out because of a change in the law. Pretty corrupt if true.
So not three months in and Ravi is proving Dawn Zimmer a prophet, a prophet of bad judgment. Way to go Stan! Hope it’s “worth” it. Holy Shite, an employment contract off Hoboken’s back and now the Russo Clan deal! Way to go.
The plan as a whole has been controversial because some residents believe the area is too flood-prone and too traffic-tied to allow the scale of development suggested in the plan. They also want more open space in the plan before the city goes forward with seeking developers.
“The lawsuit was filed in August of ’06 by five Hoboken residents: Dawn Zimmer (currently a City Council candidate), her husband Stanley Grossbard, former Councilman-At-Large Anthony Soares, Southwest Parks Coalition President Sara Stojkovic, and coalition member Nishant Amin. ”
Although the decision was viewed as a victory by critics of the proposed plan, Hoboken’s Director of Community Development Fred Bado described it as a stall tactic that “doesn’t really throw us off schedule.”
So how about when Ravi did legal representation for Dawn and Stan in a personal legal matter?
Ask Mike Russo and Cousins
The Hoboken Reporter and Hoboken411 recently reported that Councilman Ravi Bhalla serves as your attorney in a personal legal matter. The New Jersey Government Ethics Law states, “no local government officer shall engage in any business, transaction, or professional activity, which is in substantial conflict with the proper discharge of his/her duties in the public interest.” Councilman Bhalla serving as your attorney appears to be a violation of state law.
This representation raises significant questions as to whether Councilman Bhalla, who until last month was Council President, has a conflict of interest between his duties as an elected representative of Hoboken residents and his duties as your private attorney. It also erases the line that serves as a check and balance between Hoboken’s executive and legislative branches of government which creates an arms-length relationship between the mayor and City Council.
You and Councilman Bhalla have a duty to the public to explain your relationship. Accordingly, we hereby request that you and/or Councilman Bhalla answer the following questions prior to the next City Council meeting:
1. Please explain in full detail the nature of Councilman Bhalla’s representation of you and Stanley Grossbard.
2. Have you paid for his services? If so, how much have you paid and were you charged a reasonable and customary rate?
3. If his services were pro-bono does the value of his services exceed the $25 limit your executive order on ethics sets for elected officials and city employees?
4. How long has Mr. Bhalla represented you and Mr. Grossbard?
5. Does Councilman Bhalla understand he has an ethical obligation to you and Stanley Grossbard in his private capacity as an attorney to act only in their best interests?
6. Does Councilman Bhalla understand he has an ethical obligation to the city in his capacity as an elected councilman to act only in the city’s best interests?
7. Are you and Councilman Bhalla familiar with the portion of the Local Government Ethics Law that states: “No local government officer shall engage in any business, transaction, or professional activity, which is in substantial conflict with the proper discharge of his/her duties in the public interest?”
8. How can the public trust that decisions made by Councilman Bhalla were in the best interest of the city?
9. How can the public trust that when you and your administration bring a matter before the City Council that Councilman Bhalla will only consider the public’s interests rather that the interests of you as his client?
10. By way of this letter we wish to ask Councilman Bhalla what other legal representations during his term in office has he been or is currently engaged with other Hoboken council members, elected officials, city employees, commissioners/board members and their family members.
Yes, you are correct. The park group Soares and Lenz tried to infiltrate to exploit politically despite not giving a damn about parks is the SW group. Do you have any comments on the reported Lenz/ Russo deal that put Soares on the NHSA and in exchange for an HHA seat? Would you agree that if it’s true it would be disgraceful and perhaps even corrupt?
That’s the kind of wheeling and dealing that makes honest citizens sick to their stomachs.
Bhalla’s apparent evasion of Newark’s pay-to-play laws by making his contribution to a PAC rather than to a candidate demonstrates exactly the cynical sort of political dealing that Hoboken is committed to ban from its public life.
Unfortunately, Bhalla was also involved in an alleged conflict of interest issue in Hoboken only two months ago, when he voted on the City Council to award a legal contract with the City of Hoboken to Paul Condon, with whom he shares an office and a secretary. At that time POG requested clarification by the city’s Corporation Counsel of the grounds for his advice to Bhalla that there was no conflict. Mr. Kates submitted his rationale to the Council several weeks ago and said there was no conflict.
Hoboken People for Open Government (POG) expects more than a public apology from Mayor Zimmer and Councilman Bhalla; we expect action.
ALICE CROZIER
PRESIDENT, PEOPLE FOR OPEN GOVERNMENT
HOBOKEN
Wait didn’t Mike Lenz put himself on the city’s public health plan even though he was an unelected councilman serving at the pleasure of the mayor who gave him the nod to get her old seat — so he could take himself off his OTHER public plan through his low-show hack county job and pocket an extra $5,000 cash stipend instead?
Downtrodden Denizens of Hoboken where political corruption still festers like an open wound on the Hoboken taxpayer…. Please consider taking the Bonkers for Bhalla Challenge-
Any true Ravi Bhalla supporter that can defend the following:
1) Ravi Bhalla’s no show job law contract where he extracts personal profit from the office of Mayor under color of official right. Explain to how this is not unethical. I dare you.
2) Inviting Mike Russo instead of chair of Hoboken Democratic Committee and snubbing her. The Russo family has a long history of corruption and for those not familiar go to this link: http://www.RussoCorruption.com. I can assure you Straighjacket Out of Compensation smear blogger Sybil aka GA aka Nutso Nancy won’t. Defend Ravi and Russo sitting in a tree P-I-L-O-T-I-N-G. Why is a Ravi in bed with corruption?
Best argument gets free dinner and drinks on me. It has to be a good argument though. I don’t feed robots.
They attack people alive, elderly, disabled, looking for work and the deceased!
Now they will give sainthood to Russo while painting Jen and Tiffany as the Devil – literally paint them with mediocre photoshop skills
You reap what you sow. You continue to insult all of your Democratic colleagues on the Committee by calling them “robots.” The main point is, you serve all the people of Hoboken on the NHSA, a taxpayer funded public position. “Robots” pay your stipend, too. You disgrace both offices by your juvenile online antics, and have alienated every private person you insult.
If you don’t like the political discourse of a blogger, don’t read her opinions. As far as I can tell, she criticizes elected, public political figures, not the people who support them. You, on the other hand name-call everyone who supports Bhalla as a “robot” or ” nutso.” Maybe you ought to reconsider membership in the Democratic Party, as you speak like a sanctimonious fascist. That is not an insult, it is a reaction to the above comment. Grow up, Kurt.
Your mean spirited personal attack of the “nutso” blogger as a “harried hermit” is highly inappropriate. Your public allegations about a person’s private life put your own up to public scrutiny. She is not a “hermit”- has a family and an active life. You on the other hand are single, no kids. Is that why you are so angry?
You are Hoboken’s incarnation of Trump who Tweets insults against everyone who disgrees with him- you insult everyone who disagrees with you. Grow up, Kurt. You disgrace the public office you hold, paid for with “robot” and “hermit” tax money.
No it’s not a personal attack. I did not go into any personal stuff but I did mention that in the context of her job as a political operative she has shown signs of being unhinged or nuts in a political context.
Not long ago a deal with Russo would have received the sharpest rebuke from GA. In a political sense you have to be nuts to not see the insanity of defending Ravi-Russo so in a sense the moniker Nutso is quite appropriate in a political sense.
The attacks on Tiffanie via email last week via email are a coordinated robotic effort to oust her from DNC chair and hence that moniker too applies.
Of course it is a “personal attack.” You are a bully. You name-call supporters of politicians you do not like: “nutso” “hermit”, etc. You call fellow Democrats “robots” because they support a mayor you don’t like. GA blogs opinion and belief about her/our government. Nobody is forcing you to read it. Insults and name-calling cannot squelch free speech, try as you might. NEWSFLASH: Every citizen has the right to express their opinions and belief in America. Name-calling people and attacking them personally makes you look small. Not stature, but character. And you really should be ashamed of yourself because you are a public official. You are attacking people that you represent. You have no right to dictate what others should write on their personal blogs. Your sanctimony toward others is stunning. You have a blog. Instead of blowing hot air, post your PROOF of a “deal with Russo” on your own website and break some news. Stop bullying. You have disgraced your office.
For someone who dishes it out and piles the lies high day in and day out, Nancy sure can’t take it. She got behind the shady guy who is proving everyone was right he would be shady at City Hall and now in bed with Russo! What a crybaby! She gets called out and moans about bullying – just like lane and kimbo. She’s just like them but even worse!
You are a don’t. If you think attacking someone for beinh single is an intelligent strategy of behalf of Ravi you are an absolute idiot. Hoboken is home to many single people so alienating that constituency is no way to build on a paltry 32% plurality.
If you take that personally that is your problem. Answer the question is Ravi Bhalla’s contract perfectly ethical and proper. If you say yes without good reason then you are a robot who is bonkers for Bhalla.
Yeah I might admit to being guilty of some political name calling but Nutso Nancy is on full display with her vitriolic behavior. She broke the truce two weeks ago with another false narrative over my comments about Leprecon. There is no integrity left in her. Zero.
They can’t defend Ravi’s unethical contract so they lob personal attacks. Nancy is engaged in the politics of personal destruction on behalf of Ravi Bhalla who has paid her for services rendered.
The issues I raise are legitimate:
1) Ravi Bhalla’s law contract is unethical so if you disagree please explain.
2) Please try and defend Ravi and Russo being political allies.
C’mon Stan Grossbard – your wife said Ravi was the only one she trusted yet we have Ravenous Ravi with a law contract trading on the Hoboken Mayor’s office under color of official right in the name of the politics of personal enrichment. All served on a platter of a meager 32% plate of plurality.
Defend your wife’s legacy. Her historical record depends on it! Nancy has lost the ability and her other cucks can’t even offer an argument. You however a man of words with a propensity of online cross dressing in the form of Linda Lou. Hit me with your best argument. You kwow Nancy can’t deliver because you view her as your useful idiot but only so useful.
Any other Ravi supporter that does not speak out against this corrupt contract shall remain in robot status. Any time support is 100% for any politician the term robot is aptly descriptive.
Read your last line and ponder why it doesn’t work in your attempted limerick.
When you’re done pondering, if your head doesn’t hurt too much from all that thinking, ponder this:
When you call Dawn “dimwit Dawn,” call her husband “grossfart,”prattle on about the shadow, call Ravi corrupt and prattle on about Ravi Bots, you are not damaging anybody but yourself. Even people who are not supporters of the Mayor see you as unhinged.
It’s pretty obvious by now that you actually are the nasty, juvenile unintelligent person you have been presenting yourself. However, you might want to consider whether that is how you really want to continue to be perceived.
You fooled many people for a long time. Perhaps some day you’ll be able to fool them again, but not of you keep showing off the real Kurt for all to see.
The limericks on this thread are not mine. There are imitators who lack my skills at rhyme. I once wrote limericks but Ravi snowflakes and their sensitive ears could not handle them. Thus I switched to prose. Fake Striver in particular could not handle them. He could not handle Garcia either on the HHA.
As far as dimwit Dawn goes, she “trusted” Ravi and helped dupe Hoboken into supporting a corrupt contract seeking Mayor. The act of getting duped not only by Ravi but by NJ Transit with UDD shows major judgemental lapses. At least she was mostly honest even though she lied to me over NHSA. I will say Dawn would have never taken up such a contract ever. I will always give her that. She unlike a Ravi believed in good government.
Still no one defending Ravi’s corrupt deal on the contracts. The evidence of Ravi Russo will come to be public soon with a Church Square Pilot. Russo does not do something for nothing and the egg will be on your face soon and the taxpayer will suffer.
I have a very high opinion of women by the way. When they exude leadership intelligence and good judgment they get my respect. When they act like a 4 year old child like Nancy they do not get my respect. Unlike certain Ravi supporters whose misogyny have been on full display recently.
Once again, please stay on the topic of the article. Nobody cares about your back and forth petty nonsense. Since you both seem to operate blogs, please lob insults at each other on your blogs and leave the rest of us out of it.
You might want to consider that the reason no one will bother engage you in serious discussion is because it would be a waste of time given that (1) you don’t matter since you have squandered the credibility that once enabled you to help shape the opinions of others, and (2) you have neither the maturity nor the intellectual capacity to engage in thoughtful policy discussions with anybody who doesn’t view issues through your political lenz.
People laugh at you rather than engage with you because you have made yourself into a pathetic caracature, a nasty, childish buffoon interested only in hearing your own voice rather than listening and sometimes even learning from others.
You seem genuinely incapable of processing information that doesn’t fit your pre-formed, partially informed and often even delusional opinions. There’s a reason that a nut job like Roman sees you as a kindred spirit.
Self awareness is the first step toward positive change. An objective look in the mirror would do you some good. Give it a try. It’s never too late to grow up.
Look who thinks they’re some sort of moral arbiter! The guy who concocted the backroom fiasco to put Ravi into the mayor’s office. You owe the entire City of Hoboken an apology. But first, apologize to your wife. “Ravi Bhalla is the only one I trust.” Dawn Zimmer’s infamous words that will live in infamy! How’s that working out? The Shadow knows. The Shadow knows.
Hudson County View is an independent media outlet covering news and politics for Hudson County, NJ, and all of its municipalities. Owned and operated by John Heinis, an investigative reporter, Hudson County View focuses on covering elections, public policy, lawsuits, corruption and all other things related to government and politics in Hudson County. |
// Copyright 2018-present 650 Industries. All rights reserved.
#import <ABI38_0_0UMCore/ABI38_0_0UMDefines.h>
#import <ABI38_0_0UMCore/ABI38_0_0UMUtilities.h>
#import <ABI38_0_0UMCore/ABI38_0_0UMEventEmitterService.h>
#import <ABI38_0_0UMConstantsInterface/ABI38_0_0UMConstantsInterface.h>
#import <ABI38_0_0EXTaskManager/ABI38_0_0EXTaskManager.h>
#import <ABI38_0_0EXTaskManager/ABI38_0_0EXTaskService.h>
#import <ABI38_0_0UMTaskManagerInterface/ABI38_0_0UMTaskServiceInterface.h>
NSString * const ABI38_0_0EXTaskManagerEventName = @"TaskManager.executeTask";
@interface ABI38_0_0EXTaskManager ()
@property (nonatomic, strong) NSString *appId;
@property (nonatomic, strong) NSMutableArray<NSDictionary *> *eventsQueue;
@property (nonatomic, weak) id<ABI38_0_0UMEventEmitterService> eventEmitter;
@property (nonatomic, weak) id<ABI38_0_0UMConstantsInterface> constantsService;
@property (nonatomic, weak) id<ABI38_0_0UMTaskServiceInterface> taskService;
@end
@implementation ABI38_0_0EXTaskManager
ABI38_0_0UM_EXPORT_MODULE(ExpoTaskManager);
+ (const NSArray<Protocol *> *)exportedInterfaces
{
return @[@protocol(ABI38_0_0UMTaskManagerInterface)];
}
- (instancetype)init
{
return [self initWithExperienceId:@"mainApplication"];
}
// TODO: Remove when adding bare ABI38_0_0React Native support
- (instancetype)initWithExperienceId:(NSString *)experienceId
{
if (self = [super init]) {
_appId = experienceId;
_eventsQueue = [NSMutableArray new];
}
return self;
}
- (void)setModuleRegistry:(ABI38_0_0UMModuleRegistry *)moduleRegistry
{
_eventEmitter = [moduleRegistry getModuleImplementingProtocol:@protocol(ABI38_0_0UMEventEmitterService)];
_constantsService = [moduleRegistry getModuleImplementingProtocol:@protocol(ABI38_0_0UMConstantsInterface)];
_taskService = [moduleRegistry getSingletonModuleForName:@"TaskService"];
// Register task manager in task service.
[_taskService setTaskManager:self forAppId:_appId withUrl:[self _findAppUrl]];
}
- (NSDictionary *)constantsToExport
{
return @{
@"EVENT_NAME": ABI38_0_0EXTaskManagerEventName,
};
}
# pragma mark - ABI38_0_0UMEventEmitter
- (NSArray<NSString *> *)supportedEvents
{
return @[ABI38_0_0EXTaskManagerEventName];
}
/**
* When `startObserving` is called, it means the app is ready to execute new tasks.
* It also sends all events that were queued before this call.
*/
- (void)startObserving
{
if (_eventsQueue && _eventsQueue.count > 0) {
// Emit queued events
for (NSDictionary *eventBody in _eventsQueue) {
[_eventEmitter sendEventWithName:ABI38_0_0EXTaskManagerEventName body:eventBody];
}
}
_eventsQueue = nil;
}
- (void)stopObserving {}
# pragma mark - Exported methods
ABI38_0_0UM_EXPORT_METHOD_AS(notifyTaskFinishedAsync,
notifyTaskFinished:(nonnull NSString *)taskName
withResponse:(nonnull NSDictionary *)response
resolve:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
[_taskService notifyTaskWithName:taskName forAppId:_appId didFinishWithResponse:response];
resolve(nil);
}
ABI38_0_0UM_EXPORT_METHOD_AS(isTaskRegisteredAsync,
isTaskRegistered:(nonnull NSString *)taskName
resolve:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
resolve(@([self hasRegisteredTaskWithName:taskName]));
}
ABI38_0_0UM_EXPORT_METHOD_AS(getRegisteredTasksAsync,
getRegisteredTasks:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
resolve([_taskService getRegisteredTasksForAppId:_appId]);
}
ABI38_0_0UM_EXPORT_METHOD_AS(getTaskOptionsAsync,
getConfigurationForTaskName:(nonnull NSString *)taskName
resolve:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
resolve(ABI38_0_0UMNullIfNil([_taskService getOptionsForTaskName:taskName forAppId:_appId]));
}
ABI38_0_0UM_EXPORT_METHOD_AS(unregisterTaskAsync,
unregisterTaskWithName:(nonnull NSString *)taskName
resolve:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
@try {
[self unregisterTaskWithName:taskName consumerClass:nil];
} @catch (NSException *e) {
return reject(e.name, e.reason, nil);
}
resolve(nil);
}
ABI38_0_0UM_EXPORT_METHOD_AS(unregisterAllTasksAsync,
unregisterAllTasks:(ABI38_0_0UMPromiseResolveBlock)resolve
reject:(ABI38_0_0UMPromiseRejectBlock)reject)
{
[_taskService unregisterAllTasksForAppId:_appId];
resolve(nil);
}
# pragma mark - ABI38_0_0UMTaskManagerInterface
- (BOOL)hasRegisteredTaskWithName:(nonnull NSString *)taskName
{
return [_taskService hasRegisteredTaskWithName:taskName forAppId:_appId];
}
- (BOOL)taskWithName:(nonnull NSString *)taskName hasConsumerOfClass:(Class)consumerClass
{
return [_taskService taskWithName:taskName forAppId:_appId hasConsumerOfClass:consumerClass];
}
- (void)registerTaskWithName:(nonnull NSString *)taskName
consumer:(Class)consumerClass
options:(nonnull NSDictionary *)options
{
NSString *appUrl = [self _findAppUrl];
[_taskService registerTaskWithName:taskName
appId:_appId
appUrl:appUrl
consumerClass:consumerClass
options:options];
}
- (void)unregisterTaskWithName:(nonnull NSString *)taskName
consumerClass:(Class)consumerClass
{
[_taskService unregisterTaskWithName:taskName forAppId:_appId consumerClass:consumerClass];
}
- (BOOL)hasBackgroundModeEnabled:(nonnull NSString *)backgroundMode
{
return [ABI38_0_0EXTaskService hasBackgroundModeEnabled:backgroundMode];
}
- (void)executeWithBody:(NSDictionary *)body
{
if (!_eventsQueue) {
// Module's event emitter is already being observed, so we can send events.
[_eventEmitter sendEventWithName:ABI38_0_0EXTaskManagerEventName body:body];
} else {
// Otherwise add event body to the queue (it will be send in `startObserving`).
[_eventsQueue addObject:body];
}
}
- (BOOL)isRunningInHeadlessMode
{
return [[_constantsService constants][@"isHeadless"] boolValue];
}
# pragma mark - internals
- (NSString *)_findAppUrl
{
// TODO(@tsapeta): find app url for vanilla ABI38_0_0RN apps
return [_constantsService constants][@"experienceUrl"];
}
@end
|
Monoclonal antibodies: harnessing the potential.
Antibody molecules help fulfil the mandate of the mammalian immune system to discriminate between the body's own proteins and the foreign antigens of infectious agents. The exquisite specificity they exhibit for their target molecules has lent itself to exploitation both in the laboratory and clinical medicine. Nevertheless, the early reliance on polyclonal antisera as a source of antibodies, has highlighted problems of homogeneity and reproducibility between immunizations. The advent of monoclonal antibodies displaying a single predefined specificity has, therefore, revolutionised many areas of the biomedical sciences. Eighteen years after their first description, it is, however, pertinent to ask whether monoclonal antibodies have yet fulfilled their true potential. |
Marian Galik
It was 3 years ago. I was fresh Computer Science graduate, just hired to do his first full-time job. At that time I had some previous experience with full stack web development, but all the projects I worked on were small or medium size websites / applications. They all used JavaScript sparingly on few screens to add some interactivity. For those use cases, it was perfectly okay for me to use just jQuery.
A naive approach with jQuery
At first, I used the same approach as always in my new job. I’ve started writing a Flask application in Python that rendered some HTML. I’ve added some jQuery magic to do stuff like forms with a dynamic number of items that could be added without reloading the whole page and it worked. At first. This time it was a little bit different. The previous projects were usually finished before the point when the pure jQuery code started to be hard to maintain. On the contrary, this project was getting bigger and bigger every day.
Our analytics app contained multiple different screens for different analyses. Those screens contained forms that were getting more and more complex. We added advanced filtering and suddenly the forms contained a dynamic number of items that contained another dynamic number of items that displayed different subforms when switching some select boxes. The jQuery code just bloated and it was hard to maintain and understand.
Moreover, since different types of analyses used same parts of the forms, I felt like the proper way to handle this would be to encapsulate those parts to components that I could reuse and compose together. Doing this in pure jQuery was pain in the ass. I had to deal with maintaining the data model, modifying the DOM when that data model changed, modifying the model when the DOM changed, handling error messages and hiding them when user focused the correct input or removed it by removing one of its parents. This caused lot of boilerplate code and slowed down the development process.
Moving towards AngularJS
I started looking for a framework that will help me solve this problem. The problem was that there were too many of them and it was hard to do an informed decision. It was too time-consuming to evaluate every single one of them.
One of my colleagues suggested AngularJS since he had a previous experience with it. I have already watched some YouTube videos from its creator and I was sure that using it will enable me to remove a lot of the boilerplate code since AngularJS does the data binding between the model and DOM auto-magically. On the other side, I didn’t like some of the concepts like embedding the logic directly into the HTML, it just felt wrong to me.
However, I gave it a try and I started rewriting one of the analyses edit screens into it. The application was not a single page app at this point. All the screens were rendered by the Flask backend. The majority of them contained the ugly jQuery code, except for one which used AngularJS. The code became much easier to understand and it was much shorter. I used directives to turn the parts of the complex forms into smaller components. HTML templates were now easier to understand since I just saw right in the markup that the funnel-editor directive consisted of a funnel-steps component and customer-filter component and how the data was mapped to each of them.
Over the time I started to hate the legacy jQuery code and wanted to get rid of it. I rewrote all the analyses to Angular one by one and finally merged them to something that resembled a single page app. It wasn’t a true single page app since the logout section was still rendered separately by the backend. Stuff like a registration form, login screen or forgotten password were just too simple and easy to maintain that way. There was almost no JavaScript needed for those features and merging them will cause me more trouble than good at that time. Currently, we are working on moving those screens to Angular too since we want to separate our frontend from the backend, but that is a different story.
Lessons learned the hard way
So is AngularJS cure for everything? Absolutely not. After spending 3 years with it there are a lot of things I hate about it. Out of the box, it is good and easy to use on one part of an app. It is easy to use in simple single page apps, but as soon as you want to have more complex views (logged out section that looks completely differently, logged in section that uses same navigation on majority of the pages, but not on all of them) you will have to use a custom router since the default one doesn’t support inheritance of views commonly used in templating languages. This is the stuff that you as an AngularJS newbie don’t know and if you realize that after you have already written a lot of code, then I wish you a happy rewriting.
There is no built-in support for authentication and access rights in the default router, you have to build your own.
For me, the biggest drawback is the performance. For an AngularJS newbie, it is very tempting to use the two-way binding since it makes a lot of stuff easy to write. The problem is, that every time you add one two-way bound variable, you have one more expression that AngularJS have to watch and compare for changes. AngularJS do such comparisons quite often, more often that you think and the two-way bindings can be easily created dynamically for example by using several nested ng-repeats (the stuff that usually happens as soon as you write your first table with a dynamic number of columns and rows).
So yes, the Angular’s magic is cool, it can save you a lot of time, but as soon as you don’t care about it, one day you will start wondering why your application freezes for several seconds every time you have a 20 x 1000 table on your screen and you change something in a form above it that doesn’t update the table in any way.
Conclusion
Would I choose AngularJS if I was making the decision again right now? Yes, but it would definitely be AngularJS 2.0 and I would be more careful with the decisions I will be making to save me some time in future. With AngularJS the code is much easier to understand and maintain and there is no way I could write such a big application as Exponea is with just jQuery and remain a sane person at the same time.
Continue to part II: Joining Exponea frontend team & improving productivity |
White light emitting LEDs (“white LEDs”) are known and are a relatively recent innovation. It was not until LEDs emitting in the blue/ultraviolet part of the electromagnetic spectrum were developed that it became practical to develop white light sources based on LEDs. As taught, for example, in U.S. Pat. No. 5,998,925, white LEDs include one or more phosphor materials, that is photo-luminescent materials, which absorb a portion of the radiation emitted by the LED and re-emit light of a different color (wavelength). Typically, the LED chip or die generates blue light and the phosphor(s) absorbs a percentage of the blue light and re-emits yellow light or a combination of green and red light, green and yellow light, green and orange or yellow and red light. The portion of the blue light generated by the LED that is not absorbed by the phosphor material combined with the light emitted by the phosphor provides light which appears to the eye as being nearly white in color.
The phosphor typically resides within a wavelength conversion layer, in which phosphor material formed is mixed with a light transmissive carrier material, typically a plastics material. The wavelength conversion layer is operable to absorb a proportion of the blue light generated by the LEDs and convert it to light of a different wavelength by a process of photoluminescence. The combination of the different wavelength light produced by the phosphor-based wavelength conversion layer (e.g., yellow light) combined with the residue blue light that passes through the wavelength conversion layer forms light that appears white to the human eye.
A problem with existing wavelength conversion components is the degradation of the wavelength conversion layer when exposed to external environmental conditions. As noted above, the wavelength conversion layer is typically composed of a mixture of a phosphor material and a plastics carrier material. When the plastic-based wavelength conversion layer is exposed to moisture (e.g., mixture of air and water), oxygen, or other environmental contaminants, light energy being absorbed by the wavelength conversion layer may cause the contaminants to initiate chemical reactions with the phosphor material leading to accelerated degradation of the wavelength conversion layer.
The effect of water absorption on photoluminescence varies between phosphor compositions and can be more pronounced for silicate-based phosphor materials which are able to more readily form water soluble compounds. The absorption of water can occur even when the phosphor material is encapsulated in a polymer binder (e.g., carrier material/binding material), such as silicone, and a reduction in light emission of ˜10% may occur for a device with an ortho-silicate phosphor that is operated in a humid environment (i.e. ≧80% relative humidity) at a temperature of 25° C. for more than 200 hours.
Moreover, an exposed wavelength conversion layer may be prone to handling damage, such as surface scratches, which also degrade the performance and lifetime of the wavelength conversion layer over time.
Therefore, there is a need for an improved approach to implement photo-luminescent materials for a lighting apparatus which addresses these and other problems with the prior implementations. |
# RUN: llc -run-pass=arm-cp-islands -o - %s | FileCheck %s
# Test created by tweaking the register allocation after stopping the IR below
# just before constant islands. We were forwarding the table index to the end of
# the block, even though the LEA clobbered it.
# CHECK-LABEL: name: foo
# CHECK: tBR_JT
# This order is important. If the jump-table comes first then the
# transformation is valid because the LEA can be removed, see second test.
# CHECK: CONSTPOOL_ENTRY
# CHECK: JUMPTABLE_ADDRS
# CHECK-LABEL: name: bar
# CHECK: tTBB_JT $pc, killed $r1
--- |
; ModuleID = 'simple.ll'
source_filename = "simple.ll"
target datalayout = "e-m:e-p:32:32-i64:64-v128:64:128-a:0:32-n32-S64"
target triple = "thumbv6m-none--eabi"
define void @foo(i8 %in, i32* %addr) {
store i32 12345678, i32* %addr
%1 = call i32 @llvm.arm.space(i32 980, i32 undef)
%2 = zext i8 %in to i32
switch i32 %2, label %default [
i32 0, label %d1
i32 1, label %d2
i32 3, label %d3
i32 4, label %d4
i32 5, label %d5
i32 6, label %d6
i32 7, label %d7
i32 2, label %d8
i32 8, label %d9
i32 9, label %d10
i32 19, label %d11
i32 20, label %d12
i32 21, label %d13
i32 22, label %d14
i32 24, label %d15
i32 25, label %d16
i32 26, label %d17
]
default: ; preds = %0
unreachable
d1: ; preds = %0
unreachable
d2: ; preds = %0
unreachable
d3: ; preds = %0
unreachable
d4: ; preds = %0
unreachable
d5: ; preds = %0
unreachable
d6: ; preds = %0
unreachable
d7: ; preds = %0
unreachable
d8: ; preds = %0
unreachable
d9: ; preds = %0
unreachable
d10: ; preds = %0
unreachable
d11: ; preds = %0
unreachable
d12: ; preds = %0
unreachable
d13: ; preds = %0
unreachable
d14: ; preds = %0
unreachable
d15: ; preds = %0
unreachable
d16: ; preds = %0
unreachable
d17: ; preds = %0
unreachable
}
define void @bar(i8 %in, i32* %addr) {
store i32 12345678, i32* %addr
%1 = zext i8 %in to i32
switch i32 %1, label %default [
i32 0, label %d1
i32 1, label %d2
i32 3, label %d3
i32 4, label %d4
i32 5, label %d5
i32 6, label %d6
i32 7, label %d7
i32 2, label %d8
i32 8, label %d9
i32 9, label %d10
i32 19, label %d11
i32 20, label %d12
i32 21, label %d13
i32 22, label %d14
i32 24, label %d15
i32 25, label %d16
i32 26, label %d17
]
default: ; preds = %0
unreachable
d1: ; preds = %0
unreachable
d2: ; preds = %0
unreachable
d3: ; preds = %0
unreachable
d4: ; preds = %0
unreachable
d5: ; preds = %0
unreachable
d6: ; preds = %0
unreachable
d7: ; preds = %0
unreachable
d8: ; preds = %0
unreachable
d9: ; preds = %0
unreachable
d10: ; preds = %0
unreachable
d11: ; preds = %0
unreachable
d12: ; preds = %0
unreachable
d13: ; preds = %0
unreachable
d14: ; preds = %0
unreachable
d15: ; preds = %0
unreachable
d16: ; preds = %0
unreachable
d17: ; preds = %0
unreachable
}
; Function Attrs: nounwind
declare i32 @llvm.arm.space(i32, i32) #0
; Function Attrs: nounwind
declare void @llvm.stackprotector(i8*, i8**) #0
attributes #0 = { nounwind }
...
---
name: foo
alignment: 1
exposesReturnsTwice: false
legalized: false
regBankSelected: false
selected: false
tracksRegLiveness: true
liveins:
- { reg: '$r0' }
- { reg: '$r1' }
frameInfo:
isFrameAddressTaken: false
isReturnAddressTaken: false
hasStackMap: false
hasPatchPoint: false
stackSize: 0
offsetAdjustment: 0
maxAlignment: 0
adjustsStack: false
hasCalls: false
maxCallFrameSize: 0
hasOpaqueSPAdjustment: false
hasVAStart: false
hasMustTailInVarArgFunc: false
constants:
- id: 0
value: i32 12345678
alignment: 4
jumpTable:
kind: inline
entries:
- id: 0
blocks: [ '%bb.3.d2', '%bb.9.d8', '%bb.4.d3', '%bb.5.d4',
'%bb.6.d5', '%bb.7.d6', '%bb.8.d7', '%bb.10.d9',
'%bb.11.d10', '%bb.2.d1', '%bb.2.d1', '%bb.2.d1',
'%bb.2.d1', '%bb.2.d1', '%bb.2.d1', '%bb.2.d1',
'%bb.2.d1', '%bb.2.d1', '%bb.12.d11', '%bb.13.d12',
'%bb.14.d13', '%bb.15.d14', '%bb.2.d1', '%bb.16.d15',
'%bb.17.d16', '%bb.18.d17' ]
body: |
bb.0 (%ir-block.0):
successors: %bb.2.d1(0x03c3c3c4), %bb.1(0x7c3c3c3c)
liveins: $r0, $r1
$r2 = tLDRpci %const.0, 14, $noreg
tSTRi killed $r2, killed $r1, 0, 14, $noreg :: (store 4 into %ir.addr)
dead $r1 = SPACE 980, undef $r0
$r0 = tUXTB killed $r0, 14, $noreg
$r1, dead $cpsr = tSUBi3 killed $r0, 1, 14, $noreg
tCMPi8 $r1, 25, 14, $noreg, implicit-def $cpsr
tBcc %bb.2.d1, 8, killed $cpsr
bb.1 (%ir-block.0):
successors: %bb.3.d2(0x07c549d2), %bb.9.d8(0x07c549d2), %bb.4.d3(0x07c549d2), %bb.5.d4(0x07c549d2), %bb.6.d5(0x07c549d2), %bb.7.d6(0x07c549d2), %bb.8.d7(0x07c549d2), %bb.10.d9(0x07c549d2), %bb.11.d10(0x07c549d2), %bb.2.d1(0x03ab62db), %bb.12.d11(0x07c549d2), %bb.13.d12(0x07c549d2), %bb.14.d13(0x07c549d2), %bb.15.d14(0x07c549d2), %bb.16.d15(0x07c549d2), %bb.17.d16(0x07c549d2), %bb.18.d17(0x07c549d2)
liveins: $r1
$r0, dead $cpsr = tLSLri killed $r1, 2, 14, $noreg
$r1 = tLEApcrelJT %jump-table.0, 14, $noreg
$r0 = tLDRr killed $r1, killed $r0, 14, $noreg :: (load 4 from jump-table)
tBR_JTr killed $r0, %jump-table.0
bb.3.d2:
bb.9.d8:
bb.4.d3:
bb.5.d4:
bb.6.d5:
bb.7.d6:
bb.8.d7:
bb.10.d9:
bb.11.d10:
bb.2.d1:
bb.12.d11:
bb.13.d12:
bb.14.d13:
bb.15.d14:
bb.16.d15:
bb.17.d16:
bb.18.d17:
...
---
name: bar
alignment: 1
exposesReturnsTwice: false
legalized: false
regBankSelected: false
selected: false
tracksRegLiveness: true
liveins:
- { reg: '$r0' }
- { reg: '$r1' }
frameInfo:
isFrameAddressTaken: false
isReturnAddressTaken: false
hasStackMap: false
hasPatchPoint: false
stackSize: 0
offsetAdjustment: 0
maxAlignment: 0
adjustsStack: false
hasCalls: false
maxCallFrameSize: 0
hasOpaqueSPAdjustment: false
hasVAStart: false
hasMustTailInVarArgFunc: false
constants:
- id: 0
value: i32 12345678
alignment: 4
jumpTable:
kind: inline
entries:
- id: 0
blocks: [ '%bb.3.d2', '%bb.9.d8', '%bb.4.d3', '%bb.5.d4',
'%bb.6.d5', '%bb.7.d6', '%bb.8.d7', '%bb.10.d9',
'%bb.11.d10', '%bb.2.d1', '%bb.2.d1', '%bb.2.d1',
'%bb.2.d1', '%bb.2.d1', '%bb.2.d1', '%bb.2.d1',
'%bb.2.d1', '%bb.2.d1', '%bb.12.d11', '%bb.13.d12',
'%bb.14.d13', '%bb.15.d14', '%bb.2.d1', '%bb.16.d15',
'%bb.17.d16', '%bb.18.d17' ]
body: |
bb.0 (%ir-block.0):
successors: %bb.2.d1(0x03c3c3c4), %bb.1(0x7c3c3c3c)
liveins: $r0, $r1
$r2 = tLDRpci %const.0, 14, $noreg
tSTRi killed $r2, killed $r1, 0, 14, $noreg :: (store 4 into %ir.addr)
$r0 = tUXTB killed $r0, 14, $noreg
$r1, dead $cpsr = tSUBi3 killed $r0, 1, 14, $noreg
tCMPi8 $r1, 25, 14, $noreg, implicit-def $cpsr
tBcc %bb.2.d1, 8, killed $cpsr
bb.1 (%ir-block.0):
successors: %bb.3.d2(0x07c549d2), %bb.9.d8(0x07c549d2), %bb.4.d3(0x07c549d2), %bb.5.d4(0x07c549d2), %bb.6.d5(0x07c549d2), %bb.7.d6(0x07c549d2), %bb.8.d7(0x07c549d2), %bb.10.d9(0x07c549d2), %bb.11.d10(0x07c549d2), %bb.2.d1(0x03ab62db), %bb.12.d11(0x07c549d2), %bb.13.d12(0x07c549d2), %bb.14.d13(0x07c549d2), %bb.15.d14(0x07c549d2), %bb.16.d15(0x07c549d2), %bb.17.d16(0x07c549d2), %bb.18.d17(0x07c549d2)
liveins: $r1
$r0, dead $cpsr = tLSLri killed $r1, 2, 14, $noreg
$r1 = tLEApcrelJT %jump-table.0, 14, $noreg
$r0 = tLDRr killed $r1, killed $r0, 14, $noreg :: (load 4 from jump-table)
tBR_JTr killed $r0, %jump-table.0
bb.3.d2:
bb.9.d8:
bb.4.d3:
bb.5.d4:
bb.6.d5:
bb.7.d6:
bb.8.d7:
bb.10.d9:
bb.11.d10:
bb.2.d1:
bb.12.d11:
bb.13.d12:
bb.14.d13:
bb.15.d14:
bb.16.d15:
bb.17.d16:
bb.18.d17:
...
|
After successfully delivering Columbus, Atlantis is back on Earth
ESA PR 10-2008. NASA’s space shuttle Atlantis, which successfully delivered ESA’s Columbus laboratory to the International Space Station, has safely returned to Earth with its crew of seven. Landing was at 14:07 UTC (15:07 CET) on 20 February at Kennedy Space Center, Florida.
On this STS-122 mission, the shuttle spent nearly 13 days in space, including 9 days docked to the Station to conduct a major ISS assembly task: delivery of Europe’s first permanent human outpost in orbit. The 7-m long 12.8-tonne Columbus module, a state-of-the-art multidisciplinary laboratory, was attached to the Harmony (Node 2) module on 11 February.
Once leak checks and initial electrical, fluid and data connections were completed, the module’s hatch was opened on 12 February, marking Europe’s new status as a full partner and co-owner of the ISS. Outfitting work inside Columbus began only a few hours later, as the laboratory entered its commissioning phase, which was commanded and controlled by the Columbus Control Centre (Col-CC) located in Oberpfaffenhoffen near Munich, Germany.
Columbus is attached to the starboard side of Harmony
Two ESA astronauts, Hans Schlegel of Germany and Léopold Eyharts of France, were ferried to the Station by Atlantis and both contributed directly to this success. As a member of the STS-122 crew, Hans Schlegel performed one of the three spacewalks during the mission with fellow astronaut Rex Walheim of NASA. He also coordinated the other two spacewalks, supporting the Columbus module’s transfer from the shuttle payload bay to the ISS, plus the transfer of two payload suites, SOLAR and EuTEF, to external platforms on the Columbus module. Hans Schlegel returned to Earth with Atlantis.
After formal crew responsibility hand-over tasks following the docking of Atlantis with the Station, Léopold Eyharts became part of the resident ISS crew (Expedition 16), trading places with NASA astronaut Dan Tani. He provided support for Columbus docking from inside the Harmony module, activating the motorised bolts to secure the junction, and assisted the third spacewalk by operating the station’s robotic arm.
Unlike Schlegel, Eyharts remained on the ISS when Atlantis undocked two days ago. He will spend the next month in space to complete the Columbus module’s commissioning and to perform a series of experiments, both in the laboratory and in the other science facilities already operating in the Station. Léopold Eyharts is scheduled to return to earth with the next shuttle ISS mission (Endeavour/STS-123), at the end of March.
ESA builds up its contribution to the ISS
ESA astronaut Hans Schlegel during his first spacewalk
With the addition of Columbus, the pressurised volume of the Space Station was increased by a mere 15%, but its science capacity was nearly doubled. Two modules of the Japanese laboratory will be added in March and May, and a Russian Multi-Purpose Laboratory Module (MLM) will follow in 2011.
A new era is also beginning for ESA’s activities onboard. As a fully-fledged partner of the ISS programme, ESA will now not only enjoy the benefits of Columbus but will also have to contribute to ISS operations. This will be achieved through the launch of unmanned servicing missions carried out by the Automated Transfer Vehicle, designed to deliver speares, scientific experiments, crew support equipment (food, clothing), fluids and propellant and to perform reboost to compensate for orbital decay of the ISS. The first ATV, Jules Verne, will be launched by an Ariane 5 on 8 March.
ESA astronaut Léopold Eyharts on board the International Space Station
But ESA will also benefit from the Station by conducting experiments within its many science facilities, and by regularly sending European astronauts to perform long-duration stays onboard as members of the resident crew. Two ESA astronauts are already training for such missions: Frank de Winne of Belgium who will fly as a member of the ISS Expedition 19 crew in 2009; and André Kuipers of the Netherlands who will be his backup. More will follow.
Further European-built ISS elements are still under preparation to be launched to the ISS within the decade, such as the Material Science Laboratory (MSL), the Muscle Atrophy Resistive Exercise System (MARES), the European Robotic Arm (ERA), the Node 3 module and the Cupola observation deck.
As Columbus is coming to life, so too is the network of nine User Support and Operations Centres (USOCs), which has been set up all over Europe to facilitate the interface between researchers and the science payloads onboard, and to allow investigators to control their experiments and receive real-time data on their results, through an interconnection provided via the Columbus Control Centre.
Columbus Control Centre
Commissioning of the European laboratory has proceeded well and faster than planned. The two external payloads SOLAR and EuTEF have been deployed outside Columbus and already provide data. WAICO, the first experiment to be conducted inside the lab, will start this week inside Biolab. The Geoflow experiment will start up in early March inside the Fluid Science Laboratory.
Over the coming weeks and months, the USOC network’s activity will increase dramatically as the science equipment and experiments already onboard Columbus are commissioned and switched to operational status, and as more science payloads are delivered to the module by the upcoming logistics missions.
Columbus was designed to support some 500 experiments per year for ten years, in cell and plant biology, astrobiology, human physiology, fluid and material sciences, fundamental physics, astronomy, remote sensing and technology. For the European science community and industrial R&D, a new era of research has just begun. |
Adipose Triglyceride Lipase, Not Hormone-Sensitive Lipase, Is the Primary Lipolytic Enzyme in Fasting Elephant Seals (Mirounga angustirostris).
Little is known about the mechanisms that allow capital breeders to rapidly mobilize large amounts of body reserves. Northern elephant seals (Mirounga angustirostris) utilize fat reserves for maternal metabolism and to create high fat milk for the pup. Hormone-sensitive lipase (HSL) has been hypothesized to be an important lipolytic enzyme in fasting seals, but the activity of HSL and adipose triglyceride lipase (ATGL) has not been quantified in fasting adult seals, nor has their relationship to milk lipid content been assessed. Blubber and milk samples were obtained from 18 early lactation and 19 late lactation females, as well as blubber from five early and five late molting female seals. Blubber lipolytic activity was assessed with radiometric assays. HSL activity was negligible in seal blubber at all fasting stages. Total triglyceride lipase activity was stable among early and late lactation and early molt but increased in late molting seals. Relative abundance of ATGL protein increased across fasting, but neither activity nor relative protein levels were related to circulating nonesterified fatty acids or milk lipid content, suggesting the possibility of other regulatory pathways between lipolytic activity and milk lipid content. These results demonstrate that HSL is not the primary lipolytic enzyme in fasting adult female seals and that ATGL contributes more to lipolysis than HSL. |
Nailcote Hall
Nailcote Hall is a four-star 17th century country house hotel located in Berkswell, Warwickshire, United Kingdom. The hotel features 49 rooms alongside a Par 3 Champion golf course, restaurant, and leisure and conference facilities. The venue also hosts weddings and entertainment events.
History
Built in 1640, Nailcote Hall was completed just before the start of the English Civil War. Its name is believed to be derived from the Norman-French word for armourer. The house was damaged during the war by Cromwell’s troops before the assault on Kenilworth Castle, but subsequently restored after a repair bill was honoured by the Parliamentarians. The Lant family made Nailcote Hall their home for some 300 years, and during this time the property saw many alterations, including a Georgian wing which was added in 1780. When restoration work was carried out more recently, a priest hole was discovered in what is now the Oak Room restaurant.
Nailcote Hall first opened to the public in 1984, and a new extension, completed in 1989, added on additional bedrooms, a function room and a library. The present owner acquired Nailcote Hall in 1991 and subsequently built the leisure complex which forms part of the hotel today.
Features
Golf course
Nailcote Hall’s 9-hole Cromwell golf course is open members, hotel guests and visitors. It hosts both the Open Par 3 Championship and the British Par 3 Championship.
Leisure and event facilities
The Leisure and Country Club has an indoor 14-metre Roman bath-style swimming pool, steam room, jacuzzi and gymnasium, and an outdoor running track. The grounds also include a croquet lawn and petanque area, and residents have access to tennis facilities at the nearby Berkswell Tennis Club.
The venue can hold over 250 guests in the marquee, and weddings are held at the Country House Hotel throughout the year. The venue runs a yearly "Bride of The Year" competition, where the winner receives a free Wedding Reception up to the value of £5,000.
Nailcote Hall hosts conferencing events, sporting dinners, charity events and balls in Rick's Bar and the Marquee. There is also a restaurant on site (The Oak Room) for guests and external visitors.
References
External links
Nailcote Hall Hotel
Open Par 3 Championship Official Site
Category:Country houses in Warwickshire
Category:Grade II* listed buildings in Warwickshire
Category:Golf clubs and courses in Warwickshire
Category:Sports venues in Warwickshire
Category:Hotels in Warwickshire |
Plokamos is a semantic annotation tool developed by the Perseids project to support scholars and students of literary disciplines in their work with text. Plokamos, which is Greek for "something woven," provides users with the ability to assign meaning to segments of text, to share their assertions with colleagues and classmates and to visualize the result of their work in aggregate. It is a browser-side Javascript application backed by an RDF-based triple store. Our design takes into the account the need to present users with simple paradigms for annotating complex concepts, such as social networks and linguistic characterizations referencing primary source texts, while retaining the ability to retain the semantic integrity of the annotations. The Plokamos interface is intended for reuse in other workflows and by other teams. It can be embedded into an existing application and can be extended to support other ontologies and rdf-based annotation bodies. At all times, the data itself remains separate from the tool and available for export and reuse. The configuration is externalized from the code, and managed, along with the data, as RDF graphs. Perseids currently has deployed Plokamos as a plugin to the Nemo Citable Text Services browsing interface, using the Apache Marmotta triple store as a back-end data store, and the Perseids user model. Annotations adhere to the Open Annotation data model and reference the SNAP ontology. In the coming months we will be connecting Plokamos to our implementation of the multidisciplinary Research Data Collections API, which will enable us to manage the annotations as sharable, persistently identified collections of data. Frederik Baumgardt, Architect and primary developer of Plokamos, contributed substantially to this research. |
Transit Police
———————————————————————————————————————————
Transit Police spend $29 million a year – funded mainly by TransLink fares, gas taxes and property tax – and the force’s budget is slated to rise to $35 million by 2014 and $42 million by 2021.They are the highest paid police force in Canada.
——————————————————————————————————————————–
Translink Police Harass, Assault & Illegally Arrest A Man For Handing Out Fire This Time Magazines, & Make Up False Charges Against Him About Him Causing A Disturbance When He Keeps Asking To Be Told What Law He Has Broken As He Is Dragged Out Of The Station & Arrested.
————————————————————————
In late 2007, all TransLink buses became designated “fare paid zones”. Under this system, a rider is required to retain a proof of payment (transfer) while on board the bus and produce it upon request by a transit official.[3] On designated routes, larger three-door buses allow passengers to board through rear doors. As they are bypassing the driver and fare box, they must have a previously paid fare in their possession. On all other buses, passengers are required to board through the front doors and should show a valid fare to the bus driver. Fare inspections on buses are normally conducted by Transit Security Officers and by the South Coast British Columbia Transportation Authority Police Service. Failure to produce proof of payment may result in ejection from the bus and/or a fine of $173. Woops…..they forget to include intimidation and potential brutalization.
TransLink replaced its Special Provincial Constables, who held limited policing power, with the Greater Vancouver Transportation Authority Police Service (now the South Coast British Columbia Transportation Authority Police Service, or SCBCTAPS), in December 2005. The move was not without controversy, as some riders objected to armed officers patrolling the system. A court case in which a woman was awarded $52,000 for allegedly being beaten by a flashlight-wielding officer, in an incident that occurred before the transition, confirmed such fears for some.[6] In contrast to the former TransLink special constables, SCBCTAPS constables have full police powers both on and off of TransLink property. They are based in New Westminster, BC. They are the only transit security force, in all of canada, to be armed with 9mm pistols, tasers, batons, and mace. There are 169 officers prowling throughout the transit system.
Coast Mountain Bus Company operates the security department, commonly known as the Transit Security Department. Transit Security Officers are mobile, ride buses and trains, inspect fares, and patrol TransLink properties. They work closely with SCBCTAPS to ensure safety throughout the transit network. Transit Security Officers are authorized to arrest persons committing criminal offences on or in relation to any TransLink property, as per the Criminal Code of Canada. Transit Security Officers are also authorized to enforce Transit Conduct and Safety Regulations pursuant to the South Coast British Columbia Transportation Authority Act and to enforce the Transit Tariff. The Transit Security Department is also responsible for the CCTV camera system on board buses.
On November 14, 2006, the Canadian government announced that it would spend $37 million for improvements to transit security across Canada, including $9.8 million for the Vancouver area, although no details have been released as to how this money will be spent.[7] CCTV cameras & audio recording devices have been installed on some TransLink buses.[8]
On March 8, 2007, BC Minister of Transportation Kevin Falcon announced a restructuring of TransLink. Major changes include new revenue-generating measures, a restructuring of the executive body, and increases in the areas under TransLink’s jurisdiction.[11][12]
Falcon had previously called the old board “dysfunctional”,[12] saying that board members were focused on the interests of their own municipalities instead of the broader interests of the region.[14] According to Falcon, the board of directors had “no ability there to develop the skill-set to understand major, multi-billion projects.”[14]
British Columbia NDP critic David Chudnovsky responded that the reorganization was “ludicrous” and that its purpose was “to get power away from our elected municipal politicians because once in a while they disagree with the aggressive privatization agenda of Mr. Falcon”.[12]
——————————————————————————————————————–
Neil Dubord has been appointed the new chief officer of the 167-member TransLink Police that patrols the Metro Vancouver’s transit system.
Dubord, 49, who served as deputy chief of Edmonton’s Community Policing Bureau, has “distinguished himself in front-line policing, tactical and strategic development, critical incident command and as a manager, with numerous local and national awards and citations,” according to a TransLink press release.
“Our Transit Police is the first and only police service of its kind in Canada, and its unique challenges and opportunities clearly caught the attention of a number of very qualified candidates across the country,” Transit police board chairman Mark Reder said. “The Transit Police Board was looking for a person with on-the-ground policing experience who knows the value of being close to the community.”
TransLink’s chief operating officer Doug Kelsey said Dubord’s commitment to building his policing and management acumen has resulted in an impressive list of credentials. He has been with the Edmonton Police for 25 years. “I am delighted to see such a high calibre individual join the team at TransLink and Transit Police.”
Dubord was sworn in on February 1, 2012.
In September 2010, Ward Clapham was dismissed as TransLink police chief for “philosophical differences”…….
———————————————————————————————————————————–
^News-Police patrolling Greater Vancouver’s TransLink system will continue to Taser “non-compliant” passengers and fare dodgers a news conference heard Friday, providing more evidence to indicate that the notorious stun gun has become a tool of official oppression and torture.2008 |
I’m delighted to let you know that today we have reached an important milestone in our efforts to rebalance the Guardian’s business model to offset the dramatic decline in advertising: the Guardian now has the financial support of more than 200,000 members. In addition, we have 185,000 subscribers and people are buying the paper on newsstands more regularly than we expected. After responding to lots of feedback from readers suggesting they would be happy to give money to support the Guardian’s journalism, we have also now received more than 160,000 one-off contributions from around the world.
We greatly appreciate the role you all play in the Guardian. Thank you. Whether by joining as a member, taking out a print or digital subscription, buying the paper or giving a one-off contribution, you are providing crucial financial support for our independent journalism, and showing how much you value the Guardian’s fair and factual reporting, informed by our progressive and liberal values. This feels more important now than ever.
For while the business model for journalism is in crisis, so are the values to which the Guardian is committed: tolerance, equality and a belief in people’s ability to change the world for the better. In standing with us behind these beliefs, our readers mean so much more to us than just money.
I trust the Guardian to expose the truth when others won’t Christine Hopkins, Guardian member
As a mark of your impact, I wanted to remind you of some of the journalism your support has helped us produce in the past few months.
The disturbing and unsettling new politics in the US has resulted in some intensive news reporting, but it’s important to step back and look at the bigger picture, such as in Ed Pilkington’s report from Michigan, in which he discovered that voters who rarely read the news thought Trump had had a great first week. Similarly, I found Thomas Frank’s visit to Trump-voting counties in Missouri to be fresh and interesting. We continue with that work in a major new reporting series, The Promise, which asks the provocative question: can Trump really make America great again?
Trump’s election marks a perilous moment for the environment, and in January all of our teams around the world worked together to produce a 24-hour climate live blog to highlight the impact of climate change, and to demonstrate how seriously the Guardian takes the subject. We followed this with a powerful series on air pollution around the world. Trump’s election has also inspired many of our commentators to write powerfully in response — from George Monbiot, whose piece at the end of November, Frightened by Donald Trump? You don’t know the half of it was incredibly popular with readers, to Pankaj Mishra, who took a broad and deep perspective in his long read Welcome to the Age of Anger.
I really value a news platform that reports the facts as they are Zee Morris, Guardian member
I’d recommend Sabrina Siddiqui’s personal piece about what it was like to cover the election as a Muslim reporter, while our coverage of the resistance has also been strong, from the community team’s gathering of voices on why people joined the Women’s March, to Micah White’s provocative piece on how they need a path from protest to power.
As you may know, the Guardian was among those news organisations banned from a press briefing at the White House in February. That only makes us redouble our efforts to hold President Trump to account.
The other huge story for the Guardian at the moment is, of course, Britain’s historic vote to leave the European Union. Our new Brexit team, working with our world-class correspondents in parliament and across Europe, has made an immediate impact with a string of exclusives, many of them highlighting the human cost. Our Brexit dashboard, in which we return to key indicators every month to measure the economic consequences of the referendum, makes for fascinating reading. Stephen Hawking’s post-Brexit piece, This is the most dangerous time for our planet, was powerful, and it’s been great to have European writers having their say in the Guardian too. Our new series, The New Arrivals, documents the lives of refugees as they settle across Europe — it’s a 500-day project and is already producing moving reporting of human stories. John Harris and John Domokos’s video series, Anywhere But Westminster, tells the story of an alienated and polarised Britain — don’t miss their film about Stoke.
I rely on the Guardian like I rely on friends and family; it gives me hope and it enlightens me Marianne Charles, Guardian member
We’ve continued to build upon our award-winning undercover work which exposed appalling employment practices at the British retailer Sports Direct with a series of investigative pieces exposing how workers in the gig economy are being exploited: at Le Gavroche, Hermes, DPD and Parcelforce. Our reporting has forced a government inquiry.
And I’m sure you’ve followed Daniel Taylor’s painstaking and sensitive reporting which exposed child sex abuse in British football. Beginning with a devastating interview with former player Andy Woodward, the scale of the scandal we unearthed continues to grow — more than 500 potential victims have come forward, and 184 suspects have been identified in an operation that now involves 20 police forces. This was powerful, society-changing journalism at its best.
Elsewhere, we’ve had terrific scoops linked to Saudi Arabia, including showing British ministers knew that British cluster bombs were used by Saudi in Yemen. We continued our commitment to reporting on indigenous incarceration in Australia, with Calla Wahlquist’s piece on a 22-year-old woman who died in police custody. And we produced a documentary I’d recommend to everyone: The Battle for Mosul by Ghaith Abdul-Ahad.
By April 2019, we hope to be supported by the equivalent of 1 million members, who will help secure the Guardian’s future in a tough commercial environment. Advertising conditions remain highly treacherous, with advertising in the Guardian — which helps pay for our journalism — down £11m this year. For every new advertising dollar spent in the US, 99 cents is now taken up by Facebook and Google.
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National Newspaper Association
Sentiment turns against NSA’s bulk data collection
June 6, 2014
By Polo RochaNNAF News Fellow | University of Wisconsin
Rep. Jim Sensenbrenner, R-Menomonee Falls, feels misled.
Sensenbrenner, who authored the Patriot Act in the weeks following the Sept. 11, 2001 attacks, said the National Security Agency under presidents Bush and Obama, grossly misinterpreted the 2001 law and is gathering data on average Americans. So Sensenbrenner is leading efforts to ensure that NSA practices reflect the law’s intent.
“The phone records of innocent Americans do not relate to terrorism whatsoever, and they are not reasonably likely to lead to information that relates to terrorism,” Sensenbrenner said at a Cato Institute forum in Washington. “Put simply, the phone calls we make to our friends, our families and business associates are private and have nothing to do with terrorism or the government’s efforts to stop it.”
Three weeks later, Oct. 29, Sensenbrenner teamed with U.S. Senate Judiciary Committee Chair Patrick Leahy, a Vermont Democrat, to introduce the USA Freedom Act in a bipartisan effort “to rein in the dragnet collection of data” by the NSA and other government agencies. After sitting in committee for months, that bill is finally moving through the House Judiciary Committee.
Sensenbrenner’s USA Freedom Act is competing against other reform proposals, including one proposed by Obama, but privacy advocates say Sensenbrenner’s bill provides the strongest protections against bulk data collection. Negotiations are ongoing, and although the final outcome of which legislation will prevail is uncertain, observers agree the Patriot Act author’s influence in the process is clear.
“It carries more weight than if he were a Rand Paul clone,” said Norm Ornstein, a resident scholar at the American Enterprise Institute, referring to the Kentucky GOP senator and possible 2016 presidential contender who’s a libertarian.
The NSA debate comes after contractor Edward Snowden leaked documents to The Guardian and The Washington Post, detailing numerous NSA programs that had not been public before—leaks that NSA officials said have made the country less safe.
A senior intelligence official, carrying a copy of the Constitution he’s had for more than 20 years, defended the agency’s work. He said a crucial part of the NSA’s mission is to protect Americans’ privacy while keeping the country safe from terrorist attacks.
“Look around you. Who do you think works at the NSA?” the official said during a background briefing in Maryland near the NSA headquarters. “It’s your neighbor, it’s the same people that you go to worship with or you work on a community project or go to soccer [with]. They’re as interested in protecting and defending rights as you and I are.”
Bill Combs, a spokesman for the NSA, was blunt when addressing a perception that NSA analysts can listen in on Americans’ phone calls or read their e-mails.
“You know what happens when we break a rule?” Combs said. “We get fired. We go to jail.”
Still, privacy groups say even if the NSA does not look at Americans’ information, collecting data on average Americans is still problematic.
“From our perspective, and I think from the perspective of the public, the collection itself, even if no one is looking at it right now, the collection itself is harmful,” said Harley Geiger, senior counsel at the Center for Democracy and Technology.
Pew found in January 2014 that 53 percent of Americans disapprove of NSA surveillance, compared to 40 percent who support it. The poll also found a major split within the Republican Party, with 68 percent of tea party-aligned Republicans opposing NSA surveillance, compared to 52 percent opposition from non-tea party Republicans.
USA Freedom Act up against other reform bills
Obama’s proposal hasn’t been fully released yet, but in a March speech he called for the end of bulk phone metadata collection, which two review panels said was largely ineffective and violated Americans’ privacy. That program collects numbers dialed and called from, as well as the time of the call and its duration, but it does not collect the content of the phone calls.
The Obama proposal requires intelligence agencies to get approval from the surveillance court to go to telephone companies and ask for records in specific instances, rather than getting records in bulk.
But reports indicate Obama’s proposal only looks at ending bulk phone records collection, which leaves the door open for collection of other types of records like Internet metadata, e-mails or financial records.
Sensenbrenner’s bill is broader, ending bulk collection of various types of records in addition to phone records, similar to a bipartisan bill from the House Intelligence Committee. Both of those bills appear to be moving through their respective committees, setting up a decision for House Speaker Rep. John Boehner, an Ohio Republican, for which bill to bring to the floor.
Like Obama’s proposal, Sensenbrenner’s bill would require prior surveillance court approval for agencies to get records relevant to terrorism investigations. But the House Intelligence Committee bill does not require prior court approval, which has privacy advocates concerned, although courts can ask agencies to get rid of records if data collection was too broad.
Both the Sensenbrenner bill and the House Intelligence bill add transparency to secret surveillance court rulings that change how a law is interpreted. That’s a move that Tom Blanton, director of the National Security Archive, praised; his non-profit holds the largest collection of government documents obtained through open records laws.
“All the critics have agreed on that the wiretap court has been doing way too much substantive interpretation of the law in secret,” Blanton said. “The more checks and balances, and the more transparency you can bring [to the court], the better off we’ll all be.”
Combs, the NSA spokesman, said the agency would work with “whatever Congress decide[s] to go with … they tell us what to do.”
Privacy advocates encouraged after shift in NSA debate
The debate over the NSA has seen a massive shift in position by Obama and House Intelligence Committee Chair Mike Rogers, R-MI, both of whom defended the phone metadata program last summer but this year called to limit or end the program.
“I’m confident [my proposal] allows us to do what is necessary in order to deal with the dangers of a terrorist attack, but does so in a way that addresses some of the concerns that people had raised,” Obama said in late March.
Two courts weighed in and split on the issue of whether the bulk phone metadata collection program is constitutional.
Meanwhile, two review panels, including a White House committee, agreed the metadata program wasn’t effective and violated privacy. Observers said the panels’ recommendations likely changed Obama’s thinking on the NSA and led him to push for reforms.
The phone metadata bulk collection program still has its defenders, including Stewart Baker, who was the NSA general counsel in the early 1990s and was President George W. Bush’s assistant secretary for policy in the Department of Homeland Security.
Baker said the phone metadata program is legal, adhering to the Fourth Amendment that forbids unreasonable search and seizures, adhering to the Patriot Act and having appropriate oversight from Congress and the courts.
“There’s no doubt that this is constitutional. … The statutory argument is a closer call, but I think it’s a reasonable interpretation of the statutes,” Baker said.
Baker also said the program is effective, and if Obama’s proposal or others make it harder for intelligence agencies to collect telephone records, the country’s safety could suffer.
“The only way you’re going to find some numbers is if we collect all of them,” Baker said. “If you put limits on what the government collects, it will miss the calls that are most important.”
At a Georgetown University forum in November, Sensenbrenner defended the intent of the Patriot Act, while challenging the NSA’s extraordinarily broad interpretation of the Patriot Act’s provision that requires data collected to be relevant to a terrorism investigation.
“If everything is relevant, then the term ‘relevance’ ceases to have any legal significance,” said Sensenbrenner, who was unavailable for an interview. “If Congress intended to allow bulk collection, it would have authorized bulk collection. Instead, we attempted to set limits on what the government could obtain.”
Privacy groups said the call from Obama and Rogers to end the current program, which Snowden called a “turning point,” is a significant shift in the debate.
“The fact that we have these power centers converging on a consensus to end or change this program is significant progress,” Geiger, the Center for Democracy and Technology lawyer, said. “It is something people should take note of. …We think this is a milestone, or at least we’re on our way toward a milestone.”
Wisconsin delegation largely supports Sensenbrenner bill
Sensenbrenner’s bill has wide support among the 10 members of Wisconsin’s congressional delegation. The three who haven’t signed on as co-sponsors yet are Reps. Paul Ryan, R-Janesville, and Ron Kind, D-La Crosse, as well as GOP Sen. Ron Johnson.
The offices of Ryan and Johnson did not respond to requests for comment. But Kind said in an interview that although he supports some elements of the bill, he’s still trying to decide whether ending bulk phone metadata collection would endanger the country.
“[The bill’s cosponsors] have already made the determination that the metadata calling program is not necessary for national security purposes, and I think some of us aren’t quite there at that conclusion,” Kind said.
Kind supports some elements of Sensenbrenner’s proposal, including the reining in of agencies’ use of national security letters, subpoenas that do not require a court order and limit recipients to absolute secrecy unless they appeal and win in court. He also backs Sensenbrenner’s efforts to bring more transparency to the court and boost oversight.
The rest of the congressional delegation, meanwhile, backs Sensenbrenner’s proposal.
Democratic Sen. Tammy Baldwin, who voted against the Patriot Act in 2001, said in a statement she’s glad Sensenbrenner and others “have realized government surveillance has crossed the line and are now working on reforms.”
Rep. Gwen Moore, D-Milwaukee, said in a statement she’s a “proud cosponsor” of the bill because she thinks “we must balance our need for national security with our right to privacy.”
Rep. Reid Ribble, R-Sherwood, said in an interview, the NSA’s bulk data collection of everyone was a “step too far,” and called Sensenbrenner a “force in the House of Representatives” that can bring others to support his reforms.
Rep. Tom Petri, R-Fond du Lac, said in a statement he supports Sensenbrenner’s bill because the country needs an “adequate firewall … to prevent misuse of [data collection] and to ensure Americans’ right to privacy.”
Democratic Rep. Mark Pocan of Madison said in an interview that he commends Sensenbrenner for the “brave stance” he’s taken in ensuring the NSA doesn’t go further than the law intended. He also noted “this is some of the very stuff [former Sen.] Russ Feingold warned people about when he was the single [Senate] vote against the Patriot Act.”
“You can find a balance between security and privacy, and I think we’ve erred far too much on the security side. … What we are doing right now is assuming everyone does something wrong,” Pocan said.
Rep. Sean Duffy, R-Ashland, also co-sponsored Sensenbrenner’s bill. Duffy’s office did not respond to a request for comment.
Bipartisan support reflects growing division within GOP
The bipartisan support in Wisconsin reflects an alliance between numerous Democrats and Republicans nationwide who support efforts from those like Sensenbrenner.
That alliance was tested out—and narrowly lost—last summer in a House vote on an amendment to defund the NSA phone metadata collection program, a loss that some privacy advocates claimed was a victory of sorts because of how close the vote was.
That amendment, from Michigan Reps. Justin Amash, a Republican, and Rep. John Conyers, a Democrat, failed 217 to 205. Boehner, who as House speaker usually doesn’t vote, voted against the amendment.
Elizabeth Goitein, co-director of the Brennan Center for Justice’s Liberty and National Security Program, said that vote reflected a growing number of Republicans concerned with civil liberties. Those Republicans are joining some in the Democratic Party that previously didn’t have enough support to make similar votes that close, she said.
“This is an alliance that should’ve happened a long time ago,” Goitein said.
The division within the GOP was clear when the Republican National Committee approved on a voice vote a resolution condemning the NSA. The resolution asked GOP lawmakers to “immediately take action to halt current unconstitutional surveillance programs.”
The Republican National Committee resolution got a strong rebuke from prominent Republican intelligence officials, according to The Daily Beast, which obtained a letter from those officials to RNC Chair Reince Priebus that said, “Count us out.”
But although there may be a growing libertarian sentiment within the Republican Party, Ornstein said the resolution was likely a reflection of Republicans’ desire to criticize Obama and wouldn’t have happened if a Republican were in the White House.
A Rand Paul 2016 candidacy for the GOP presidential nominee could once again highlight the split within Republicans on national security. Ornstein said if he runs, Paul could pick up younger voters who are more concerned about privacy issues.
Still, Ornstein noted the neoconservatives in the party remain strong and heavily funded, ready to challenge prominent GOP libertarians like Paul in a 2016 primary.
“Even if they’re no longer as dominant as they used to be, the internationalist neoconservative wing of the party is still strong on the establishment side and on the financial side,” Ornstein said. “Paul can get plenty of money from libertarian hedge fund guys, but you’d see some mobilization against him if he really emerged as a serious contender for the nomination, and I think there’s a real chance he could.” |
Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma.
To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (131I-MIBG) treatment of patients with resistant neuroblastoma. One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of 131I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease. Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year. The high response rate and low nonhematologic toxicity with 131I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma. |
Mundo Deportivo. Oldest and leading sports daily newspaper in Spain. Published in Barcelona and Spain. Mundo Deportivo covers all sports but focuses heavily on FC Barcelona. Owned by Godo Group who also own La Vanguardia newspaper. |
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149 Ind. App. 255 (1971)
271 N.E.2d 471
ELMER SARRINGHAUS, ET AL.
v.
CITY OF SHELBYVILLE.
No. 171A19.
Court of Appeals of Indiana.
Filed July 20, 1971.
Rehearing denied August 30, 1971.
Transfer denied November 3, 1971.
*256 Bob Good, of Shelbyville, for appellants.
George R. Glass, Glass & Moberly, of Shelbyville, for appellee.
SHARP, J.
On October 8, 1968, the Common Council of the City of Shelbyville, Indiana, passed Ordinance No. 1463 purporting to annex certain territory. The Appellants filed a timely remonstrance. It is stipulated that Appellants-Remonstrators constituted a majority of the owners of land in the territory sought to be annexed or were owners of more than 75% of assessed valuation of the real estate in such territory.
After the trial on the remonstrance the trial court found for the City and against the remonstrators.
The evidence must be examined in the light most favorable to the Appellee-City.
The Appellants' sole contention is stated in three sentences in their brief as follows:
"The remonstrators rely completely upon the case of City of Aurora v. Bryant, (1960) 165 N.E.2d 141. That case clearly held that a city could not annex territory exclusively for the purpose of increased revenue. The evidence in the case showed no other reason for the annexation."
The Appellants are wrong in their sole reliance on City of Aurora v. Bryant, 240 Ind. 492, 165 N.E.2d 141 (1960), as applicable to this case.
There is evidence from which the trial court could determine that this annexation was in the best interests of the City and the territory to be annexed within the meaning of Acts 1905, ch. 129, as amended and found in Ind. Ann. Stat. § 48-702 (Burns 1963). For example, the area was urban in character. It was an economic and social part of the City. The City was financially able to provide municipal services to the annexed area in the reasonably near future. The lines of annexation were so drawn as to form a compact area abutting the municipality. *257 This City is now furnishing some municipal services to the area. There is evidence that the area will benefit by having sewage facilities, the cleaning of a ditch which is a health hazard, street cleaning services, garbage collection, municipal incinerators, mosquito spraying, weed control, street lights, park facilities and assured police and fire protection.
The fact that some of these services are already provided by the City does not form the basis, as a matter of law, for this annexation ordinance to be held invalid. See Kleinknecht v. City of Evansville, 137 Ind. App. 345, 204 N.E.2d 872 (1965).
In City of Aurora v. Bryant the trial court made a factual determination and our Supreme Court refused to disturb it. Likewise in this case, we will not disturb the factual determination of the trial court. City of Aurora v. Bryant does not compel us to do so.
There is a substantial body of authority to support the result here. See Smith v. Town of Culver, 249 Ind. 665, 234 N.E.2d 494 (1968); Arnholt v. City of Columbus, 128 Ind. App. 253, 145 N.E.2d 660 (1957); and Baker v. City of South Bend, 148 Ind. App. 596, 268 N.E.2d 623 (1971).
The record contains sufficient evidence to support the finding of the trial court that this annexation was in the best interests of both the City of Shelbyville and the territory sought to be annexed.
Judgment affirmed.
Hoffman, C.J., Staton, and White, JJ., concur.
NOTE. Reported in 271 N.E.2d 471.
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Or even now talks and Packers football. Joining us now on the Schneider orange outline our agree gore analysts is Paula made par you don't today man. Our door while so. On the tour talk more about this with that Miller coming up here shortly regarding the police report and some of the draft positions but. I still go back to it some of the things that Ted said about the pre and post a draft in what's available out there and who he I don't mess necessarily thinks he's going to get but the holes that need to be filled. Barry he's really quiet right now do you expect much more action in the next couple weeks. No I don't think so I mean in less a running back with the Packers like like a veteran Eddie let's say they. Are just waiting for Adrian Peterson's place to drop let just say there waiting for Jamaal Charles is the drop or whatever the case might be. And old guys call coming in eventually begging and playing you know I'll take. Two million bucks. We signed me today may be bad and that is an extremely unlikely scenario more likely those guys that Peterson's child with air on gonna wait until after the draft and they know that some team work she worked three. Are due to not leave draft weekend with the running back they had hopes to get. Whatever round might be first second or the guards could maybe come in day one. And be contributing starter at running back is going to be used human I think they'll guide him at landed their bats on especially Peterson. On that happening but it's part of the Packers and really for any other team if if there are signing the next couple weeks and next few weeks early next month. I think it be surprising that they and the guys who've been targeted the guys have been identified by other teams. Has signed and have gone to those teams not just pointing to probably going to say in the packers' most read most specifically. Gonna say what the other draft shakes out and it we don't get a guy at a position that we need. Let's let's reconfigure after the draft and so if anything happened signing like next week I'll be surprised if that is. All Sicily draft season in full force. Not just for the for the GM of the executives would make those decisions. But but for the free agent players stellar out there probably assume that they're light Brett how about on until after the draft. So looking forward. Is there anybody as you start to decipher all the stripped information by the way you're going to be Wear this on draft night. Which we're doing it again this year yours truly Gary Ehlers and no it won't have my Clemens up in Green Bay you're going to be with us and we're going to be to Q club Wisconsin on walker shock. But is as we start to go through this I'm starting to look more and more into corners into pass rushers. I don't think they're gonna take a running back early on but to even our lads now has Fabian Morrow. The corner out of UCLA possibly going to Green Bay what do you think is the number one position the Green BayPackers look to fill. Good question I assume the answer to that is. Warner and as rusher I don't know when what order. I think they have more guy to give chances to an edge rusher like you don't have in the quarterback room you don't have. A pilot back and what I mean by that is you don't have a guy drafted last year you and I and I highbrow in the third round of the upper 60% in the draft. Who you kind of need to find out what. I think the Packers and a position that they need to find out sooner or sooner than later actually. Because it was because the tackled aiding more demands second player. You need to find out what he has the quarterback room doesn't have. I think you know going into this thirteen and you have a lot find out about Randall Rollins and Gunter especially Randall and Rollins. Because Gunter had a better seat in and both of those guys but you don't have a guy who. You know you really curious about as you know I mean like those guys have been given chances back hadn't been given much chance he'll kind of yours similar technology Iran Elliott and the chances but he's. You being told or is expecting to get as an edge rusher so. From that perspective I'd lean quarter but from the perspective up to really think being nick Perry Tyler back Ruggiero and Elliott. Pass rushing him up and them were trio or 20 from the outside in this going at the 1980 Clint happy spend more aren't inside. And he has in at least is actually made he goes back to the days when. When he 142013. When he played more inside than outside. So I it from a from a true depth perspective built like a quarter but I think that you're looking from the value perspective I'm Michael Ed rush or one and one B. In some order they definitely need it need to target. Third round or round who could come indeed want to at least compete for that starting job and we can reference Corey lately. Was it fifth round pick and was able to come and as a starter and start setter. You know that's built arc on it especially when you get that capped the draft. So you know in a perfect ideal scenario. First round edge rusher second round corner third round running back fourth round are perfect world. That's how the draft board called in my opinion for the Packers but of course you don't know. Which players lack should be their work. Work the value at that round at that position at. I started listening to some of the other talk shows will say he sports talk and what have you in Minneapolis and Chicago and Detroit. Just kind of get a feel on the pulse for what it is because they're all chase agreement Tigers only talk about as well do right you have something to be with what Aaron Rodgers is about to throw up. Most of them seem to think that if you can do is bolster your defense enough to slow down. The Packers offensively. That they all feel the Packers defensively aggressive and they don't think there's enough out there there's an up and adrenaline even help this team to get into the top fifteen. And therefore it's all going to be shoot outs and if you get them on your home turf you're going to be able to beat the Green BayPackers is that a legitimate concerns legitimate thought. Yeah I mean I think it is I think what have the Packers done this offseason thus far out it is not over so let's let's keep adding that at our. As part of our point. Alec yup you know they haven't even draft it would not. They might do post draft used it on and work there we have no idea but at stand today I think it's very rare or. Chicago Bears and more specifically though Vikings and an audience who. Those two teams could legitimately you know on beat the Packers index this upcoming see I think that. 022 under close enough that they're both right there that was the right to the cadets will be right there not conduct with the Packers for the top division. I would look at that I would say well okay let's just go and has a Vikings fan or lines and assume you know the Packers put up thirty. Spot can we put 35 on them. And I think you'll say okay you're the wind you know like you add enough offensive fire power. It's within the realm of possibility you could be able to do because. Those two teams today have better defense is and the Packers knock they don't have Aaron Rodgers and that's of course the big difference maker that. I've been controlling this division for the past many years and going to control the division clinic several. It's you know you need to have enough body at key positions defensively to keep the Packers under thirty. You know usually almost okay they put up 27 because you can expect. A rock went off at the point seven so it it makes total sense that Aaron Rodgers in recent years in recent public for the past six years at the next six years to come. Is having a lot to do with how the players out of my strap and out of Lions draft. It you have the subway on. Coach and play called by my card so I I totally bald like to think that you. You're just trying to see what kind of rushing to put together that can keep at least either eight outscored rotten look up to it and got a Albert weaker going to be 2030 points. Or to say he'll achieve in the European initial doubt because the Packers defense is. Well as an octave but you could probably do that with the right not I. Bomb Packers hosting Joseph makes in in deprive her work out obviously comes a lot of we'll say emotional baggage when it comes to how fans feel about his past. If he's there and say second round. You do the Packers take a murder they jump up to get. Well we of course don't know how the you know how public meetings went but the fact that they're exploring it is interesting and it's it's made plenty of headlines already. In the past 48 hours 24 hours that he couldn't or visit let's say those visits went well. Let's say didn't we know we know legitimate supplement your talent perspective would be drafted higher without this as part of its history we know that. So you know if he's old enough in the second round and if the Packers liked their visit with him. I think you'll have a very interesting show built the next day after that would happen because. Like that would probably be Friday night pick and people have 48 hours to think about it and talk about it before your your sure would start following Monday. And I'm wondering you know where the majority of a Packers fans would land on that could at the very moment it you know it would know. The fact that Nixon has been hitting it all told you that there is interest. The question is at what round at what value. Pure football lies you know it gets booed the overriding factor that Packers ultimately going to be judged on. If it worked out or not or did they take a risk and not have the payoff sport so. Military billet sounds more and more like. But it's at least possible and I think that is. Like the problems that it's at least in the realm of possibilities could there have been teams reportedly looked completely dead now and taking them off their board one or the draft and start. So. Yeah let's let's wait to see if he if he's there. He did late second round and if if in fact the Packers are ready to take that. You know that that player and and see how they would handle the follow some. As stubborn as always in all talk again on Monday is even any breaks over the weekend all right. Went to regulated degas that is a polity joining us for a couple of minutes in the Schneider warned challenge shatter hiring drivers right now you're currently treat you fair eighty plus years at beginning you don't call an 844 prior to go to Schneider jobs dot com 844 pride. Or go to Schneider jobs dot cal. |
Series of bombings in Baghdad area kill dozens
A man lies in a hospital bed after being injured in a bomb blast in the Shiite enclave of Sadr City, in Baghdad, Iraq, Sunday, Feb. 17, 2013. A series of car bombs exploded within minutes of each other as Iraqis were out shopping in and around Baghdad on Sunday, killing and wounding scores of people, police said. (AP Photo/ Karim Kadim)
BAGHDAD (AP) — Multiple car bombs exploded within minutes of each other as Iraqis were out shopping in and around Baghdad on Sunday, killing at least 37 people and wounding more than 100 in mainly Shiite areas.
The attacks come amid rising sectarian discord in Iraq and appear aimed at shaking Iraqis’ confidence in the Shiite-led government. The explosions struck at the start of the local work week and primarily targeted outdoor markets.
Violence in Iraq has fallen since the height of sectarian fighting in 2006 and 2007, but insurgents still frequently launch lethal attacks against security forces and civilians. It was at least the third time this month that attacks have claimed more than 20 lives in a single day.
The detonation of a parked car loaded with explosives in the sprawling Shiite district of Sadr City heralded the start of the attacks Sunday morning. Two more parked cars later exploded elsewhere in the neighborhood.
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Nima Khadum, a government employee, said the blasts shattered the windows of his Sadr City house. He said the air was heavy with smoke, while burning cars littered the street and the bodies of the dead and wounded lay nearby.
“The scene was a bloody one that brought to my mind the painful memories of the violent past,” he said. “I don’t see the benefit of security checkpoints that only cause traffic jams and don’t do anything to secure Baghdad. The government, with its failing security forces, bears full responsibility for the bloodshed today.”
Simultaneous explosions hit the southeastern Baghdad neighborhood of al-Amin, where the force of the blasts left behind little except the mangled chassis of two cars that delivered their payloads.
An open-air market in Husseiniya, just northeast of the capital, and the Kamaliya area in Baghdad’s eastern suburbs were also hit.
Another car bomb exploded near street vendors and a police car in the central commercial district of Karradah.
Police and hospital officials provided the death toll, and said more than 130 people were wounded. They spoke on condition of anonymity because they weren’t authorized to brief reporters.
Casualties could have been even higher. Authorities carried out controlled explosions of two other car bombs they discovered in Husseiniya and Habibiya, near Sadr City, according to police.
There was no immediate claim of responsibility for the attacks, but similar ones have been orchestrated by Sunni extremists, such as al-Qaida’s local affiliate. The group, known as the Islamic State of Iraq, favors large-scale, coordinated attacks. It considers Shiite Muslims to be heretics and accuses them of being too closely aligned with neighboring Shiite powerhouse Iran.
As sectarian strife mounts, protesters drawn overwhelmingly from Iraq’s Sunni community have been staging weekly demonstrations and sit-ins since late December to rally against the government, which is led by Shiite Prime Minister Nouri al-Maliki. The protesters have rejected calls for violence and distance themselves from extremist groups such as al-Qaida.
There are also concerns that Sunni insurgents could step up attacks ahead of provincial elections scheduled for April 20. The ballot would be the first country-wide vote since the U.S. troop withdrawal more than a year ago.
The United Nations envoy to Iraq, Martin Kobler, quickly condemned the attacks and said “all Iraqi leaders have a responsibility to stand up against these atrocious crimes.”
The blasts came a day after a suicide bomber pretending to ask for help assassinated Brig. Gen. Ali Aouni, the head of the Iraq Defense Ministry’s intelligence academy, and three of his bodyguards in the northern city of Tal Afar.
Sunday’s attacks brought to more than 100 the number of people killed in violent attacks in Iraq since the start of the month. A total of 178 were killed in January attacks, according to an Associated Press count. |
Editorial: Offering historical tours
The Continental Army fired cannonballs at Nassau Hall during the Battle of Princeton, and Albert Einstein taught in what is now the Frist Campus Center. These moments in Princeton history figure prominently in the typical Orange Key campus tour attended by many undergraduates when they were prospective students. Less well-known is that the world’s first telegraph line was set up between Joseph Henry’s Princeton home and his laboratory in the University’s Philosophical Hall or that Pete Conrad '53, commander of Apollo 12, brought small Princeton flags to the moon in November 1969. Currently, no outlet for sharing these aspects of Princeton lore with interested Princeton students, community members and other campus visitors exists. To address this programming gap, the Editorial Board proposes that Orange Key creates and advertises a weekly Historical Tour focused on Princeton’s architecture, history and traditions. Furthermore, we recommend the Admission Office offer tours of this nature during the upcoming Princeton Preview days for admitted students and their families.
Orange Key offers admissions tours throughout the year that anyone may join without pre-registration. Only groups of 10 or more need to pre-register with the admissions office and when they do so they may indicate that they would like their tour to have a historical focus, which is primarily done by groups of adults from outside organizations. However, this option is not advertised on the the office’s website. At a minimum, the website should state that historical tours are available upon request so interested groups know to take advantage of this opportunity. Yet this still does not meet the needs of individual community members or visitors in smaller groups who may be interested in Princeton’s history. While these individuals may attend a regular Orange Key campus tour, according to Orange Key’s Guide for Guides, any tour that has at least one prospective student must focus on Princeton’s academics and student life.
Therefore, the Board proposes the development of regularly scheduled Historical Tours that include information about the history, architecture, and traditions of many locations on campus beyond just Nassau Hall (the primary historical focus of current Orange Key tours). We recommend offering such a tour once or twice a week and advertising it on the admissions website as open to any members of the public and University students. Finally, we propose that the Historical Tour be offered during Princeton Preview for prospective students and in particular for their parents or siblings who may have already taken the regular Orange Key tour (which will be offered during Preview) and want a new option for Preview.
There is great value in regularly providing such Historical Tours. For residents of Princeton and surrounding areas, they may learn more about the University with which they share a home. Providing community members with greater access to the University fosters improved town-gown relationships, which is always in the University’s interest as it seeks to continue its positive collaboration with the town of Princeton. For students, education need not end in the classroom, and creating an environment rich in learning experiences is one of the University’s goals. That current campus tours focus in part on historical facts demonstrates that Orange Key and the admissions office share our belief that such information is of interest to campus visitors and important to be shared. We urge the University to provide an additional educational opportunity for interested students and the 700,000 people who visit Princeton each year by instituting regularly scheduled Historical Tours and making this an option for Princeton Preview activities.
The Editorial Board is an independent body and decides its opinions separately from the regular staff and editors of The Daily Princetonian. The Board answers only to its Chair, the Opinion Editor and the Editor-In-Chief. |
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