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The SANUS Euro Series wire management clips work with Euro Series AV furniture. The clips easily snap onto shelves and bases to route wires for a clean, organized appearance. Five replacement clips are included.
Take A Look At These Specs
Supported VESA Patterns
Universal Mounting
VESA patterns are measured by the center of one mounting hole to the center of another on the back of a television in millimeters. In the example above, the VESA measurements are 100 (width) x 100 (height). The example TV would be able to use a VESA 100 x 100 mount. |
Opinion issued February 28, 2013
In The
Court of Appeals
For The
First District of Texas
————————————
NO. 01-12-00590-CR
———————————
ERIC EARL FISHER, Appellant
V.
THE STATE OF TEXAS, Appellee
On Appeal from the 184th District Court
Harris County, Texas
Trial Court Case No. 1313629
MEMORANDUM OPINION
Appellant, Eric Earl Fisher, was charged by indictment with robbery. 1
Appellant pleaded not guilty. A jury found him guilty. The trial court found two
1
See TEX. PENAL CODE ANN. § 29.02(a)(2) (Vernon 2011), § 31.03(a) (Vernon
Supp. 2012).
enhancement paragraphs to be true and sentenced appellant to 45 years’
confinement. In three issues on appeal, appellant argues that (1) the trial court
abused its discretion by denying his motion to suppress because he was improperly
arrested without an arrest warrant, (2) his due process rights were violated when
the State failed to timely disclose Brady evidence, and (3) the trial court erred by
denying his motions to instruct the jury to disregard certain hearsay evidence.
We affirm.
Background
Engram Wilkinson was traveling through Houston on his way from Austin
to New Orleans. He stopped for gas at a station in east Houston. While he was
filling his gas tank, a black male approached him and asked for money. Wilkinson
told him he did not have any money, and the man walked away. A moment later,
the man returned asking for cigarettes or marijuana. Wilkinson said he did not have
any and got into his car to leave. Once Wilkinson was in the car, the man stepped
up to the open car door and told Wilkinson not to move or he would shoot him.
The man took Wilkinson’s wallet, cell phone, car keys, iPod, and iPod charger.
The man then walked to another car and got in. Before the car drove away,
Wilkinson read the license plate number. After the car left, Wilkinson walked into
the store at the gas station and asked the clerk to call the police. Wilkinson later
identified appellant in a photo line-up.
2
A few hours later, Deputy J. Lewis heard a police broadcast that the car used
in the robbery had been spotted in an area of town near him. Deputy Lewis spotted
the car and pulled it over. Appellant was in the car. Deputy Lewis immediately
put him under arrest. During the search incident to the arrest, Deputy Lewis found
in appellant’s pockets a number of items that had been in Wilkinson’s wallet.
Wilkinson’s cell phone was later found in the car.
The day before appellant’s trial setting, the State filed a notice that a deputy
from the Harris County Sherriff’s Department who was involved in the case and
had been subpoenaed to appear at trial had been terminated for policy violations
and for supplying drugs to his girlfriend. The next day, the State filed a subpoena
for another deputy to testify. The same day, appellant moved for a continuance.
During the hearing, the State explained that it had provided a Brady notice
as soon as it was aware of the termination. Appellant’s counsel then stated, “Well,
as far as Brady, I don’t have a problem with it. It’s the subpoena that we’re
addressing here.” Appellant’s counsel explained that they needed additional time
to learn more about the substituted deputy. The trial court denied the motion.
Before trial, appellant had filed a motion to suppress based on the State’s
failure to get a search warrant before searching appellant. During trial, appellant
proceeded on the motion. Appellant argued that the State had sufficient time to get
3
a search warrant before his arrest and, by failing to do so, the warrantless search
was improper. The trial court denied the motion to suppress.
During the State’s examination of two deputies at trial, the deputies testified
about hearsay statements. For four of these instances, appellant objected, and the
trial court sustained the objections. Appellant then moved for instructions for the
jury to disregard and for mistrial. The trial court denied these motions.
Motion to Suppress
In his first issue, appellant argues that the trial court abused its discretion by
denying his motion to suppress because he was improperly arrested without an
arrest warrant. The State argues that this issue has not been preserved for appeal.
We agree.
The State correctly points out that appellant’s brief repeatedly fails to
recognize the distinction between an arrest warrant and a search warrant. In fact,
appellant identifies his first issue as “The lapse of several hours between the
robbery, the identification of a possible suspect in the case, and the eventual arrest
of [appellant] required the State to obtain a search warrant before arresting
[appellant] and seizing property from him.” Throughout his argument of this issue,
appellant uses the terms “search warrant” and “arrest warrant” interchangeably.
The legal authority appellant relies on, however, almost exclusively
concerns the legality of warrantless arrests. See, e.g., TEX. CODE CRIM. PROC.
4
ANN. arts. 14.01–.04 (Vernon 2005 & Supp. 2012) (concerning arrests without
warrants). Appellant dedicates the vast majority of this section of his brief arguing
that the State failed to establish that it had met the requirements under article 14.04
of the Texas Code of Criminal Procedure for a warrantless arrest. See TEX. CODE
CRIM. PROC. ANN. art. 14.04 (permitting warrantless arrest when it has been
adequately shown to a police officer that a felony has been committed and that the
offender is about to escape without any time to procure a warrant). Appellant only
cites to two cases on warrantless searches and only for general propositions of law.
See Amores v. State, 816 S.W.2d 407, 413 (Tex. Crim. App. 1991) (holding “[t]he
‘totality of the circumstances’ test applies in Texas for determining probable cause
for a warrantless search and seizure”); Minnesota v. Dickerson, 508 U.S. 366, 372
113 S. Ct. 2130, 2135 (1993) (holding warrantless searches “are per se
unreasonable under the Fourth Amendment—subject only to a few specifically
established and well delineated exceptions”). Appellant provides no specific
argument for why the warrantless search was improper other than to say it derived
from a warrantless arrest.
At trial, however, appellant’s argument in his motion to suppress and the
hearing on the motion concerned only the validity of the warrantless search.
Appellant argued that the State lacked a reasonable basis to search him. Appellant
made no complaint about the warrantless arrest.
5
Complaints about a warrantless arrest are distinct from complaints against a
warrantless search. Raising one does not preserve the other. See Buchanan v.
State, 207 S.W.3d 772, 777 (Tex. Crim. App. 2006) (holding that constitutional
complaints about warrantless search at trial did not preserve for appeal statutory
complaints about warrantless arrest). When an appellant’s complaint at trial does
not comport with the issue raised on appeal, the issue on appeal has not been
preserved for our review. Swain v. State, 181 S.W.3d 359, 367 (Tex. Crim. App.
2005) (citing TEX. R. APP. P. 33.1). To the degree appellant was attempting to
raise a complaint about the warrantless search with two legal citations but no
accompanying legal analysis, we hold it is has been inadequately briefed. See TEX.
R. APP. P. 38.1(i); Cardenas v. State, 30 S.W.3d 384, 393 (Tex. Crim. App. 2000)
(overruling points of error as inadequately briefed when appellant failed to present
argument and authorities as required by Texas Rule of Appellate Procedure 38.1).
Accordingly, we overrule appellant’s first issue.
Brady Violation
In his second issue, appellant argues that his due process rights were violated
when the State failed to timely disclose Brady2 evidence. The State argues this
issue was explicitly waived at trial. We agree.
2
See Brady v. Maryland, 373 U.S. 83, 87, 83 S. Ct. 1194, 1196–97 (1963) (holding
“the suppression by the prosecution of evidence favorable to an accused upon
6
The day before appellant’s trial setting, the State filed a notice that a deputy
from the Harris County Sherriff’s Department, who was involved in the case and
had been subpoenaed to appear at trial, had been terminated for policy violations
and for supplying drugs to his girlfriend. The next day, the State filed a subpoena
for another deputy to testify. The same day, appellant moved for a continuance.
During the hearing, the State explained that it had provided Brady notice as
soon as it was aware of the termination. Appellant’s counsel then stated, “Well, as
far as Brady, I don’t have a problem with it. It’s the subpoena that we’re
addressing here.” Appellant’s counsel explained that they needed additional time
to learn more about the substituted deputy. The trial court denied the motion.
On appeal, appellant argues that the State failed to provide timely notice that
the original deputy had been fired and the reasons for the firing. Appellant argues
this is a Brady violation. Appellant makes no mention of the need to investigate
the substituted deputy. The issue on appeal does not comport with the complaint
made at trial. Accordingly, the issue on appeal has not been preserved. See Swain,
181 S.W.3d at 367 (citing TEX. R. APP. P. 33.1). Instead, it was expressly waived.
We overrule appellant’s second issue.
request violates due process where the evidence is material either to guilt or to
punishment”).
7
Instruction to Disregard
In his third issue, appellant argues the trial court erred by denying his
motions to instruct the jury to disregard certain hearsay evidence. In his harm
analysis, however, appellant does not argue that this error, standing alone, created
reversible error. Instead, his argument for reversible error is contingent upon our
having sustained his first issue concerning the warrantless arrest. Without the
evidence obtained stemming from his arrest, appellant argues the bolstering
hearsay evidence would have had a more significant and injurious effect.
Because we have overruled his first issue, appellant’s basis for alleging harm
in this issue necessarily fails. Accordingly, we overrule appellant’s third issue.
Conclusion
We affirm the judgment of the trial court.
Laura Carter Higley
Justice
Panel consists of Chief Justice Radack and Justices Higley and Brown.
Do not publish. TEX. R. APP. P. 47.2(b).
8
|
Saint Blaise (disambiguation)
Saint Blaise was a physician and bishop of Sebaste, martyred in 316.
Saint Blaise may also refer to:
Saint Blaise of Amorion, d. 908
Places
In Canada:
Saint-Blaise-sur-Richelieu, Quebec, a municipality in the province of Quebec
In France:
Saint-Blaise, Alpes-Maritimes, in the Alpes-Maritimes département
Saint-Blaise, Haute-Savoie, in the Haute-Savoie département
Saint-Blaise-du-Buis, in the Isère département
Saint-Blaise-la-Roche (St. Basien (bei Rappoltsweiler)), in the Bas-Rhin département
L'Hôpital-Saint-Blaise, a village and commune in the Pyrénées-Atlantiques département of southwestern France
Lentillac-Saint-Blaise, a village and commune in the Lot département of south-western France
In Germany:
Kolleg St. Blasien a Catholic boarding school
Otto of St. Blasien was a German Benedictine chronicler
St Blaise, the English name for the town of Sankt Blasien, in Baden-Württemberg
St. Blaise Abbey in the Black Forest
St. Blaise church in Balve, in Westphalia
In Switzerland:
Saint-Blaise, Neuchâtel, a municipality in the Canton of Neuchâtel
In the United Kingdom:
St. Blaise's Well, a well in Bromley
St Blaise, an alternate spelling for St Blazey in Cornwall
Other uses
St. Blaise (horse) winner of the 1883 Epsom Derby
See also
San Blas (disambiguation)
San Biagio (disambiguation)
Blaise (disambiguation)
Blasius (disambiguation) |
Germinoma of the pineal body with syncytiotrophoblastic giant cells.
Almost all types of germ cell tumors are known to occur in the third ventricle-pineal region. In this paper we report the case of a 16-year-old boy having a particular subtype of germinoma of the pineal body in which scattered syncytiotrophoblastic cells positive for human chorionic gonadotropin were found. This tumor is considered the central nervous system counterpart of seminoma with syncytiotrophoblastic giant cells and dysgerminoma with syncytiotrophoblastic giant cells. |
Electrotonic junctions between teleost spinal neurons: electrophysiology and ultrastructure.
Electrotonic transmission between spinal neurons is correlated with distinctive apposition of cell processes involving membrane fusion. In the same neurons, postsynaptic potentials appear to arise at typical synaptic knobs where there is an intercellular space. |
Ability of nucleus cochlear implantees to recognize music.
Eight adults with cochlear implants participated in experiments to test their ability to recognize music. Some subjects showed good ability to recognize songs that were sung with instrumental accompaniment but poor ability to recognize songs played on an electronic keyboard without verbal cues, indicating that they were recognizing the songs by verbal cues rather than by musical qualities such as tones and melodic intervals. This conclusion was strengthened by the finding that subjects were barely able to distinguish between songs with the same rhythm and pitch range, and they showed poor ability to discriminate musical intervals. (The closest discrimination was 4 semitones.) Subjects had good ability to distinguish among the synthesized sounds of various musical instruments played on the electronic keyboard. We speculate that subjects could distinguish the various musical instruments in the same way they distinguish among human voices using spectrographic patterns such as formants or maxima. |
Q:
Using query in a while loop causing android application to freeze
I am having some troubles with the while loop + query. What I'm trying to do is track the user location (using onlocationChanged) and keep querying a FeatureLayer until the query returns a result and then stop the while loop is using a boolean.
The problem once the "while" loop is launched is that the application freezes, here's my code:
boolean noResults=true
while(noResults)
{
pointGeometry=MyPosition;
//myPosition is changing it's value in "onLocationChanged" using the listener, see code below
Graphic pointGraphic = new Graphic(pointGeometry, simpleMarker);
SpatialReference spatialRef = MapFragment.mMapView.getSpatialReference();
Unit unit = spatialRef.getUnit();
double adjustedAccuracy = b_dist;
Polygon p = GeometryEngine.buffer(pointGeometry, spatialRef,adjustedAccuracy, unit);
Query q = new Query();
q.setGeometry(p);
q.setSpatialRelationship(SpatialRelationship.INTERSECTS);
fLayer.selectFeatures(q, SELECTION_METHOD.NEW, callback4);
}
public void onLocationChanged(Location loc) {
double locy = loc.getLatitude();
double locx = loc.getLongitude();
Point wgspoint = new Point(locx, locy);
mLocation = (Point) GeometryEngine.project(wgspoint,
SpatialReference.create(4326),
mMapView.getSpatialReference());
//Here's where myPosition changes its value.
myPosition = mLocation;
}
CallbackListener<FeatureSet> callback4 = new CallbackListener<FeatureSet>() {
public void onCallback(FeatureSet fSet) {
Graphic[] grh=fSet.getGraphics();
if(grh.length>0){
noResults=false;
showTaost("there's a result");
}
});
Is there an alternative to the while loop to fix this? If not, how can I use something like a delay (query the Feature Layer every 5 secondes or something like that)?
A:
I resolved the problem using a "Handler" that query the Feature Layer every 5 seconds, this stops the main thread from generating application not responding error:
Handler m_handler=new Handler();
Runnable m_runnable;
m_runnable = new Runnable(){
public void run() {
//query code here
m_handler.postDelayed(m_runnable, 5000);
}
};
m_handler.postDelayed(m_runnable, 0);
|
Introduction {#s1}
============
According to the ambivalence model of craving (Breiner et al., [@B3]; McEvoy et al., [@B25]), the decision to consume alcohol is determined by the balance between motivational inclinations to indulge ("approach") and to abstain ("avoidance"). Approach and avoidance inclinations might arise from the desire for intoxication or the wish to keep a clear head for the next day, respectively. Motivational conflict (or ambivalence), which plays an important role in alcohol use disorders and their treatment (Hettema et al., [@B16]), arises when a person has the motivation to drink and to abstain at the same time. Importantly, these motivational orientations can operate in both controlled (or explicit) and automatic (or implicit) cognitive processes. Controlled processes are rule-based and reflective, they operate within conscious awareness and they can be assessed with self-report measures. Automatic processes are activated spontaneously and they are typically assessed with indirect tasks such as computerized measures of attentional bias and automatic approach tendencies (Stacy and Wiers, [@B41]). One theoretical model proposed that subjective craving (a controlled process) and attentional bias (an automatic process) have reciprocal causal influences on each other (Field and Cox, [@B10]), although an alternative account is that automatic and controlled processes are both outputs of underlying processes that cannot be measured directly (motivational orientations; see Christiansen et al., [@B6]). In this paper we report results from three studies in which we experimentally manipulated motivational orientations for alcohol in order to thoroughly investigate the independence of approach and avoidance in both controlled and automatic processing.
Regarding controlled processes, the Approach and Avoidance of Alcohol Questionnaire (AAAQ; McEvoy et al., [@B25]) was developed to capture the strength of approach and avoidance inclinations for alcohol. The initial factor analysis of non-dependent drinkers\' responses on the AAAQ yielded three subscales, two representing approach inclinations (inclined-indulgent and obsessed-compelled subscales, corresponding to mild and strong inclinations, respectively), and one representing inclinations to avoid drinking alcohol (the resolved-regulated subscale). Subsequent studies employed the AAAQ with different populations of drinkers and performed factor analysis on participants\' responses. Each of these studies confirmed that approach and avoidance represent distinct underlying factors, although some studies with alcohol dependent patients (Klein et al., [@B20]; Schlauch et al., [@B35]; but see Klein and Anker, [@B19]) identified a single underlying factor to approach inclinations rather than the qualitative distinction between mild and strong approach that was reported in the initial study (McEvoy et al., [@B25]). Many of these studies demonstrated that both approach and avoidance inclinations are independently associated with drinking-related variables. For example, approach and avoidance inclinations account for unique variance in quantity and frequency indices of alcohol consumption in both non-dependent (McEvoy et al., [@B25]) and alcohol dependent (Klein et al., [@B20]) drinkers. Approach and avoidance inclinations also have differential predictive validity in alcohol-dependent patients: following treatment, relapse to drinking is predicted by the strength of approach inclinations, but avoidance inclinations are not predictive (Schlauch et al., [@B36]; Klein and Anker, [@B19]; see also Schlauch et al., [@B35]). On the other hand, avoidance inclinations (but not approach inclinations) predict the likelihood of entering into and engaging with treatment (Schlauch et al., [@B36]). Taken together, these findings provide support for the ambivalence model of craving (Breiner et al., [@B3]) because they demonstrate that self-reported approach and avoidance inclinations for alcohol are separable constructs that are uniquely associated with past and future drinking behavior (see also Curtin et al., [@B7]; Schlauch et al., [@B33],[@B34]).
Regarding automatic processes, there is evidence for co-existence of appetitive (approach) and aversive (avoidance) alcohol-related processing biases in problem drinkers in a variety of sub-domains, including affective associations (Dickson et al., [@B8]), attentional bias (Stormark et al., [@B42]), and approach and avoidance tendencies (Barkby et al., [@B2]). Regarding attentional bias, heavy drinkers who are not seeking treatment have an attentional bias for alcohol cues (Townshend and Duka, [@B43]; Field et al., [@B14]). The strength of this attentional bias is reliably associated with the strength of subjective craving (Field et al., [@B15]) and is potentiated by experimental manipulations that increase the motivation to drink, such as induction of negative mood and exposure to alcohol-related cues (see Field and Cox, [@B10]). By contrast, alcohol-dependent patients who are tested in treatment contexts show initial attentional bias that is quickly followed by attentional avoidance (Stormark et al., [@B42]; Noël et al., [@B28]; Townshend and Duka, [@B44]; Vollstädt-Klein et al., [@B45]; Field et al., [@B13]). The latter pattern of attentional bias may reflect ambivalence, with appetitive motivational processes mapped to the initial attentional bias and aversive motivational processes mapped on to the subsequent attentional avoidance (see Field et al., [@B13], for discussion). Consistent with this interpretation, a recent eye tracking study demonstrated that heavy drinkers who were identified as ambivalent (as assessed with the AAAQ) had an approach-avoidance pattern of attentional bias for alcohol cues (i.e., the initial attentional bias quickly followed by attentional avoidance that is characteristic of alcohol-dependent patients), whereas heavy drinkers who were not ambivalent maintained their attentional bias for alcohol cues (Lee et al., [@B24]).
Automatic approach and avoidance tendencies evoked by alcohol-related cues have been assessed with the alcohol-related stimulus-response compatibility (SRC) task (Field et al., [@B11]) and related tasks (Wiers et al., [@B48]). These tasks reveal that in heavy drinkers who are not seeking treatment, alcohol cues evoke automatic approach tendencies (Field et al., [@B11], [@B9]; Wiers et al., [@B48]; Christiansen et al., [@B5]; Sharbanee et al., [@B37],[@B38]; Kersbergen et al., [@B18]), and in some studies the strength of these approach tendencies was associated with the strength of subjective craving (Field et al., [@B12], [@B11]). A different pattern is seen in alcohol-dependent patients: one study reported no reliable tendency to approach or avoidance (Barkby et al., [@B2]) whereas another study found an automatic avoidance tendency, the strength of which was predictive of subsequent relapse (Spruyt et al., [@B40]). One explanation for these findings is that the standard version of the SRC task yields an index of automatic approach that is *relative* to avoidance. This means that the pattern that is observed in heavy drinkers who are not seeking treatment (Field et al., [@B11], [@B9]; Christiansen et al., [@B5]; Kersbergen et al., [@B18]) could be attributed to strong automatic approach, weak automatic avoidance, or a combination of the two. Among alcohol-dependent patients, if alcohol cues simultaneously evoke strong automatic approach at the same time as strong automatic avoidance, this may explain why this population display either no overall bias (Barkby et al., [@B2]) or an avoidance bias (Spruyt et al., [@B40]) depending on the strength of their motivational orientations to avoid alcohol at the time of testing.
Findings from the cross-sectional and prospective studies described above are consistent with the ambivalence model (Breiner et al., [@B3]) because they suggest that approach and avoidance motivational orientations for alcohol may exist independently of each other, rather than lying at opposite ends of a single continuum. More compelling evidence for the independence of approach and avoidance can be derived from experimental studies that attempt to influence one motivational orientation (approach or avoidance) in order to investigate if the opposing motivational orientation is (un)affected. Regarding automatic processes, we recently demonstrated that subliminal priming of approach or avoidance motivational orientations for alcohol had no effect on attentional biases or automatic approach or avoidance tendencies, although methodological issues complicated interpretation of those findings (Baker et al., [@B1]). Regarding controlled processes, several studies investigated the effects of exposure to alcohol cues on self-reported approach and avoidance inclinations for alcohol, and all reported findings that were suggestive of partially independent approach and avoidance responses to those cues (Curtin et al., [@B7]; Jones et al., [@B17]; Schlauch et al., [@B33],[@B34]). For example, in one study exposure to alcohol cues (pouring, holding, and sniffing a beer) led to increases in approach inclinations (AAAQ inclined-indulgent and obsessed-compelled subscales), but avoidance inclinations (AAAQ resolved-regulated subscale) were unaffected (Jones et al., [@B17]).
Although these studies are informative, a more rigorous experimental test of the independence of approach and avoidance would be to contrast the effects of experimental manipulations that are intended to increase approach or avoidance motivational orientations for alcohol. To achieve this, we were inspired by methods used in a previous study (Roefs et al., [@B31]) in which participants\' automatic processing of food-related words was assessed in contexts that were intended to activate either approach (focusing on the preparation of a tasty meal) or avoidance (focusing on the importance of a healthy diet, and therefore avoiding unhealthy foods). In the present studies, participants viewed short videos that depicted either the positive or negative aspects of alcohol consumption, which should in principle activate approach or avoidance, respectively. Control groups of participants viewed videos that were unrelated to alcohol consumption. Immediately after watching the videos, participants completed the AAAQ (all studies) followed by computerized measures of attentional bias (study 1) and automatic approach and avoidance tendencies (studies 2 and 3). In addition, in study 3 we investigated if thought suppression (see Moss et al., [@B27]) would moderate the influence of videos on implicit measures.
Our general hypotheses were that the video depicting the positive consequences of alcohol consumption would increase self-reported approach (inclined-indulgent and obsessed-compelled subscales of the AAAQ) and indices of automatic approach (attentional bias in study 1, automatic approach tendencies in studies 2 and 3), but would not influence self-reported and automatic avoidance, as assessed by the resolved-regulated subscale of the AAAQ and attentional avoidance (study 1) and automatic avoidance tendencies (studies 2 and 3), respectively. By contrast, the video depicting the negative consequences of alcohol consumption would increase self-reported and automatic indices of avoidance, but indices of approach would be unaffected.
Study 1 {#s2}
=======
The alcohol-related visual probe task (see Field et al., [@B14]) is a computerized measure of attentional bias that can distinguish between attentional bias toward and attentional bias away from alcohol-related pictorial stimuli (hereafter referred to as *attentional avoidance*). In each trial of the task, an alcohol-related picture and a matched neutral picture are briefly presented on opposite sides of a computer screen before a visual probe replaces one of the pictures. Participants\' manual reaction times to probes are used to infer biases in the allocation of visuospatial attention. An attentional bias for alcohol cues is inferred if the participant is faster to react to probes that replace alcohol pictures (congruent trials), rather than probes that replace neutral pictures (incongruent trials). If, however, this pattern is reversed (i.e., if the participant is faster to respond on incongruent trials), this is interpreted as attentional avoidance of alcohol cues. Biases in automatic attentional capture or delayed disengagement of attention can be inferred by comparing reaction times on these trials with those on other trials in which only neutral pictures are presented (Koster et al., [@B22]; see Baker et al., [@B1]). Although the literature on group differences is inconsistent (see Field and Cox, [@B10]), several studies demonstrated that heavy drinkers who are not seeking treatment have an attentional bias for alcohol cues when those cues are presented for 500 ms or longer (Townshend and Duka, [@B43]; Field et al., [@B14]; Baker et al., [@B1]), and this has been corroborated by studies of eye movements toward those cues (Lee et al., [@B24]). Conversely, alcohol-dependent patients who are tested in treatment settings show initial attentional bias for briefly-presented alcohol cues (50--100 ms), that is followed by attentional avoidance when those cues are presented for longer periods (upwards of 500 ms; Stormark et al., [@B42]; Noël et al., [@B28]; Townshend and Duka, [@B44]; Vollstädt-Klein et al., [@B45]; Field et al., [@B13]).
In the present study, participants watched a brief video that depicted either the positive consequences of alcohol consumption (alcohol-positive group), the negative consequences of alcohol consumption (alcohol-negative group), or that had no alcohol-related content (control group). Immediately after watching the video, participants completed the AAAQ and an alcohol-related visual probe task in which picture pairs were presented for 50 or 500 ms. We hypothesized that, relative to the control group, participants in the alcohol-positive group would have elevated scores on the inclined-indulgent and obsessed-compelled subscales of the AAAQ, and elevated attentional bias for alcohol cues presented for both 50 and 500 ms; however, scores on the resolved-regulated subscale of the AAAQ would not differ between alcohol-positive and control groups. By contrast, compared to the control group, participants in the alcohol-negative group would have elevated scores on the resolved-regulated subscale of the AAAQ and would exhibit an "approach-avoidance" pattern of attentional bias on the visual probe task, with bias toward alcohol cues presented for 50 ms followed by attentional avoidance of those cues presented for 500 ms; however, scores on the inclined-indulgent and obsessed-compelled subscales of the AAAQ would not differ between the alcohol-negative and control groups.
Methods
-------
### Participants
Ninety participants (69 Female, mean age 21.70, *SD* = 5.04) were recruited from the students and staff at the University of Liverpool via online and poster advertising. Inclusion criteria included fluency in English, age between 18 and 45, normal or corrected-to-normal vision and self-reported alcohol consumption in excess of the current UK government guidelines for safe drinking (these are 14 units per week for females and 21 units per week for males, where 1 unit equals 8 g of alcohol). Exclusion criteria included any history of alcohol use disorders. Participants who had taken part in studies 2 or 3 were ineligible to participate. All participants provided informed consent before taking part in the study, which was approved by the University of Liverpool Research Ethics Committee.
### Materials
#### Self-report measures
#### Timeline followback drinking diary (Sobell and Sobell, [@B39])
Participants indicated their alcohol consumption over the previous 2 weeks. From this, we were able to calculate the total amount of alcohol consumed in standard UK units.
#### Alcohol use disorders identification test (AUDIT; Saunders et al., [@B32])
This 10-item self-report questionnaire contains questions about frequency and quantity of alcohol consumption, and alcohol-related problems and harms. It yields a total score ranging between 0 and 40, with scores of 8 or above indicative of hazardous drinking.
#### Approach and avoidance of alcohol questionnaire, right now version (AAAQ; McEvoy et al., [@B25])
This 14-item questionnaire assesses subjective tendencies to approach or avoid drinking at that moment in time. Respondents are asked to rate how strongly they agree with each item on a 9-point Likert scale, from 0 (not at all) to 8 (very strong). There are three underlying sub-scales: "Inclined-Indulgent" (mild approach, akin to desire to drink) "Obsessed-Compelled" (strong approach, akin to obsessive thoughts about drinking); and "Resolved-Regulated" (motivation to avoid drinking).
#### Positive and negative affect schedule (PANAS; Watson et al., [@B46])
The PANAS is a 20-item Likert scale that yields scores on positive affect (PA) and negative affect (NA). Results are reported in the Supplementary Materials.
#### Video questionnaire
This eight-item questionnaire was developed to measure participants\' perception of and engagement with the videos. Participants responded to each item on a 5-point Likert scale, with labels ranging from "strongly disagree" to "strongly agree." Items are shown in Tables [S2A](#SM4){ref-type="supplementary-material"}--[C](#SM4){ref-type="supplementary-material"}.
#### Visual probe task (for similar tasks see Field et al., [@B9]; Koster et al., [@B22])
This task was programmed in Psychopy v.1.74 (Peirce, [@B30]) and was administered on a desktop computer with a 15-inch monitor. On each trial, a small white fixation cross was presented in the center of the screen for 500 ms. Immediately after offset, a pair of pictures (each 65 mm high × 80 mm wide) was presented on the left and right of the screen, 130 mm apart, for either 50 or 500 ms. Immediately after the screen was cleared, the visual probe (a small white arrow that pointed up or down) was presented on either the left or right side of the screen, in the position that had been occupied by one of the pictures. The probe remained on the screen until participants made a response by pressing a key labeled "up" or "down" on the computer keyboard.
Participants were instructed to rest the index fingers of their left and right hands on the "up" and "down" keys, to fixate on the fixation cross at the beginning of each trial, and to rapidly categorize the visual probe as soon as it appeared. The latency and accuracy of responses were recorded. There was an initial practice block of 10 trials in which four pairs of affectively neutral pictures, taken from the International Affective Picture System (IAPS; Lang et al., [@B23]) were presented. The main block of trials then followed, and this comprised two different types of trials: alcohol-neutral trials, and neutral-neutral trials. For alcohol-neutral trials, a set of seven alcohol-related pictures were each paired with neutral pictures that depicted items of stationery. We used a subset of picture pairs that had been used in earlier studies (Field et al., [@B9]; Barkby et al., [@B2]) and the pictures in each pair were matched on perceptual characteristics including brightness and complexity. On neutral-neutral trials, we used four pairs of affectively neutral pictures from the IAPS, as described above. During the main block of trials, there were 112 alcohol-neutral trials and 64 neutral-neutral trials. Each picture pair was presented 16 times, and picture location (left or right), stimulus onset asynchrony (SOA; 50 or 500 ms), probe position (left or right) and probe type (up or down arrow) were counterbalanced for all picture pairs. Trials were presented in a random order.
#### Video stimuli
We created three different videos in order to manipulate participants\' inclinations to drink alcohol or to refrain from drinking. Videos were created in Windows Movie Maker (version 2.6) and were presented in Windows Media Player (version 7) player in full-screen mode on the computer. Participants wore headphones while watching the videos, all of which were 3 min and 45 s in duration. All video files are available from the Corresponding Author on request.
The *alcohol-positive* video was intended to evoke motivational inclinations to approach alcohol. It comprised still images depicting people having fun while drinking alcohol, together with some text slides that provided information about the positive consequences of drinking and was accompanied by an upbeat soundtrack. The *alcohol-negative* video was intended to evoke motivational inclinations to avoid alcohol. It comprised still images depicting the negative consequences of drinking, including scenes of alcohol-related violence and vomiting, and other slides depicting graphic government advertisements that warned of the consequences of drink-driving and alcohol-related organ damage and was accompanied by a downbeat soundtrack. The *neutral* video comprised still photos of office equipment and furniture, and was accompanied by non-descript jazz music. All images were obtained using a Google Images search.
### Procedure
Participants were randomly allocated to experimental condition. They were tested in a laboratory in the Department of Psychological Sciences at the University of Liverpool. After providing informed consent participants completed the timeline follow back drinking diary, AUDIT, AAAQ, and PANAS (time 1). Then, participants put on the headphones and watched one of the videos (depending on experimental condition), before completing the Video Questionnaire and the AAAQ and PANAS again (time 2). Finally, participants completed the visual probe task. After completing the study, participants were debriefed and offered either course credit or a £5 Shopping Voucher to compensate them for their time.
Results
-------
### Group characteristics
Participants reported consuming 20.55 (*SD* = 11.53) units of alcohol per week, and the mean score on the AUDIT was 12.18 (*SD* = 5.28). There were no between-group differences in weekly alcohol consumption or AUDIT scores (Kruskal--Wallis tests *ps* \> 0.09), although there was a trend for participants in the alcohol-positive group to be older than participants in the other two groups (Kruskal--Wallis *p* = 0.05). There were no group differences in gender ratio (χ^2^ = 0.45, *p* \> 0.1).
### Effects of video manipulation on AAAQ ratings (Figure [1A](#F1){ref-type="fig"})
AAAQ ratings were analyzed using a mixed design ANOVA, with within-subject factors of sub-scale (3: inclined-indulgent, obsessed-compelled, resolved-regulated), time (2: before video, after video), and group (3: alcohol-positive, alcohol-negative, control). The sub-scale x time x group interaction was statistically significant \[*F*~(4,\ 174)~ = 27.05, *p* \< 0.001\]. Subsequent *post-hoc* ANOVAs confirmed that the time x group interaction was significant for all three sub-scales \[inclined-indulgent *F*~(2,\ 87)~ = 25.29, *p* \< 0.001\]; obsessed-compelled *F*~(2,\ 87)~ = 5.72, *p* \< 0.01; resolved-regulated *F*~(2,\ 87)~ = 28.32, *p* \< 0.001\].
{#F1}
There were no group differences on any of the AAAQ sub-scales before participants watched the video \[inclined-indulgent *F*~(2,\ 89)~ = 1.12, *p* \> 0.1; obsessed-compelled *F*~(2,\ 89)~ = 0.26, *p* \> 0.1; resolved-regulated *F*~(2,\ 89)~ = 0.22, *p* \> 0.1\]. As predicted, groups differed on all three sub-scales after watching the video, \[inclined-indulgent *F*~(2,\ 89)~ = 9.13, *p* \< 0.001; resolved-regulated *F*~(2,\ 89)~ = 17.57, *p* \< 0.01\], although this fell short of significance for the obsessed-compelled sub-scale \[*F*~(2,\ 89)~ = 2.93, *p* = 0.059\]. *Post-hoc* LSD contrasts confirmed that scores on both the inclined-indulgent and obsessed-compelled sub-scales were higher in the alcohol-positive group compared to the alcohol-negative group (*ps* \< 0.01), but this pattern was reversed for the resolved-regulated subscale (*p* \< 0.01). The direct test of our hypotheses requires contrasts between these groups and the control group. These contrasts revealed that alcohol-positive and control groups did not differ on any subscale (*p* \> 0.1). However, scores on the resolved-regulated subscale were higher, and scores on the inclined-indulgent subscale lower, in the alcohol-negative compared to the control group (*ps* \< 0.01). Alcohol-negative and control groups did not differ on the obsessed-compelled subscale (*p* \> 0.1).
Paired-samples *t*-tests revealed that among participants in the alcohol-positive group, scores on the inclined-indulgent and obsessed-compelled sub-scales increased after watching the video \[*t*~(28)~ = 2.92, *p* \< 0.01 and *t*~(28)~ = 2.29, *p* \< 0.05\], whereas scores on the resolved-regulated sub-scale did not change \[*t*~(28)~ = 0.61, *p* \> 0.1\]. A different pattern was seen in the alcohol-negative group: inclined-indulgent and obsessed-compelled scores decreased \[*t*~(31)~ = 6.41, *p* \< 0.001 and *t*~(31)~ = 2.24, *p* \< 0.05\], whereas scores on the resolved-regulated sub-scale increased \[*t*~(31)~ = 6.34, *p* \< 0.001\]. In the control group, scores on both the inclined-indulgent and resolved-regulated sub-scales decreased after watching the video, although the former failed to reach significance \[*t*~(28)~ = 1.95, *p* = 0.06 and *t*~(28)~ = 2.66, *p* \< 0.05\]; scores on the obsessed-compelled sub-scale did not change \[*t*~(29)~ = 0.30, *p* \> 0.1\].
We also re-ran the omnibus Three-Way ANOVA on AAAQ scores but added PANAS positive and PANAS negative affect after the video as covariates. The three way interaction sub-scale × time × group remained statistically significant \[*F*~(4,\ 170)~ = 17.25, *p* \< 0.001\]. Therefore, statistically controlling for positive and negative mood at the time did not modify the influence of the videos on the AAAQ.
### Visual probe task (Table [1](#T1){ref-type="table"})
Data were analyzed in accordance with previous studies (e.g., Field et al., [@B14]). Firstly, trials with errors were discarded, and then outlying reaction times were removed if they were faster than 200 ms, slower than 2000 ms, and then if they were more than three standard deviations above the individual mean. All data from three participants were excluded as they had an outlying high rate (\>28%) of missing data due to errors and outliers. For the remainder of the sample, on average 7% of trials were missing due to errors and a further 1% due to outliers, and these values did not differ between groups (*ps* \> 0.1).
######
**Mean reaction times (in milliseconds) from the different trials of the visual probe task in study 1**.
**Alcohol-positive** **Alcohol-negative** **Control**
--------------------- ---------------------- ---------------------- ----------------
**50 ms TRIALS**
Congruent alcohol 732.20 ± 59.29 725.82 ± 70.42 710.73 ± 67.41
Incongruent alcohol 734.37 ± 58.31 726.36 ± 73.72 699.75 ± 67.06
Neutral-neutral 729.02 ± 53.73 729.39 ± 73.26 699.35 ± 65.39
**500 ms TRIALS**
Congruent alcohol 669.01 ± 59.49 670.54 ± 62.12 654.20 ± 68.86
Incongruent alcohol 680.24 ± 43.37 670.88 ± 62.30 664.84 ± 60.43
Neutral-neutral 675.89 ± 48.14 671.86 ± 67.49 648.36 ± 73.90
*Values are means ± SD*.
Mean reaction times for different trial types and SOAs were analyzed using a 3 × 2 × 3 mixed design ANOVA, with within-subject factors of trial type (3: congruent alcohol trials, incongruent alcohol trials, neutral-neutral trials) and SOA (2: 50, 500 ms), and a between-subjects factor of group. The predicted trial type x SOA x group interaction was not statistically significant \[*F*~(4,\ 170)~ = 1.16, *p* \> 0.1\]. There was a significant main effect of SOA \[*F*~(1,\ 85)~ = 390.10, *p* \< 0.001\], indicating faster reaction times on 500 ms trials compared to 50 ms trials. Importantly, the non-significant main effect of trial type \[*F*~(2,\ 84)~ = 1.09, *p* \> 0.1\], and trial type × SOA interaction \[*F*~(2,\ 84)~ = 2.12, *p* \> 0.1\] demonstrate that there was no reliable attentional bias for alcohol cues overall, at either SOA.
Discussion
----------
Overall, results from this study did not support the independence of approach and avoidance orientations for alcohol in either controlled or automatic processes. Data from the AAAQ could be interpreted as independence of self-reported approach and avoidance inclinations for alcohol after watching a video depicting the positive consequences of alcohol consumption, because participants who watched this video reported an increase in self-reported approach inclinations (inclined-indulgent and obsessed-compelled subscales) but no corresponding reduction in avoidance inclinations (the resolved-regulated subscale). However, a video that depicted the negative consequences of alcohol consumption prompted an increase in self-reported avoidance inclinations (the resolved-regulated subscale) in parallel with a decrease in self-reported approach inclinations (the inclined-obsessed and resolved-regulated subscales). Comparisons between these groups and a control group revealed that approach and avoidance inclinations were similar in the control group and the group that had watched the video depicting the positive consequences of alcohol consumption, whereas approach inclinations were lower, and avoidance inclinations higher, in the group that had watched the video depicting the negative consequences of alcohol consumption, compared to the control group.
The visual probe task revealed no evidence of attentional bias or attentional avoidance of alcohol cues in any group (or in the sample as a whole), therefore our hypotheses regarding the influence of the videos on attentional bias can be rejected. One interpretation is that attentional bias is insensitive to experimental manipulations of the motivation to drink or to avoid alcohol, although the absence of attentional bias in the control group argues against this interpretation. In the next study we repeated the general methodology of study 1 so that we were again able to investigate the effects of the different videos on self-reported approach and avoidance of alcohol. Given the null results from the visual probe task, we omitted this task and replaced it with a measure of automatic approach and avoidance tendencies for alcohol cues.
Study 2 {#s3}
=======
In the alcohol version of the stimulus-response compatibility (SRC) task (Field et al., [@B11]), a manikin is presented on a computer screen either above or below an alcohol-related or neutral picture. Participants must move the manikin toward or away from the pictures as quickly as possible. On some blocks of the task, participants must make the manikin move toward alcohol pictures and away from neutral pictures, whereas these instructions are reversed in other blocks of the task. Automatic approach tendencies for alcohol cues are inferred if participants are faster to respond on blocks of the task when alcohol pictures require the "approach" movement in comparison to blocks when alcohol pictures require the "avoidance" movement. By contrast, if participants are faster on the "avoid alcohol" blocks compared to the "approach alcohol" blocks, this would suggest that alcohol cues evoke automatic avoidance tendencies. Heavy drinkers who are not seeking treatment display automatic approach tendencies for alcohol cues (Field et al., [@B11], [@B9]; Christiansen et al., [@B5]; Kersbergen et al., [@B18]), whereas alcohol-dependent patients may show the opposite pattern, i.e., they are faster to avoid rather than approach alcohol-related pictures (Spruyt et al., [@B40]; but see Barkby et al., [@B2]).
Findings obtained from the standard version of the SRC task must be interpreted cautiously because this task yields an index of automatic approach that is *relative* to automatic avoidance, therefore an apparent bias in automatic approach could be attributed to either strong automatic approach, weak automatic avoidance, or a combination of the two. Among alcohol-dependent patients, if alcohol cues simultaneously evoke strong automatic approach at the same time as strong automatic avoidance, this may explain why they display either no reliable bias on the task (Barkby et al., [@B2]) or a bias to faster avoidance (Spruyt et al., [@B40]) depending on the strength of their automatic tendencies to avoid alcohol at the time of testing. In the present study, we overcame this limitation by modifying the task so that it is able to distinguish automatic alcohol approach and avoidance tendencies from each other. This modified version of the task includes neutral movements (to the side) in addition to the standard approach and avoidance movements, and is split into four blocks instead of two (see Baker et al., [@B1]).
The present study was identical to study 1 with the important difference that participants completed a modified SRC task instead of the visual probe task that was used in study 1. We hypothesized that we would replicate the effects of the videos on the AAAQ that were observed in study 1. Regarding the indices of approach and avoidance tendencies from the SRC task, we hypothesized that, relative to the control group, participants in the alcohol-positive group would show stronger automatic alcohol approach tendencies but these groups would not differ in automatic avoidance tendencies. By contrast, relative to the control group we anticipated stronger automatic avoidance tendencies in the alcohol-negative group, but these two groups would not differ in automatic approach tendencies.
Methods
-------
### Participants
Ninety participants (56 Female, mean age 24.56, *SD* = 5.34) were recruited from the local community and students and staff at the University of Liverpool via online and poster advertising. Inclusion and exclusion criteria were identical to those described for study 1. Participants who had taken part in studies 1 or 3 were ineligible to participate. Participants provided informed consent before taking part in the study, which was approved by the University of Liverpool Research Ethics Committee.
### Materials
#### The modified stimulus-response compatibility task
The modified stimulus-response compatibility Task (Baker et al., [@B1]) is used to measure automatic approach and avoidance responses evoked by alcohol-related cues. Participants are instructed to rapidly categorize alcohol-related and stationery-related (control) pictures by moving a manikin either toward or away from the pictures, or to the left (neutral movement), as quickly as possible by pressing one of three specific keys on the keyboard, which were labeled with arrows pointing up, down, and left. The task was programmed in Inquisit software (Millisecond Software, [@B26]) and presented on a laptop computer with a 13 inch screen.
The format of the task, trial structure, and perceptual characteristics of the pictorial stimuli were identical to those used in previous studies (Field et al., [@B9]; Barkby et al., [@B2]). Fourteen colored pictures (a subset of the picture set used in Barkby et al., [@B2]) were used in the task: seven pictures of alcoholic drinks and close-ups of individuals holding or consuming those drinks, and seven control pictures of stationery items and close-ups of models interacting with those items.
There were four sub-blocks of the task, which differed according to task instructions. In the "approach alcohol" block, participants were required to move the manikin toward alcohol pictures, and to the left for stationery pictures. In the "avoid alcohol" block, participants moved away from alcohol pictures and to the left for stationery pictures. In the "approach control" block, participants moved toward stationery pictures and to the left for alcohol pictures. Finally, in the "avoid control" block, participants moved away from stationery pictures and to the left for alcohol pictures. Note that in the case of approach and avoidance movements, the position of the manikin was crucial: if the manikin was above the picture, an "approach" response required participants to press the "down" key, and an "avoidance" response required participants to press the "up" key. This was reversed if the manikin was below the picture. Participants were instructed to respond quickly and accurately on each trial. If they pressed the correct key, the manikin moved up, down or to the left in an animation lasting 500 ms. If they pressed the wrong key, error feedback was provided in the form of a large red cross presented in the center of the screen for 500 ms. There was an inter-trial interval of 500 ms.
Each sub-block of the task comprised four practice trials, in which two alcohol pictures and two control pictures were presented, once with the manikin above each picture type and once with the manikin below. If participants did not understand the task, this practice block was repeated. There then followed 28 "critical" trials, in which each of the 14 pictures was presented twice: once with the manikin above the picture and once with the manikin below. Trials were presented in a new random order for each participant. Participants completed the sub-blocks in a counterbalanced order. Responses and reaction times (in milliseconds) to initiate the manikin movement were recorded on each trial.
### Procedure
Participants were randomly allocated to experimental conditions. They were tested in a laboratory in the Department of Psychological Sciences or in quiet public places in which alcohol was not available (e.g., cafes and libraries). After providing informed consent, participants completed the timeline followback drinking diary, AUDIT, AAAQ, and PANAS (time 1). Then, participants put on the headphones and watched one of the videos, before completing the Video Questionnaire and the AAAQ and PANAS again (time 2). Finally, participants completed the SRC task. After completing the study, participants were debriefed and offered either course credit or a £5 Shopping Voucher to compensate them for their time.
Results
-------
### Group characteristics
Participants reported consuming 30.21 (*SD* = 23.53) units of alcohol per week, and the mean score on the AUDIT was 12.85 (*SD* = 5.34). There were no between-group differences in age, weekly alcohol consumption, or AUDIT scores (all Kruskal--Wallis tests *p* \> 0.1). There were no group differences in gender ratio (χ^2^ = 0.66, *p* \> 0.1).
### Effects of video manipulation on AAAQ ratings (Figure [1B](#F1){ref-type="fig"})
AAAQ ratings were analyzed using a mixed design ANOVA, with within-subject factors of sub-scale (3: inclined-indulgent, obsessed-compelled, resolved-regulated), time (2: before video, after video), and group (3: alcohol-positive, alcohol-negative, control). The sub-scale × time × group interaction was statistically significant \[*F*~(4,\ 174)~ = 19.16, *p* \< 0.001\]. Subsequent *post-hoc* ANOVAs confirmed that the time x group interaction was significant for all three sub-scales \[inclined-indulgent *F*~(2,\ 87)~ = 19.67, *p* \< 0.001\]; obsessed-compelled *F*~(2,\ 87)~ = 5.28, *p* \< 0.01; resolved-regulated *F*~(2,\ 87)~ = 13.80, *p* \< 0.001\].
Groups did not differ on the inclined-indulgent \[*F*~(2,\ 89)~ = 1.56, *p* \> 0.1\] or obsessed-compelled \[*F*~(2,\ 89)~ = 1.26, *p* \> 0.1\] sub-scales before watching the video. However, there was a group difference in the resolved-regulated sub-scale before the video \[*F*~(2,\ 89)~ = 3.90, *p* \< 0.05\], and *post-hoc* LSD contrasts revealed that scores were lower in the control group compared to both the alcohol-positive and alcohol-negative groups (*p* \< 0.05), who did not differ from each other (*ps* \> 0.1). As predicted, groups differed on all three sub-scales after watching the video \[inclined-indulgent *F*~(2,\ 89)~ = 10.78, *p* \< 0.001; obsessed-compelled *F*~(2,\ 89)~ = 4.85, *p* = 0.01; resolved-regulated *F*~(2,\ 89)~ = 20.78, *p* \< 0.001\]. *Post-hoc* LSD contrasts revealed that scores on both inclined-indulgent and obsessed-compelled sub-scales were higher in the alcohol-positive group compared to both alcohol-negative and control groups (*p* \< 0.01), who did not differ from each other (*p* \> 0.1). On the other hand, scores on the resolved-regulated sub-scale were higher in the alcohol-negative group compared to both alcohol-positive and neutral groups (*ps* \< 0.01), who did not differ from each other (*p* \> 0.08).
Paired-samples *t*-tests revealed that among participants in the alcohol positive group, scores on the inclined-indulgent and obsessed-compelled sub-scales increased after watching the video \[*t*~(29)~ = 2.74, *p* = 0.01 and *t*~(29)~ = 2.84, *p* \< 0.01\], whereas scores on the resolved-regulated sub-scale decreased \[*t*~(29)~ = 2.90, *p* \< 0.01\]. The reverse pattern was seen in the alcohol negative group: the decrease in inclined-indulgent ratings and the increase in resolved-regulated ratings after watching the video were statistically significant \[*t*~(29)~ = 6.70, *p* \< 0.001 and *t*~(29)~ = 3.15, *p* \< 0.01\], although there was no significant change in scores on the obsessed-compelled sub-scale \[*t*~(29)~ = 0.32, *p* \> 0.1\]. In the control group, scores on both the inclined-indulgent and resolved-regulated sub-scales decreased after watching the video \[*t*~(29)~ = 2.56, *p* \< 0.05 and *t*~(29)~ = 2.63, *p* \< 0.05\], but scores on the obsessed-compelled sub-scale did not change \[*t*~(29)~ = 0.27, *p* \> 0.1\].
We also re-ran the omnibus Three-Way ANOVA on AAAQ scores but added PANAS positive and PANAS negative affect after the video as covariates. The three way interaction sub-scale × time × group remained statistically significant \[*F*~(4,\ 170)~ = 9.55, *p* \< 0.001\]. Therefore, statistically controlling for positive and negative mood at the time did not influence the influence of the videos on the AAAQ.
### SRC task (Table [2](#T2){ref-type="table"})
Data were analyzed in accordance with previous studies (e.g., Field et al., [@B9]). Firstly, trials with errors were discarded, and then outlying reaction times were removed if they were faster than 200 ms, slower than 2000 ms, and then if they were more than three standard deviations above the individual mean. All data from three participants were excluded as they had an outlying high rate (\> 40%) of missing data due to errors and outliers. For the remainder of the sample, on average 5% of trials were missing due to errors and a further 9% due to outliers, and these values did not differ between groups (*ps* \> 0.1).
######
**Mean reaction times (in milliseconds) from the different blocks of the SRC task in study 2**.
**Alcohol-positive** **Alcohol-negative** **Control**
--------------------- ---------------------- ---------------------- -----------------
Approach alcohol 826.51 ± 165.05 855.10 ± 186.92 871.38 ± 208.88
Approach stationery 855.99 ± 198.96 878.74 ± 186.11 917.37 ± 195.66
Avoid alcohol 835.32 ± 133.79 893.49 ± 207.91 895.22 ± 208.31
Avoid stationery 878.81 ± 174.65 918.22 ± 202.01 902.41 ± 211.75
*Values are means ± SD*.
Mean reaction times in the different blocks of the task were then analyzed using a mixed design 2 × 2 × 3 ANOVA, with within-subject factors of movement type (2: approach, avoidance) and picture type (2: alcohol, stationery; this refers to the type of picture that the approach or avoidance movement had to be directed toward or away from, with the sideways movement required for the other type of picture), and a between-subjects factor of group. The hypothesized three way interaction was not statistically significant \[*F*~(2,\ 84)~ = 0.80, *p* \> 0.1\]. There were, however, significant main effects of picture type \[*F*~(1,\ 84)~ = 4.75, *p* \< 0.05; participants were faster to respond on blocks when the approach or avoidance movement had to be made in response to alcohol pictures rather than stationery pictures\], and movement type \[*F*~(1,\ 84)~ = 4.82, *p* \< 0.05; participants were faster on "approach" blocks than "avoid" blocks of the task). The picture type x movement type interaction was not statistically significant \[*F*~(1,\ 84)~ = 0.19, *p* \> 0.1\]. Overall, these results show that participants were faster to make approach rather than avoidance movements, and they were faster to make both approach and avoidance movements in response to alcohol pictures in comparison to stationery pictures. However, the video manipulation had no effect on performance on the task.
Discussion
----------
Consistent with results from study 1, results from this study did not provide clear support for the independence of self-reported approach and avoidance inclinations for alcohol following an experimental manipulation of those inclinations. Between-group contrasts demonstrated that, relative to the control group, scores on the inclined-indulgent and obsessed-compelled subscales of the AAAQ were elevated in participants who had watched a video depicting the positive consequences of alcohol consumption, but this video did not influence scores on the resolved-regulated subscale. The complete opposite pattern was seen in participants who had watched a video depicting the negative consequences of alcohol consumption: increased scores on the resolved-regulated subscale, but there was no difference between this group and the control group in scores on the inclined-indulgent and obsessed-compelled subscales. These contrasts support predictions made by the ambivalence model of craving (Breiner et al., [@B3]), because they suggest that it is possible to experimentally manipulate subjective approach and avoidance inclinations for alcohol independently of each other. Unfortunately, this conclusion must be heavily caveated given the presence of group differences on the resolved-regulated subscale at baseline, and because within-subject contrasts suggest that increases in approach inclinations were accompanied by decreases in avoidance inclinations in the alcohol positive group, and vice versa for the alcohol negative group.
The data from the SRC task also did not support our hypotheses: there was no evidence that participants were faster to approach or slower to avoid alcohol cues compared to stationery (control) cues, and the experimental manipulation did not influence the task. Therefore, even though our experimental manipulation had a clear influence on self-reported approach and avoidance inclinations for alcohol, there were no parallel changes in automatic approach or avoidance tendencies evoked by alcohol cues. In our third and final study, we again investigated the influence of alcohol-positive and alcohol-negative videos on self-reported (AAAQ) and automatic (modified SRC task) indices of approach and avoidance motivational orientations for alcohol, but we combined this with an experimental manipulation of thought suppression in an attempt to maximize the influence of the video manipulation on automatic measures of approach and avoidance.
Study 3 {#s4}
=======
People who are attempting to reduce their alcohol consumption often attempt to suppress unwanted thoughts, such as intrusive cravings, in order to achieve their goal (Moss et al., [@B27]). Unfortunately, thought suppression has unwelcome consequences because it increases, rather than decreases the frequency of intrusive thoughts that are the target of suppression, but only when competing demands are placed on cognitive resources (Wenzlaff and Wegner, [@B47]). Indeed, attempting to suppress thoughts about alcohol paradoxically increases the accessibility of alcohol-related cognitions as evidenced by increased attentional bias for alcohol words (Klein, [@B21]) and accessibility of alcohol-related semantic associations (Palfai et al., [@B29]).
We hypothesized that if participants were primed to think about the positive or negative consequences of alcohol consumption and were then instructed to suppress those thoughts, this should provoke an increase in the accessibility of those thoughts that would manifest itself as a bias in automatic approach or avoidance tendencies in response to alcohol cues. Specifically, participants who viewed a video depicting the positive consequences of alcohol and then attempted to suppress thoughts about alcohol should have stronger automatic approach tendencies for alcohol cues compared to participants who watched the same video but did not attempt to suppress their thoughts. We expected comparable moderating effects of thought suppression on automatic avoidance tendencies in participants who watched a video depicting the negative consequences of alcohol.
Methods
-------
### Participants
One hundred participants (53 Female, mean age 27.87, *SD* = 6.97) were recruited from the local community and students and staff at the University of Liverpool via online and poster advertising. Inclusion and exclusion criteria were identical to those described for studies 1 and 2. Participants who had taken part in studies 1 or 2 were ineligible to participate. All participants provided informed consent before taking part in the study, which was approved by the University of Liverpool Research Ethics Committee.
### Procedure
Participants were randomly allocated to one of four experimental conditions: (1) alcohol-positive video combined with thought suppression, (2) alcohol-positive video combined with control manipulation, (3) alcohol-negative video combined with thought suppression, or (4) alcohol-negative video combined with control manipulation. Note that none of the participants in this study watched the neutral video that we used in studies 1 and 2. Participants were tested in a laboratory in the Department of Psychological Sciences or in quiet public places in which alcohol was not served (e.g., cafes, libraries). After providing informed consent, participants completed the timeline follow back drinking diary, AUDIT, AAAQ, and PANAS (time 1). Then, participants put on the headphones and watched one of the videos, before completing the Video Questionnaire and the AAAQ and PANAS again (time 2).
Participants in the thought suppression groups were then instructed to think about anything, but to make every effort to suppress thoughts of alcohol; the importance of the latter was emphasized. Participants in the control groups were instructed to think about anything that came to mind, including alcohol. All participants were then given a 5 min to think freely and to write notes about what they were thinking about on a piece of paper. They were also instructed to place a mark in the right hand margin of the paper each time they thought about alcohol; these marks were subsequently counted up and cross-checked with the content of participants\' notes.
Immediately after this 5-min period, participants were asked to respond to two questions by placing a mark on 100 ms visual analog scales (VAS). The questions, which were the same for both groups, were: "To what extent did you think about alcohol"? (anchors "I did not think about alcohol at all" and "I thought about alcohol a lot") and "To what extent did you succeed in complying with the instructions" (anchors "totally unsuccessful" and "totally successful").
Participants then completed the SRC task. The thought suppression or control instructions were re-iterated to participants before each block of the task. In order to increase demands on working memory, participants were given a seven-digit number at the beginning of each sub-block of the task. They were given 50 s to memorize the number and then instructed to hold it in memory, as they would be asked to recall it at the end of each sub-block of the task. Recall of this number was recorded at the end of each sub-block and the process was repeated with a different number at the beginning of each sub-block (see Bryant et al., [@B4]). After completing all blocks of the SRC task, participants again completed the two 100 ms VAS to indicate the extent to which they had thought about alcohol, and had complied with instructions, whilst they were doing the task. Finally, participants were debriefed and offered either course credit or a £5 Shopping Voucher to compensate them for their time.
Results
-------
### Group characteristics
Participants reported consuming 22.53 (*SD* = 15.63) units of alcohol per week, and the mean score on the AUDIT was 10.56 (*SD* = 4.52). There was no group difference in gender ratio (χ^2^ = 4.62, *p* \> 0.1), although there were group differences in both weekly alcohol consumption and AUDIT scores (Kruskal--Wallis tests, *ps* \< 0.05). Participants in both thought suppression groups had higher weekly alcohol consumption and higher scores on the AUDIT compared to participants in both control groups. Therefore, we repeated all primary analyses (detailed below) with the addition of weekly alcohol consumption and AUDIT scores as covariates.
### Effects of video manipulation on AAAQ ratings (Figure [1C](#F1){ref-type="fig"})
AAAQ ratings were analyzed using a mixed design ANOVA, with within-subject factors of sub-scale (3: inclined-indulgent, obsessed-compelled, resolved-regulated), time (2: before video, after video), and between-subject factors of video group (2: alcohol-positive, alcohol-negative), and thought suppression group (2: thought suppression, control). The sub-scale x time x video group interaction was statistically significant \[*F*~(2,\ 95)~ = 41.60, *p* \< 0.001\] but the four way interaction sub-scale × time × video group × thought suppression group was not \[*F*~(2,\ 95)~ = 1.17, *p* \> 0.1\]. The three way interaction remained significant after adding AUDIT scores and weekly alcohol consumption as covariates \[*F*~(2,\ 93)~ = 38.40, *p* \< 0.001\]. Subsequent *post-hoc* ANOVAs confirmed that the time x video group interaction was significant for all three sub-scales \[inclined-indulgent *F*~(1,\ 98)~ = 40.51, *p* \< 0.001; obsessed-compelled *F*~(1,\ 98)~ = 23.84, *p* \< 0.001; resolved-regulated *F*~(1,\ 98)~ = 34.35, *p* \< 0.001\].
Groups did not differ on any of the sub-scales before watching the video \[inclined-indulgent *t*~(98)~ = 0.08, *p* \> 0.1; obsessed-compelled *t*~(98)~ = 1.62, *p* \> 0.1; resolved-regulated *t*~(98)~ = 1.46, *p* \> 0.1\]. As predicted, groups differed on all three sub-scales after watching the video \[inclined-indulgent *t*~(98)~ = 4.06, *p* \< 0.001, higher in the alcohol-positive video group; obsessed-compelled *t*~(98)~ = 2.15, *p* \< 0.05, also higher in the alcohol-positive video group; resolved-regulated *t*~(98)~ = 5.68, *p* \< 0.001, higher in the alcohol-negative video group\].
Paired-samples *t*-tests revealed that in the alcohol-positive video group, scores on the inclined-indulgent and obsessed-compelled sub-scales increased after watching the video \[*t*~(49)~ = 1.96, *p* \< 0.05 and *t*~(49)~ = 3.12, *p* \< 0.01), whereas scores on the resolved-regulated sub-scale decreased \[*t*~(49)~ = 2.20, *p* \< 0.05\]. The reverse pattern was seen in the alcohol-negative group: scores on the inclined-indulgent and obsessed-compelled sub-scales decreased after watching the video \[*t*~(49)~ = 6.16, *p* \< 0.001 and *t*~(49)~ = 3.95, *p* \< 0.001\] whereas scores on the resolved-regulated sub-scale increased \[*t*~(49)~ = 5.45, *p* \< 0.001\].
We also re-ran the omnibus Four-Way ANOVA on AAAQ scores but added PANAS positive and PANAS negative affect after the video as covariates. The three way interaction sub-scale x time x group remained statistically significant \[*F*~(2,\ 93)~ = 30.79, *p* \< 0.001\]. Therefore, statistically controlling for positive and negative mood at the time did not influence the influence of the videos on the AAAQ.
### SRC task (Table [3](#T3){ref-type="table"})
All data were missing from two participants due to an experimenter error. Data were analyzed as described for study 2. All data from two additional participants were excluded as they had an outlying high rate (\> 35%) of missing data due to errors and outliers. For the remaining participants, on average 4% of trials were missing due to errors and a further 7% due to outliers; these values did not differ between groups (*ps* \> 0.1).
######
**Mean reaction times (in milliseconds) from the different blocks of the SRC task in study 3**.
**Suppress positive** **Suppress negative** **Control positive** **Control negative**
--------------------- ----------------------- ----------------------- ---------------------- ----------------------
Approach alcohol 905.47 ± 256.62 815.36 ± 242.46 943.52 ± 261.85 871.95 ± 244.25
Approach stationery 1018.24 ± 308.49 877.71 ± 236.56 960.42 ± 234.93 928.08 ± 289.12
Avoid alcohol 934.29 ± 219.92 842.58 ± 238.03 954.69 ± 207.22 882.97 ± 223.72
Avoid stationery 936.15 ± 244.13 871.00 ± 234.06 941.56 ± 207.04 915.88 ± 249.54
*Values are means ± SD*.
Mean reaction times in the different blocks of the task were then analyzed using a mixed design 2 × 2 × 2 × 2 ANOVA, with within-subject factors of movement type (2: approach, avoidance) and picture type (2: alcohol, stationery; this refers to the type of picture that the approach or avoidance movement had to be directed toward or away from, with the sideways movement required for the other type of picture), and between-subject factors of video group (2: alcohol-positive, alcohol-negative), and thought suppression group (2: thought suppression, control). The hypothesized four way interaction was not statistically significant \[*F*~(1,\ 92)~ = 0.99, *p* \> 0.1\]. There was, however, a significant main effect of picture type \[*F*~(1,\ 92)~ = 11.22, *p* \< 0.01\] which was subsumed under a significant picture type x movement type interaction \[*F*~(1,\ 92)~ = 7.85, *p* \< 0.01\]. Paired-samples *t*-tests revealed that participants were significantly faster to approach alcohol rather than control pictures \[*t*~(95)~ = 4.45, *p* \< 0.001\], but reaction times to avoid alcohol and control pictures did not differ \[*t*~(95)~ = 0.97, *p* \> 0.1\].
There were no other significant main effects or interactions (*F*s \< 1.68, *ps* \> 0.1), and results were unaffected when the analysis was repeated with AUDIT scores and weekly alcohol consumption added as covariates. Overall, these results show that participants were faster to make approach movements to alcohol pictures than control pictures, but there was no difference in the speed of avoidance movements. Most importantly, neither the video manipulation or the thought suppression manipulation, or the interaction between the two, had any effect on performance on the task.
### Thought suppression and working memory load manipulation checks
Responses on the visual analog scales, and the number of alcohol-related thoughts that participants recorded, are shown in Table [4](#T4){ref-type="table"}. Each VAS was analyzed using a separate 2 × 2 ANOVA, with between-subject factors of video group (2: alcohol-positive, alcohol-negative), and thought suppression group (2: thought suppression, control). There were no main effects or interactions for the "To what extent did you succeed in complying with the instructions"? VAS at either time (*Fs* \< 2.99, *p*s \> 0.08). There were no main effects or interactions for the "To what extent did you think about alcohol" question immediately after the thought suppression and thought listing exercise (*Fs* \< 2.24, *ps* \> 0.1), which suggests that the thought suppression manipulation was not effective. However, the main effect of thought suppression group was statistically significant for this question immediately after participants had completed the SRC task \[*F*~(1,\ 99)~ = 8.74, *p* \< 0.001\], as participants in the thought suppression group reported significantly fewer alcohol-related thoughts while completing the SRC task than participants in the control group. There were no other main effects or interactions (*Fs* \< 1.80, *ps* \> 0.1). Finally, there were no significant main effects or interactions for the number of alcohol-related thoughts that participants recorded during the thought suppression and thought listing exercise (*Fs* \< 0.72, *ps* \> 0.1).
######
**The effect of thought suppression on self-reported alcohol-related thoughts and task instructions**.
**Suppress positive** **Suppress negative** **Control positive** **Control positive**
------------------------------------------------------------------------- ----------------------- ----------------------- ---------------------- ----------------------
**IMMEDIATELY AFTER THOUGHT SUPPRESSION AND THOUGHT LISTING EXERCISE:**
"To what extent did you think about alcohol"? 30.92 ± 27.23 37.96 ± 31.43 43.60 ± 32.34 43.60 ± 31.08
"To what extent did you succeed in complying with instructions"? 67.48 ± 26.71 59.76 ± 32.48 74.60 ± 22.63 71.36 ± 25.57
Number of alcohol-related thoughts recorded 3.92 ± 3.92 4.68 ± 3.81 4.32 ± 2.82 4.76 ± 3.50
**IMMEDIATELY AFTER COMPLETING SRC TASK:**
"To what extent did you think about alcohol"? 27.64 ± 26.23 18.16 ± 20.45 36.72 ± 32.61 42.32 ± 31.51
"To what extent did you succeed in complying with instructions"? 75.36 ± 15.16 75.76 ± 25.08 78.72 ± 21.35 74.88 ± 21.24
*Visual analog scales are 100 ms VAS. Values are means ± SD*.
Overall, these results indicate that the thought suppression manipulation was not successful, because there were no differences in perceived suppression success or the number of alcohol-related thoughts recorded between thought suppression and control groups during the thought listing exercise. However, when asked immediately after completing the SRC task, participants in the thought suppression group reported that they thought about alcohol significantly *less* than participants in the control group. Furthermore, the lack of significant thought suppression x video group interactions for these measures suggests that the alcohol positive and alcohol negative videos did not have differential effects on the success of attempted thought suppression.
Finally, 97% of participants successfully recalled the 7-digit number at the end of each sub-block of the SRC task, which demonstrates that compliance with the manipulation of working memory load was very high.
Discussion
----------
Consistent with the findings from studies 1 and 2, results from this study demonstrated that participants who watched a video depicting the positive consequences of alcohol reported an increase in approach inclinations for alcohol that was accompanied by a reduction in avoidance inclinations; the converse pattern was seen among participants who watched a video depicting the negative consequences of alcohol consumption.
The primary novel feature of this study was the incorporation of a thought suppression manipulation in an attempt to magnify the influence of the videos on automatic approach and avoidance responses evoked by alcohol-related cues. Contrary to our hypotheses, we observed no evidence that the thought suppression manipulation led to an increase in alcohol-related thoughts; by contrast, participants\' self-reports indicated that they were able to suppress alcohol when instructed to do so. We observed that participants were faster to approach alcohol rather than control pictures, thereby replicating previous findings using a related task (Field et al., [@B11], [@B9]; Christiansen et al., [@B5]; Kersbergen et al., [@B18]). However, this pattern of results was unaffected by the videos, the thought suppression manipulation, or the interaction between the two.
Combined analysis {#s5}
=================
Results from all three studies demonstrated that self-reported inclinations to approach and avoid alcohol were not independent of each other: increases in approach inclinations were accompanied by parallel decreases in avoidance inclinations, and vice versa. This interpretation could be bolstered by investigating the strength of the associations between *changes* in subjective approach and avoidance inclinations for alcohol after exposure to videos depicting the positive and negative consequences of alcohol consumption.
To this end, we combined the AAAQ data from all three studies, but disregarded data from the control groups (participants who watched the neutral video) in studies 1 and 2. Given that the thought suppression manipulation had no influence on the AAAQ in study 3, we collapsed these data across thought suppression groups. This combined analysis, with a total sample size of 221, confirmed that the sub-scale × time × group interaction was highly statistically significant, and that the time × group interactions were highly significant for all three of the AAAQ subscales (all *ps* \< 0.001). Furthermore, paired samples *t*-tests confirmed that in the combined alcohol-positive group, scores on the inclined-indulgent and obsessed-compelled subscales increased, whereas scores on the resolved-regulated subscale decreased, after watching the video. The reverse pattern was seen in the combined alcohol-negative group. Data are shown in Table [S4](#SM4){ref-type="supplementary-material"}.
We then computed change scores to capture the change in each AAAQ subscale after participants watched the videos. By correlating these change scores with each other we were able to investigate the strength of the association between changes in self-reported approach and avoidance inclinations: as approach inclinations increase, do avoidance inclinations decrease by a similar magnitude (and vice versa)? Overall, intercorrelations between these change scores were statistically significant but small. After watching a video depicting the positive consequences of alcohol consumption, the magnitude of the increase in scores on the inclined-indulgent and obsessed-compelled subscales was associated with the magnitude of the decrease in scores on the resolved-regulated subscale, although the size of the correlation co-efficients (*r* = −0.20) suggests only 4% shared variance. After watching a video depicting the negative consequences of alcohol consumption, the magnitude of the increase in scores on the resolved-regulated subscale was weakly associated with the reduction in scores on the inclined-indulgent subscale (*r* = −0.36; 13% shared variance), but was unrelated to the reduction in scores on the obsessed-compelled subscale.
Finally, we are grateful to the reviewer who suggested the following additional analyses, which are detailed in Table [S5](#SM4){ref-type="supplementary-material"}. We performed hierarchical linear regression analyses to investigate if the change score for self-reported approach inclinations would be predicted by the video manipulation, even after entering the change score for self-reported avoidance inclinations in the first step of the model. With the score on the inclined-indulgent subscale as the dependent variable, the score on the resolved-regulated subscale accounted for 22% of variance \[*F*~(1,\ 279)~ = 77.29, *p* \< 0.01\], but addition of experimental group as a predictor in the subsequent step of the regression accounted for an additional 8% of variance \[*FΔ*~(1,\ 277).~ = 29.73, *p* \< 0.01\]. Similarly, with the score on the obsessed-compelled subscale as the dependent variable, the score on the resolved-regulated subscale accounted for 7% of variance \[*F*~(1,\ 279)~ = 22.20, *p* \< 0.01\], but addition of experimental group as a predictor accounted for an additional 6% of variance \[*FΔ*~(1,\ 277).~ = 18.42, *p* \< 0.01\].
However, we did not observe the same pattern when scores on the resolved-regulated subscale were entered as the dependent variable, and scores on the inclined-indulgent and obsessed-compelled subscales were entered as independent variables (in separate analyses). In the first case, after accounting for the 22% of variance attributable to the inclined-indulgent subscale \[*F*~(1,\ 279)~ = 77.29, *p* \< 0.01\], the addition of experimental group as a predictor did not account for additional variance in scores on the resolved-regulated subscale \[ \< 1% of additional variance; *FΔ*~(1,\ 277).~ = 1.07, *p* = 0.30\]. Similarly, after accounting for the 7% of variance attributable to the obsessed-compelled subscale \[*F*~(1,\ 279)~ = 22.20, *p* \< 0.01\], the addition of experimental group as a predictor did not account for additional variance in scores on the resolved-regulated subscale \[ \< 1% of additional variance; *FΔ*~(1,\ 277).~ = 0.20, *p* = 0.66\].
These analyses reveal that self-reported approach and avoidance inclinations for alcohol can operate at least partly independently of each other, but the effect is not symmetrical. Changes in self-reported avoidance inclinations after watching videos depicting the positive or negative consequences of alcohol consumption were completely accounted for by changes in self-reported approach inclinations. However, the changes in self-reported approach inclinations that were evoked by these videos were at least partly independent of changes in self-reported avoidance inclinations.
General discussion {#s6}
==================
A number of consistent findings emerged from the three studies reported here. When participants viewed short videos that depicted the positive or negative consequences of alcohol consumption, their self-reported approach and avoidance inclinations for alcohol tended to change in parallel: as approach inclinations increased, avoidance inclinations decreased, and vice versa. However, between-group contrasts suggested some degree of independence of approach and avoidance inclinations, although these findings were not consistent across studies. In addition, although *changes* in approach and avoidance inclinations tended to be inversely correlated (as one increased, the other decreased), these correlations were small and there was some evidence that changes in approach inclinations were partly independent of changes in avoidance inclinations. Finally, we found no evidence in support of our predictions that alcohol-related implicit cognitions would be influenced by experimental manipulations of motivational orientations for alcohol, regardless of whether we measured attentional biases or automatic approach / avoidance tendencies, or whether the experimental manipulation was combined with a thought suppression exercise.
One of the primary aims of these studies was to expand on findings from previous studies that used the Approach and Avoidance of Alcohol Questionnaire (AAAQ) in order to test predictions made by the ambivalence model of craving (Breiner et al., [@B3]). Specifically, if subjective approach and avoidance inclinations for alcohol are independent of each other, it should be possible to dissociate them by exposing participants to experimental manipulations that are designed to increase one but not the other. Overall, our findings demonstrated that approach and avoidance inclinations tend to change in parallel because as one increased, the other tended to decrease. This casts doubt on the independence of these constructs as predicted by the ambivalence model. Specifically, within-subject contrasts revealed that, after watching a video depicting the positive consequences of alcohol consumption, approach inclinations increased and avoidance inclinations decreased, whereas the reverse pattern was seen in participants who watched a video depicting the negative consequences of alcohol consumption. Although there were some minor inconsistencies between studies, the results of a combined analysis of data from all studies confirmed that approach and avoidance inclinations tended to fluctuate alongside each other. Furthermore, the combined analysis revealed that the magnitude of changes in approach and avoidance inclinations over time were reliably negatively correlated with each other: the magnitude of the increase in the strength of approach inclinations was associated with the magnitude of the corresponding decrease in avoidance inclinations, and vice versa. Finally, the regression analysis confirmed that variation in the change in avoidance inclinations after watching the videos was completely accounted for by the change in approach inclinations.
However, other analyses suggested that self-reported approach and avoidance inclinations could be characterized as at least partly independent of each other. Although the combined analysis confirmed inverse correlations between the magnitude of changes in approach and avoidance inclinations over time, these relationships were weak (with, at most, 13% shared variance), and regression analyses demonstrated that changes in approach inclinations were at least partly independent of changes in avoidance inclinations. More importantly, between-subject contrasts with a control group suggested that approach inclinations increased without a corresponding change in avoidance inclinations, and vice versa. Unfortunately, we have limited confidence in these group differences because they were only seen in study 2; in study 1, group differences in approach inclinations were accompanied by group differences in avoidance inclinations.
Our findings are consistent with some previous observations that subjective approach and avoidance inclinations for alcohol tend to change in parallel after exposure to appetitive alcohol cues (Curtin et al., [@B7]), although one study reported a dissociation between approach and avoidance inclinations after cue exposure (Jones et al., [@B17]). Importantly, the studies reported here are the very first to investigate the influence of an experimental manipulation that was intended to activate motivational orientations to avoid drinking; findings from participants in the alcohol-negative groups in all studies clearly suggest that this manipulation led to the predicted increase in self-reported avoidance inclinations that was accompanied by a decrease in approach inclinations. However, it is important to clarify that previous studies demonstrated that approach and avoidance inclinations have independent predictive validity for individual differences in drinking behavior and prospective drinking behavior (Curtin et al., [@B7]; Schlauch et al., [@B36], [@B33],[@B34],[@B35]; Klein and Anker, [@B19]). The three studies reported here cannot speak to the predictive validity of these constructs.
In contrast to the robust effects on self-reported approach and avoidance motivational orientations (assessed with the AAAQ), the videos depicting the positive and negative consequences of alcohol consumption had no effect on measures of motivational orientations operating within automatic processes, that is attentional biases (study 1) and approach / avoidance tendencies (studies 2 and 3). To our knowledge, these are the first studies that experimentally manipulated the motivation to avoid drinking and our findings suggest that these automatic processing biases are impervious to motivational orientations to avoid drinking. This interpretation is consistent with findings from an earlier study (Baker et al., [@B1]) in which we attempted to prime motivational orientations by presenting alcohol-positive and alcohol-negative primes below the threshold of conscious awareness; this manipulation also failed to influence attentional biases and approach / avoidance tendencies. However, on the basis of previous demonstrations of robust, albeit weak associations between subjective craving (typically assessed with self-report instruments that capture only "approach" inclinations) and attentional bias (Field et al., [@B15]), and demonstrations that experimental manipulations of craving such as negative mood induction, exposure to alcohol cues, and acute alcohol intoxication all lead to increases in attentional bias (see Field and Cox, [@B10]), we anticipated elevated attentional biases in the "attend positive" vs. the control groups. This pattern of results was not seen. Perhaps most importantly, with one exception (the bias to more rapidly approach alcohol rather than control images in study 3), we found no evidence of attentional or approach or avoidance biases in any of the studies, and no evidence that individual differences in alcohol consumption, hazardous drinking or scores on the AAAQ were associated with these implicit processing biases in any of the studies (see Supplementary Materials). These findings cast doubt on the validity and sensitivity of the tasks that were used in the current studies, all of which were slightly modified versions of tasks that are more commonly used in the literature. Future investigations of this research question should attempt to develop measures of approach and avoidance inclinations operating in automatic processes that have acceptable construct validity and sensitivity for this purpose.
The studies reported here have other weaknesses in addition to the questionable construct validity of the implicit measures. All participants consumed alcohol in excess of UK government guidelines and therefore their alcohol consumption was placing their health at risk. However, we did not attempt to recruit participants who were concerned about or attempting to limit their alcohol consumption, and we did not measure participants\' motivation to change using a validated self-report measure, so it is possible that our participants were relatively insensitive to our experimental manipulations that were designed to exaggerate their ambivalence about alcohol consumption. Future studies could investigate this issue by recruiting heavy drinking participants who are currently motivated to reduce their alcohol consumption (and are actively attempting to do so), because motivational orientations in these participants might be expected to be more sensitive to the experimental manipulations that were used in the present study. A further limitation is that we did not record participants\' occupational or socioeconomic status so we are unable to fully characterize participants who took part in these studies. In addition, it is possible that the videos had robust effects on self-report but not computerized measures because participants always completed the former before the latter; this could be investigated by counterbalancing the order in which assessments are administered in future studies. Our study also had strengths, including measurements of participants\' subjective mood after they had watched the videos, which enabled us to rule out changes in mood as a contributor to the influence of those videos on self-reported and automatic motivational orientations.
In conclusion, findings from the three studies reported here question the degree of independence of self-reported approach and avoidance inclinations for alcohol, which tended to co-vary in response to experimental manipulations of inclinations to drink or inclinations to avoid alcohol. However, results from a combined analysis of data from all studies suggest that changes in inclinations to drink may be at least partially independent of changes in inclinations to avoid alcohol. Our findings also suggest that measures of alcohol-related motivational orientations that operate in automatic processes are impervious to these experimental manipulations, although the modified tasks that we used here have questionable construct validity and sensitivity which suggests that these findings should be interpreted with caution.
Funding
=======
Funded by a research grant from the Wellcome Trust, reference 086247/Z/08/Z, awarded to MF and JD.
Conflict of interest statement
------------------------------
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We thank Abigail Kirkland, Georgina Schwarz, and Michael Tapp for their help with data collection.
Supplementary material {#s7}
======================
The Supplementary Material for this article can be found online at: <http://journal.frontiersin.org/article/10.3389/fpsyg.2015.01465>
######
Click here for additional data file.
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[^1]: Edited by: Frank Ryan, Imperial College, UK
[^2]: Reviewed by: Thomas Edward Gladwin, Ministry of Defense, Netherlands; Kim Mitchell Caudwell, Curtin University, Australia
[^3]: This article was submitted to Psychology for Clinical Settings, a section of the journal Frontiers in Psychology
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/// \file RunAction.hh
/// \brief Definition of the RunAction class
//
//
//....oooOO0OOooo........oooOO0OOooo........oooOO0OOooo........oooOO0OOooo......
//....oooOO0OOooo........oooOO0OOooo........oooOO0OOooo........oooOO0OOooo......
#ifndef RunAction_h
#define RunAction_h 1
#include "G4UserRunAction.hh"
#include "globals.hh"
//....oooOO0OOooo........oooOO0OOooo........oooOO0OOooo........oooOO0OOooo......
class DetectorConstruction;
class Run;
class PrimaryGeneratorAction;
class HistoManager;
//....oooOO0OOooo........oooOO0OOooo........oooOO0OOooo........oooOO0OOooo......
class RunAction : public G4UserRunAction
{
public:
RunAction(DetectorConstruction*, PrimaryGeneratorAction*);
~RunAction();
public:
virtual G4Run* GenerateRun();
virtual void BeginOfRunAction(const G4Run*);
virtual void EndOfRunAction(const G4Run*);
private:
DetectorConstruction* fDetector;
PrimaryGeneratorAction* fPrimary;
Run* fRun;
HistoManager* fHistoManager;
};
//....oooOO0OOooo........oooOO0OOooo........oooOO0OOooo........oooOO0OOooo......
#endif
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Tips & Tricks For Space Scenes
Since most of us never will get a chance to step off this big blue marble, I figured it would be nice to have a thread to share your tips, tricks and ideas on how to get what you think is a great space picture or animation. It doesn't matter if it's reality based or science fiction.
For me, I'll start with an example of how I would light a scene with the sun peaking out from behind the Earth.
Comments
I set the scene up with the model and three lights. One bulb light, one spot light and one distance light. I set the scene's ambient light to zero.
The bulb light is just the default settings. I used the bulb for the sunlight. I went to the light's effects tab and enabled the 3D light sphere and the lens flare. I'll include screen shots of what I did. The Light Sphere makes the sun's disk and the lens flare is self explanatory. A bulb usually works better for this than the distant light, as the distant light doesn't have the Light Sphere under it's effects. For the lens flare, I dialed the radius down from it's default. I could have gone for a smaller radius on the light sphere as well.
The spotlight is positioned to provide a rim light or crescent on the earth model, because the bulb light doesn't light enough of the Earth relative to the camera. This is completely incorrect I know. Consider it artistic license. Be careful though, or it goes from taking minor liberties to taking your viewers out of the picture. I'm actually pushing it a bit myself, but I wanted it to be fairly obvious to illustrate my point.
The distant light is used to provide a low level fill light. I could have gone a bit brighter in this scene, but my model uses a sphere with a glow channel to simulate the atmosphere, and if I had it brighter, it would show the effect up too much. I also have a nice glow channel for the surface to simulate city lights and I wanted that to really stand out.
The position of the lights relative to the model and the camera is scene specific, but generally I like the low level fill light coming from maybe a 45º angle from the camera, aiming back towards the primary light. Again, this is scene specific, and depends on what you're going for.
The other thing to consider is your color scheme. If I'm doing a scene with a fairly pedestrian star field, I tend to have the primary light a yellow/white color and the fill light a blue/grey color to match what I imagine the star shine would look like.
Very nice.This is basically what I lucked into doing in my render in the other thread minus the spotlight to give that extra light. I had a light from a premade scene pointed at the planet. I think it's a distant light. (It looks like a cylinder with a cone on top of it.) Did you use indirect lighting at all? Or the built in ambient light? (I assume that's what the scenes start with. It also looks like a cylinder with a cone on top.)
Okay, I really suck at space stuff. Partially because I guess it bores the crap out of me. Unless it's like really surrealistic and gorgeous like some of the nebulas and that kind of stuff. But I'm not much into spaceships, etc.
But I do see a lot of repeating practices that people might want to reconsider.
First, cameras in space operate under the same principles as they do on earth. When the scene is dark, and the subject is relatively close or zoomed, then stuff in the background is usually blurred due to a shallow depth of field. And adding DOF helps to give a sense of distance, which is often missing in space-y renders with spaceships that are thousands or millions of miles away from planets and stuff. Unfortunately it obscures that cool planet you spent so much time on, but I think it adds some realism that sells the image a bit better.
Now of course, bright subjects and wide angle lenses increase the DOF, so you wouldn't see it as much in that case.
Second, objects in space still interact with light from other objects. Including planets and other ships, etc. And that's very important to place the object in the scene, instead of making it seem like the objects were copied and pasted into the image. So if you have a spaceship that is nearing a planet, the reflected light from the planet should interact with the ship. Also the sun/moon/star light should interact with the ship. And so on...
Also, textures are real important on spaceships. Often you'll see real dull, uninteresting textures with no light interaction whatsoever, and it just looks like a plastic model was stuck in the image. And engine glow should be made interesting, not just a single color that looks like a bad Photoshop splotch.
Here's a crappy, standard spaceship image with some depth of field and reflections of light to clearly place the ship in the scene. I think the DOF is way overdone, but I'm not sure. If you check some real life space station photos and stuff you see the DOF when the lighting is low, but I don't know, it just doesn't look right. But anyway you get the point. And I made the spaceship a shiny metallic to enhance the reflections and interest.
Again, don't take the image as a good example because it's sucky and boring, but hopefully it illustrates the points.
Very nice.This is basically what I lucked into doing in my render in the other thread minus the spotlight to give that extra light. I had a light from a premade scene pointed at the planet. I think it's a distant light. (It looks like a cylinder with a cone on top of it.) Did you use indirect lighting at all? Or the built in ambient light? (I assume that's what the scenes start with. It also looks like a cylinder with a cone on top.)
The default light that Carrara gives you when creating a scene is the distant light. The shape is supposed to resemble and arrow and indicates the direction it is pointing. In the image I posted I didn't use any GI and I had the scene's ambient light set to zero.
If anybody has ideas or suggestions that they use in their own space or sci-fi scenes, please share!
JoeMama: I actually tried to do DOF in my space render I posted in the render thread. However, my objects were fairly close together and I had trouble getting it working right so I eventually gave up on it.
JoeMama: I actually tried to do DOF in my space render I posted in the render thread. However, my objects were fairly close together and I had trouble getting it working right so I eventually gave up on it.
When I do a space image and I want DOF it can be difficult, because as JoeMama said, there's incredible distances involved, so I tend to force the perspective. The built in DOF isn't that great either, so what I use is a depth render pass available under Multi-Pass in the Render room. It creates a greyscale image that can be used in Photoshop (and I assume other sophisticated image editing apps) to create a layer mask. Unfortunately, the depth pass doesn't respect alpha channels, volumetric clouds, hair, or primitives such as fire, fountains and fog. If you have any of those, you'll have to edit the depth pass image.
The following picture uses a depth pass for DOF. I'm still working on the shaders and lighting for this one, and I may change the background planet as well.
I put "photoreal" in quotes because what the sun really *looks* like to the naked eye seems to be debatable, and also what structures we want to show of the sun is definitely subjective. But I'll post this "final" render while I organize the tutorial...
The pic uses Primivol, but the tutorial is going to focus on the surface shader, so Primivol won't be needed...
Seriously though, when it comes to space scenes I say; keep the rules in mind then just break 'em.
They can be very beautiful and worthy but ultimately blend into the background..
Forget correct lighting, if you lit accurately for space you wouldn't see very much.
To touch on Hollys last post, the Sun as seen from the naked eye is as big as the sky and pure white just before it burns through your retina. Not a good picture.
Depth of field is a handy trick to portray separation but don't get hung up on it, it's most useful for things very close and very far but since most objects will be in the mid distance (apart from the occasional special shot) you can do without it. (Using a blurred backround image does the job quite well)
Forget correct lighting, if you lit accurately for space you wouldn't see very much.
Well, you're the astrophysicist, but I've seen tons of NASA/space station/etc. photos where you can see a lot, and I don't even think they bring lighting rigs on the Space Shuttle when they go up :)
Depth of field is a handy trick to portray separation but don't get hung up on it, it's most useful for things very close and very far but since most objects will be in the mid distance (apart from the occasional special shot) you can do without it. (Using a blurred backround image does the job quite well)
I agree, DOF is one of those things that can get overused. Kinda like lens flares. Sorry, one of my personal "peeves". However, I think that one of the most common issues with space image renders is lack of interaction with the objects and the rest of the scene. Since there arent' generally the large number of surrounding objects nearby to interact with, it's real easy to get a spaceship and a planet and whatever that look totally unrelated. As well as losing the sense of scale and distance, which is extremely common, IMO. And don't forget, distance isn't the only deciding factor, magnification is also a factor. So if you're on a ship and taking a zoom photo of a fighter coming towards you, it's entirely possible to have quite a bit of lens blur, just like on Earth.
Also, as I think you're implying, in space there can tend to be less overall light unless you've got a direct reflection, so it's more likely your camera would have a wide open iris, which again is reason for considering lens blur.
And again, I didn't mean to tweak anyone with my opinions on space shots, though I figured it was inevitable, but personally there's only so much I can take of Star Wars and Star Trek fighters battling it out in space. But that's just me, someone who's been seeing the same stuff in films since the 80's. Or was it the 70's. Nice visual eye candy in the beginning, but there's only so much of the same ol' visual eye candy I can take without getting, well, bored. But that's just me, and that's just an opinion.
One of my favorite scenes that I did used a photo of a nebula that the Hubble had taken. I used that as a backdrop for my scene and used a couple Star Trek models bursting out of a volumetric cloud that I had colored to match the nebula. I did quite bit of work on getting the lighting to match.
I did two versions. One with a more modern style ship and another with the classic movie Enterprise and a classic Klingon Bird of Prey. I tried an experiment with the model of the old school ship and added the NASA image to the scene's background and enabled the Skylight, so it would act like an IBL. I like the effect, but there is quite a bit of noise/ashiness in the image and in my opinion not worth the render time.
The image with the more modern ship is just the standard renderer with no bells and whistles.
BTW, Rogue, not to pick on you but, I agree with Evil that the first and last images are much nicer.
And I think the reason is partly because of the consistency in lighting as well as the sense of distance and perspective. The other two, IMO, seem a bit jumbled with different ships and different light levels just mangled together without a clear focus nor a clear sense of depth and perspective and action. And that's exactly the point I'm making, that 90% of images you see of space scenes look like an inconsistent jumble of ships and planets with little or no clear focus and composition and interaction.
The first and last images are, OTOH, quite nice and have some nice composition, as well as all that other stuff.
Heh, I think that bottom image is looking pretty sexy actually - whatever turns you on I guess ....
Dynamic composition, lots to look at - maybe a little oversaturated colour wise but its looking great,
I can almost hear those x wings whizzing by.... hold on, you can't hear in space.... well you can, but you can't (because of space earwax)
Who cares if its true to the phyics of the situation? As long as it looks good, that's what I reckon :)
And BTW, Rogue, I realize that you and many others here like to take the attitude of "know the rules yet break them", but I think your images provide a clear example of why NOT to break the rules. In this case, the rules of composition.
I'll bet that a majority of people here would agree that the second and third images in your post are less pleasing than the first and last. And why is that? Well, probably because you broke the rules of composition.
Nothing wrong with breaking those rules if you don't care that a majority of people will enjoy the images less. But if you care about how others receive your images you'll be very, very hesitant about breaking those rules unless you have a really, really good reason.
Of course for those who don't want to learn the rules, it's easier to just say 'rules are made to be broken' :)
And also BTW, in the same way that the rules of light and cameras and all that stuff still apply in space as they do on earth, the rules of image composition also apply in space... :)
Heh, I think that bottom image is looking pretty sexy actually - whatever turns you on I guess ....
Dynamic composition, lots to look at - maybe a little oversaturated colour wise but its looking great,
I can almost hear those x wings whizzing by.... hold on, you can't hear in space.... well you can, but you can't (because of space earwax)
Who cares if its true to the phyics of the situation? As long as it looks good, that's what I reckon :)
Funny that you should say that, because the top three images are built in the same scene and have exactly the same light rig, the only thing that changes is the camera position and treatment in post. It's based on a 2 point binary star system.
If you really want accurate deep space lighting then you're only allowed one light source with very local indirect light. When close to a planet, moon or nebula the reflected light becomes significant. Ship running lights or space station floods are very handy. The NASA nebula pics are enhanced and colour shifted to make them more attractive but I say 'what the heck, if that's what works'.
The composition is a personal choice to indicate a building battle and confusion. A personal choice and necessary to the story, so I suppose that's the intended reaction from you. I know that I miss on composition sometimes but I get very few critiques, so thank you for that.
The first one looks good (has more depth and feel of motion) because I massively forced the perspective. I boosted the ambient in post to give more pleasing shadows. I used the same tricks on the last one and but also lit counter intuitively to the background. The framing on both helps to sell the sense of motion, something that the panavision aspect ratio is really good for.
The YouTube compression really kills the details but I was working with that in mind to match some posted live action videos.
The starfield gets lost but can be briefly seen during the lens flare.
The setup is one distant light (soft shadows) to act as the sunlight. A bulb (turned down) is parented to a glowing Sun object to provide the disc and the flare at the right time. Another distant light is shining up through the earth to provide a little reflected light.
The final light is a spot parented to the camera to provide a floodlight from the 'orbiting' shuttle camera. That's why you can still see the ISS all the way around.
And that's it for the lights, zero ambient.
I tried to time the shuttle manoevers to the music and it comes out quite pleasantly.
The YouTube compression really kills the details but I was working with that in mind to match some posted live action videos.
The starfield gets lost but can be briefly seen during the lens flare.
The setup is one distant light (soft shadows) to act as the sunlight. A bulb (turned down) is parented to a glowing Sun object to provide the disc and the flare at the right time. Another distant light is shining up through the earth to provide a little reflected light.
The final light is a spot parented to the camera to provide a floodlight from the 'orbiting' shuttle camera. That's why you can still see the ISS all the way around.
And that's it for the lights, zero ambient.
I tried to time the shuttle manoevers to the music and it comes out quite pleasantly.
I've been plugging away at an animation for awhile now, but I haven't been moving very fast at it. This thread has given me the impetus to get it done. There's a few more grand shots I need to do, a couple cut-aways and a couple shots that are just going to be a chore. It's these shots that usually get me out of the mood to do anything.
Ok, here's the first part of my SUN TUTORIAL in Comicbook format™... YAY! :coolgrin:
Step-by-step, and suitable for beginners! This section covers building a sun model and texturing the photosphere with sunspots. I had to stop there because it has been 3-days working on this and I need a break, lol. Also the next steps require plugins and elaborate "tricks" to get the effects, so I will add them later as "bonus" pages...
Eventually I will put it in PDF and upload it to my website... or maybe CARRARA CAFE would be so kind as to host...
Please let me know if any part is unclear or contains typos or mistakes.... |
Following the Saturday, October 2nd lecture will be
Tibetan Tantric Chanting for Peace (approx. 7:00 p.m.)
Donation based series – suggested $12 per or $65 for the series.
About Ven. Thupten Tsondu (Tashi):
Venerable Gyudmed Ngarampa Thupten Tsondu (Tashi) was born in Tibet but fled to India in 1959 to seek political asylum along with his parents and the Dalai Lama. At age 13 he entered Gyudmed Tantric University to become a monk according to his wishes. In 1995 he was given a dialectic exam in front of 400 monks which resulted in the Geshe Ngarampa degree, a Ph.D. in Tibetan Tantric Buddhism.
He has visited the USA, Canada, Switzerland, England, Mongolia, Japan, Vietnam, Thailand, Nepal and India and has taught ritual chanting, sand mandala construction and dialectic debate to monks at the Gyudmed Tantric, Gaden Jangtse and Drepung Gomang Monasteries of India and the Pethub Stengeyling and Gyud Monasteries of Mongolia. Tashi also served as chief administrator of Gyudmed Tantric University and wrote a book on tantric ritual. |
Background
Total thoracoscopic and laparoscopic esophagectomy (TLE) has attracted attention with the advantage of better operative field and minimal wound for the esophageal cancer. However, various severe complications are also reported during the TLE such as cervical anastomotic leakage, chylothorax, and tracheal injury. The aim of this study was to introduce a new optimized TLE procedure for the esophageal cancer and assess its safety and clinical effects.
Methods
We retrospectively collected the clinical data of 30 patients with esophageal cancer who underwent optimized TLE procedures between January 2014 and December 2014. The optimized TLE procedures mainly include as follows: (1) 50 ml of sesame oil-milk mixture (1:1) is injected via gastric tube after endotracheal intubation; (2) patients are intubated with a single lumen endotracheal tube; (3) patients were positioned at 150° in the left prone position rather than lateral decubitus position; and (4) duodenal feeding tube was not placed intraoperatively and however triple lumen nasojejunal feeding tube was placed on the second postoperative day under imaging guidance. Operation time, amount of blood loss, number of dissected nodes, length of hospital stays, and complications were recorded.
Results
The mean operation time of the optimized TLE group was 202.13 ± 13.74 min. The mean visible blood loss of the optimized TLE group was 300.00 ± 120.12 ml. The postoperative hospital stays in the optimized TLE group were 16.27 ± 4.51 days. The number of dissected nodes in the optimized TLE group was 13.57 ± 2.76. The postoperative complications for the optimized TLE procedure were seen in one case (3.3 %).
Conclusions
The method of optimized TLE is an effective, reliable, and safe procedure for the treatment of esophageal cancer, which provide favorable outcomes in terms of operation time, blood loss, length of hospital stays, the number the dissected nodes, and reduced incidence of postoperative complications compared to previous literatures. Further studies with a large number of samples are warranted.
China has a high incidence of esophageal cancer, with a mortality rate ranking fourth of all malignant tumors [1]. Esophageal resection is one of the primary therapeutic methods for the esophageal cancer [2]. However, because of the relatively high mortality and morbidity associated with esophagectomy for esophageal cancer [3–5], there have been many efforts to reduce its invasiveness [3, 6, 7]. Minimally invasive esophagectomy (MIE) has become increasingly used and been accepted with reported outcomes comparable with those of open approaches [8–13]. The techniques used can be thoracoscopic, laparoscopic, or both. As the experience and skills for thoracoscopic and laparoscopic surgery improve, total thoracoscopic and laparoscopic esophagectomy (TLE) has attracted more and more attention with the advantage of better operative field and minimal wound [14–18]. However, various severe complications are also reported during the TLE such as cervical anastomotic leakage, chylothorax, and tracheal injury. Thus, how to avoid surgical risks and improve surgical efficiency further has become the focus. The aim of this study was to introduce an optimized TLE procedure for esophageal carcinoma and assess its safety and outcomes.
Patients
The study was approved by the Ethics Committee of the Hebei Provincial People’s Hospital and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all subjects. We retrospectively evaluated 30 patients with esophageal cancer who underwent optimized thoracoscopic and laparoscopic esophagectomy between January 2014 and December 2014. Histological diagnosis of esophageal cancers was confirmed by esophagoscopy in all patients prior to surgery. The inclusion criteria were (1) patients with clinical stage I, II, and IIIa and IIIb esophageal cancer. The exclusion criteria were (1) patients with clinical stage IIIc and IV esophageal cancer; (2) patients with dyscrasia, or severe heart, liver, brain, and kidney concomitants, (3) patient who cannot subject one-lung ventilation due to poor lung function, and (4) patients have history of thoracic and abdominal surgery. The clinical characteristics of the 30 cases were summarized in Table 1.
Surgical technique
The surgeries were performed by a group of three surgeons who have more than 15 years’ surgical experience. Intrathoracic pressure of 8 mmHg and intraabdominal pressures of 12 mmHg were used for thoracic and abdominal surgery, respectively. The difference of conventional procedure and our optimized procedures was as follows:
During the conventional TLE procedure, the patient is often intubated with a double lumen endotracheal tube for single lung ventilation in the normal side and positioned in the left lateral decubitus position. The stomach contents are aspirated to the greatest extent to empty the stomach using a normal stomach tube before surgery. Whereas during our optimized TLE group, the patient is intubated with a single lumen endotracheal tube for bilateral lung ventilation and positioned in the prone position with a 150° left lateral tilt. After endotracheal intubation, 50 ml of sesame oil-milk mixture (1:1) is injected via gastric tube.
The procedure was conducted in three stages. Firstly, thoracoscopic dissection was done with the patient in the left lateral decubitus position in conventional group and prone position in the optimized group. Four thoracoscopic ports are placed. The l2-mm camera port is placed at the seventh intercostal space on the midaxillary line. Two 5-mm ports (shaft handle’s hole) are placed, one at the fifth intercostal space posterior to the posterior axillary line and one at the fourth intercostal space at the anterior axillary line. One additional 12-mm port (assistant handle hole) is placed at the eighth intercostal space, posterior to the posterior axillary line. The lung was retracted laterally using an atraumatic instrument. Ultrasound knife or electrocautery was used to separate the mediastinal pleura overlying the esophagus to detect whether there exists the extra-esophagus invasion such as thoracic aorta, membranous part of the trachea, and left main bronchus. The azygos vein was divided using Hemolok clips (Weck; Teleflex Medical, Durham, NC, USA), and then the esophagus was circumferentially mobilized from the esophageal hiatus up to the thoracic inlet. Paraesophageal lymph nodes were dissected and removed or mobilized en bloc with the resected specimen. Then complete hemostasis was performed using hook electrode, and the chest cavity was flushed with normal saline. A 32F chest tube was inserted through the camera port for postoperative chest drainage.
In the second stage, the patient was placed in the supine position. The surgeon stands on the patient’s right side and the assistant on the left side. Five abdominal ports were placed on the anterior abdominal wall. The l2-mm camera port is placed at 1 cm superior to umbilicus. Two shaft handle’s ports are placed (12- and 5-mm), one at 5 cm lateral to the lateral border of the rectus abdominis muscle and one at the junction between the right midclavicular line and costal arch. Two additional 5-mm ports (assistant handle hole) are placed, one at the epigastrium, approximately 3 cm below the xiphoid process and one at the junction areas between the costal arch and the left anterior axillary line. The operator stands on the right side of the patients. After detecting the abdominal cavity, the entire greater curvature of the stomach was mobilized, preserving the right gastroepiploic vessels. The left gastroepiploic artery, short gastric artery, and the peritoneum overlying the abdominal esophagus were isolated and divided with an ultrasound knife (HARMONIC ACE36E, Johnson & Johnson, New Brunswick, NJ, USA). With a bowel forceps, the left lobe of the liver is retracted upward to expose the gastrohepatic ligaments and abdominal esophagus. The lesser omentum was dissected with ultrasound knife. The gastrohepatic ligament, the peritoneum overlying the abdominal esophagus and the diaphragm’s esophageal hiatus, was divided. Left gastric vessels overlying the pancreas superiorly were retracted with the endoscopic bowel forceps, and then the two ends of left gastric vessels were clamped and divided with ligature forceps. Lymph nodes around the left gastric artery, splenic artery, and common hepatic artery were resected. After the bilateral crus of the diaphragm is exposed, the abdominal esophagus is retracted to the abdominal cavity. The pneumoperitoneum was removed, and incision below the xiphoid cardiac was expanded approximately 3 cm. The gastric tube was then created by dividing the stomach starting at the distal lesser curve and ending at the cardiac notch (angle of His) using the linear cutting staplers, preserving the right gastric vessels. The gastric tube was then sutured to prevent twisting and the mobilized esophagus for tunneling to the neck using the interrupted seromuscular sutures.
In the third stage, a 4-cm horizontal neck incision is made just above the suprasternal notch, and then the cervical esophagus is exposed. The cervical esophagus is divided, and the esophagogastric specimen was pulled out of the abdomen incision. As traction is applied to the specimen in the neck, another surgeon guides the specimen in its proper alignment into the mediastinum. The specimen is removed from the field. An anastomosis is performed between the esophagus and gastric tube with PROXIMATE ILS Curved and Straight Intraluminal Staplers (Ethicon Endo-Surgery, LLC). The duodenal feeding tube and stomach tube were placed across the anastomosis. Fundus of the gastric tube was excised using a linear cut stapler, and the margin was closed with interrupted seromuscular suture in a figure-of-8 pattern using non-absorbable Sutures Mersilk (braided silk).
Postoperative care
The differences of our optimized procedures and conventional optimized procedures were as follows:
During conventional procedures, patients started nasogastric nutritional support with duodenal feeding tube and gastrointestinal decompression with stomach tube on the second postoperative day due to gastric emptying time which is about 24–48 h after gastroenteric surgery. Oral diet was started after duodenal feeding tube, and stomach tube was removed on the fifth postoperative day.
During optimized group, patients started nasogastric nutritional support with triple lumen nasojejunal feeding tube (Freka-Trelumina; Fresenius, Bad Homberg, Germany) on the second postoperative day. Distal intestinal feeding tube was passed from pylorus to the jejunum through Treitz’s ligament. Oral diet was started after triple lumen nasojejunal feeding tube was removed on the 10th postoperative day.
Statistical analysis
Data analyses were performed using SPSS version 17.0 for windows (SPSS Inc., Chicago, IL, USA). All data are expressed as the mean and standard deviation and number or percentage as appropriate.
The patients consisted of 21 males and 9 females. The mean age was 66 years (range, 56–72 years). The characteristics of 30 patients undergoing optimized TLE for esophageal cancer with regard to age, sex distributions, incidence of comorbidities, tumor location, histology except preoperative staging, and American Society of Anesthesiologists (ASA) grade are shown in Table 1.
Surgical outcomes are shown in Table 2. The mean total operation time for the optimized procedures was 202.13 ± 13.74 min. The mean blood loss was 300.00 ± 120.12 min. The postoperative hospital stays for the optimized procedures were 16.27 ± 4.51 days. The number of total lymph nodes removed was 13.57 ± 2.76 per patient in the optimized TLE group. Our perioperative outcomes were slightly better compared with the previous literatures [17–21].
Table 2
Surgical outcomes of patients receiving optimized TLE procedures
Optimized procedure (n = 30)
Operation time (min)
202.13 ± 13.74
Blood loss (ml)
300.00 ± 120.12
Length of hospital stay (days)
16.27 ± 4.51
Number of dissected nodes
13.57 ± 2.76
With regard to the postoperative complications, the cervical anastomotic leakage was seen in one case (3.3 %) in our series. No other complications such as chylothorax, tracheal fistula, recurrent laryngeal nerve injury, and atelectasis were observed (Table 3). Our findings were significantly lower than the previous literatures [1, 14, 17, 18, 20–22].
Thoracoscopic esophagectomy is currently accepted by more and more thoracic surgeon due to minimal trauma and rapid recovery [19]. With the recent advance in thoracoscopic surgery, endoscopic esophagectomy gradually modified from the endoscopic-assisted mini-incision to total thoracoscopic and laparoscopic esophagectomy. This modification helps to the decrease of the surgical time and postoperative trauma [23]. However, with the number of the operation increase, some complications which rarely reported in the conventional three-port surgery also occur because the operations are more complex than those required for other malignancies [18, 24–27]. After reviewing the aforementioned literatures, we found the overall postoperative complications following TLE can reach up to about 47.6 % [17, 20, 28, 29]. Thus, how to reduce complications has become one issue that needs to be addressed urgently. We analyzed the clinical data of cases undergoing conventional TLE procedures in our hospital and found that most of the patients develop tracheal fistula 4–14 days after surgery when the gastric tube was removed and diet was begun. We consider that it may be due to the strong pressure difference between the negative intrathoracic and positive intraabdominal pressure. In addition, bilateral vagal neurectomy is liable to cause pyloric obstruction, which may enhance the pressure difference. Optimized TLE is a modification of conventional TLE, intended to diminish surgical trauma and decrease technical complications related to esophagectomy and associated lymph node dissection and reconstruction of the gastrointestinal tract, such as anastomotic leakage, recurrent laryngeal nerve palsy (RLNP), and chylothorax. In the current study, we optimized the protocols of the endoscopic esophagectomy. Patients receiving optimized TLE started nasogastric nutritional support with triple lumen nasojejunal feeding tube on the second postoperative day. Tubular stomach was maintained in a condition of negative pressure via cutting multiple-side holes into the gastric tube lateral wall. Distal intestinal feeding tube was passed from pylorus to the jejunum through Treitz’s ligament. Oral diet was started after triple lumen nasojejunal feeding tube was removed on the 10th postoperative day. These procedures resolved the difficulties such as functional obstruction at the pylorus, nutritional solution aggregation at the duodenum, and early postoperative enteral nutrition, and meanwhile reduce the surgical time. Our findings showed that the rate of postoperative complications in patients receiving the optimized TLE procedures was 3.3 %, which significantly improved compared to the previous reports.
In this study, patients in the optimized TLE group are intubated with a single lumen endotracheal tube for bilateral lung ventilation and positioned in the lateral prone position. Through these procedures, the operative field of the esophagus bed was similar in the conventional and optimized TLE group under the application of artificial pneumothorax. Due to the absence of two-lumen endotracheal tubes cuffs, the membranous part of the trachea is retrieved, which can clearly visualize lymph around the recurrent laryngeal nerve in the left side. In this study, patients treated with optimized TLE did not develop any recurrent laryngeal nerve injury. With regard to the number of retrieved total lymph nodes collected, our study demonstrated slightly higher number of lymph nodes dissected in the optimized TLE group compared to the previous reports.
Thoracic duct injury is a rare but serious complication following chest surgeries and major neck dissections, which may lead to nutritional deficiencies, respiratory dysfunction, and immunosuppression with a mortality up to 50 % in untreated patients [30, 31]. Clinically, it can present as cervical chylous fistula, chylothorax, or chylopericardium. As reported, 60~70 % of fat intake come together into cisterna chili via lymph vessels. Enterogenous lymph has a clinical presentation of milky white appearance due to a high content of triglycerides and chylomicrons. The flow and the characteristics of chyle from thoracic duct cannulae vary with the diet and usually about 60–100 ml/h. This flow will increase obviously with a presentation of chyle appearance after feeding (fat intake) and reduce with a presentation of clear appearance under hungry or fasting conditions. Patients should be fasted before the esophagectomy which go against the intraoperative distinguishment of the thoracic duct injury due to the clear lymphatic fluid in the thoracic duct. In the optimized TLE group, we infused the triglyceride and protein-rich oil-milk mixtures via gastric tube after tracheal intubation. Once the intraoperative thoracic duct injury occurs, it will accompany white fluid flow, which contributes to the prevention of the thoracic duct injury. In this study, we found no thoracic duct injury based on the above modifications of the TLE.
Optimized TLE is a safety and efficient surgical modality for esophageal cancer, which provide favorable outcomes in terms of operation time, blood loss, length of hospital stays, the number the dissected nodes, and reduced incidence of postoperative complications compared to previous literatures. Further studies with randomized controlled trials are necessary for confirming the surgical efficacy of our technique.
Acknowledgements
None.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Competing interests
The authors declare that they have no competing interests to declare.
Authors’ contributions
SZ conceived the study and participated in the literature search, writing of the manuscript, and editing the article. SZ submitted the manuscript and is the corresponding author. YS, LL, and HC participated in the study design, data analysis, and manuscript writing and editing. All authors read and approved the final manuscript. |
Prisoners across the country say they are gearing up for an end-of-summer nationwide strike against inhumane living conditions and unpaid labor — or, in their words, “modern-day slavery.”
The strike was announced in an April 24 press release and shared by a number of advocacy groups. According to one of the outside organizers who was contacted by In These Times, the press released was developed and written by prisoners. The strike, which is primarily being organized by the prisoners, will start on August 21 and last until September 9.
The action will involve work stoppages, sit-ins and a boycott of purchases from prison stores. The prisoners are demanding improved living conditions and an end to unpaid labor, as well as progressive sentencing reform and access to rehabilitation programs.
Organizers say they derived their boycott tactics from the Redistribute the Pain campaign, a plan put forward by the prisoners’ rights group Free Alabama Movement earlier this year. That campaign declares that “our goal is to remove the assets and monetary gain from those who practice slavery, especially those in the U.S. and their allies.”
“It is time that we take a new look and what is taking place across our nation in our prisons,” reads the April 24 statement from prisoners. “Not only is it important for us to take a look, but we must also take in consideration that for years we have neglected what is actually taking place.”
The strike comes in response to a riot that broke out at Lee Correctional Institution in Lee County, South Carolina on April 15. Seven prisoners were killed and 17 were seriously injured in an incident allegedly sparked by a gang rivalry within the prison. It is the deadliest U.S. prison riot in 25 years. Prison authorities say they didn’t send guards to intervene until they had assembled enough officers to do it safely. This took more than four hours. Prison killings have reached a critical mass in South Carolina, as they’ve quadrupled from 2015 to 2017.
South Carolina activist Malcolm Harris, one of the organizers outside of prisons helping to coordinate the upcoming strike, told In These Times that the violence in South Carolina is “reflective of what’s going on in the rest of the nation.” Nineteen percent of male prisoners in the United States say they’ve been assaulted by other prisoners, and 21 percent of them say they’ve been assaulted by prison guards. Women only make up 7 percent of the total prison population, but 33 percent of prisoners who are sexually victimized by prison staff members are women.
South Carolina corrections department director Bryan Stirling claims he’s identified the specific cause of the riot: cell phones. “Our preliminary investigation has found that this is gangs fighting over territory,” declared Stirling shortly after the riot. “And if they’re incarcerated, then they’re going to have to have a cellphone to continue their criminal ways from behind bars.”
Many have pushed back on this analysis, pointing out that without cell phones, the grisly details of South Carolina’s riot wouldn’t be known to the public. Critics also mention that South Carolina’s Department of Corrections has been pushing for the Federal Communications Commission (FCC) to allow authorities to use cell phone jammers for years. This effort is taking place nationwide: In 2016, 10 GOP governors wrote a letter to FCC Chairman Thomas Wheeler asking the agency to grant states the “flexibility and authority” to stop communication within prisons. One of the lawmakers who signed the letter is former South Carolina Governor Nikki Haley, current United States Ambassador to the United Nations.
Critics of mass incarceration attribute incidents like the South Carolina riot to the overall conditions of our punitive justice system, like the eradication of incentive programs for prisoners. “They’ve steadily cut back what little programs they had, and they’re just warehousing people in understaffed, overcrowded prisons,” Paul Wright, the director of the Human Rights Defense Center, a nonprofit that advocates on behalf of people in detention, told CBS. According to Wright, “Prison and penal operations have been studied pretty extensively for the last 15 years. When you take away all hope and you take away any reason for [prisoners] to behave themselves, then that’s when you start having higher levels of violence, assaults, and attacks.”
Harris echoed Wright’s sentiments. “All these things we’re fighting against with the strike, they’ve exacerbated everything in the prisons and they’ve bred violent reactions,” he said. He also pushed back on the narrative that more guards would necessarily mean less violence. “There’s always going to be more prisoners than guards,” he said. “More guards are not going to stop the problem.”
Isaac Bailey, whose brother is imprisoned at Lee, wrote an editorial for the The Charlotte Observer on April 18th summarizing what he had heard about the riot from his brother. According to Bailey, the actions of prison authorities helped facilitate the gang violence. “Prisoners knew officers would not come to the rescue if they were attacked — which provided a major incentive to join gangs as a means of self-preservation,” wrote Bailey. “After every incident, prisoners are locked down longer, which leads to more resentment and unrest and more violence, a vicious cycle.”
This strike is slated to follow similar collective actions throughout the country’s prison system. Last December, 45 prisoners in Iowa Park, Texas began a hunger strike. The following month, prisoners in eight Florida prisons initiated a work stoppage to protest against unpaid wages and inhumane living conditions. Many claim that they faced retaliation for their efforts, with some allegedly sent to solitary confinement for participating. That same month, 45 prisoners in Iowa Park, Texas began a hunger strike. This past Easter, roughly 1,000 prisoners at Washington State Penitentiary participated in a hunger strike to protest the quality of their food. A couple weeks later, prisoners in Huntsville, Texas went on a hunger strike in response to an imposed lockdown in their prison.
It’s unclear how many prisons throughout the country will end up participating in the action, but the organizers are calling on individuals to “spread the strike and word of the strike in every place of detention.” |
WO 02/09480 has already disclosed an operating method and a system for the resonant operation of high-pressure lamps in longitudinal mode. Specified there is a method for finding the second longitudinal acoustic resonant frequency. It assumes that during the continuous sweeping of the frequency range including the longitudinal mode the resonant frequency in the vertical operating position can be found by an occurrence of a relative increase in the operating voltage of the lamp. It emerges that the longitudinal frequency for a segregated arc state is found in vertical resonance with the aid of this method, and then maintained. However, depending on the composition of the metal halide filling and the timing of the expiry of the search procedure, this frequency thus found can be established far too high, and so an excitation of the acoustic resonance at the frequency found with the aid of the abovemetioned method produces an inadequate mixing and does not eliminate the segregation satisfactorily. However, it is expensive to implement in an electronic ballast. |
Published: December 13, 2018
Introduction {#sec1}
============
The CRISPR-Cas9 system has quickly become the preferred tool for genome engineering, enabling site-specific alterations in a variety of organisms and cellular contexts ([@bib11]). The system relies on the combined use of the bacterial Cas9 endonuclease and a single-guide RNA (sgRNA) to substitute, insert, or delete DNA sequences in almost any desired location in the genome ([@bib11]). Regardless of the experimental setting and application, genome editing by the CRISPR-Cas9 system entails three steps: (1) scanning of the genome by the RNA-guided Cas9 nuclease (RGN) to find the DNA sequence complementary to the sgRNA, (2) creation of a DNA double-strand break (DSB) by Cas9, and (3) repair of the lesion by the endogenous DNA repair machinery ([@bib11]). Both the accuracy and efficiency of the processes involved in each of these steps strongly affect the outcome of CRISPR-mediated editing and consequently the utility of the technology. Since the adaptation of the CRISPR system as an engineering tool, several studies have provided insights into the mechanisms affecting CRISPR-mediated DNA editing and have improved the method ([@bib3], [@bib9], [@bib10], [@bib11], [@bib12], [@bib27], [@bib24], [@bib25]). However, fundamental questions about how the mammalian genome and proteins interact with Cas9 and the sgRNAs and how cells respond to CRISPR-induced DNA damage remain unanswered. Increasing our knowledge of the mechanisms regulating these interactions is crucial to maximize the potential and safety of CRISPR-based approaches.
A key prerequisite for a good editing tool is the ability to discriminate between on-target and homologous off-target sites. Characterization of selected sgRNAs using both *in vitro* and cellular assays has provided important information about parameters influencing RGN specificity identifying the seed region of guide RNAs (the 10- to 12-nt sequence adjacent to the protospacer adjacent motif \[PAM\] sequence) as critical for recognition of target sequences ([@bib11]). This characterization has guided sgRNA-designing algorithms and improved CRISPR fidelity. However, systematic investigation of off-target cleavage sites has shown that predicting the specificity of any given RGN is not straightforward and has revealed that our understanding of how RGNs scan the mammalian genome is incomplete ([@bib24]). Importantly, by showing that truncated guide RNAs (17--18 nt) exhibit substantially reduced off-target DSBs, this large-scale analysis has proposed modifications that can considerably improve the technology and benefit various applications ([@bib24]). This example illustrates how systematic characterization of CRISPR-induced alterations in experimental systems may provide information about how RGNs interact with complex genomes and help optimize editing outcome.
In addition to specificity, activity is another feature that can vary widely across RGNs. While direct measurement of cleavage activity at a given target is not simple, sgRNA efficacy has been inferred either by quantifying the frequency of insertion and/or deletion (indel) formation or by evaluating the ability of an sgRNA to induce an expected phenotype. Analysis of large-scale studies has revealed sequence patterns correlating with sgRNA activity and has guided refinement of algorithms for sgRNA design ([@bib6], [@bib28]). Although *in silico* predictions of sgRNA efficacy have improved considerably, concordance between predicted and empirically measured indel activity remains moderate ([@bib9]). Thus, while we have achieved a qualitative understanding of RGN activity determinants, additional parameters not included in the current algorithms likely contribute to the overall outcome. The epigenetic status of target sequences may be one such factor. Although correlative evidence and *in vitro* studies have implicated chromatin in the modulation of RGN activity ([@bib10], [@bib25]), formal demonstration that the chromatin status of an endogenous locus affects its editing potential is still lacking.
DSBs induced by RGNs at target sites are recognized by the cell's DNA damage response pathways and repaired. Failure of accurate repair creates a chance for sequence alteration. When an exogenous repair template is provided, the homologous recombination (HR) repair pathway allows introduction of precise modifications in the DNA sequence, including single point mutations or insertion of exogenous sequences ([@bib11]). In the absence of a template, RGN-induced DSBs are often repaired through relatively error-prone mechanisms that result in insertions or deletions of variable length. Indels disrupting gene open reading frames lead to production of truncated, often nonfunctional proteins, making RGN-induced editing an effective means to induce gene knockout (KO) ([@bib11]). Despite the wide use of the CRISPR system to generate KO alleles, our understanding of the mechanisms driving indel formation is still limited, making the functional outcome of genome editing unpredictable and often preventing a rational use of the technology. Based on the type of indels observed upon RGN-mediated editing, two major repair pathways have been implicated in the formation of RGN-induced indels: canonical non-homologous end joining (cNHEJ), which is known to induce small indels, and microhomology-mediated end joining (MMEJ), which typically generates larger deletions at regions of microhomology (MH) ([@bib5]). Of note, genetic studies examining the general role of these pathways in the formation of CRISPR-mediated indels are currently lacking and the predominant method of repair of RGN-induced DSBs remains unclear. Based on the assumption that NHEJ is the main pathway involved in CRISPR-mediated indel formation, repair outcome was thought to be random. However, recent characterization of indel patterns at multiple genomic locations revealed that individual targets show reproducible repair outcome, with distinct preferences for class (insertion or deletion) and size of indels ([@bib27]). This finding suggests a deterministic nature of RGN-induced break repair and raises questions about the factors involved in defining these nonrandom patterns. Here, we performed a large-scale genomic characterization of indel patterns examining over 1,000 sites in the genome of human cells, with the aim of understanding how genetic and epigenetic factors influence CRISPR-mediated DNA editing. We find that Cas9-induced DSBs are repaired in a predictable or unpredictable way, depending on the target site. Precise targets, which show a dominant indel, can be identified *in silico* and their likely repair outcome inferred by their DNA sequence. Our findings suggest that selection of a predictable target is an effective strategy to induce desired CRISPR-mediated alterations.
Results {#sec2}
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Large-Scale Analysis of Indel Patterns {#sec2.1}
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To characterize general patterns of RGN-induced indels, we selected 1,491 target sites across the genome and retrieved the corresponding sgRNAs from a previously generated arrayed lentiviral library ([Table S1](#mmc2){ref-type="supplementary-material"}) ([@bib9]). The library targets 450 nuclear genes with multiple sgRNAs and has shown overall high activity ([@bib9]). At least three sites for each gene were selected, spacing the target regions along genes ([Figure S1](#mmc1){ref-type="supplementary-material"}A) and using sgRNAs with high predicted activity ([@bib4], [@bib6]) ([Figure S1](#mmc1){ref-type="supplementary-material"}B). Retrieved sgRNAs were combined and sequenced to confirm homogeneous representation in the resulting pools ([STAR Methods](#sec4){ref-type="sec"}) ([Figures 1](#fig1){ref-type="fig"}A and [S1](#mmc1){ref-type="supplementary-material"}C). Pooled sgRNAs were then transduced into HepG2 cells expressing Cas9 and allowed to edit their target sites for 5 days, a time frame sufficient to reach a plateau in terms of generated indels ([@bib3], [@bib27]) ([Figure S1](#mmc1){ref-type="supplementary-material"}D) but short enough to avoid KO-induced phenotypic changes that may confound the results ([Figure S1](#mmc1){ref-type="supplementary-material"}E). Upon isolation of genomic DNA, target regions were captured by pull-down using custom probes and sequenced at ∼6,000- to 8,000-fold coverage ([Figures 1](#fig1){ref-type="fig"}A, [S2](#mmc1){ref-type="supplementary-material"}A, and S2B). As expected, infection with pooled sgRNAs resulted in a high proportion of cells with unedited sequence at each target site, since only a small fraction of cells within the population expressed each sgRNA and could edit the corresponding site ([Figure S2](#mmc1){ref-type="supplementary-material"}B). Therefore, we developed a custom computational pipeline to filter reads from unedited cells for a given sgRNA, which enabled robust detection of indels ([STAR Methods](#sec4){ref-type="sec"}) ([Figure S2](#mmc1){ref-type="supplementary-material"}B). In total, 1,248 sites showed detectable indels, ranging from 1 to 188 per target, with a median count of 32 ([Figure S2](#mmc1){ref-type="supplementary-material"}C). This is a likely underestimation of induced indels, due to the limited sensitivity of our experimental approach, but it provides sufficient repair events to identify general indel patterns. Analysis of target sites in unedited control cells showed minimal indel counts, confirming robust and specific detection of on-target indels ([Figures S2](#mmc1){ref-type="supplementary-material"}C and S2D). Furthermore, high-coverage analysis of cells transduced with individual sgRNAs showed indel profiles very similar to those detected when using pooled sgRNAs ([Figure S2](#mmc1){ref-type="supplementary-material"}E). Targets with at least 10 reads containing indels (649 sites) were selected for downstream analysis.Figure 1General Specificity and Reproducibility of CRISPR-Mediated Indel Profiles(A) Overview of the experimental setup.(B) Frequency at which each detected indel occurs at each target site in two biological replicates.(C) Indel profiles for two biological replicates at the indicated target sites. Indel nomenclature: \[start coordinate relative to cleavage site\]:\[size\]\[insertion or deletion\]. Counts are normalized to the total library size for each experiment. Numbers in gray indicate indel frequency.(D) Size distribution of the commonest indel size at each target.(E) Percentage of indels resulting in a frameshift mutation at each target. Inset pie chart shows the proportion of targets for which the commonest observed indel is a frameshift mutation.(F) Heatmap visualizing the frequency at which indels of a given size occur at each target. Sites are clustered using Ward D2 hierarchical clustering. The bar plot above indicates the number of indels observed at the corresponding sites. Only data from targets from the 450 pools (524 targets) are used to enable fair comparisons.See also [Figures S1](#mmc1){ref-type="supplementary-material"} and [S2](#mmc1){ref-type="supplementary-material"} and [Table S1](#mmc2){ref-type="supplementary-material"}.
In agreement with previous studies that examined a limited number of sites ([@bib2], [@bib27]), we observed that RGN-induced editing was highly reproducible across biological replicates (Spearman's coefficient 0.75, p \< 2.2 × 10^−16^), indicating that repair outcome is nonrandom ([Figures 1](#fig1){ref-type="fig"}B and 1C). Validated sites confirmed these results, showing almost identical indel patterns in two independent experiments ([Figure S2](#mmc1){ref-type="supplementary-material"}F). Furthermore, our ability to probe a large number of sites simultaneously allowed us to reveal general patterns of CRISPR-mediated DNA editing and make a number of observations. First, single-nucleotide indels were the most frequent type of indel for the majority of targets, with 44% and 26% of targets showing 1-nt insertions or deletions, respectively, as their commonest indel ([Figure 1](#fig1){ref-type="fig"}D). Nevertheless, sites showing a preference for longer deletions (up to 41 nt) were also observed ([Figure 1](#fig1){ref-type="fig"}D). Second, in line with the observed bias for single-nucleotide alterations, CRISPR-induced indels often resulted in frameshift alterations ([Figure 1](#fig1){ref-type="fig"}E). On average, 80.1% of indels induced at a given site disrupted the gene coding frame, a percentage significantly higher than the theoretical 66% assuming a random outcome (p \< 2.2 × 10^−16^, χ^2^ test) ([Figure 1](#fig1){ref-type="fig"}E). Moreover, 81% of all detected indels resulted in a frameshift ([Figure 1](#fig1){ref-type="fig"}E). Thus, the probability of achieving protein loss of function through CRISPR-induced indels is typically relatively high. However, three sites showed strong preference for in-frame indels (in-frame indels ≥ 70%), suggesting that in certain cases, it may be difficult to successfully induce gene KO. Third, unsupervised hierarchical clustering identified four groups of targets showing similar indel patterns ([Figure 1](#fig1){ref-type="fig"}F). Based on the relative frequency of the observed indels, targets could be broadly divided into sites that preferentially show small insertions, small deletions, long deletions, or have no clear preference ([Figure 1](#fig1){ref-type="fig"}F). Fourth, sgRNA activity, as measured by quantifying indel counts at each site, was highly variable, ranging from 0 to 188 ([Figures S2](#mmc1){ref-type="supplementary-material"}C and [1](#fig1){ref-type="fig"}F). Indel count did not correlate with abundance of sgRNAs in the pools, suggesting that sgRNA activity is intrinsically variable ([Figure S2](#mmc1){ref-type="supplementary-material"}G). This observation is in agreement with previous findings obtained by inferring sgRNA activity from their ability to induce an expected phenotype ([@bib6], [@bib28]). Of note, several inactive sgRNAs had high predicted activity scores, indicating that predicting algorithms can be further improved and that, in addition to DNA sequence, other factors may affect sgRNA activity at a given site ([Figure S1](#mmc1){ref-type="supplementary-material"}B). Activity did not correlate with preference for a certain type of indel pattern ([Figure 1](#fig1){ref-type="fig"}F).
Precision of CRISPR-Induced DNA Editing Varies Considerably across Sites {#sec2.2}
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The observation that different targets display distinct preferences for certain indel types prompted us to examine the degree of editing precision (i.e., recurrence of a specific indel) across sites. To do so, we first calculated the relative frequency of each distinct indel, defined by its coordinates and base composition, at each site and then ranked all sites based on the frequency of the commonest indel. This analysis revealed a large range of editing precision, with some targets displaying up to 79 distinct, infrequent indels (frequency \< 5%) and others showing one dominant indel (up to 94% frequency) and only a few additional ones ([Figures 2](#fig2){ref-type="fig"}A, 2B, and [S3](#mmc1){ref-type="supplementary-material"}A). Overall, we found that for approximately one-fifth of the targets, there is at least a 50% chance of inducing a specific indel, but the majority of sites are more unpredictable. On average, the commonest indel frequency for a given site was 34.1%, and the median number of observed distinct indels was 12.Figure 2Site-Specific Precision of DNA Editing(A) Heatmap visualizing the frequency of each indel at each target. Red, commonest indel; blue, indels ranking 2--19; gray, indels ranking higher than 20. Bar plot shows the normalized number of distinct indels at each site.(B) Indel profiles of two imprecise (left) and two precise (right) targets. Indels are ordered by start coordinate relative to the cleavage site (arrowhead), with insertions having priority over deletions. The inset number indicates the total number of indels detected at that site.See also [Figure S3](#mmc1){ref-type="supplementary-material"}.
Editing Precision Correlates with Editing Efficiency, Indel Type, and Indel Size {#sec2.3}
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To examine the relationship between editing precision and indel features, we categorized target sites into three groups: imprecise (0 \< commonest indel frequency ≤ 0.25), middle (0.25 \< commonest indel frequency ≤ 0.5) and precise sites (0.5 \< commonest indel frequency ≤ 1), with each group containing comparable numbers of sites ([Figure 3](#fig3){ref-type="fig"}A). Notably, editing precision correlated with efficiency of indel formation (p \< 2.2 × 10^−16^, Kruskal-Wallis test) ([Figure 3](#fig3){ref-type="fig"}B). Precise targets showed on average twice as many indels as imprecise targets, and the most active sites showed a strong preference for specific indels (commonest indel frequency \> 0.57) ([Table S2](#mmc3){ref-type="supplementary-material"}). This pattern was not due to differences in sgRNA abundance or sequencing depth among groups ([Figures S3](#mmc1){ref-type="supplementary-material"}B and S3C). We then asked whether editing precision correlated with preference for insertions or deletions. Imprecise targets showed a high proportion of deletions, with insertions being on average only 20% of the total indels, whereas insertions were more frequent in the middle group of targets ([Figure 3](#fig3){ref-type="fig"}C). Precise targets segregated into two distinct subsets; 68.4% showed a strong preference for insertions, whereas the rest mainly repaired RGN-induced breaks by inducing deletions ([Figure 3](#fig3){ref-type="fig"}C). The two subsets were clearly separated, likely reflecting their tendency to induce mainly one dominant indel. Editing precision also correlated with absolute indel size ([Figure 3](#fig3){ref-type="fig"}D). While imprecise and middle targets showed a range of indel sizes, with deletions as long as 2,315 bp, precise targets displayed a strong bias toward single-nucleotide indels ([Figures 3](#fig3){ref-type="fig"}D, 3E, and [S3](#mmc1){ref-type="supplementary-material"}A). Combining insertion and deletions, 71.5% of edited sequences in the precise group had a single-nucleotide alteration. We conclude that RGN-related editing precision varies considerably across sites and correlates with editing efficiency and the type of resulting indels.Figure 3Relationship between Editing Precision and Indel Features(A) Distribution of commonest indel frequencies at target sites. The background indicates three groups of sites as defined based on their editing precision. Inset numbers indicate the number of target sites in that group.(B--D) Relationship between precision and indel count (B), type of indel (C), and indel size (D). Only data from the 450 pools are used in (B) to enable fair comparisons.(C) Percentage of indels that are insertions at each target. I, imprecise; M, middle; P, precise. Statistical analysis was done using the Kruskal-Wallis test followed by Dunn's test for multiple comparisons with Benjamini-Hochberg correction for multiple testing.(E) Relationship between the median absolute indel size and the commonest indel frequency (i.e., the measure of editing precision at each target). The background is colored as in (A).See also [Figures S3](#mmc1){ref-type="supplementary-material"} and [Table S2](#mmc3){ref-type="supplementary-material"}.
Precise Targets Exhibit Primarily Homology-Associated Insertions and Deletions {#sec2.4}
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Although indel profiles have been shown to be dependent on both MH-dependent and MH-independent mechanisms ([@bib1], [@bib3], [@bib27]), a quantitative assessment of their relative contribution across many target sites is lacking. In the absence of genetic or pharmacological interference with specific repair pathways (e.g., NHEJ, homology directed repair \[HDR\], or MMEJ), characterization of indel profiles is insufficient to determine which specific mechanism led to an observed outcome. We therefore performed a pathway-agnostic analysis of indels that searched for any homology at the indel boundaries. This analysis revealed that MH of variable size, ranging from 1 to 18 nt, characterized the majority of deletions ([Figures 4](#fig4){ref-type="fig"}A--4C; [Table S3](#mmc4){ref-type="supplementary-material"}). 73.3% of all deletions showed evidence of MH-mediated repair (MH deletions), and on average, 74.3% of deletions at a given site were characterized by MH ([Figure 4](#fig4){ref-type="fig"}A). Deletions associated with shorter MHs (1--4 nt) were also enriched above the expected frequency, indicating that the effect of sequence homology on repair outcome is not limited to longer MH stretches (5--25 nt) used by the MHEJ pathway ([Figure 4](#fig4){ref-type="fig"}B). MH deletions were enriched in the groups of precise and middle targets (p = 1.36 × 10^−5^, Kruskal-Wallis test) ([Figure 4](#fig4){ref-type="fig"}D). Furthermore, regardless of editing precision, 80% of targets had a MH deletion as their commonest.Figure 4Precise Targets Are Enriched for Homology-Associated Indels(A) Percentage of microhomology (MH)-associated deletions at each target site. Inset pie chart shows the proportion of all detected MH deletions.(B) Percentage of deletions that have MH of a given size. The gray bar indicates the expected percentage for each *k*-mer size. Statistical analysis was done using the χ^2^ test.(C) Deletions detected at the ARID1D.7 site. In the gray panel is the reference sequence, with the PAM sequence emboldened in blue and the expected cleavage site indicated with a red line. Below, each line represents a detected deletion. In the dashed box is the MH in the deletion, and emboldened in red is the corresponding MH in the unedited part of the sequence.(D) Percentage of MH deletions at individual sites grouped by precision. I, imprecise; M, middle; P, precise. Statistical analysis was done using the Kruskal-Wallis test followed by Dunn's test for multiple comparisons with Benjamini-Hochberg correction for multiple testing.(E) Frequency of the commonest insertion at a target site. Only targets with 5 or more insertions are considered to obviate a low-count bias. The inset count is the number of target sites included.(F) Insertions detected at the indicated sites. In the gray panel is the reference sequence, with the PAM sequence emboldened in blue and the expected cleavage site indicated with a red line. The −4 position is underlined. Below, the edited sequence is shown with the insertion homology (either a mono- or dinucleotide) emboldened in red.(G) Percentage of homologous insertions at individual target sites grouped by precision. Statistical analysis was done using the Kruskal-Wallis test followed by Dunn's test for multiple comparisons with Benjamini-Hochberg correction for multiple testing.(H) Percentage of all homologous insertions in a group (filled bars) and corresponding percentage of commonest insertions (outlined bars).(I) Nucleotide inserted as the commonest insertion for each precision group.See also [Tables S3](#mmc4){ref-type="supplementary-material"} and [S4](#mmc5){ref-type="supplementary-material"}.
Although sequence homology has not been implicated in the formation of insertions, surprisingly, we found that many target sites showed recurrent insertions containing a common inserted base, suggesting that the choice of inserted nucleotide is nonrandom ([Figures 4](#fig4){ref-type="fig"}E and [S3](#mmc1){ref-type="supplementary-material"}A; [Table S4](#mmc5){ref-type="supplementary-material"}). Moreover, the recurrently inserted base was often homologous to the nucleotide at position −4 from the PAM sequence, which is typically the nucleotide upstream of the cleavage site ([@bib14]) (82% of the commonest insertions at each target) ([Figure 4](#fig4){ref-type="fig"}F); we termed this feature "insertion homology." As observed for deletions, the prevalence of insertion homology correlated with editing precision (p \< 2.6 × 10^−16^, Kruskal-Wallis test) ([Figures 4](#fig4){ref-type="fig"}G and 4H). Precise targets displayed 96% of homologous insertions, whereas this percentage was only 57% in the imprecise group (p \< 2.6 × 10^−16^, χ^2^ test) ([Figure 4](#fig4){ref-type="fig"}H), suggesting that template-mediated insertions are a strong determinant of the observed site-specific indel profiles. Even at imprecise targets, homologous insertions were often the commonest ones ([Figure 4](#fig4){ref-type="fig"}H). Notably, precise targets showed a strong bias for inserted "A"s and "T"s, suggesting that sequence features underlie the correlation between editing precision and homologous insertions ([Figure 4](#fig4){ref-type="fig"}I). Altogether, these observations suggest that homology-mediated end joining strongly influences DNA repair outcome, for both insertions and deletions, and correlates with site-specific precision of CRISPR-mediated editing.
The DNA Sequence Determines Editing Precision {#sec2.5}
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To examine whether editing precision depends on the base composition of target sites and, if so, to identify critical positions in the protospacer, we employed a machine learning approach. We trained a neural network that predicts editing precision (i.e., commonest indel frequency) using 80% of the targets selected randomly to train the network, with the remaining 20% kept unseen for testing. We found a significant correlation between the estimated and observed indel frequencies for the 130 test target sites (correlation coefficient R = 0.49, p = 4.73 × 10^−9^, Wald test) ([Figures 5](#fig5){ref-type="fig"}A and [S4](#mmc1){ref-type="supplementary-material"}A). Analysis of an independent dataset characterizing indel profiles at 96 distinct sites ([@bib27]) confirmed these findings (R = 0.53, p = 7.26 × 10^−8^) ([Figures 5](#fig5){ref-type="fig"}B and [S3](#mmc1){ref-type="supplementary-material"}E). Importantly, targets analyzed by van Overbeek et al. were selected differently from ours and showed distinct overall nucleotide composition, indicating that the neural network has learned generalizable features ([Figures S3](#mmc1){ref-type="supplementary-material"}D and [S4](#mmc1){ref-type="supplementary-material"}B). Although the predictive power of the model was only moderate (coefficient of determination R^2^ = 0.24), it allowed us to identify important positions in the protospacer. If certain positions have a significant influence on editing precision, then randomizing those nucleotides is expected to dramatically reduce the correlation between estimated and observed indel frequencies. To investigate this, we performed a permutation "nucleotide" importance analysis, systematically randomizing each position in test sequences and examining the resulting effect on the neural network output. This analysis revealed that the nucleotide at position −4 from the PAM sequence had the strongest influence on editing precision as a single nucleotide, reducing the model's accuracy by 78% ± 9% upon randomization (R^2^ = 0.05 ± 0.02) ([Figure 5](#fig5){ref-type="fig"}C). Nucleotide positions −2, −3, and −5 also showed an effect, although weaker, reducing R^2^ by 29% ± 9%, 15% ± 5%, and 50% ± 13%, respectively. Simultaneous randomization of all four nucleotides reduced R^2^ by over 98% ± 2% and abolished the predictive significance of the trained model (average R^2^ = 0.01 ± 0.01; p \> 0.1 for all permutations, Wald tests), indicating that these positions within the protospacer, especially the one upstream of the cleavage site, are critical for defining editing precision of a target site ([Figure 5](#fig5){ref-type="fig"}D). We refer to these combined nucleotides as the "precision core" of a target site. Similar results were obtained using a least absolute shrinkage and selection operator (LASSO) linear regression model ([Figures S4](#mmc1){ref-type="supplementary-material"}C and S4D).Figure 5A Neural Network Identifies Protospacer Nucleotide Positions that Determine Editing Precision(A and B) Correlation between the observed precision at a given target site and that predicted by the neural network, using our test set (A) and independent dataset ([@bib27]) (B). R, correlation coefficient. Statistical analysis was done using the Wald χ^2^ test.(C and D) Contribution of the indicated protospacer nucleotides (C) or combination of nucleotides (D) to editing precision. The effect of nucleotide randomization is shown as reduction of the model's accuracy (R^2^). Values are mean and SD from 10 different permutations. Bars in red indicate randomized positions that increased p values of Wald tests across the majority of permutations to nonsignificant levels (p \> 0.05).(E) Sequence logos for the precision core for the different precision groups. Precise targets are split based on their preference (commonest indel) for insertions or deletions. The most important −4 nucleotide position is highlighted in a yellow box.(F and G) Proportion (F) and percentage (G) of targets that have the indicated nucleotide at the −4 position. Sites are grouped based on their precision and their preference (commonest indel) for insertions or deletions.(H) Likelihood of editing outcome for sites having the indicated nucleotides at the −5 and −4 positions. Numbers represent the median commonest frequency and the insertion rate for each mono- or dinucleotide as measured in our dataset. See also [Table S5](#mmc1){ref-type="supplementary-material"}.See also [Figure S4](#mmc1){ref-type="supplementary-material"} and [Table S5](#mmc1){ref-type="supplementary-material"}.
Targets in different precision groups revealed differences in protospacer nucleotide composition ([Figures 5](#fig5){ref-type="fig"}E and [S4](#mmc1){ref-type="supplementary-material"}E). Notably, precise targets showed distinct base preferences depending on whether the commonest indel was an insertion or a deletion ([Figure 5](#fig5){ref-type="fig"}E). As expected, nucleotide −4 showed the biggest differences, followed by nucleotide −5, which was frequently a "C," specifically in precise targets ([Figure 5](#fig5){ref-type="fig"}E). We then examined to what extent nucleotide −4 on its own could predict editing outcome. Different bases at position −4 showed distinct association with indel types (insertions versus deletions) and precision groups ([Figure 5](#fig5){ref-type="fig"}F). The vast majority of target sites that contained an "A" or a "T" upstream of the cleavage site repaired RGN-induced DSBs via insertions (77% and 91% of targets, respectively) ([Figure 5](#fig5){ref-type="fig"}G). These were mostly precise or middle targets (median commonest indel frequency: 0.42 and 0.56 for targets with "A" and "T," respectively) ([Figures 5](#fig5){ref-type="fig"}G and [S4](#mmc1){ref-type="supplementary-material"}F). When taking into account positions −5 and −4 together, the correlation with precision further increased (median commonest indel frequency: 0.53 and 0.65 for targets with "CA" and "AT," respectively) ([Figure 5](#fig5){ref-type="fig"}E; [Table S5](#mmc1){ref-type="supplementary-material"}). In contrast, 79% of targets containing a "G" at position −4 showed deletions and were mostly imprecise targets (median commonest indel frequency: 0.21) ([Figures 5](#fig5){ref-type="fig"}G and [S4](#mmc1){ref-type="supplementary-material"}F). Moreover, 76.4% of targets containing "CC" at positions −5 and −4 induced relatively precise deletions (median commonest indel frequency: 0.39) ([Figure 5](#fig5){ref-type="fig"}E; [Table S5](#mmc1){ref-type="supplementary-material"}). Notably, similar distributions were observed at the sites edited by [@bib27] ([Figures S4](#mmc1){ref-type="supplementary-material"}F and S4G). Given the large number of sites examined, the observed percentages assume a predictive value with respect to the editing outcome that may occur at similar protospacers ([Figure 5](#fig5){ref-type="fig"}H). We conclude that precise targets can be identified by examining the base composition of the precision core and that position −4 is sufficient to predict with a high degree of confidence whether a site will acquire insertions or deletions.
Chromatin States Affect RGN Activity {#sec2.6}
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Our findings, in agreement with previous small-scale studies ([@bib2], [@bib27]), suggest that DNA sequence features strongly affect RGN-induced indel profiles in a site-specific manner, influencing editing precision and efficiency. However, even within precision groups, the number of induced indels and their patterns varied across sites ([Figure 3](#fig3){ref-type="fig"}B). Furthermore, the neural network model, based solely on the protospacer sequence, was unable to fully recapitulate observed frequencies, suggesting other factors at play. We therefore examined whether chromatin structure may contribute to the observed editing outcome. To do so, we selected six target sites characterized by variable editing precision and efficiency of indel formation ([Figure 6](#fig6){ref-type="fig"}A) and individually transduced the corresponding sgRNAs in Cas9-expressing cells in the presence of chromatin-modulating compounds. We used the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to induce histone hyperacetylation at the target sites ([Figures S5](#mmc1){ref-type="supplementary-material"}A and S5B) using concentrations of the inhibitor that do not impair cell proliferation or induce DNA damage ([Figures S5](#mmc1){ref-type="supplementary-material"}C and S5D). TSA treatment significantly increased the efficiency of indel formation, inducing dose-response changes (p \< 0.001, paired Wilcoxon test) and reaching almost a 2-fold increase for the ACTL6A.5 site ([Figure 6](#fig6){ref-type="fig"}B). The effect was highly reproducible across biological replicates ([Figures 6](#fig6){ref-type="fig"}B and 6D; [Table S6](#mmc6){ref-type="supplementary-material"}), varied depending on the target, and inversely correlated with the endogenous levels of histone acetylation ([Figures 6](#fig6){ref-type="fig"}B, 6C, and [S5](#mmc1){ref-type="supplementary-material"}B). Sites characterized by low levels of acetylated H3 showed a greater response to the treatment than those that already had high levels of the endogenous mark (MSH6.2 and SMARCD2.1), suggesting a direct effect of chromatin modulation on indel formation ([Figures 6](#fig6){ref-type="fig"}B, 6C, and [S5](#mmc1){ref-type="supplementary-material"}B). Editing efficiency was also affected, to a lower extent, by treatment of cells with EZH2i inhibitors, which decreased H3K27me3 levels ([Figure S5](#mmc1){ref-type="supplementary-material"}A). Contrary to TSA, EZH2i inhibited indel formation ([Figure 6](#fig6){ref-type="fig"}B). Analysis of individual indels indicated that the effect of TSA and EZH2i was not restricted to a few indels and that both insertions and deletions were affected ([Figures 6](#fig6){ref-type="fig"}D and [S6](#mmc1){ref-type="supplementary-material"}A; [Table S6](#mmc6){ref-type="supplementary-material"}). We conclude that the chromatin state of target sites affects the activity of RGNs and that transient induction of histone acetylation enhances DNA editing efficiency.Figure 6Chromatin Modulation Affects RGN Activity(A) Indel profile at the indicated target sites in untreated cells. Indels are ordered by start coordinate relative to the cleavage site (arrowhead), with counts normalized by the effective library size at each site. The mean across both replicates is shown.(B) Editing efficiency (above) and log~2~ fold-change in efficiency relatively to untreated cells (NT) (below) for each target site in the indicated conditions. Biological replicates are shown separately in the upper graphs and averaged in the bottom graphs.(C) Mean chromatin immunoprecipitation sequencing (ChIP-seq) signal for H3K9ac and H3K27ac and DNase-seq signal in untreated HepG2 cells ([@bib17]). Signal in a 500-nt window centered on the cleavage site at each target site is shown as a heatmap.(D) Chromatin modulation affects both insertions and deletions. Count of individual indels at the indicated sites in untreated cells (above), and log~2~ fold-change in efficiency induced by TSA or EZH2i relative to untreated cells (below). Indel count is normalized to the effective library size at each site for each replicate. Only indels with a normalized count of at least 1 in any condition are included. The indel nomenclature is \[start coordinate relative to cleavage site\]:\[size\]\[insertion or deletion\].See also [Figures S5](#mmc1){ref-type="supplementary-material"} and [S6](#mmc1){ref-type="supplementary-material"} and [Table S6](#mmc6){ref-type="supplementary-material"}.
Chromatin States Influence Indel Profiles but Do Not Alter Dominant Indels at Precise Sites {#sec2.7}
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Although changes in editing efficiency by TSA or EZH2i were observed for most indels at each site, some indels were preferentially affected ([Figure 6](#fig6){ref-type="fig"}D). Furthermore, shorter and longer indels appeared differentially altered by treatment ([Figure S6](#mmc1){ref-type="supplementary-material"}B). These observations suggest that chromatin modulation may affect indel profiles. We therefore examined the relative changes in the abundance of individual indels, focusing on the effect of TSA, which induced greater and more consistent changes in indel formation ([Figures 6](#fig6){ref-type="fig"}B and 6D). Across all sites, we observed dose-dependent changes in the relative frequency of indels, with some being favored at the expense of others ([Figures 7](#fig7){ref-type="fig"} and [S7](#mmc1){ref-type="supplementary-material"}). Although the observed changes were small in extent and the overall indel patterns were maintained, confirming robustness of the editing profiles, the most frequent indels showed reproducible and dose-dependent changes ([Figure 7](#fig7){ref-type="fig"}). At some sites (MBD3L1.6, MSH6.2, and SMARCD2.1), the preference for their commonest indel was enhanced, while at others (ACTL6A.5, ASF1B.7, and BRD2.7), it was decreased ([Figure 7](#fig7){ref-type="fig"}C). Importantly, changes induced by chromatin modulation had distinct impact on sites, depending on their editing precision; for instance, the identity of the commonest indel changed at the imprecise BRD2.7 site, whereas the dominant indel at the precise ACTL6A.5 site was not altered, despite significant changes in its frequency ([Figures 7](#fig7){ref-type="fig"}A and 7C). Thus, editing of precise targets is not substantially affected by differences in chromatin states, whereas dominant indels can vary at imprecise targets depending on chromatin state. This observation has implications for DNA editing in different cell types.Figure 7Chromatin Modulation Induces Small Changes in Indel Profiles(A) Normalized indel frequency for the indicated targets in untreated cells (gray bars) and in cells treated with 100 nM TSA (red outline). Indel nomenclature: \[start coordinate relative to cleavage site\]:\[size\]\[insertion or deletion\]. The 10 commonest indels for each site are shown.(B) Log~2~ fold change in the indel frequency for the indicated targets. The 10 commonest indels across both replicates are shown.(C) Change in frequency for the three commonest indels (ranks 1, 2, and 3) for all validated target sites. The line indicates the mean of both replicates, and the shaded area represents the mean ± 1 SD. NT, untreated cells.See also [Figures S5](#mmc1){ref-type="supplementary-material"} and [S7](#mmc1){ref-type="supplementary-material"} and [Table S6](#mmc6){ref-type="supplementary-material"}.
As a complementary approach to experimental modulation of chromatin, we analyzed the van Overbeek dataset, which examined indel profiles at 96 sites in different cell types characterized by distinct chromatin landscapes. HCT116 cells were excluded from this analysis, as their deficiency in mismatch repair may modulate indel profiles independently of chromatin differences. Embryonic kidney HEK293 cells and lymphoblastoid K562 cells displayed very similar but not identical indel profiles, indicating that these are primarily, but not entirely, determined by DNA sequence ([Figure S5](#mmc1){ref-type="supplementary-material"}E). Sites with major differences in histone acetylation levels showed different indel profiles. As observed in our dataset, some imprecise targets showed different dominant indels in the two cell lines, whereas precise sites showed conserved indel profiles ([Figure S5](#mmc1){ref-type="supplementary-material"}F). Altogether, these results show that chromatin structure contributes to the establishment of site-specific indel profiles. While the DNA sequence appears to be the major determinant of CRISPR-mediated editing outcome, the chromatin state of a given site may modulate the relative abundance of individual indels and contributes to defining the site's indel profile. Despite chromatin-mediated differences in indel profiles, precise targets display a conserved and highly reproducible editing outcome.
Discussion {#sec3}
==========
Precision of Editing Outcome {#sec3.1}
----------------------------
Although the bacterial CRISPR system has been widely adopted as the preferred genome engineering tool, our ability to predict the editing accuracy, efficacy, and outcome at specific sites is still limited. A major obstacle in defining precise genome editing rules is our incomplete understanding of how RGNs interact with eukaryotic cellular components---complex genomes containing repetitive sequences, the packaging of DNA into chromatin, and the presence of various cellular pathways that recognize and repair RGN-induced DSBs. Various studies have provided insights into some of these interactions ([@bib3], [@bib12], [@bib13], [@bib16], [@bib18], [@bib27]). However, due to the limited number of characterized target sites, discerning whether the observed patterns are general or site-specific features is not straightforward. Through systematic analysis of indel formation at over 1,000 different sites in the human genome, this study reveals general trends of CRISPR editing and provides simple rules to predict how a given target may respond to RGN-induced DSBs.
Extending the observation that indel profiles are nonrandom ([@bib27]), we find that precision of DNA editing varies considerably among sites, with some targets showing one highly preferred sequence alteration and others displaying a wide range of infrequent, yet reproducible, indels. We show that editing precision is an intrinsic feature of the target site and depends on four nucleotides located around the cleavage site within the protospacer, with the most influential position being the nucleotide at position −4 from the PAM sequence. Strikingly, the mere presence of a "T" here gives a site a 51% probability of repairing in a predictable manner and 91% chance of introducing an insertion. Our finding that editing precision is site-specific and can be predicted has important implications. Practically, knowing what editing outcome is likely to occur at a given site maximizes the chance of having a desired sequence alteration, for both clinical and research applications. Although pharmacological modulation of repair pathways alters indel profiles, the induced changes are subtle, and for many applications, the use of inhibitors may not be suitable ([@bib27], [@bib22]). Targeting a precise site would be a more effective way of steering CRISPR-mediated editing toward a desired outcome. Moreover, given the extreme reproducibility of indel patterns, the selection of a precise target combined with experimental validation in model systems could considerably increase safety in clinical applications. This is particularly relevant in light of recent studies reporting the occurrence of large on-target deletions that may have pathological consequences ([@bib16]).
Relationship between Editing Precision and Indel Type {#sec3.2}
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Our findings also reveal a strong correlation between editing precision and preference for repairing RGN-induced DSBs via insertions. We show that targets with "A"s or "T"s at nucleotide −4 mainly show insertions, with the commonest insertion being highly recurrent and representing on average approximately half of the indels detected at a given site ([Figure 5](#fig5){ref-type="fig"}H). DSB repair via insertions may be kinetically faster compared to other types of indel, partly explaining the higher efficiency of precise targets and the general bias toward single-nucleotide indels. Notably, recent studies have reached similar conclusions using experimental approaches complementary to ours, based on synthetic target sites ([@bib29], [@bib21], [@bib23]). The identity of the recurrent insertions can also be predicted, as the inserted nucleotide is nearly always homologous to the −4 nucleotide ([Figures 4](#fig4){ref-type="fig"}G--4I). Such predictions could, for instance, allow efficient introduction of a stop codon (TAA) when an in-frame TA dinucleotide is present at positions −5 and −4 of the targeted region. In contrast, targets with "G"s at nucleotide −4 are the most imprecise and repair mainly induces a variety of unpredictable deletions ([Figures 5](#fig5){ref-type="fig"}G and 5H). Thus, choosing target sites with "A"s or "T"s at nucleotide −4 is an effective way to induce predictable insertions at regions of interest.
Critical Role of Nucleotide −4 in Defining Site-Specific Indel Profiles {#sec3.3}
-----------------------------------------------------------------------
The key role of nucleotide −4 in influencing editing precision and preference for indel type is particularly interesting in light of recent findings that revealed flexible scissile profiles by Cas9 and generation of 5′ overhangs upstream of the canonical cleavage site due to asymmetric cleavage of the two DNA strands ([@bib22]). Notably, 5′ overhangs are mostly observed at position −4 on the non-complementary strand. These findings, together with our results, explain the prevalence of single-nucleotide insertions homologous to the −4 nucleotide, as the overhanging nucleotide can be used as a template before ends are rejoined. Thus, paradoxically, imprecision of Cas9 cleavage is the likely cause of precision in the insertion outcome. Similarly, the high frequency of single-nucleotide deletions is likely related to the asymmetric cleavage of DNA by Cas9.
Envisioning how the base composition of position −4 may influence editing precision is not straightforward. One possibility is that the nature of the 5′ overhanging nucleotide may recruit distinct proteins involved in DNA repair. Alternatively, it may affect Cas9 binding to the broken ends, and this may, in turn, affect the repair outcome. The other nucleotides in the precision core may act similarly. Structural analysis of RGNs with distinct −4 nucleotides may help shed light on this issue.
Our observation that the vast majority of detected insertions show homology, combined with the finding that NHEJ-mediated repair of CRISPR-induced DSBs is mostly error-free ([@bib8]) and that deletions generated by sgRNA pairs can be repaired with a high level of precision ([@bib22]), suggests a model whereby flexible cleavage by Cas9 influences DNA repair fidelity; when blunt ends are generated at nucleotide −3, cells repair DSBs in an error-free manner, reconstituting the original sequence, whereas indels occur mainly when asymmetric cleavage generates overhanging ends. This model may also reconcile apparently conflicting results about the fidelity of NHEJ in CRISPR-independent and CRISPR-dependent contexts ([@bib3], [@bib7], [@bib8], [@bib26], [@bib22]). Interestingly, both outcomes are useful for genome editing, as blunt ends allow precise genomic deletions and insertions of exogenous sequences, while overhanging ends enable induction of indels resulting in gene KO.
Influence of the Chromatin Environment on Site-Specific Editing Outcome {#sec3.4}
-----------------------------------------------------------------------
Although DNA sequence is a major determinant of site-specific indel profiles, we show that packaging of DNA into chromatin may affect editing efficiency and the relative frequency of indels at a given locus. We find that histone hyperacetylation and reduction of the heterochromatin-associated mark H3K27me3 induce opposite changes in editing efficiency, enhancing and inhibiting indel formation, respectively. Although the effect of TSA was observed at all tested sites, the effect was particularly pronounced at sites with low endogenous levels of histone acetylation, suggesting that transient TSA treatment may be a strategy to enhance editing efficiency at sites located in repressive chromatin environments. While our results do not unequivocally prove that local chromatin changes are responsible for the observed effects, they are in agreement with the reported correlations between sgRNA activity and open chromatin at the genome-wide levels and evidence from *in vitro* studies indicating that nucleosome positioning impairs binding of Cas9 to DNA and inhibits its activity ([@bib10], [@bib25]). In addition to interfering with Cas9 binding to a target site, chromatin may also affect its cleavage profile, favoring either blunt ends that can be precisely repaired or overhanging ends that promote the formation of indels. We also show that modulation of chromatin differentially affects individual indels at a target site and can change the identity of the commonest indel at imprecise sites ([Figure 7](#fig7){ref-type="fig"}). Notably the magnitude of changes observed upon TSA treatment, albeit small, is comparable to those observed when inhibitors of specific DNA repair pathways are used ([@bib27]). These results show that the chromatin configuration of a given site contributes to defining its indel profile. Given the established role of chromatin in DNA repair ([@bib15]) and the involvement of multiple DNA repair pathways in mediating CRISPR-induced DNA editing ([@bib20], [@bib27], [@bib22]), altered recruitment of factors involved in different pathways may underlie the observed difference upon chromatin modulation. Importantly, regardless of chromatin states, precise targets show consistent dominant indels, suggesting that editing outcome at these sites is conserved across cell types.
In summary, our findings uncover general principles guiding CRISPR-mediated DNA editing in human cells and provide guidelines for a more effective and safer use of the technology, with important implications for clinical applications. They also reveal a striking influence of the DNA sequence in dictating DSBs repair outcomes and lay the foundation for future mechanistic studies that can increase our understanding of end-joining processes in human cells.
STAR★Methods {#sec4}
============
Key Resources Table {#sec4.1}
-------------------
REAGENT or RESOURCESOURCEIDENTIFIER**Antibodies**Rabbit polyclonal anti-trimethyl-Histone H3 (Lys27)MilliporeCat\# 07-449; RRID: [AB_310624](nif-antibody:AB_310624){#intref0010}Mouse monoclonal anti-Ezh2 (AC22)Cell Signaling TechnologyCat\# 3147; RRID: [AB_2102420](nif-antibody:AB_2102420){#intref0015}Rabbit polyclonal anti-Histone H3 (acetyl K27)AbcamCat\# ab4729; RRID: [AB_2118291](nif-antibody:AB_2118291){#intref0020}Rabbit polyclonal anti-mouse IgG H&LAbcamCat\# ab46540; RRID: [AB_2614925](nif-antibody:AB_2614925){#intref0025}Mouse monoclonal anti-phospho-Histone H2A.X (Ser139)MilliporeCat\# 05-636; RRID: [AB_309864](nif-antibody:AB_309864){#intref0030}HRP goat anti-rabbit IgG (Peroxidase)Vector LaboratoriesCat\# PI-1000; RRID: [AB_2336198](nif-antibody:AB_2336198){#intref0035}Donkey polyclonal anti-mouse IgG AF488Thermo FisherCat\# A-21202; RRID: [AB_141607](nif-antibody:AB_141607){#intref0040}Donkey polyclonal anti-mouse IgG AF568Thermo FisherCat\# A10037; RRID: [AB_2534013](nif-antibody:AB_2534013){#intref0045}Donkey polyclonal anti-mouse IgG AF647Thermo FisherCat\# A-31571; RRID: [AB_162542](nif-antibody:AB_162542){#intref0050}Donkey polyclonal anti-rabbit IgG AF488Thermo FisherCat\# A-21206; RRID: [AB_2535792](nif-antibody:AB_2535792){#intref0055}Donkey polyclonal anti-rabbit IgG AF568Thermo FisherCat\# A10042; RRID: [AB_2534017](nif-antibody:AB_2534017){#intref0060}**Chemicals, Peptides, and Recombinant Proteins**Trichostatin ASigmaCat\# T1952GSK126 (EZH2 inhibitor)Cayman ChemicalCat\# 15415**Critical Commercial Assays**MiSeq Reagent Kit v3IlluminaCat\# MS-102-3003DNeasy Blood & Tissue KitQIAGENCat\# 69506SureSelectXT Custom 0.5-2.9Mb libraryAgilentCat\# 5190-4816QIAquick Gel Extraction KitQIAGENCat\# 28706QIAquick PCR Purification KitQIAGENCat\# 28106Herculase II Fusion DNA polymeraseAgilentCat\# 600675CellTiter 96 Aqueous One SolutionPromegaCat\# G3582**Deposited Data**Targeted DNA-seq of Human HepG2 cells following editing with CRISPR/Cas9EBI ArrayExpressArrayExpress: [E-MTAB-7095](array-express:E-MTAB-7095){#intref0065}Targeted DNA-seq of Human HepG2 cells following editing with CRISPR/Cas9 upon chromatin modulation with TSA and EZH2iEBI ArrayExpressArrayExpress: [E-MTAB-7091](array-express:E-MTAB-7091){#intref0070}**Experimental Models: Cell Lines**Human: HepG2 cellsThe Francis Crick Cell Services DepartmentN/AHuman: HEK293-T cellsThe Francis Crick Cell Services DepartmentN/A**Oligonucleotides**Primers used in this study (see [Table S7](#mmc7){ref-type="supplementary-material"})This paperN/A**Recombinant DNA**pLenti_BSD_sgRNA[@bib9]N/A**Software and Algorithms**FastQC<https://www.bioinformatics.babraham.ac.uk/projects/fastqc/>N/ABBMap 36.59<https://sourceforge.net/projects/bbmap/>N/AR 3.3.2 - 3.4.4The R Project for Statistical Computing<https://www.r-project.org/>CrispRVariants<https://github.com/HLindsay/CrispRVariants>N/APython 3.7Python Software Foundation<https://www.python.org/>Apache MXNet (v1.2.0) (python 3 API)The Apache Software Foundation<https://mxnet.apache.org/>Custom analysis scriptsThis paper<https://github.com/luslab/crispr-indels>**Other**[@bib27]Sequence Read ArchiveSRP076796HepG2 H3K9ac, H3K27ac ChIP-seq and DNase-seq[@bib17]<http://www.roadmapepigenomics.org/>HEK293 K3K9ac ChIP-seqCistrome DB58997HEK293 K3K27ac ChIP-seqCistrome DB43073HEK293 DNase-seqGene Expression OmnibusGSM1635901-6K562 K3K9ac ChIP-seqCistrome DB45406K562 K3K27ac ChIP-seqCistrome DB55731K562 DNase-seqCistrome DB45020 & 45021
Contact for Reagent and Resource Sharing {#sec4.2}
----------------------------------------
Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Paola Scaffidi (<paola.scaffidi@crick.ac.uk>).
Experimental Model and Subject Details {#sec4.3}
--------------------------------------
### Cell lines {#sec4.3.1}
HepG2 cells, of male origin, were cultured in Minimum Essential Media (MEM) with 10% FBS, and HEK-293T cells, of likely female origin, were cultured in Dulbecco's Modified Eagle's Medium (DMEM) with 10% FBS. All media was supplemented with 2mM L-glutamine, 100U/mL penicillin, and 100 μg/mL streptomycin. All cell lines were maintained at 37°C and 5% CO~2~. Cas9-expressing HepG2 cells were generated as previously described ([@bib9]). For all experiments, Cas9 expression was induced with 1 μg/mL doxycycline 1 day prior to infection with the sgRNAs and sustained until cells were harvested for genomic DNA extraction (QIAGEN). All cell lines were obtained from the Francis Crick Institute Cell Services Department and have been STR authenticated and tested negative for mycoplasma.
Method Details {#sec4.4}
--------------
### sgRNAs pool generation {#sec4.4.1}
sgRNA pools were generated by combining equal volumes of saturated bacterial culture from the arrayed library described in [@bib9], and extracting the resulting plasmid libraries. Six different pools were generated and independently transduced into HepG2 Cas9-expressing cells. This was necessary to reduce the library complexity and allow efficient detection of indels despite the high number of unedited sequences in the cell population -- each sgRNA only infected a limited number of cells. We first tested three pools targeting 100 sites each (pools 100_1, 100_2 and 100_3). Once we confirmed efficient indel detection, we generated three sgRNA pools targeting 450 sites each (pools 450_5, 450_6, 450_7). 450 pools contained three distinct sgRNAs targeting the same 450 genes. 100 pools mainly contained sgRNAs present in the 450 pools with a few additional ones ([Table S1](#mmc2){ref-type="supplementary-material"}). Although pools were transduced and processed independently, indel analysis was performed integrating data from the different pools. When assessing efficiency of indel formation, only data from 450 pools were used. This was done because indel counts for sgRNAs present in both 450 and 100 pools were artificially higher than those detected at sites targeted only with the 450 pools. When assessing editing precision, data from both 100 and 450 pools was combined, as frequencies of individual indels are not affected by differences in indel counts.
### Viral transductions {#sec4.4.2}
Transduction of sgRNAs was performed using high titer virus, at an estimated MOI of at least 10, to increase the fraction of edited cells in the population for each sgRNA. To produce virus, 80% confluent HEK293T cells were transfected with the sgRNA pools (pLenti_BSD_sgRNA plasmids), packaging plasmids (psPax2 and pMD2G) and pAdVantage at a ratio of 3:1 DNA to FugeneHD (Promega). 24h after transfection viral particles were collected, filtered through a 0.45 μm filter and used to infect Cas9-expressing HepG2 cells in the presence of 5μg/ml Polybrene (Santa Cruz). To increase infection efficiency, plated cells were spun for 2h at 2000rpm soon after the virus-containing supernatant was added. A second infection was carried out using viral particles collected 48h after transfection. Cells were not spun for the second infection. Transduced cells were selected with 4 μg/mL blasticidin (Merck), starting 24h after the first infection, and genomic DNA was extracted 5 days after infection (QIAGEN).
### Timing of CRISPR-mediated editing {#sec4.4.3}
In order to experimentally determine the kinetics of indel formation, sgRNAs targeting 3 sites (ACTL6A.5, ASF1B.7 and SMARCD2.1) were individually transduced into Cas9-expressing HepG2 cells, using high titer virus to ensure efficient infection of all cells. Genomic DNA was isolated from infected cells (QIAGEN) for 5 consecutive days and editing of the target sites quantified by Sanger sequencing (Herculase II Fusion, Agilent) and TIDE analysis (<https://tide.deskgen.com/>) (See [Table S7](#mmc7){ref-type="supplementary-material"} for primers). To confirm the absence of possible phenotypic consequences induced by gene knock-out after 5 days, which may confound the results, cells infected with an EZH2-targeting sgRNA were analyzed by immunofluorescence to quantify the levels of both EZH2 and its associated mark H3K27me3. Based on these experiments, 5 days post-infection was concluded to be the optimal length for performing all subsequent experiments.
### Protein detection {#sec4.4.4}
Western blot analysis and immunofluorescence microscopy were performed using anti-H3K27ac (Abcam ab4729), anti-H3K27me3 (Millipore 07-449), anti-ɣH2A.X (Millipore 05-636), anti-EZH2 (CST 3147) and Alexa Fluor- or HRP-conjugated secondary antibodies following standard protocols.
### Chromatin modulation and ChIP-qPCR {#sec4.4.5}
To investigate the effect of chromatin on CRISPR-mediated DNA editing, HepG2 cells were treated with the HDAC inhibitor Trichostatin A (Sigma), which induces histone hyperacetylation, and the EZH2 inhibitor GSK126 (Cayman Chemical), which globally reduces H3K27me3 levels. Cells pre-treated with TSA (11nM or 100nM) or GSK126 (0.3μM and 3μM) for 5 days were infected with sgRNAs targeting the ACTL6A.5, ASF1B.7, BRD2.7, MBD3L1.6, MSH6.2 and SMARCD2.1 sites. Treatment was continued for an additional 5 days while indels were induced. Compounds were refreshed daily over the course of the experiment. Successful alteration of histone acetylation at the target sites was confirmed by ChIP-qPCR of H3K27ac in cells either untreated (NT) or treated with TSA (100nM). For both conditions, 8 million HepG2 cells were fixed with 1% formaldehyde for 10 min at room temperature, treated with 125mM glycine for 5min at RT, washed three times with ice-cold PBS and scraped off cell culture plates in PBS supplemented with 10% FBS. Cell pellets were resuspended in 0.6mL of IP buffer (1:1 of SDS buffer (0.5% SDS, 0.2% NaN~3~, 5mM EDTA pH 8, 50mM TRIS pH 8, 100mM NaCl): Triton buffer (5% Triton X, 0.2% NaN~3~, 5mM EDTA pH 8, 100mM NaCl, 100mM TRIS pH 8)) supplemented with protease inhibitors (1:100, Cell Signaling Technology) and incubated for 15 min on ice. Chromatin was subsequently sheared to 200-500bp with 2 cycles of 30sec ON/OFF using the Bioruptor sonicator (Diagenode). Chromatin from each biological replicate was divided into 2 and 200μg of sample were incubated overnight at 4°C with 8μg of either anti-acetyl H3K27 (Abcam ab4729) or control anti-rabbit IgG (Abcam ab46540). In all cases, 10% of each sample was kept as input. Next, 30μL of Pierce Protein G magnetic beads (Invitrogen) were added per sample and incubated an additional 4h at 4°C. All samples were then washed 3x with low salt wash buffer (1% Triton X, 0.1% SDS, 2mM EDTA pH 8, 20mM TRIS pH 8, 150mM NaCl) and 1x with high salt wash buffer (1% Triton X, 0.1% SDS, 2mM EDTA pH 8, 20mM TRIS pH 8, 500mM NaCl) with the use of a magnetic rack. Subsequently, 120μL of decrosslinking buffer (1% SDS, 100mM NaHC0~3~) was added to all samples and inputs and incubated overnight at 65°C. All decrosslinked samples were purified using the QIAquick PCR purification kit (QIAGEN) and eluted in 45μL of Nuclease-free water. ChIP samples were analyzed on a CFX96 real-time PCR detection system (Bio-rad) using SsoAdvanced Universal SYBR Green Supermix (Bio-rad). All samples were run in triplicates and normalized to the 10% input that was retained before pulldown.
### Cell proliferation {#sec4.4.6}
To examine the effect of the chromatin-modulating compounds on HepG2 cell proliferation, 8,000 HepG2 cells were plated per well of a 96-well plate and treated with TSA (11nM or 100nM) or GSK126 (0.3μM or 3μM) for 5 days. On a daily basis, 20μL of Cell-Titer 96 Aqueous One Solution (Promega) were added per well in triplicates and following incubation at 37°C for 1h, the Optical Density of each well was read at 490nm as a measure of the number of cells per well. The growth rate of the cells was normalized to the number of cells on day 1.
### Library preparation and deep sequencing {#sec4.4.7}
#### sgRNA representation in pools {#sec4.4.7.1}
To assess the representation of individual sgRNAs in the plasmid library, amplicons containing the sgRNA sequences were generated as previously described ([@bib9]). Briefly, PCR amplicons containing the P5 and P7 Illumina adaptors were generated using the high-fidelity Herculase II polymerase kit (Agilent), and the resulting products extracted from an agarose gel (QIAGEN). Purified products were sequenced with either a HiSeq 2500 or a MiSeq using custom sequencing and indexing primers (SeqP and IndexP, [Table S7](#mmc7){ref-type="supplementary-material"}). Following sample demultiplexing, all sgRNA sequences were trimmed and aligned to the target sequences to assess sgRNA representation (normalized read count).
#### Large scale indel sequencing {#sec4.4.7.2}
To identify CRISPR-mediated editing at targeted regions, DNA libraries enriched for the targeted sites were generated using the SureSelect Target enrichment kit (Agilent) following the manufacturer's instructions. Capture probes were designed to cover 2Kb regions centered on each target site. When multiple target sites were located in the same exon, the 2Kb region was centered on the exon middle point. Probe tiling parameters were: Tiling density: 1x; Masking: Least Stringent; Boosting: Maximize Performance. All samples were sequenced using Paired End 100bp runs on a HiSeq 4000 sequencer, multiplexing 2 samples per lane. Approximately 200 million reads were obtained for each sample. Analysis of sequenced regions confirmed good enrichment of the targeted regions ([Figure S2](#mmc1){ref-type="supplementary-material"}A).
#### Small scale indel sequencing {#sec4.4.7.3}
For validation experiments and experiments assessing the effect of chromatin modulation, indels induced at 6 selected sites were examined. In these experiments, a two-step PCR was performed on biological duplicates to generate a library of PCR amplicons. For the first PCR, 150ng of the corresponding gDNA were amplified for 20-22 cycles using the Herculase II polymerase kit yielding products of ∼500bp (See [Table S7](#mmc7){ref-type="supplementary-material"} for primers). Next, PCR products were purified as per manufacturer's instructions (QIAGEN) and 1μl of the resulting product was used as a template for the second nested PCR reaction in which primers containing barcodes and adapters for the sequencing reaction were added. Overall, a library of 60 individually barcoded amplicons of ∼300bp was generated (See [Table S7](#mmc7){ref-type="supplementary-material"} for primers). Samples were purified in a 96-well format (Zymo Research) and sequenced on a 300bp paired-end run on a MiSeq using standard Illumina sequencing primers (See [Table S7](#mmc7){ref-type="supplementary-material"} for primers). The long 300bp reads allowed assessment of both long and short indels.
### Sequencing read alignment {#sec4.4.8}
The quality of the sequenced reads was assured using FastQC. For alignment, we used BBMap (v. 36.59) as it is a global aligner that is able to align longer indels. Alignment was carried out against the UCSC hg19/GRCh37 genome assembly.
### Indel identification {#sec4.4.9}
#### Large scale indel sequencing {#sec4.4.9.1}
In order to robustly identify the reads that contained indels we adopted a two-stage alignment strategy. In the first phase we aligned the reads to the genome disallowing any reads that contained indels. We discarded reads that aligned in a proper pair in this phase and took the remainder forward. In the second phase we aligned the remaining reads to the genome, this time setting a soft threshold allowing indels up to 2000bp. Duplicates were marked using Picard (v. 2.1.0). Reads that were marked as duplicates, or that had a mapping quality score of less than 38 were filtered using samtools (v. 1.2) and sambamba (v. 0.6.0). This two-phase approach was necessary to delineate, for a given target amplicon, between reads from cells uninfected with the corresponding sgRNA and reads from cells with successful transfections, on account of the pooling of sgRNAs. For a given amplicon, only a small proportion of the total number of cells would have been transfected with the sgRNA targeting the site contained within it. We know that aligned reads containing indels arise from appropriately transfected cells. However, our approach forces the aligner to choose an alignment with no indels over one with indels for the multiple possibilities for a given read. With this approach we can improve our confidence that the reads with indels are not background noise or alignment errors. Because of the experimental approach, the sensitivity of our method is inherently limited, and it is likely that indels occurring at low frequency are not detected. Furthermore, kinetically slow repair events may be underrepresented in our dataset. Nevertheless, the observation that most targets are identified as imprecise or middle indicates that there is no significant bias toward most frequent indels. Furthermore, complementary studies using alternative experimental approaches ([@bib21]) observed a very similar distribution of precision groups, confirming the reliability of our method.
Indel identification was performed in R (v. 3.4.4) using custom scripts. The location and size of indels in reads were identified from the CIGAR string. Indels were only considered valid if they occurred within 5 nucleotides of the Cas9 cleavage site (defined as 6 nucleotides upstream of the end of the guide RNA including the PAM sequence). Any indels that could also be detected in the control HepG2 sample were removed as probable somatic mutations in this cancer cell line. To ensure robust estimate of indel frequencies, we filtered out target sites that had a low overall indel count (indels identified in fewer than 10 reads in total across all samples and replicates, where present).
#### Assessment of indel identification approach {#sec4.4.9.2}
To assess possible confounding effects from sequencing errors, particularly given the depth of sequencing, we performed two complementary analyses. First, we assessed the number of indels detected at each target site (within 5 nucleotides of the Cas9 cleavage site) in the wild-type sample without Cas9 induction and sgRNA transduction (without filtering for probable HepG2 somatic mutations). Second, we leveraged the fact that all targeted regions in the whole library were pulled down and sequenced to a similar depth in all experiments, irrespective of whether they were targeted in that particular pool or not. Therefore we compared the number of indels in both replicates from the 450 pool experiments at each target site in the experiment where the corresponding sgRNA was in the transfected pool, with the mean of the number of indels in both replicates from the two other 450 pool experiments where the corresponding sgRNA was not. This provided an estimate of the occurrence of sequencing errors in our experimental setup within 5 nucleotides of the Cas9 cleavage site.
#### Small scale indel sequencing {#sec4.4.9.3}
Before alignment, paired end reads were merged using BBMerge (v. 36.59). After alignment, duplicates were marked using Picard (v. 2.1.0). Reads that were marked as duplicates, or that had a mapping quality score of less than 38 were filtered using samtools (v. 1.2) and sambamba (v. 0.6.0). The R package CrispRVariants ([@bib19]) was used to identify indels.
### Characterization of target sites {#sec4.4.10}
Throughout, we used all detected indels from both 100 and 450 pools to characterize the targets, except when assessing for efficiency where indels from the 450 pools only were used to ensure an unbiased analysis of each target site as explained above.
#### Frameshifts and indel size {#sec4.4.10.1}
Indels were assessed for their frameshift potential by the divisibility of their size by 3. To identify patterns in the indel size profiles at target sites, we calculated the frequency of each size of indel (considered in bins of insertions greater than 1 nucleotide, insertions of 1, and deletions of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and greater than 10). We performed unsupervised hierarchical clustering using the Ward D2 method to categorize groups of target sites based on their indel size profiles.
#### Precision {#sec4.4.10.2}
We also categorized target sites by calculating the frequency of each distinct indel at each target site. The most frequent indel was termed the commonest; ties were broken by prioritizing insertions over deletions, and then by longest deletion. The precision of indel generation at a target site was defined based on the frequency of the commonest indel: imprecise ≤ 0.25, 0.25 \< middle ≤ 0.5, precise \> 0.5.
#### Sequence homology {#sec4.4.10.3}
The presence of MH of *n* nucleotides was assessed in the deletions. The 5′ *n* nucleotides of the deleted sequence were compared with the first *n* nucleotides downstream of the 3′ join. Likewise, the 3′ *n* nucleotides of the deleted sequence were compared with the last *n* nucleotides upstream of the 5′ join. If there was a match, this was considered as MH. For each deletion sequence, values of *n* ranging from 1 to 50 (or the length of the deletion, whichever was shortest) were used. The largest matching *n* was considered the size of the MH.
Insertion homology was assessed by extracting the inserted nucleotide from the read sequence using the CIGAR string. This was compared with the nucleotide in the −4 position of the protospacer to assess for matches. When assessing the commonest insertion, we only considered target sites that had 5 or more insertions. Where the inserted nucleotide either creates, or lies within a short repetitive stretch; e.g., "A" inserted adjacent to "A" creating "AA," or "T" inserted adjacent to/within "TT" creating "TTT"; it is not possible to identify precisely which of these nucleotides is the inserted position. The aligner arbitrarily assigns the first position to the inserted nucleotide.
### Analysis of van Overbeek data {#sec4.4.11}
For the van Overbeek 'spacer' target sites, aligned BAM files were obtained from the Sequence Read Archive for all time points in HCT116, HepG2 and K562 cell lines. Indel identification was performed in R (v. 3.4.4) using custom scripts. The location and size of indels in reads were identified from the CIGAR string. Indels were only considered valid if they occurred within 5 nucleotides of the Cas9 cleavage site (defined as 6 nucleotides upstream of the end of the guide RNA including the PAM sequence). For a given time point and cell type, indels that occurred with \< 1% frequency were filtered, as were sites that had \< 10% editing efficiency. Downstream analyses were performed as detailed in '[Characterization of target sites](#sec4.4.10){ref-type="sec"}' above.
### Indel profiles upon chromatin modulation {#sec4.4.12}
Mutation efficiency was assessed using the mutationEfficiency function from CrispRVariants ([@bib19]), considering single nucleotide variants as non-variants. To compare the counts of indels across the different conditions, in order to assess the contribution of each indel to the changes in efficiency, the raw counts for each indel in each condition were normalized to the library size for that condition. Indels that constituted less than 1% of the library size in any condition were filtered out.
To assess the effects of chromatin modulation on the indel profile of target, over and above the effects on efficiency, we performed a different normalization on the raw counts. We divided by a size factor (the total number of indels detected in a condition). In this way, we could compare the relative contribution of each indel to the overall indel profile across the different conditions. After normalization, only the most frequent 10 indels in the untreated condition were used.
### Analysis of chromatin environment {#sec4.4.13}
DNase-seq and H3K9ac and H3K27ac ChIP-seq fold-enrichment data for in HepG2 cells were obtained pre-processed from the Roadmap Epigenomics consortium ([@bib17]). We calculated the mean fold-enrichment signal in a 500bp window centered on the cleavage site of the six validation targets. For the van Overbeek 'spacer' target sites, preprocessed coverage files were obtained for DNase-seq, H3K9ac and H3K27ac ChIP-seq for HEK293 and K562 cell lines aligned to GRCh38 from sources indicated in the Key Resources table. Data quality was assessed using Cistrome's tools and manual inspection. 500bp windows centered on the cleavage site were created and converted from GRCh37 to GRCh38 using the UCSC liftOver tool. The signal in each window was extracted using Deeptools. For visualization, the mean signal for each dataset was centered and scaled across all the target sites.
### Analysis of nucleotide influence {#sec4.4.14}
#### Artificial neural network {#sec4.4.14.1}
To estimate editing precision, we designed an artificial neural network (ANN) that uses the raw sgRNA sequences as input: 20 individual nucleotides, plus the PAM sequence (as a rudimentary internal control). All variable nucleotides were encoded using one hot encoding. The input layer of the network therefore has 86 nodes, with each of the 21 variable nucleotide positions in the 23nt sgRNA target sequence represented by 4 binary inputs, and the 2 constant 'G's in the PAM sequence represented as single constant values. These are followed by a single hidden layer containing 512 neurons using rectified linear unit (ReLU) activation functions, connected to a single output node, followed by a softplus activation function. Our loss function was mean square error (L2 norm loss). The model parameters were initialized using Xavier initialization. In summary, the weights were initially filled with random numbers \[-*c*, *c*\] where:$$C = \sqrt{\frac{2.24}{0.5\ \times \left( {n_{in} + n_{out}} \right)}}$$Here, *n*~*in*~ is the number of neurons preceding weights and *n*~*out*~ is the number of neurons proceeding weights. 80% (n = 519) of our sgRNAs were randomly selected for use as a training set, with 20% (n = 130) held out as a test set. To ensure consistency and to mitigate bias introduced by particular sets of sgRNAs in the training set, we validated our model by performing bootstrapping with replacement (taking a random sample of 80% (n = 415) of our training sgRNAs each time) before training the final model (final validation RMSE = 0.15 ± 0.003). The final ANN was trained for 800 epochs using stochastic gradient descent with Nesterov momentum set to 0.9, a learning rate of 0.001, and a batch size of 100. The final model's RMSE was 0.14 for the train set, 0.18 for the test set, and 0.16 for van Overbeek et al. To identify key sequence positions with the greatest influence on editing precision, we conducted a permutation nucleotide importance analysis by systematically randomizing each nucleotide in the test set at the respective position. We maintained the original prior-distribution by shuffling the column values before one hot encoding. The mean decrease in accuracy was recorded as the reduction in R^2^ from predictions made with the unaltered sequences. We also recorded the difference in predictive statistical significance (Wald test p values). We performed the nucleotide randomization 10 times and report the average percentage reduction in R^2^ for neutralized positions. We considered an average increase in Wald test p values to \> 0.05 as having abolished the predictive significance of the model. The ANN was built, trained, and deployed using *Apache MXNET* (python 3 API) v. 1.2.0.
#### LASSO multi-regression model {#sec4.4.14.2}
To corroborate the results of our non-linear ANN model, and obtain the coefficients of the most important linear correlations with observed indel frequencies, we constructed a linear model optimized for generalization using L~1~ regularization by deploying a least absolute shrinkage and selection operator (LASSO) algorithm. Here the aim is to minimize the objective function:$$\left. \frac{1}{2n_{samples}} \right\|\left. {Xw - y} \right\|_{2}^{2} + \left. \alpha \right\|\left. w \right\|_{1}\ $$Where regularization parameter α is a constant and $\left\| w \right\|_{1}$is the L~1~ regularized parameter coefficient vector. Our training set was 80% of our data (n = 519) selected at random, with 20% (n = 130) held out to test the model. The coefficients were fitted using coordinate descent and the regularization parameter α (0.002592943797404667) selected by 10-fold cross validation on the training set. The final model's RMSE was 0.15 for the train set, 0.17 for the test set, and 0.15 for van Overbeek et al. The LASSO was built, trained, and deployed using *scikit-learn v. 0.19.1* for python 3.
Quantification and Statistical Analysis {#sec4.5}
---------------------------------------
Non-parametric statistical tests were used as appropriate and p-values were adjusted for multiple testing where necessary. Each specific test is indicated in the main text or figure legend, as well as the exact value of N and what N represents. In boxplots, the bottom and top of boxes indicate the 25th and 75th percentiles, respectively, and middle lines indicate medians. Whiskers indicate the lowest and highest data points within 1.5 × interquartile range from the box. A significance level of 0.05 was used throughout.
Data and Software Availability {#sec4.6}
------------------------------
The accession numbers for the sequencing data generated in this study are EBI ArrayExpress: E-MTAB-7091, E-MTAB-7095. Custom scripts are available at <https://github.com/luslab/crispr-indels>.
Supplemental Information {#app2}
========================
Document S1. Figures S1--S7 and Table S5Table S1. Mapping Location for Each sgRNA with Its Associated Gene and Pool Composition, Related to Figure 1Location of each sgRNA is based GRCh37 Ensembl Gene ID and HGNC Gene Name.Table S2. Precision Groups, Related to Figure 3Precision groups for the characterized 649 target sites, with the associated frequency of the commonest indel and the total number of indels detected at each site.Table S3. Characterization of All Detected Deletions, Related to Figure 4The microhomology status of each deletion is indicated.Table S4. Characterization of All Detected Insertions, Related to Figure 4The insertion homology status of each insertion indicated.Table S6. Effect of Chromatin Modulation of Indel Formation, Related to Figures 6 and 7Raw counts for the commonest 25 indels at each targeted location for each replicate of the chromatin modulation treatments.Table S7. Primers Used in the Study, Related to STAR MethodsDocument S2. Article plus Supplemental Information
We thank the Crick Advanced Sequencing and Bioinformatics and Biostatistics facilities for preparing and sequencing NGS libraries and for help with data processing. We thank Her Majesty Queen Elizabeth II for starting the sequencing run containing our samples and Andrew J. Steele for comments on the machine learning analysis. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (grants FC001110 and FC001152); the UK Medical Research Council (grants FC001110 and FC001152); and the Wellcome Trust (grants FC001110 and FC001152), and by the CRUK Drug Discovery Award (C50796/A19448) to P.S. N.M.L. is a Winton Group Leader in recognition of the Winton Charitable Foundation's support towards the establishment of the Francis Crick Institute. This work was also supported by a Wellcome Trust PhD Training Fellowship for Clinicians Award (110292/Z/15/Z) to A.M.C. and a postdoctoral fellowship by the Peter and Traudl Engelhorn Foundation to A.R.P.
Author Contributions {#sec5}
====================
A.M.C. performed most of the computational analysis and wrote the manuscript with P.S. T.H.-B. generated all reagents used in the study and performed the large-scale experiment and ANN analysis. J.M. performed the chromatin modulation experiments. A.R.P. and N.M.L. supervised the computational work and provided input on the manuscript. P.S. conceived the study, analyzed the data, supervised the work, and wrote the manuscript.
Declaration of Interests {#sec6}
========================
The authors declare no competing interests.
Supplemental Information includes seven figures and seven tables and can be found with this article online at [https://doi.org/10.1016/j.molcel.2018.11.031](10.1016/j.molcel.2018.11.031){#intref0130}.
[^1]: These authors contributed equally
[^2]: Lead Contact
|
Image copyright Shutterstock
Charting the travails of two out-of-work actors in the dying days of the 1960s, British film comedy Withnail and I has staggered to its 30th birthday. Star Richard E Grant looks back at its filming and considers whether anyone else could have tackled the role that put him on the road to Hollywood. Chin chin!
Camden Town. Two sleep-deprived thespians wallow in filth, battling drug-induced paranoia, a worrying lack of booze and stalled careers.
What follows - an ill-fated jaunt "to the country" and run-ins with an assortment of misfits and malcontents - would marry with caustic dialogue to produce an oft-quoted classic.
Largely unnoticed on its release in April 1987, standout performances by Grant as the acid-tongued Withnail and Paul McGann as the more introspective I helped the film gradually gather a dedicated following.
No less memorable was its supporting cast of colourful characters, among them the love-struck Uncle Monty (Richard Griffiths), drug-dealer Danny (Ralph Brown) and poacher Jake (Michael Elphick).
Initially created as a semi-autobiographical novel by Bruce Robinson more than a decade and a half earlier, the writer-turned-director would largely use his one-time flatmate Vivian MacKerrell as the inspiration for the scabrous Withnail, while I - identified as Marwood in the script - was a version of Robinson himself.
It was, as he has outlined, "a tale of English hopelessness" and threw a spotlight on his "appalling lifestyle" as he struggled to find work after leaving London's Central School of Speech and Drama.
Image copyright Shutterstock Image caption "Wait till the morning and we'll go in together" - Marwood pleads with Withnail to abandon plans to tackle the fetid kitchen sink
With each set-piece so perfectly penned, the stale cigarette smoke and alcohol fumes almost seeped through the screen.
But while the story may have been loaded with laughs, Robinson demanded his dialogue was delivered with a straight face.
"Bruce was very exacting and did not brook any improvisation or word substitutions," says Grant, who himself had been without work for nine months and become increasingly beset by nagging doubts about his chosen career, having emigrated from Swaziland to Britain at the turn of the 80s.
"He was also adamant that as there were no jokes or punchlines, it had to be played with deadly seriousness.
"The script was so accurate in expressing the frustrations of being an out-of-work actor that as soon as Paul and I played everything 'for real', Bruce was very open and accommodating.
"That experience [of being unemployed] proved invaluable. Withnail is so staggeringly self-obsessed and entitled, which anyone who has been to drama school will be all too familiar with!"
Auditioning for the part would almost mirror the character's woes, as Grant competed against a gaggle of better-known names in a casting merry-go-round as dizzying as the concoction of drink and drugs downed throughout the film.
Image copyright Shutterstock Image caption "I've been watching you" - poacher Jake warns the hapless pair
Daniel Day-Lewis had turned down the role and other leading contenders included Bill Nighy and Ed Tudor-Pole.
It was not much easier for McGann, with the role of Marwood offered to Michael Maloney.
Having stepped into his shoes, his strong Liverpudlian accent promptly saw him sacked before an equally swift reinstatement.
So what was it that Robinson eventually identified in the duo?
"Finding a contrasting pair of actors made the audition process protracted," Grant recalls, "as Bruce was very determined to secure two people who looked and sounded like Vivian and himself.
"Paul is incredibly handsome and had the quality of 'an innocent abroad', which Bruce was after."
While it may seem almost inconceivable for fans to imagine anyone else in the role of Withnail, Grant modestly disagrees.
Here's to you, Mr Robinson
Image copyright Shutterstock Image caption "We want the finest wines available to humanity" - the drunkards offend the owner of the Penrith Tea Rooms
Bruce Robinson paid for the filming of additional scenes out of his own pocket after Handmade refused to stump up the extra cash
Producer Denis O'Brien wanted filming shut down as he had expected a comedy more akin to Monty Python
Devoted fans make pilgrimages to many of the film's locations. However, anyone visiting Penrith for its tea rooms will be sorely disappointed - that scene was filmed 240 miles away in Stony Stratford, Milton Keynes
Paul McGann had only just passed his driving test when shooting began, and for the motorway scenes was replaced behind the wheel by Robinson
Despite his acclaimed portrayal of a desperate drunk, Richard E Grant is famously allergic to alcohol
"I absolutely believe that all those illustrious names could have essayed the role, as it is so brilliantly well written.
"Bruce writes stage directions with the same exactitude as his dialogue - hugely entertaining, mordant, witty, and conveying the precise mood so that you simultaneously 'see' and 'feel' what the scene is about."
Indeed so expertly crafted was Robinson's dialogue, fans delight in reciting the characters' one-liners and stinging rebukes - and sometimes in the most unexpected of places.
Image copyright Shutterstock Image caption "Oh, my boys" - Uncle Monty shows his affection at the cottage dinner table
"[Some years later] I was filming in the Australian outback beside a dirt road in the middle of nowhere," says Grant.
"The only car that drove past all day was a battered yellow 1959 Ford Anglia - my dreaded primary school maths teacher drove one - and the driver leant out of his window and yelled 'scrubbers!' at me - to the bewilderment of the film crew."
Shooting got under way in August 1986, but, like the pair's rain-lashed on-screen drive from London to the Lakes, the film's journey to the cinema screen was tortuous.
A modest million-pound budget would come from Beatles legend George Harrison's Handmade Films and a New York businessman.
Decamping to Cumbria's Wet Sleddale to begin work at isolated cottage "Crow Crag" (the real-life Sleddale Hall, near Shap), interference from its backers threatened to derail production, causing Robinson to issue a "back me or sack me" ultimatum.
For Grant, that period of time was difficult for an altogether more tragic reason as he and his wife, Joan, grieved the loss of their daughter Tiffany, born prematurely at seven months and pronounced dead within a few minutes.
"She is the size of a little bird," he recalled in his book With Nails: The Film Diaries of Richard E Grant.
"She is warm but dead. And perfect. Ten toes, ten fingers. Eyes, mouth, all. Broken. No breath.
"Our hearts are broken and will we ever cease weeping."
Image copyright Shutterstock Image caption "I want something's flesh" - Withnail goes fishing for lunch
The film would have its own sense of sadness and loss as McGann's I packs his bags having landed the lead role in a Manchester-based play - leaving the desperate Withnail railing in despair with only a bottle of Uncle Monty's wine and the Regent's Park wolves for company.
Just as eloquently it would sum up the end of the 60s dream, replaced by commercialism and cynicism with the selling of "hippy wigs in Woolworths".
Although Withnail and I failed to make a commercial splash upon its release, McGann would establish a solid stage and screen career, while Grant had Hollywood hot-shots Robert Altman, Francis Ford Coppola and Martin Scorsese all come calling.
He has hardly stopped working since.
It is, he admits, "some irony… playing an unemployed actor opened every subsequent career door I've walked through".
Robinson would have more mixed fortunes. Follow-up How to Get Ahead in Advertising, also starring Grant, was an altogether more patchy affair while Jennifer 8 and The Rum Diary also met with criticism.
Thirty years on, though, Withnail and I's popularity shows no sign of waning and a series of screenings are being staged by fans across the country throughout the coming months - with Sleddale Hall itself among the venues in July.
Image copyright Shutterstock Image caption "Are you a sponge or a stone?" - Monty propositions Marwood
So just what does the now 59-year-old Grant believe lies at the heart of its enduring appeal, and does he ever feel trapped by the role which, for many, defines his career?
"The film is so accurate about Bruce's experience of being an unemployed actor at the end of the 60s, encompassing his breadline, booze and drugged desolation, and being friends with the coruscating and charismatic MacKerrell, that it is indelibly authentic.
"His portrayal of a symbiotic male friendship is the core of the story, and its disintegration is painful and poetic.
"If I had only been offered 'alcoholic actor' roles I might have something to complain about, but that never happened. Playing someone so extreme has meant I've been cast in roles that demand a certain level of intensity or mania, which I've hugely enjoyed.
"I'm genuinely amazed that a film made so long ago, which initially met with such a lukewarm response, has accrued the status and cult following it has done.
"For that, I am eternally grateful." |
Characterization of a cysteine proteinase inhibitor induced during neuronal cell differentiation.
A rat homolog of human cystatin E/M was identified by differential display of transcripts induced during neuronal cell differentiation. A member of the family 2 cystatins, rat cystatin E/M is secreted, glycosylated and developmentally regulated. Rat cystatin E/M is expressed in brain, and is induced during differentiation of a conditionally immortalized E17 rat hippocampal cell line (H19-7) by bFGF or activated Raf via MEK-dependent and -independent signaling pathways. Rat cystatin E/M protein is increased post-transcriptionally in PC12 cells, and the protein is secreted into the medium of primary embryonal hippocampal cultures. Analysis of the K (i) of recombinant His-tagged rat cystatin E/M toward cathepsins B and H revealed that rat cystatin E/M has an inhibitor profile distinct from that of other members of the cystatin family. Motif swapping between rat cystatin E/M and human cystatin C, a well-characterized cystatin, identified some residues that can contribute to the specificity of inhibition. Taken together, these results describe a member of the cystatin family that has a distinct inhibitor profile and may play a role in neuronal development. |
# Docker
variable "image" {}
variable "image_pull_policy" {
default = "IfNotPresent"
}
# Kubernetes
variable "namespace" {}
variable "enabled" {}
variable "replicas" {}
variable "cpu_limit" {}
variable "cpu_request" {}
variable "memory_limit" {}
variable "memory_request" {}
variable "node_selector_label" {}
variable "kubectl_executable_name" {}
variable "kubectl_context_name" {}
# Environment
variable "jvm_memory_limit" {}
variable "graphite_hostname" {}
variable "graphite_port" {}
variable "graphite_enabled" {}
variable "graphite_prefix" {
default = ""
}
variable "env_vars" {}
# App
variable "kafka_endpoint" {}
variable "group_id" {}
variable "topic" {}
variable "key_deserializer" {}
variable "value_deserializer" {}
variable "elasticsearch_endpoint" {}
variable "elasticsearch_port1" {}
variable "elasticsearch_port2" {}
variable "elasticsearch_scheme" {}
|
THE HARD FACTS Is size important?
Anxiety provoking as it may be, starting this book with this topic is my way of assuring you that if knowledge of male sexuality is what you seek, that is exactly what you’ll find here. You can rely on this guide for comprehensive answers and honest advice, no subject is off limits.
Is size important? Men have been asking themselves (and the women in their lives) this question for centuries. Is size important? Ask a group this question and you’ll get a variety of answers but most fall into one of two categories: bigger is better or it’s not the size of the ship but the motion of the ocean.
Both schools of thought have points, don’t they? But they are not really talking about the same thing. In fact, bigger is better has nothing to do with the ocean and its motions. Each statement could be either true or false when viewed independently from the other. Moreover, each answer illustrates a truth, but each observation highlights something quite different. On the one hand, bigger is better is obviously a size issue, a mass issue, and altogether a material issue. Size is a matter of fact; it is genetic, predestined, and hereditary. The motion of the ocean, however, introduces a completely different concept.
To some, usually men with small penises, this idea is more valuable than bigger is better because it explains what to do after having a “God fucked me with a tiny dick” moment. The motion of the ocean is not a matter of fact and it cannot be assumed directly from genetics. Rather, it is a matter of function and how effectively you use what has been given to you. It is, if I may, success compensatory capability, and I think you’re starting to get it. Bigger is better is a material thing while the motion of the ocean is a functional thing. But let’s consider each more carefully.
If there is one truth about the size of a man’s Johnson it is that men care about the size of a man’s Johnson. At the very least, they care about the size of their Johnson. Women may say they do or they do not care but I challenge you to find a man that does not care about the size, shape, and stiffness of what he considers his most vital organ.
And we’re not the only breed with varying penis sizes. Let’s take a closer look at how other mammalian species match up to humans.
(Section on selected species and their penises, including animals with small cocks.)
It is important to note that not all men are the same. That being said, it is also important to see that we are not very different. While there certainly are men who have very small or very large phalluses, most men are within a couple of inches of one another. Unfortunately, for the psyche of many men, an inch may as well be a mile and thus, I fear my comments have not provided much relief. |
1. Technical Field
The present invention relates to angular rate sensors and electronic devices.
2. Related Art
Information devices, such as, digital cameras and car navigation systems carry an angular rate sensor in order to prevent blurring of images due to hand movement or to detect the position of a vehicle. As the angular rate sensor, for example, a 32 kHz tuning-fork quartz oscillator is still used as it can utilize the existing design resource and energy saving properties. However, when forming a 32 kHz tuning-fork quartz oscillator, the length of the prongs of the tuning fork becomes as large as several millimeters, whereby the entire length including the package becomes as large as almost 10 mm.
In recent years, piezoelectric vibration devices that use a driving section having a piezoelectric thin film interposed between upper and lower electrodes and formed on a silicon substrate, instead of quartz, have been developed. Known structures of such piezoelectric vibration devices include a beam type structure (see FIG. 1 of JP-A-2005-291858) and a structure having a tuning fork vibration device formed with two beams (see FIG. 1 of JP-A-2005-249395) are known. When utilizing such piezoelectric vibration devices, since the thickness of a silicon substrate can only be reduced to about 100 μm, the prong length of the beams may become as much as several millimeters or greater in order to obtain a resonance frequency at several tens kHz. This makes it difficult to reduce the size of the angular rate sensor having such a piezoelectric vibration device. |
"Patients are seeing these numbers and are scared about how they're going to pay for access," Erickson said. "That's a car or rent payment without any help from insurance. There needs to be alternatives for low or fixed-income patients to be able to afford access." |
Nat Sherman is at it again, hosting a traditional cigar dinner with Chef Geoffrey Zakarian. The night, which will cost you about $250 a ticket, will include a three course meal, with a different cigar paired for each course. This type of cigar dinner is an almost extinct tradition, which is why I’m so excited to see Nat Sherman bringing it back. Hopefully this event will remain a tradition for many years to come. Event information below
~~~ |
Q:
copy data from a worksheet till a condition
I have a worksheet which contains data in column B to column D. I want to copy the data from B4 to till the cell value which has space infront of it and paste it in a separate sheet and change the sheet as the value B4 and then it has to copy the next cell values untill the cell value with space infront and it continues till column B has empty cells.
In addition to that i have to enter serial no in column A respect to the data without space inits intial stage. i have attached the input and expected output image for your reference.
input:
expected output:
please help on this issue.
A:
Assuming your sheet is as follows:
Enter the following formula in the Cell A4
=IF(LEFT(B4,1)<>" ",COUNTA($A$2:A3)+1-COUNTBLANK($A$2:A3),"")
Drag/Copy down formula as required.
If you are looking for a VBA solution, following should work:
Sub Demo()
Dim ws As Worksheet
Dim lastRow As Long, index As Long, i As Long
Dim rng As Range
index = 1
Set ws = ThisWorkbook.Sheets("Sheet1") '---->change the sheet name as required
lastRow = ws.Cells(Rows.count, "B").End(xlUp).Row
Set rng = ws.Range("B4:B" & lastRow)
For i = 4 To lastRow
If Left(ws.Cells(i, 2).Value, 1) <> " " Then
ws.Cells(i, 1).Value = index
index = index + 1
End If
Next i
End Sub
_______________________________________________________________________________
EDIT 1 : First copy data from Sheet1 to Sheet2 and then add serial numbers.
Sub Demo()
Dim ws1 As Worksheet, ws2 As Worksheet
Dim lastRow As Long, index As Long, i As Long
Dim rng As Range
index = 1
Set ws1 = ThisWorkbook.Sheets("Sheet1") '---->change the sheet name as required
Set ws2 = ThisWorkbook.Sheets("Sheet2")
lastRow = ws1.Cells(Rows.count, "B").End(xlUp).Row
ws1.Range("B2:D" & lastRow).Copy Destination:=ws2.Range("B2")
Set rng = ws2.Range("B4:B" & lastRow)
For i = 4 To lastRow
If Left(ws2.Cells(i, 2).Value, 1) <> " " Then
ws2.Cells(i, 1).Value = index
index = index + 1
End If
Next i
End Sub
_______________________________________________________________________________
EDIT 2 :
Sub Demo()
Dim srcWS As Worksheet, destWS As Worksheet
Dim lastRow As Long, index As Long, i As Long
Dim copyRng As Range, rng1 As Range, rng2 As Range
index = 1
Set srcWS = ThisWorkbook.Sheets("Sheet1") '---->change the sheet name as required
lastRow = srcWS.Cells(Rows.count, "B").End(xlUp).Row
Set rng1 = srcWS.Cells(4, 2)
For i = 4 To lastRow
If Left(srcWS.Cells(i, 2).Value, 1) <> " " Then
srcWS.Cells(i, 1).Value = index
index = index + 1
If i <> 4 Then
Set rng2 = srcWS.Cells(i - 1, 4)
Set destWS = Sheets.Add(After:=Sheets(Sheets.count))
srcWS.Range(rng1, rng2).Copy Destination:=destWS.Range("B4")
Set rng1 = srcWS.Cells(i, 2)
End If
End If
Next i
Set rng2 = srcWS.Cells(lastRow, 4)
Set destWS = Sheets.Add(After:=Sheets(Sheets.count))
srcWS.Range(rng1, rng2).Copy Destination:=destWS.Range("B4")
End Sub
|
Q:
Java parenthesis order {[()]}
There are a lot of questions concerning how to check if parenthesis are balanced, with many answers. But how do I find out the order of the parenthesis? For example {} should be first before [], and [] should be before (). Can anyone help me form a method that will do this for me?
String parenthesis = "([{}])"
At this point I was thinking of using an ArrayList<String> type but what if I had jargon in between (6[6{6}6]6)? I know how to check for charAt(0), but thats as far as my knowledge goes. Any tips would be nice.
(6[6{6}6]6) should turn to {6[6(6)6]6} with the stuff in between unchanged. And also since its based on user input in a scanner class, please show me a method that will not limit the character length.
A:
I would use regex for this task. Here's an example of how this could be implemented:
parenthesis.matches(".*\\(.*\\[.*\\{.*\\}.*\\].*\\).*")
This will return true if the different parentheses are balanced as you described in your question, and false if not. If you want to automatically fix these errors, you could write a replace operation:
parenthesis = parenthesis.replaceAll("(.*)[{\\[(](.*)[{\\[(](.*)[{\\[(](.*)[}\\])](.*)[}\\])](.*)[}\\])](.*)", "$1{$2[$3($4)$5]$6}$7");
This replaces all the different types of parentheses with the correct types, and preserves the content in between.
If you want to have your program check for more advanced stuff, your idea of using ArrayLists sounds like the best plan. If you want to allow multiple levels of nesting, so there could only be two levels, but there could also be three, and you want to allow blocks to be re-opened (i.e. (a{b}c{d}e)), I would use the following piece of code. Note that this is much more complex than the two regex options above, and if you can make some assumptions, there may be stuff you can cut out of it. Be sure to read the comments, as they explain each line of code:
String parenthesis = "{a[b]c}(d)[e]"; //test string
ArrayList<Character> currentlyOpen = new ArrayList<>(); //all currently open parenthesis types
ArrayList<Character> opens = new ArrayList<>(); //all used open parenthesis types
Stack<Character> closes = new Stack<>(); //all used close parenthesis types
String[] openOrder = new String[] { "{", "[", "(" }; //correct open parenthesis order
String[] closeOrder = new String[] { ")", "]", "}" }; //correct close parenthesis order
Matcher regex = Pattern.compile("[{\\[()\\]}]").matcher(parenthesis); //match any open or close parenthesis type
ArrayList<String> parts = new ArrayList<>(); //list of the separate top-level groups
int removedChars = 0; //to keep track of index in the input string
while (!parenthesis.isEmpty()) {
while (regex.find()) { //iterate over all regex matches
char c = regex.group().charAt(0); //get the matched character
switch (c) {
case '}':
if (currentlyOpen.get(currentlyOpen.size() - 1) == '{') { //if the last currently open parenthesis is the correct type
currentlyOpen.remove(currentlyOpen.size() - 1); //remove this open parenthesis type from the currently open list (it is now closed)
if (!closes.contains(c)) {
closes.add(c); //add this parenthesis type to the closed parenthesis list if it's not already there
}
break;
}
throw new RuntimeException("unbalanced"); //else cough and die (or you could return false or -1 or something)
case ']': //same as the above case
if (currentlyOpen.get(currentlyOpen.size() - 1) == '[') {
currentlyOpen.remove(currentlyOpen.size() - 1);
if (!closes.contains(c)) {
closes.add(c);
}
break;
}
throw new RuntimeException("unbalanced");
case ')': //same as the above case
if (currentlyOpen.get(currentlyOpen.size() - 1) == '(') {
currentlyOpen.remove(currentlyOpen.size() - 1);
if (!closes.contains(c)) {
closes.add(c);
}
break;
}
throw new RuntimeException("unbalanced");
default: //if this is an open parenthesis
if (!opens.contains(c)) {
opens.add(c); //add this to the "all open parentheses" list if it's not already there
}
currentlyOpen.add(c); //add this to the "currently open parethesis" list
}
if (currentlyOpen.isEmpty()) { //if we are back at the top level
parts.add(parenthesis.substring(0, regex.end() - removedChars)); //add the top-level group to the list
parenthesis = parenthesis.substring(regex.end() - removedChars); //remove the top-level group from the input string
removedChars = regex.end(); //update removedChars
break; //break out of the loop and process this top-level group only
}
}
for (int i = 0; i < opens.size(); i++) { //iterate over all the open parentheses used
parts.set(parts.size() - 1, parts.get(parts.size() - 1).replace(opens.get(i).toString(), Character.toString((char) i))); //replace them all with intermediate characters (in this case numbers, you could use something else)
}
for (int i = 0; i < opens.size(); i++) { //iterate over all the open res again
parts.set(parts.size() - 1, parts.get(parts.size() - 1).replace(Character.toString((char) i), openOrder[i + openOrder.length - opens.size()])); //this time replace all the intermediate characters with the proper parentheses
}
for (int i = 0; i < closes.size(); i++) { //do the same thing for close parentheses
parts.set(parts.size() - 1, parts.get(parts.size() - 1).replace(closes.get(i).toString(), Character.toString((char) i)));
}
for (int i = 0; i < closes.size(); i++) { //do the same thing for close parentheses
parts.set(parts.size() - 1, parts.get(parts.size() - 1).replace(Character.toString((char) i), closeOrder[i]));
}
opens.clear(); //reset the list of open parenthesis types
closes.clear(); //reset the list of close parenthesis types
}
StringBuilder sb = new StringBuilder(); //use a string builder to put all the parts together again
parts.forEach(sb::append); //append all the parts to the string builder
String res = sb.toString(); //get the string from the string builder
System.out.println(res); //print it out so you can see it
|
<?php
/*
* This file is part of the Symfony package.
*
* (c) Fabien Potencier <fabien@symfony.com>
*
* For the full copyright and license information, please view the LICENSE
* file that was distributed with this source code.
*/
namespace Symfony\Component\VarDumper\Tests\Caster;
use PHPUnit\Framework\TestCase;
use Symfony\Component\VarDumper\Caster\Caster;
use Symfony\Component\VarDumper\Caster\DateCaster;
use Symfony\Component\VarDumper\Cloner\Stub;
use Symfony\Component\VarDumper\Test\VarDumperTestTrait;
/**
* @author Dany Maillard <danymaillard93b@gmail.com>
*/
class DateCasterTest extends TestCase
{
use VarDumperTestTrait;
/**
* @dataProvider provideDateTimes
*/
public function testDumpDateTime($time, $timezone, $xDate, $xTimestamp)
{
$date = new \DateTime($time, new \DateTimeZone($timezone));
$xDump = <<<EODUMP
DateTime @$xTimestamp {
date: $xDate
}
EODUMP;
$this->assertDumpEquals($xDump, $date);
}
/**
* @dataProvider provideDateTimes
*/
public function testCastDateTime($time, $timezone, $xDate, $xTimestamp, $xInfos)
{
$stub = new Stub();
$date = new \DateTime($time, new \DateTimeZone($timezone));
$cast = DateCaster::castDateTime($date, array('foo' => 'bar'), $stub, false, 0);
$xDump = <<<EODUMP
array:1 [
"\\x00~\\x00date" => $xDate
]
EODUMP;
$this->assertDumpEquals($xDump, $cast);
$xDump = <<<EODUMP
Symfony\Component\VarDumper\Caster\ConstStub {
+type: 1
+class: "$xDate"
+value: "%A$xInfos%A"
+cut: 0
+handle: 0
+refCount: 0
+position: 0
+attr: []
}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $cast["\0~\0date"]);
}
public function provideDateTimes()
{
return array(
array('2017-04-30 00:00:00.000000', 'Europe/Zurich', '2017-04-30 00:00:00.0 Europe/Zurich (+02:00)', 1493503200, 'Sunday, April 30, 2017%Afrom now%ADST On'),
array('2017-12-31 00:00:00.000000', 'Europe/Zurich', '2017-12-31 00:00:00.0 Europe/Zurich (+01:00)', 1514674800, 'Sunday, December 31, 2017%Afrom now%ADST Off'),
array('2017-04-30 00:00:00.000000', '+02:00', '2017-04-30 00:00:00.0 +02:00', 1493503200, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.100000', '+00:00', '2017-04-30 00:00:00.100 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.120000', '+00:00', '2017-04-30 00:00:00.120 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.123000', '+00:00', '2017-04-30 00:00:00.123 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.123400', '+00:00', '2017-04-30 00:00:00.123400 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.123450', '+00:00', '2017-04-30 00:00:00.123450 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
array('2017-04-30 00:00:00.123456', '+00:00', '2017-04-30 00:00:00.123456 +00:00', 1493510400, 'Sunday, April 30, 2017%Afrom now'),
);
}
/**
* @dataProvider provideIntervals
*/
public function testDumpInterval($intervalSpec, $ms, $invert, $expected)
{
if ($ms && \PHP_VERSION_ID >= 70200 && version_compare(PHP_VERSION, '7.2.0rc3', '<=')) {
$this->markTestSkipped('Skipped on 7.2 before rc4 because of php bug #75354.');
}
$interval = $this->createInterval($intervalSpec, $ms, $invert);
$xDump = <<<EODUMP
DateInterval {
interval: $expected
%A}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $interval);
}
/**
* @dataProvider provideIntervals
*/
public function testDumpIntervalExcludingVerbosity($intervalSpec, $ms, $invert, $expected)
{
if ($ms && \PHP_VERSION_ID >= 70200 && version_compare(PHP_VERSION, '7.2.0rc3', '<=')) {
$this->markTestSkipped('Skipped on 7.2 before rc4 because of php bug #75354.');
}
$interval = $this->createInterval($intervalSpec, $ms, $invert);
$xDump = <<<EODUMP
DateInterval {
interval: $expected
}
EODUMP;
$this->assertDumpEquals($xDump, $interval, Caster::EXCLUDE_VERBOSE);
}
/**
* @dataProvider provideIntervals
*/
public function testCastInterval($intervalSpec, $ms, $invert, $xInterval, $xSeconds)
{
if ($ms && \PHP_VERSION_ID >= 70200 && version_compare(PHP_VERSION, '7.2.0rc3', '<=')) {
$this->markTestSkipped('Skipped on 7.2 before rc4 because of php bug #75354.');
}
$interval = $this->createInterval($intervalSpec, $ms, $invert);
$stub = new Stub();
$cast = DateCaster::castInterval($interval, array('foo' => 'bar'), $stub, false, Caster::EXCLUDE_VERBOSE);
$xDump = <<<EODUMP
array:1 [
"\\x00~\\x00interval" => $xInterval
]
EODUMP;
$this->assertDumpEquals($xDump, $cast);
if (null === $xSeconds) {
return;
}
$xDump = <<<EODUMP
Symfony\Component\VarDumper\Caster\ConstStub {
+type: 1
+class: "$xInterval"
+value: "$xSeconds"
+cut: 0
+handle: 0
+refCount: 0
+position: 0
+attr: []
}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $cast["\0~\0interval"]);
}
public function provideIntervals()
{
return array(
array('PT0S', 0, 0, '0s', '0s'),
array('PT0S', 0.1, 0, '+ 00:00:00.100', '%is'),
array('PT1S', 0, 0, '+ 00:00:01.0', '%is'),
array('PT2M', 0, 0, '+ 00:02:00.0', '%is'),
array('PT3H', 0, 0, '+ 03:00:00.0', '%ss'),
array('P4D', 0, 0, '+ 4d', '%ss'),
array('P5M', 0, 0, '+ 5m', null),
array('P6Y', 0, 0, '+ 6y', null),
array('P1Y2M3DT4H5M6S', 0, 0, '+ 1y 2m 3d 04:05:06.0', null),
array('PT1M60S', 0, 0, '+ 00:02:00.0', null),
array('PT1H60M', 0, 0, '+ 02:00:00.0', null),
array('P1DT24H', 0, 0, '+ 2d', null),
array('P1M32D', 0, 0, '+ 1m 32d', null),
array('PT0S', 0, 1, '0s', '0s'),
array('PT0S', 0.1, 1, '- 00:00:00.100', '%is'),
array('PT1S', 0, 1, '- 00:00:01.0', '%is'),
array('PT2M', 0, 1, '- 00:02:00.0', '%is'),
array('PT3H', 0, 1, '- 03:00:00.0', '%ss'),
array('P4D', 0, 1, '- 4d', '%ss'),
array('P5M', 0, 1, '- 5m', null),
array('P6Y', 0, 1, '- 6y', null),
array('P1Y2M3DT4H5M6S', 0, 1, '- 1y 2m 3d 04:05:06.0', null),
array('PT1M60S', 0, 1, '- 00:02:00.0', null),
array('PT1H60M', 0, 1, '- 02:00:00.0', null),
array('P1DT24H', 0, 1, '- 2d', null),
array('P1M32D', 0, 1, '- 1m 32d', null),
);
}
/**
* @dataProvider provideTimeZones
*/
public function testDumpTimeZone($timezone, $expected)
{
$timezone = new \DateTimeZone($timezone);
$xDump = <<<EODUMP
DateTimeZone {
timezone: $expected
%A}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $timezone);
}
/**
* @dataProvider provideTimeZones
*/
public function testDumpTimeZoneExcludingVerbosity($timezone, $expected)
{
$timezone = new \DateTimeZone($timezone);
$xDump = <<<EODUMP
DateTimeZone {
timezone: $expected
}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $timezone, Caster::EXCLUDE_VERBOSE);
}
/**
* @dataProvider provideTimeZones
*/
public function testCastTimeZone($timezone, $xTimezone, $xRegion)
{
$timezone = new \DateTimeZone($timezone);
$stub = new Stub();
$cast = DateCaster::castTimeZone($timezone, array('foo' => 'bar'), $stub, false, Caster::EXCLUDE_VERBOSE);
$xDump = <<<EODUMP
array:1 [
"\\x00~\\x00timezone" => $xTimezone
]
EODUMP;
$this->assertDumpMatchesFormat($xDump, $cast);
$xDump = <<<EODUMP
Symfony\Component\VarDumper\Caster\ConstStub {
+type: 1
+class: "$xTimezone"
+value: "$xRegion"
+cut: 0
+handle: 0
+refCount: 0
+position: 0
+attr: []
}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $cast["\0~\0timezone"]);
}
public function provideTimeZones()
{
$xRegion = \extension_loaded('intl') ? '%s' : '';
return array(
// type 1 (UTC offset)
array('-12:00', '-12:00', ''),
array('+00:00', '+00:00', ''),
array('+14:00', '+14:00', ''),
// type 2 (timezone abbreviation)
array('GMT', '+00:00', ''),
array('a', '+01:00', ''),
array('b', '+02:00', ''),
array('z', '+00:00', ''),
// type 3 (timezone identifier)
array('Africa/Tunis', 'Africa/Tunis (%s:00)', $xRegion),
array('America/Panama', 'America/Panama (%s:00)', $xRegion),
array('Asia/Jerusalem', 'Asia/Jerusalem (%s:00)', $xRegion),
array('Atlantic/Canary', 'Atlantic/Canary (%s:00)', $xRegion),
array('Australia/Perth', 'Australia/Perth (%s:00)', $xRegion),
array('Europe/Zurich', 'Europe/Zurich (%s:00)', $xRegion),
array('Pacific/Tahiti', 'Pacific/Tahiti (%s:00)', $xRegion),
);
}
/**
* @dataProvider providePeriods
*/
public function testDumpPeriod($start, $interval, $end, $options, $expected)
{
$p = new \DatePeriod(new \DateTime($start), new \DateInterval($interval), \is_int($end) ? $end : new \DateTime($end), $options);
$xDump = <<<EODUMP
DatePeriod {
period: $expected
%A}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $p);
}
/**
* @dataProvider providePeriods
*/
public function testCastPeriod($start, $interval, $end, $options, $xPeriod, $xDates)
{
$p = new \DatePeriod(new \DateTime($start), new \DateInterval($interval), \is_int($end) ? $end : new \DateTime($end), $options);
$stub = new Stub();
$cast = DateCaster::castPeriod($p, array(), $stub, false, 0);
$xDump = <<<EODUMP
array:1 [
"\\x00~\\x00period" => $xPeriod
]
EODUMP;
$this->assertDumpEquals($xDump, $cast);
$xDump = <<<EODUMP
Symfony\Component\VarDumper\Caster\ConstStub {
+type: 1
+class: "$xPeriod"
+value: "%A$xDates%A"
+cut: 0
+handle: 0
+refCount: 0
+position: 0
+attr: []
}
EODUMP;
$this->assertDumpMatchesFormat($xDump, $cast["\0~\0period"]);
}
public function providePeriods()
{
$periods = array(
array('2017-01-01', 'P1D', '2017-01-03', 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) to 2017-01-03 00:00:00.0', '1) 2017-01-01%a2) 2017-01-02'),
array('2017-01-01', 'P1D', 1, 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) recurring 2 time/s', '1) 2017-01-01%a2) 2017-01-02'),
array('2017-01-01', 'P1D', '2017-01-04', 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) to 2017-01-04 00:00:00.0', '1) 2017-01-01%a2) 2017-01-02%a3) 2017-01-03'),
array('2017-01-01', 'P1D', 2, 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) recurring 3 time/s', '1) 2017-01-01%a2) 2017-01-02%a3) 2017-01-03'),
array('2017-01-01', 'P1D', '2017-01-05', 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) to 2017-01-05 00:00:00.0', '1) 2017-01-01%a2) 2017-01-02%a1 more'),
array('2017-01-01', 'P1D', 3, 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) recurring 4 time/s', '1) 2017-01-01%a2) 2017-01-02%a3) 2017-01-03%a1 more'),
array('2017-01-01', 'P1D', '2017-01-21', 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) to 2017-01-21 00:00:00.0', '1) 2017-01-01%a17 more'),
array('2017-01-01', 'P1D', 19, 0, 'every + 1d, from 2017-01-01 00:00:00.0 (included) recurring 20 time/s', '1) 2017-01-01%a17 more'),
array('2017-01-01 01:00:00', 'P1D', '2017-01-03 01:00:00', 0, 'every + 1d, from 2017-01-01 01:00:00.0 (included) to 2017-01-03 01:00:00.0', '1) 2017-01-01 01:00:00.0%a2) 2017-01-02 01:00:00.0'),
array('2017-01-01 01:00:00', 'P1D', 1, 0, 'every + 1d, from 2017-01-01 01:00:00.0 (included) recurring 2 time/s', '1) 2017-01-01 01:00:00.0%a2) 2017-01-02 01:00:00.0'),
array('2017-01-01', 'P1DT1H', '2017-01-03', 0, 'every + 1d 01:00:00.0, from 2017-01-01 00:00:00.0 (included) to 2017-01-03 00:00:00.0', '1) 2017-01-01 00:00:00.0%a2) 2017-01-02 01:00:00.0'),
array('2017-01-01', 'P1DT1H', 1, 0, 'every + 1d 01:00:00.0, from 2017-01-01 00:00:00.0 (included) recurring 2 time/s', '1) 2017-01-01 00:00:00.0%a2) 2017-01-02 01:00:00.0'),
array('2017-01-01', 'P1D', '2017-01-04', \DatePeriod::EXCLUDE_START_DATE, 'every + 1d, from 2017-01-01 00:00:00.0 (excluded) to 2017-01-04 00:00:00.0', '1) 2017-01-02%a2) 2017-01-03'),
array('2017-01-01', 'P1D', 2, \DatePeriod::EXCLUDE_START_DATE, 'every + 1d, from 2017-01-01 00:00:00.0 (excluded) recurring 2 time/s', '1) 2017-01-02%a2) 2017-01-03'),
);
if (\PHP_VERSION_ID < 70107) {
array_walk($periods, function (&$i) { $i[5] = ''; });
}
return $periods;
}
private function createInterval($intervalSpec, $ms, $invert)
{
$interval = new \DateInterval($intervalSpec);
$interval->f = $ms;
$interval->invert = $invert;
return $interval;
}
}
|
Jan 2008 Journal
Letters to the Editor
THE YOUNGEST KINDERTRANSPORT REFUGEE?
Sir - Re Erika Klausner’s letter ‘The youngest Kindertransport refugee?’ (December), according to the vague rules for permitting children to come to Britain from December 1938 till the outbreak of war, children were supposed to be over five. I know of two three-year-olds and two babies who arrived at Harwich. One of the former was Leah Roth from Borken. She came a few weeks before the war, aged three, with her sisters Hilde, seven, and Friedchen, five. Today, she is Leah Traub and lives in east or north-east London. She has nine children and 45 grandchildren. I saw her again, as an adult, when we held a reunion in London for our former refugee hostel (Windermere) in the summer of 1989. We were told that at the last minute the parents sent Leah instead of the older brother, as they feared England would not be orthodox enough for the boy. Remarkably, Leah’s father survived, a changed and physically damaged man; the mother, older brother and two tiny Roth siblings perished. Another friend is Ruth Schwiening (née Auerbach), who came from near Breslau on the KT aged 3. Today she lives in Market Bosworth, Leicestershire.
The two babies mentioned above were twins - Susi and Lotte Bechhöfer - whose desperate mother had put them on a train leaving Munich in a basket/cradle. Fostered by a Welsh Baptist minister and his wife, they knew nothing of their origins. Lotte died as an adolescent. Susi, living in Rugby today, heard by chance a broadcast in 1989 about the KT. She wondered, then investigated. The BBC helped her trace her origins. You can imagine the shock that the rest of us did not have to go through. I am glad to know Susi - an extraordinary woman.
Ruth L David and Ames, Iowa, USA
Sir - I believe I was younger than Erika Klausner as I arrived on 20 April 1939 at the age of 2 years, 10 months, my third birthday being 17 June.
We always look forward to the AJR magazine - such a well-informed and interesting read.
Helga Lazarus (née Singer), London N3
Sir – The youngest ‘Kind’ was four months old, according to Bertha Leverton’s records. I actually met her, and spoke to her, last summer in Hyde Park.
(Mrs) Annette Saville, London NW4
WHO IS A JEW?
Sir - Mr Phillips should have read my very brief discourse ‘On Being or Not Being a Jew’ with a little more attention to detail. I clearly state that the question as to who is and who is not a Jew is not a value-free judgement: it depends on who asks the question and who answers it. Although I am not quite sure what he means by ‘been brought up in the Jewish way of life’ (Hassidic? secular?), I am quite happy to accept the paternal line as equally valid for being Jewish - but then, I am also ready to accept ‘Jews for Jesus’ as being Jews. Hitler would not have disagreed with either proposition. Conversely, and I said so explicitly, if the answer depends on Halachic Law, then neither would qualify.
Mr Phillips refers vaguely to a ‘Muslim race’. If he means the Islamic Umah, then, generically, Jews are a ‘race’ by analogous definition. If, on the other hand, as I believe, race is defined by the DNA molecule, then Mr Phillips and I may be of the same race; our Ethiopian fellow-Jews, however, are not.
Harold Saunders, Manchester
KRISTALLNACHT COMEMMORATED IN KOSZALIN
Sir - I would like to draw your readers’ attention to an event that occurred in Koszalin, Poland, on 15 November - especially as, judging from previous correspondence, there are still some who are unwilling to recognise that the Poles are undergoing a profound change of attitude.
To commemorate Kristallnacht, a candlelight march was organised, and this was attended by some 140 people, including 30 youngsters from a local school. The organisers were Henryk Romanik, a Catholic priest, poet and local historian, and Zdzislaw Pacholski, a professional photographer. I have known these two for seven years and they have been responsible for other events that I have written about in the past in our Journal. They have become good friends of mine. Present, too, were the mayor’s wife, the head of the Jewish community in Szczeczin (formerly Stettin), the local bishop, a poet living some 100 km away and, significantly, several members of the local Jewish community who normally keep themselves to themselves.
The event began after dark in a small church, where Mr Pacholski described the significance of Kristallnacht and the catalytic role I had played in getting the town to remember its pre-war past. Prayers were said by the bishop and, in Hebrew, by the man from Szczeczin, and messages of support were read out from an Austrian journalist and writer (Ute Hoeschele) whose family had lived in the town before the war, as well as from me. The marchers then solemnly proceeded to several former Jewish sites, now marked with monuments of one kind or another - the synagogue, the old cemetery (rededicated two years ago and containing my great-uncle’s grave stone – see photograph), and what used to be the ‘new’ cemetery, now within the Technical University. This was the third annual march; the weather was reasonable for once but there was snow on the ground.
The Poles were clearly not responsible for Kristallnacht and its aftermath, yet they feel it appropriate to remember the event as a warning to future generations. Such acts of remembrance do occur all over Poland and it is important for us to acknowledge and welcome this. Significantly, as you will know, Warsaw is to have – at last – a Holocaust museum.
Leslie Baruch Brent, Emeritus Professor, London N19
AMSTERDAM STRIKE REMEMBERED
Sir - On 25 February 1941, under German occupation, a strike took place in Amsterdam protesting against the brutal Nazi treatment of Jews. The strikers were public transport and other municipal employees, workers in shipbuilding and steel, large stores and many shops and offices. Public transport in Amsterdam was halted for a whole day. The next day, other Dutch cities joined in. More details are to be found at http://www.februaristaking.nl/english.html
Please come and join me at the annual commemoration of these events, just after 4 pm on 25 February 2008 at the Jonas Daniel Meijerplein, very close to the Waterlooplein Metro station, Amsterdam. The mayor, the Israeli ambassador and Dutch Jewish groups will be there. Old and frail visitors will be looked after.
Nothing like this strike happened where we came from, which makes it all the more important for us to join in honouring those Dutch heroes. For more information, contact me at landers@heatherhouseoxford.com or at Skinner 58, Nea Chora, Chania 73100, Crete, Greece.
George Landers, Crete
AFTER ANNAPOLIS
Sir – Peace negotiations between Israel and the Palestinians are bound to take a long time and it is therefore necessary to take some small steps to alleviate the sufferings of the Palestinians, particularly the 30,000 Palestinians who live in the compound of Hebron ruled by the Israeli army. Its main street, Shuhuda Street, is reserved for Jews only, i.e, the 700 settlers who live above the town. Palestinians must climb with ladders on the roofs to get into their own homes. My daughter Alison was in Shuhuda Street on a study tour and, when she entered the market, she wondered why there were nets above the streets: the settlers regularly throw rubbish, stones and bottles from their homes onto the market and the nets prevented the rubbish from falling onto the stallholders and Palestinian shoppers.
Yehuda Shaul is a religious Jew who, on a visit to this country, told me that when he did his military service in Hebron he took off his yarmulka because he didn’t want the Palestinians to see that a religious Jew could tolerate such conditions. The settlers belong to the Kach group. Baruch Goldstein, who killed 29 Muslims praying in the Hebron mosque, belonged to this group, whose members the Israeli Government considers terrorists.
Peter Prager, Ilford, Essex
ANNA ESSINGER
Sir - I was delighted to see the piece about Anna Essinger in October’s journal. Anna Essinger was a relative of my dear late husband. He used to tell me about her school. I didn’t realise she was so well known or I would have paid more attention!
Mary D. Essinger, Leicester
MISSING THE POINT
Sir – Guy Bishop’s apocryphal anecdote (December, Letters) about my grandfather, Julius Fromm, unfortunately misses the point and does not make any sense as it stands, for the correct translation of Reklamationen is ‘complaints’, not ‘advertisements’ (Reklame). Thus the large group of children with which my grandfather is supposed to have been seen refers to faulty condoms, not to any marketing of the product he invented. Whilst on the subject of faulty or burst condoms - something that obviously never happened with a genuine Frommser - my grandfather would invariably shift such unfortunate occurrences on to the competition, when he said, equally apocryphally, ‘Die Konkurrenz soll platzen!’ It is hoped your readers will understand the dual meaning of ‘platzen’.
Ray Fromm, London NW7
NORTH AND SOUTH
Sir – I would like to thank everyone involved in the three-day trip to London in November. Special thanks must go to Susanne Green and Barbara Dresden Dorrity for their hard work and the professional manner in which they organised it.
The choice of venues was well thought out - from the tour of the Bevis Marks Synagogue to the tour of the Jewish East End. We were shown things too humorous to mention, with a tour guide so knowledgable and full of enthusiasm about his subject, and a lovely lunch, eaten on the go, from Rinkoff’s bakery.
When we had gathered our breath, we were taken to Belsize Square Synagogue for a first-class dinner and a talk by the vivacious and straight-talking Anna Raeburn. There was a trip to see the Wallace Collection of fine art. On our last day, we were taken to the AJR Centre for a very tasty lunch (thank you, chef!) and a very moving Kristallnacht service by Rabbi Rodney Mariner. Thank you all concerned!
Liverpool
Mrs Sabine Barton and Mrs Ruth Eisikovits, Liverpool
Sir - Just want to thank Susanne (and all concerned) once more for the splendid time you gave us in London. Whenever I tell anyone about all we did, it leaves them speechless with admiration. Firstly, that we did it all and, secondly, how clever the organisers must have been to fit it all in! How true!
When you come to plan next year’s event, how about Liverpool, City of Culture! I can see there is going to be lots going on and I think it would make a splendid holiday. High time that the Londoners travelled north - and a bit west as well, don’t you think?
Dorothy Fleming, Sheffield
Sir - I believe I was younger than Erika Klausner as I arrived on 20 April 1939 at the age of 2 years, 10 months, my third birthday being 17 June. |
Q:
How to combine all unique values of a dataframe column into a string
I have created a dataframe that looks like this
data <- data.frame(col1,col2,col3)
>data
col1 col2 col3
1 a1 b1 c1
2 a1 b2 c2
3 a1 b3 c3
and would like to transform into
col1 col2 col3
1 a1 b1,b2,b3 c1,c2,c3
It seems that rbind is what I am looking for. But after reading the description, I still have no clue how to implement this.
A:
Create example dataset:
df <- data.frame(
col1 = c("a1","a1","a1"),
col2 = c("b1","b2","b3"),
col3 = c("c1","c2","c3"),
stringsAsFactors = FALSE
)
Short version:
data.frame(lapply(df, function(x) paste(unique(x), collapse=",")))
With explanation and intermediate steps:
#create a custom function to list unique elements as comma separated
myfun <- function(x) {
paste(unique(x), collapse=",")
}
#apply our function to our dataframe's columns
temp <- lapply(df, myfun)
#temp is a list, turn it into a dataframe
result <- data.frame(temp)
|
Joseph Hallman
Joseph Hallman (born Nov. 20, 1979) is a composer. A functional orphan, Hallman was born and raised in the Kensington neighborhood of Philadelphia, Pennsylvania. He attended Girard College from first to twelfth grades. Based in Philadelphia, United States, Hallman's works have been performed internationally. His music has been described as eclectic, merging classical, Renaissance, and contemporary popular styles. Hallman also teaches composition at Drexel University.
Early life
Hallman began composing at the age of 12. He graduated from the Cleveland Institute of Music, where he studied with Margaret Brouwer. He continued his studies with masterclasses by George Crumb. Christopher Rouse, John Corigliano, Steven Mackey, John Harbison and others.
Career
Hallman is composer-in-residence at the Rosenbach Museum & Library of Philadelphia and the Pikes Falls Chamber Music Festival. He has collaborated with leading performers and ensembles. Cellist Alisa Weilerstein performed his concerto for cello and chamber ensemble with the St. Petersburg Chamber Philharmonic in Russia. A series of concerti grossi, inspired by Johann Sebastian Bach's Brandenburg Concertos, was performed by members of the Philadelphia Orchestra, New York Philharmonic, Pittsburgh Symphony, and Cleveland Orchestra. The Cavani Quartet has premiered his compositions. His ballet Alice was performed in April 2010 by the Colette Harding Dance Company in San Diego. He has worked closely with poet Jessica Hornik, and his settings of three of her poems is included in the album "Sprung Rhythm" by the Washington DC ensemble Inscape, which was nominated for the 2014 Grammy award.
Hallman has worked with many other writers including the Vermont Poet Laureate, Sydney Lea. Lea called his collaboration with Hallman, which was sponsored by the Vermont College of Fine Arts, “a high point of my term as poet laureate. It’s been so refreshing and so different, a great shot in the arm.” He also collaborated on a new choral work with the writer and director Antwone Fisher.
Awards and accolades
Hallman's compositions have won numerous awards, including the Marcel Dik prize, the Donald Erb prize, and the Darius Milhaud award He has won numerous accolades, including selection as one of the 100 leading composers under 40 by NPR in 2011, and was nominated for a 2014 Grammy Award.
Critics have praised Hallman's work. "[Hallman's music] is for acoustic instruments -- no computers, no electronic processing -- and it is music that is long on harmonic and melodic interest and blessedly short on intellectual or mathematical gimmicks, without sounding overly neo-Romantic or derivative", wrote music critic Charles Downey of the Washington Post "Two pieces by Joseph Hallman singled him out as the one to watch, especially 'Imagined Landscapes,' six atmospheric miniatures inspired by the nightmares of H. P. Lovecraft. Even the use of whispers, shouts and other noises did not seem like a cheap effect but part of a musical whole, a complement to the composer’s skillful handling of each instrument," wrote Downey in a separate review. of his "Three Hornik Poems" the critic Steve Smith stated in the New York Times [that it is] "a buoyant song cycle by Mr. Hallman that simply must be heard". Ronni Reich of the Washington post wrote that Hallman's compositions are "reminiscent of Dominick Argento, contemporary soundscapes and Renaissance music."
References
External links
Category:1979 births
Category:Living people
Category:American male classical composers
Category:American classical composers
Category:Cleveland Institute of Music alumni |
α 1-acid glycoprotein inhibits lipogenesis in neonatal swine adipose tissue.
Serum α1-acid glycoprotein (AGP) is elevated during late gestation and at birth in the pig and rapidly declines postnatally. In contrast, the pig is born with minimal lipid stores in the adipose tissue, but rapidly accumulates lipid during the first week. The present study examined if AGP can affect adipose tissue metabolism in the neonatal pig. Isolated cell cultures or tissue explants were prepared from dorsal subcutaneous adipose tissue of preweaning piglets. Porcine AGP was used at concentrations of 0, 100, 1000 and 5000 ng/ml medium in 24 h incubations. AGP reduced the messenger RNA (mRNA) abundance of the lipogenic enzymes, malic enzyme (ME), fatty acid synthase and acetyl coA carboxylase by at least 40% (P<0.001). The activity of ME and citrate lyase were also reduced by AGP (P<0.05). Glucose oxidation was reduced by treatment with 5000 ng AGP/ml medium (P<0.05). The 14C-glucose incorporation into fatty acids was reduced by ~25% by AGP treatment for 24 h with 1000 ng AGP/ml medium (P<0.05). The decrease in glucose metabolism by AGP appears to function through an inhibition in insulin-mediated glucose oxidation and incorporation into fatty acids. This was supported by the analysis of the mRNA abundance for sterol regulatory element-binding protein (SREBP), carbohydrate regulatory element-binding protein (ChREBP) and insulin receptor substrate 1 (IRS1), which all demonstrated reductions of at least 23% in response to AGP treatment (P<0.05). These data demonstrate an overall suppression of lipogenesis due to AGP inhibition of lipogenic gene expression in vitro, which the metabolic data and SREBP, ChREBP and IRS1 gene expression analysis suggest is through an inhibition in insulin-mediated events. Second, these data suggest that AGP may contribute to limiting lipogenesis within adipose tissue during the perinatal period, as AGP levels are highest for any serum protein at birth. |
I dated a Russian woman here in the United States and I fell in love with the culture. I treat the one I'm with with the utmost respect! I'm a gentlemen by nature. I'm very athletic, good looking, and hard working! I hope to have children at some point.
Hello ladies,
I want to spoil a Chinese girl that will come live with me in America. I'm looking to marry my future partner and live my days happy. I will not be tricked into sending money or gifts but I'm looking for someone for my future and she needs to not want me for stuff but for me.
Seeking to make my dream girl a r...
Morgantown,
West Virginia, United States
Seeking: Female 40 - 55 for MarriageStar sign: Libra
I am a gentleman, wealthy and retired. I am honest, devoted and curious. I'm a good friend and enjoy a great sense of humor. I love to travel and dine at fine restaurants. I enjoy cooking and playing the piano. The only thing I need is a loving wife.
Here are 12 Reasons why Am I am "different" from the other guys you have met online:
12. I am passionate about everything I do......Whether its tennis, learning, business, romance, etc I am passionate and put in 110%. My philosophy is how a person does 1 thing influences how they do everything. Giving 110% to everything helps me excel.
11. I am somewhat famous in my industry (started a 7 figure business from my kitchen table). Most would call me a leader.
10. I thrive on a strong mental and intellectual connection - not purely hormones...It takes a strong mental and intellectual connection for me to really feel connected to someone. Being a man I have needs....but this is only a part of the picture.
9. I would love to get married if I find the right chemistry. I am at the point in my life where I am looking for someone to share my life with.....Assuming I meet the right person.
8. What am I like? I have the passion of a Colombian/Brazilian....combined with the reserved nature of an Asian (I think before I speak).
7. Tennis lessons - I have played tennis for 10 years and play in several leagues.......I am rated in the top 15-17% of players who play competitive leagues and would be happy to help you learn.
6. I love pleasing my partner - I prefer to give rather than receive...I also hate to fight and place a high value on harmony in relationships.....I fit the Libra profile very well. Google is your friend.
5. I am a great listener and believe listening is very important if you want to understand your partner....Because it's impossible to make your partner happy if you don't listen to their needs.
4. Home cooked meals - How does fish (salmon), rice and steamed veggies sound? Living a healthy lifestyle is very important to me.. I enjoy cooking for my partner as it motivates me to learn/experiment with new dishes. Maybe we could cook something together?
3. Honesty - What is more important in a relationship that this? One of my grandfathers is from Philadelphia....My honest direct nature comes from him....I am a horrible liar, very transparent....so I stick with the truth.
2D. One of my goals over the past year has been to become the best version of "myself" I can be. This means getting in peak shape, working on increasing my emotional intelligence, and taking my business to the next level.....
2C. I have been told I am the least photogenic guy online. The last few people I met said I looked considerably better in person. Its my curse...but also means I won't disappoint you if we meet.
2B. I have dated two physicians in the past 5 years (5'2" and 5'3"). Both swore to me I was "the perfect size" to please them. I only mention this because this seems to be very important to some women.
2A. I am financially stable. Home and car are paid off and have a 7 figure net worth....
Curious @ 1? Simply E-mail me your and I will text you the 1 reason!
P.S. yes I work in marketing. Blame my profile on the day job...:)
I want life to spend with happiness. I love traveling, watching movies and trekking on mountain. I am here to find a good friend who brings more happiness in my life and I also let her smile. I love my pets. I have dog and cat. I understand feeling of my friends and take care of them.. ... I work in Los angels, HK and Shenzhen.
I'm 26 years old and a single father of 2 beautiful boys. I raise them both and am currently looking for someone that is okay with that. I work full time and love my kids more than anything else in the world. I am very strong, smart, funny, easy goin
I am an African immigrant hailed from West Africa. I am intelligent, honest, and straight forward and open minded person. I obtained an Associate Degree in the field of Information Technology (Computer Networking). Presently, I am pursing a Bachelor degree in the area of Computer Management Information Systems. Love people, and my favorite sports are soccer and basketball.
Hi, Im Darrick I don’t know what to say about myself I not shore I have enough room on this sit but I wanted to see what is out there. I joined the Marine Corps when I was 19 years old, after two combat deployments and a field marriage I got out. Not knowing what to do with my life I became a pilot and then had another divorce due to wife cheating. I think I’m to nice but I love to love people and I’m funning out going and playful. I take what I do in life as most important but would love to me that someone I just don’t think American woman is my type and I always love the culture of Asians just hoping to find the right one.
I'm 56 years old and live in Las Vegas, Nevada. I'm 6' tall, 185 lbs with brown hair and very blue eyes. I am retired. I enjoy cycling, music, watching TV, movies, gardening and snuggling with my sweetie. I want someone to share my life with. I'm very kind and gentle and treat everyone with respect.
I like to smile always, i believe it expresses a good heart and calmness, I like to eat as much as i love to cook also, I like Asian food, sea food and also continental.
Sometimes i exercise at my home gym and sometimes i go to the public gym so i could exercise with other people, I love movies and when i am free i love to travel always and see other parts of the world, other fashions and other cultures.
I like to joke and i have the ability to make people laugh and ease their stress, I also like shopping, i guess everyone does too, and iwould go out and see a new place.
It is important to understand that life is a gift and so i always pursue my reason for existence. I live and I love, I win and I cry, I love fitness and i wander the earth in search of adventure,fun,learning and upgrade.
I smile at my past without any regrets and I am impatient for what the future has in store for me.
I am a self made man, have my own business and love the ocean.
looking for someone to share many things in life. I love to travel, very active outdoors, very passionate and love surfing and exploring new places I will be in China
in August for a few weeks.
I am an International Surfboard designer and will be doing some new
designs for next year's models
I LOVE passionate people!!!! ...and dancing. The desire to constantly dance seems to be infused into my blood. Been around music all my life, sing and enjoy playing acoustic guitar. My background is unique to say the least... I'm not arrogant, yet I am confident in my abilities. I've done everything from machining parts for hydrogen fuel cell prototypes and design engineering, to breaking horses and building houses.
I am looking for someone to dance with, play basketball, tennis, pool, or just cuddle up with a good movie - Ultimately, a lifelong partner.
I can speak Chinese, I can read some, but I can't write it very well, unless I use a computer. I guess I am a little different from other Americans. I don't like bars, clubs, or getting drunk. I like cool forests, beautiful views and quite moments. I can't stand cigarette smoke. I run, exercise, take vitamins, read, drink tea and coffee and listen to classical or new age music. I am a romantic person. I can spot liars very quickly. I am not rich by American standards, so if you are looking for that, try somebody else.
LOOKING FOR MY TRUE LOVE
New York,
New York, United States
Seeking: Female 35 - 55 for MarriageStar sign: Libra
I am sincere and honest with strong spiritual interest to know more on a higher level about peace and tranquil stability for my life and those I am with. I don't have the time for B/S or phoney people, I offer down to earth kindness and seek the same. I am a communicative man of noble character with ethics and of good character. I live in Queens, New York near Forest Hills, Rego Park, Richmond Hill and Kew Gardens area about 35 minutes from New York City.
There can be pleasant surpises and unpleasant in life, but I tend to think that the best will surely come my way because my energy is good and strong to attract goodness..
I like going to flea markets, outdoor concerts, festivals fun stuff. I enjoy all types of music, except for rap, and have to admit I am partial to country music but not the hill billy type. Beautiful sounds are very pleasing to the ears.
WHAT I WANT
A no game playing lady, attractive and just a real down to earth person with a good honest and sincere heart. You must have a high spiritual interest to know the highest of yourself. Spirituality is essential for me to be turned on to you as well as attractive to eye appeal.
If you like yoga or meditation then I am more interested in you and if you want to learn about these things then I'm happy to share my own experiences with you that may enhance your life and our relationship for greater love and stability.
Looking For One Good Woman To Spe...
Salt Lake City,
Utah, United States
Seeking: Female 35 - 50 for MarriageStar sign: Libra
My name is Frank Underwood a US army leutenant colonel. I was born in the States but my mother is by birth, from England, and this made me go to Kent, England at the age of 13 yrs for my High school education, but i had my undergraduate education for business management at USC, California in the states.
Tall_and_Pretty
New York,
New York, United States
Seeking: Female 18 - 35 for MarriageStar sign: Libra
Who am I? . . . I'm Super-Man. Wait, no, that was a movie! . . . . . I would describe myself as stable in my career and goal-oriented. I enjoy making people laugh. I am intelligent and can carry on meaningful conversations. I care about other people's feelings. . . . . . When I'm with someone special I like being spontaneous, adventurous, romantic, surprising them with little gestures, sensual, playful, and basically having that type of fun you see two people who just met in the movies having! Someone to laugh with, hang out with, be spontaneous with, and have fun with! I'm looking for someone who has similar qualities and desires, someone that I can connect with . . . . . . I feel there has to be mutual physical attraction for there to be good chemistry between two people. So being fit and having good looks are important, as well as sensuality and affection. . . . . . Having some similar interests helps--some things I enjoy are fine dining, walking on the beach at night, going dancing, watching movies including foreign films, travelling, going snowboarding, going on day trips to local attractions, spontaneous exotic getaways, having romantic nights at home, cuddling, and basically having a blast together. . . .
I'm a researcher in the University of Wisconsin, Madison. Being good at my job is very important to me, but relationships are the things that make life worth living. I love to windsurf, sail, dance, cook, watch movies, and of course have a great conversation. I love to be affectionate. I want to hear from you!
I am most proud of the fact that I am attractive, I have a great career, and I'm a great and giving lover.
Hey Whats Up & Ni Hao!
My name is Kamal that means "Lotus" in Indian.
I am an American with Indian descent. I am a fun loving romantic person.
I hope to make a best friend I can love and marry as well as possibly have a family.
One who I can know she is my best friend and know better already... meet spend time with and hopefully marry one day. I would cook for my wife, love her, feed her, hold hands and share all good things. I have been to mainland China twice, Once in 2009 to visit and also In 2010 I taught English in Nanjing. I am an entrepreneurial creative professional with ambition living in the USA and working.
Do you like Art, Music, Going Out, Apple computers, DJs Dancing, Cooking, Camping, Festivals? Or any other ways of having fun, like experiencing nature?
Please share with me your life.
Very attractive and very family oriented! I enjoy being around people. I build custom motorcycles and i also do home theaters and race cars. Thats my first Job secondly i am
an Engineer for GE Wind division. I Keep very busy but i would like to find someone i can slow down with! LOL and maybe start a family with. |
Q:
How to optimize this code in java?
public class factorize {
public static void f(int n) {
int i = 2;
while( n > 1) {
if (n%i == 0) {
System.out.println("Factors " + i);
n = n / i;
}
else {
i++;
}
}
}
Hello, I am doing in java a function of factorize but it takes many times to excute,I try to see on the internet some theorems but the result is the same.
Can you advise me some algorithms to excute this factorize as fast as possibile? this code takes like 2 mins.
A:
Try this:
public static void f(int n) {
int i = 2;
while(i*i <= n) {
if (n%i == 0) {
System.out.println("Factors " + i);
n = n / i;
}
else {
i++;
}
}
if (n > 1) {
System.out.println("Factors " + n);
}
}
This works because you can only have a single prime factor larger than sqrt(n): if you had two, their product would exceed n, since sqrt(n)*sqrt(n) = n. So it suffices to check those and then if n > 1, that remaining n is another prime factor.
Note: 2732983441203969650 is a large number that will not fit in an int. You should consider using a long if you want your algorithm to work for it. Note that its square root is also very large, and so the algorithm might still be very slow. For such large numbers, factorization is very hard. One algorithm you could try that will probably work for 64 bit numbers in decent time is Pollard's Rho algorithm.
Other things you can optimize in your code:
Check 2 separately and then only check divisibility by odd numbers;
Use the Sieve of Eratosthenes to generate primes lower than the square root of n and check for divisibility against those primes.
|
Mr Trump, who has described himself as Mr Obama's "worst nightmare," told the president he was "a very, very good man."
On the campaign trail he repeatedly described him as weak, "a disaster," ineffective and "the most ignorant president in our history.”
On Thursday, however, both men struck a conciliatory note after they met to discuss the transition from one administration to the next.
"We want to do everything we can to help you succeed, because if you succeed we all succeed," said Mr Obama.
There circumstances of the meeting were extraordinary. Mr Trump spent years claiming Mr Obama was born outside the US and was therefore not a legitimate president, while Mr Obama savaged him throughout the campaign as irresponsible and dangerous.
The wounded male ego ...
The US election shows the wounded male ego is one of the most dangerous forces in politics, writes Cristina Criddle:
At Donald Trump’s acceptance speech, the only thing louder than the president-elect was the braying of victorious male voices. Now, the blue-collared white man will beat his chest and roar until his throat is sore, because the Grand Old Party has won a vote to "make America great again" — and by great, they mean "male".
Japan 'pays enough for US troops already'
Japan's defence minister says his country already pays enough for US troops based there, a response to repeated demands by President-elect Donald Trump that countries hosting American forces should pay more.
Mr Trump's remarks during the election campaign have raised concern in Japan about a possibility his administration may seek Japan's increased spending for American forces.
Tomomi Inada, the Defence Minister, stressed the presence of US troops in Japan serves as a key deterrence in the Asia-Pacific region and they should stay.
Japan pays about 200 billion yen ($1.9 billion) a year in so-called host-nation support for 50,000 US troops.
Inada said on Friday: "I believe it's enough. We pay what we are supposed to cover."
Emerging markets extend post-Trump slump
An emerging-markets selloff deepened amid concern developing economies will face capital outflows and weakening exports once Donald Trump is in The White House, Bloomberg reports. Treasuries capped their worst week since 2009 before a US holiday on Friday.
MSCI gauges of emerging-market equities and currencies sank to four-month lows since the election of Mr Trump, who plans to adopt a more protectionist trade stance while introducing fiscal stimulus that's seen hastening interest-rate hikes by the Federal Reserve.
More than $1 trillion was wiped off the value of bonds this week, something that's happened only once before in the last two decades, and Bloomberg's dollar index is headed for its biggest weekly gain since May 2015. Shanghai shares were set to enter a bull market.
Zuckerberg denies fake stories swayed election
Mark Zuckerberg has rejected the idea that fake news on Facebook influenced the US presidential election and said echo-chambers aren't really a problem on the site.
The co-founder of the social network was responding to criticism following Donald Trump's victory in the elections, from people who argued the company allowed false information to run rampant on its site and that its algorithm tended to amplify the voices people wanted to hear, instead of providing a full picture of what was going on.
Mr Zuckerberg, speaking at the Technonomy conference in Half Moon Bay, California, said the company certainly has work to do to improve the news feed, but said false stories were a small portion of the content shared.
"That it influenced the election in any way is a pretty crazy idea," he said. People vote based on their life experiences, and anyone who thinks fake news contributed to the outcome betrays a "profound lack of empathy" for Mr Trump's camp, he said.
Facebook has constantly studied the effect of its news feed. Mr Zuckerberg says the idea that it shields people from diverse opinions is a misconception -- a particularly difficult theory for him to quash.
"All of the research we have suggests that this hasn't really been a problem. The biggest filter in the system is not that the content isn't there, but just that you don't click on it."
Actor Voight urges Trump to build wall
Hollywood star Jon Voight has urged President-elect Donald Trump to stick to his pledge to build a wall on America's border with Mexico.
The Oscar-winning actor, who has been a vocal supporter of Mr Trump, made the comments at the world premiere of Fantastic Beasts And Where To Find Them in New York , which was also attended by JK Rowling - a fierce critic of the president-elect.
On the day of the debate, Ms. Kelly writes, she woke up feeling great. Then an overzealous, suspiciously enthusiastic driver picked her up to take her to the convention center. He insisted on getting her coffee, though she’d repeatedly declined his offer. Once it was in her hand, she drank it. And within 15 minutes, she was violently ill, vomiting so uncontrollably that it was unclear if she’d be able to go on and help moderate that evening. It was so bad that she kept a trash pail beneath her desk throughout the debate, just in case.
She also hints that the Trump campaign was in collusion with Fox, or at the very least, Roger Ailes, the network’s chairman until July, and that he was being leaked information.
The day before the first presidential debate, Mr. Trump was in a lather again, Ms. Kelly writes. He called Fox executives, saying he’d heard that her first question “was a very pointed question directed at him.” This disconcerted her, because it was true: It was about his history of using disparaging language about women.
Warren has spoken to Clinton
US Senator Elizabeth Warren says she has spoken with Hillary Clinton after her defeat in the election on Tuesday.
In an interview with MSNBC’s Rachel Maddow, she was asked how Clinton was doing. Warren paused before hesitantly stating, “Good.”
“Look, it’s hard. It’s really hard. She worked hard. She has had 25 years of public service. . . She has fought for women, for children, for health insurance, for human rights. That has been a defining feature of her life. And this is hard. I respect what she has done and tried to do for this country and for people around the world.”
"We are going to be smart, we are going to be organised, we're going to use our time and talents in a strategic and careful way, but we are going to fight back. We are not going to turn this country over to what Donald Trump has sold."
Trump bucks protocol on press access
Donald Trump is keeping Americans in the dark about his earliest conversations and decisions as president-elect, bucking a long-standing practice intended to ensure the public has a watchful eye on its new leader.
Mr Trump on Thursday refused to allow journalists to travel with him to Washington for his historic first meetings with Barack Obama and congressional leaders, the AP reports. The Republican's top advisers rebuffed news organisations' requests for a small "pool" of journalists to trail him as he attended the meetings.
Hope Hicks, a Trump spokeswoman, said the president-elect's team expects "to operate a traditional pool and look forward to implementing our plans in the near future."
But that didn't ease fears among reporters. The White House Correspondents' Association, which coordinates press pools and advocates for transparency at the White House, urged Trump to allow journalists to cover his meetings and other movements.
"This decision could leave Americans blind about his whereabouts and well-being in the event of a national crisis," said Jeff Mason, White House correspondent for Reuters and the group's president. "Not allowing a pool of journalists to travel with and cover the next president of the United States is unacceptable."
She said she had created an event on Facebook for her friends that ended up attracting thousands.
Earlier on Thursday, demonstrators - mostly students who skipped classes - also marched in San Francisco, Los Angeles and other cities.
Some 1,000 students, most of them high-schoolers, marched through San Francisco's financial district toward City Hall chanting "Not my president!" and blocking traffic. Some also carried placards that read "Trans Against Trump" and "Make America Safe For All."
Trump's body langauge
A body language expert has given his verdict on the awkward meeting between Barack Obama and Donald Trump. Given both men had shown disdain for each other in recent years, the encounter was always going to draw extra scrutiny.
Trump and ObamaCredit:
AP
Trump and ObamaCredit:
Rex
Analysing the way both men sat and used their hands, expert Patti Wood said Mr Obama was "extremely fatigued, resigned and not hopeful", while Mr Trump was "tentative, serious and perhaps fearful".
"If you look at the seating position - their lower legs, they are both in the male, alpha position saying 'I am a man'," Ms Woods told MailOnline. However, she adds that Mr Obama's legs are much further apart, suggesting "I'm still on top".
It was Mr Trump's hands that caught Ms Wood's attention - he put them in a "downward prayer position".
"My read is that he has learned something he didn't know before. It's a tentative hand position."
Hillary Clinton pictured walking her dog
Martin Shkreli makes good on Wu-Tang Clan promise
Martin Shkreli, the pharmaceutical executive who enraged America by buying an Aids drug and hiking the price by 5,000 per cent, has released music from the only known copy of a Wu-Tang Clan album he owns exclusively - to celebrate Trump's victory, Harriet Alexander writes.
On October 27 the businessman, who faces a fraud trial in July, announced he would release the music if Trump won.
He bought the only-known copy of the album for $2 million.
And after the election, he appeared on the livestream platforms Periscope and Hitbox and said: “I will be releasing this music over a long period of time. But let me play a little bit of it now.”
Sipping from a Coca-Cola can, he grinned and bopped his head a few times as he played the introduction of the album, “The Wu — Once Upon a Time in Shaolin.”
He said he was still deciding how to play other portions of the music.
“I’ve got to decide how to put out — there’s about 30, 35 tracks.
“I actually have a contract with the Wu-Tang Clan where I’m not allowed to do this. Obviously, I own the music and I bought it and I paid a lot of money for it. In many ways, the contract shouldn’t matter that much.
New Yorkers vent Trump anger on subway Post-it notes
New York commuters are venting anger and frustration over Donald Trump's shock victory by indulging in collective therapy - writing messages on Post-it notes and sticking them on a subway wall.
"Am I the only one who is scared?" "I need a hug" and "I am angry" number among the thousands of messages written on multicolored squares of paper fixed to a tiled wall in a tunnel at Union Square station.
By Thursday afternoon, it boasted some 3,000 notes, an astonishing production in just 24 hours since New York artist Matthew Chavez parked himself there with a table and a sign advertising free "subway therapy."
He got the idea earlier this year of setting himself up in the subway from time to time offering stressed-out New Yorkers opportunities to let off steam by writing little notes.
Mexico President Pena Nieto optimistic about US relationship
Mexican President Enrique Pena Nieto has said he was optimistic Mexico could come up with a new, positive bilateral relationship with the United States after the election of Donald Trump as president.
"I have real optimism that we will be able to build a new working agenda in the bilateral relationship that would be positive," Pena Nieto told a conference. "It will also benefit the societies of both countries."
Pena Nieto said on Wednesday that he and Trump have agreed to meet, possibly during the transition period before his inauguration on Jan. 20.
Nigel Farage to be Donald Trump's go-between amid claims Special Relationship with US is faltering
Government ministers will use Nigel Farage as an unofficial intermediary to build bridges with Donald Trump following accusations that the “special relationship” is faltering in the wake of his election.
The Telegraph understands that ministers will be forced to seek Mr Farage’s advice because they have no links to the President-elect’s inner circle.
Nigel Farage and Donald TrumpCredit:
Getty
Mrs May spoke to Mr Trump for the first time since his victory – but not until after he had spoken to the leaders of at least nine other nations.
Downing Street said that during the call, Mr Trump said that the UK is a “very, very special place for me and for our country” and suggested that he wants their relationship to be similar to the one enjoyed by Margaret Thatcher and Ronald Reagan.
But the delay in talking to the President-elect led to accusations that the Government had undermined its relationship with Washington by failing to anticipate Mr Trump's success. |
New Features:
Memory intrinics: To enable memory intrinics two changes are required:
- Produce the memory op codes by changing the compiler
- Expose the appropriate APIs through playeglobal.swc to leverage these opcodes |
Q:
Maven layout: How to be sure that src/main does not depend on src/test?
This must be quite elementary, but I'm fairly new to Maven and I didn't find this info.
I have the typical mavenized Java project (I use Eclipse), with a main artifact (src/main/java -> mylib.jar ) and the additional classes in src/test/java (not only unit tests, but also miscellanous code, samples, etc, that I don't want to include in the main jar).
My question is: how I can be sure that there are no circular dependencies inside the classes-artifacts of my project? Specifically, how can be sure that inadvertently some class of main is depending on some test\? I'm concerned about the possibility of releasing a broken mylib.arj. Eclipse knows about dependency among projects, but here we have only one project. Is there some standard way?
A:
Maven won't actually let you do this. Everything in the src/test directory structure is not on the class path when maven tries to execute the compile goal.
For instance, let's say I accidentally add the following code to my HelloWorld program:
public void badDependency() {
new HelloWorld_UT();
}
Where HelloWorld_UT is just a standard junit test.
Even though eclipse will report no compile errors in my project, when I try to do a maven compile, I get this error:
[INFO] ------------------------------------------------------------------------
[INFO] BUILD FAILURE
[INFO] ------------------------------------------------------------------------
[INFO] Total time: 1.297s
[INFO] Finished at: Sat May 10 23:08:29 CDT 2014
[INFO] Final Memory: 7M/17M
[INFO] ------------------------------------------------------------------------
[ERROR] Failed to execute goal org.apache.maven.plugins:maven-compiler-plugin:3.1:compile (default-compile) on project scratch: Compilation failure
[ERROR] /C:/eclipse/workspace/Scratch/src/main/java/org/drc/HelloWorld.java:[11,21] C:\eclipse\workspace\Scratch\src\main\java\org\drc\HelloWorld.java:11: cannot find symbol
[ERROR] symbol : class HelloWorld_UT
[ERROR] location: class org.drc.HelloWorld
|
Ex situ NMR in highly homogeneous fields: 1H spectroscopy.
Portable single-sided nuclear magnetic resonance (NMR) magnets used for nondestructive studies of large samples are believed to generate inherently inhomogeneous magnetic fields. We demonstrated experimentally that the field of an open magnet can be shimmed to high homogeneity in a large volume external to the sensor. This technique allowed us to measure localized high-resolution proton spectra outside a portable open magnet with a spectral resolution of 0.25 part per million. The generation of these experimental conditions also simplifies the implementation of such powerful methodologies as multidimensional NMR spectroscopy and imaging. |
/*
* Copyright (c) 2004-2005 The Trustees of Indiana University and Indiana
* University Research and Technology
* Corporation. All rights reserved.
* Copyright (c) 2004-2005 The University of Tennessee and The University
* of Tennessee Research Foundation. All rights
* reserved.
* Copyright (c) 2004-2005 High Performance Computing Center Stuttgart,
* University of Stuttgart. All rights reserved.
* Copyright (c) 2004-2005 The Regents of the University of California.
* All rights reserved.
* Copyright (c) 2008 Cisco Systems, Inc. All rights reserved.
* Copyright (c) 2008-2018 University of Houston. All rights reserved.
* Copyright (c) 2018 Research Organization for Information Science
* and Technology (RIST). All rights reserved.
* $COPYRIGHT$
*
* Additional copyrights may follow
*
* $HEADER$
*/
/**
* @file
*
* MCA fs base framework public interface functions.
*/
#ifndef MCA_FS_BASE_H
#define MCA_FS_BASE_H
#include "ompi_config.h"
#include "mpi.h"
#include "opal/mca/base/base.h"
#include "ompi/mca/common/ompio/common_ompio.h"
#include "ompi/mca/fs/fs.h"
BEGIN_C_DECLS
OMPI_DECLSPEC int mca_fs_base_file_select(struct ompio_file_t *file,
mca_base_component_t *preferred);
OMPI_DECLSPEC int mca_fs_base_file_unselect(struct ompio_file_t *file);
OMPI_DECLSPEC int mca_fs_base_find_available(bool enable_progress_threads,
bool enable_mpi_threads);
OMPI_DECLSPEC int mca_fs_base_init_file (struct ompio_file_t *file);
OMPI_DECLSPEC int mca_fs_base_get_param (struct ompio_file_t *file, int keyval);
OMPI_DECLSPEC void mca_fs_base_get_parent_dir (char *filename, char **dirnamep);
OMPI_DECLSPEC int mca_fs_base_get_fstype(char *fname);
OMPI_DECLSPEC int mca_fs_base_get_mpi_err(int errno_val);
OMPI_DECLSPEC int mca_fs_base_get_file_perm(ompio_file_t *fh);
OMPI_DECLSPEC int mca_fs_base_get_file_amode(int rank, int access_mode);
OMPI_DECLSPEC int mca_fs_base_file_delete (char* file_name, struct opal_info_t *info);
OMPI_DECLSPEC int mca_fs_base_file_sync (ompio_file_t *fh);
OMPI_DECLSPEC int mca_fs_base_file_get_size (ompio_file_t *fh, OMPI_MPI_OFFSET_TYPE *size);
OMPI_DECLSPEC int mca_fs_base_file_set_size (ompio_file_t *fh, OMPI_MPI_OFFSET_TYPE size);
OMPI_DECLSPEC int mca_fs_base_file_close (ompio_file_t *fh);
/*
* Globals
*/
OMPI_DECLSPEC extern mca_base_framework_t ompi_fs_base_framework;
END_C_DECLS
#endif /* MCA_BASE_FS_H */
|
Yesterday we put out a call for the viciously panned script of I Hope They Serve Beer In Hell, the upcoming film written by I-totally-fucked-that-chick blogger Tucker Max. We immediately received about a dozen copies of the script, which is apparently being forwarded around Hollywood like a list of bad lawyer jokes. I also could have said "like herpes," and I could also follow up by joking that the script is about as funny as a bad lawyer with herpes, haha. Friends, it opens with Tucker Max fucking a deaf girl and screaming "DON'T TAZE ME, BRO!." It is that bad. After the jump, three of the most terrible moments from the film's first half. Jesus, bro:
1. The Dramatic Opening Scene:
2. Bar Scene One: Tucker Max Has A Way With Women And Dudes Better Not Give Him Any Shit Bro:
3. Bar Scene Two: Tucker Max Can Steal Your Sorostitute You Dumb Frat Boy So Watch Out Bro:
If we have the stomach, we'll bring you more lowlights soon bro! |
According to BuzzFeed News, on February 1 Chinese state television broadcaster CGTN America registered as a foreign agent in the United States, to comply with the Foreign Agent Registration Act (FARA). CGTN America director-general Jing Ma remained upbeat, claiming the registration was not a reflection on the editorial professionalism of staff, but it is bad news for China’s soft power efforts. Registration directly links CGTN America to propaganda messaging of the Chinese state, thereby weakening public diplomacy objectives of building trust and credibility.
Unfortunately, this setback is part of a pattern of failure in Chinese media capacity building since the turn of the 21st century. In 2002, China designated “culture” as an industry and named it as integral to the “going out” policy of internationalization, with the aim of increasing Chinese soft power. Through media content that countered U.S.-Anglo cultural hegemony and anti-China news narratives, it was hoped that the soft power dividends would support China’s geopolitical and economic interests. According to David Shambaugh at George Washington University, China spends $10 billion a year on efforts to improve soft power, but thus far, the track record of the Chinese film and television industries has been abysmal. CGTN breaks no international news, not helped by the fact that content must be sanctioned by Beijing. With regards to cinema, ticket sales of domestically popular Chinese films were limp elsewhere in 2018, with films such as Operation Red Sea, Detective Chinatown 2, and Dying to Survive barely leaving an imprint on box offices of international markets. Chinese media is — generally speaking — considered neither attractive nor influential to non-Chinese.
But there is one continent where China’s international push for media influence is making inroads, with the help of a state affiliated but privately-held pay television company. StarTimes, with content focused on sport and entertainment, is partnering with African state broadcasters and other organisations to provide both new channels and digital satellite infrastructure. Its influence is only likely to increase, as research predicts that this company will be the biggest beneficiary of the pay TV market subscription growth in the coming years in Africa. Digital TV Research claims StarTimes subscribers, currently at around 7.75 million, will have jumped to 14.85 million by 2024.
StarTimes, founded in 1988 in Beijing, is both a beneficiary of economic diplomacy and a creator of unprecedented access for African television consumers. Despite being private, it is funded to the tune of hundreds of millions of dollars by Chinese state banks as part of the Forum on China-Africa Cooperation (FOCAC) agreements. It is contracted by Beijing to implement Africa’s ITU digital switchover process and provide new channels for African television, a sector characterized by poor resources in finances, staff training, and technology.
Aside from digital migration, to widen access, StarTimes money has been carving out the new subscriber landscape. The company traverses vast but previously disregarded territories in within countries such as Uganda, Zambia, Guinea, Botswana, Ghana, Senegal, and the Democratic Republic of Congo for an operation called the 10,000 Villages Project. This provides digital satellite television to rural regions of sub-Saharan Africa, venturing into parts of the continent left unserved by former colonial powers Britain and France. These populations were also not a priority for Cold War rivals the United States and the Soviet Union and were not a lucrative enough customer base during TV de-regulation and marketization in the 1990s, which delivered pay television to urban African elites. But now, in regions with deficient electricity, StarTimes partners with solar energy companies such as Azuri Technologies and Mobisol in nations including Nigeria, Tanzania, Rwanda, and Kenya, offering low-cost subscriptions and hardware installation packages. DStv, owned by MultiChoice which is part of South Africa’s Naspers, targets the most affluent viewers, offering the English Premier League and UEFA Champions League, but StarTimes is step-by-step making incursions at the cheaper end, providing the Europa League, Bundesliga, and last year’s FIFA World Cup.
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As a result of this economic diplomacy, China benefits in numerous ways. Local officials act as “borrowed boats,” praising China profusely when the 10,000 Villages Project reaches their region. This is a soft power drive that potentially delivers China intelligence gathering penetration deeper than any other foreign country. Additionally, it is snapping up broadcasting rights deals, which might reap intellectual property rewards in the future. It sponsors national leagues in Ghana, Uganda, and Senegal, thereby creating leagues that it can broadcast on its newly created channels.
But this economic and soft power push has not been without controversy. While it curries favor by sponsoring sports writer associations, among those not drinking the Kool Aid is Gregory Chifire, a Zambian anti-corruption critic. He is particularly concerned about TopStar Communications, a partnership that hands StarTimes 60 percent of Zambia’s state-owned broadcaster, ZNBC, for 25 years. Chifire blasts the deal as “one of the biggest financial scandals in modern-day Zambia.” Meanwhile, the Guardian newspaper quotes the Ghana Independent Broadcasters Association (GIBA) as warning that “If StarTimes is allowed to control Ghana’s digital transmission infrastructure and the satellite space … Ghana would have virtually submitted its broadcast space to Chinese control and content.”
In addition, as with other areas of China’s media internationalization, StarTimes has not met expectations. It was hoping for 20 million subscribers by 2019. Chief Executive Officer Justin Zhang was replaced on February 1 by David Zhang.
But others admire StarTimes’ contribution to change. A partnership with charity SOS Villages helps boost the company’s credibility, while production companies utilize StarTimes’ resources for local language programming, encouraging Africans to take up subscriptions.
Since it is undoubtedly a state proxy for Beijing, this aiding of African broadcasting is a win for Chinese soft power. China would be better off continuing to deploy more non-state actors, another example being Alibaba Pictures, the Chinese backers of award season smash Green Book. While CGTN America’s state-owned status is a turn off, private content partnerships and collaborations are a model of soft power that any average American could warm to – and that people across Africa are already embracing.
Angela Lewis is a Ph.D. candidate in the International Communications department of Nottingham University in Ningbo, China. |
est to -0.1? (a) w (b) 0.3 (c) p
a
Let y be 1/(5/2) + 45/(-50). Which is the closest to 0? (a) y (b) 1.7 (c) -6 (d) -0.3
d
Let u = -0.15 - 5.85. Which is the closest to u? (a) -0.5 (b) 3/7 (c) -4
c
Let t(f) = 32*f + 900. Let d be t(-28). What is the nearest to -0.8 in -7, -1/2, 1, d?
-1/2
Let u = 11.02 - 11. Let s = u - -0.48. Let v = 11 + -11.3. What is the nearest to v in -2/9, -3/4, s?
-2/9
Let r be 3/(-4) + 540/400. What is the nearest to -13 in -1, r, 1?
-1
Let g = -6.9 + -0.1. Let d = 4 - g. Let s = -8.07 - -7.77. Which is the nearest to 0? (a) 3/4 (b) d (c) s
c
Let s = -1271 + 1265. What is the closest to 1 in 0.5, s, -5, -4?
0.5
Suppose -3*d + 9 = -3. Suppose 3*h = -3*p - p + 34, 58 = 5*p - d*h. Suppose 11*y - p = 6*y. Which is the nearest to -0.1? (a) y (b) -0.3 (c) -0.1
c
Let q = 223 + -222.7. Which is the closest to -11? (a) -5 (b) -3/2 (c) q
a
Let v = 3.9 + -5.8. Let f = -1.8 - v. What is the nearest to -0.1 in 0.4, 3/4, f?
f
Let w(x) = -x - 5. Let v be w(-6). Let r = -1 + 1.04. Let m = -12.8 - -12.3. Which is the closest to v? (a) m (b) 0.4 (c) r
b
Suppose -t + 6 = -2*h, -2*h - t + 4*t = 6. Let v = h - -7. Suppose w + 5 = -4*x, 4*x - 6 - 4 = 2*w. What is the closest to 0.1 in v, x, -4?
x
Let g = -529 + 530. Which is the nearest to -1/3? (a) -1/3 (b) 0.2 (c) -4 (d) g
a
Let m = 15 + -15.4. Which is the closest to -16? (a) 3 (b) m (c) 1/6
b
Suppose 5*l - 100 = 7*a - 12*a, 3*a + 5*l - 70 = 0. Let c be (20/12)/(a/6). What is the closest to 0 in 22, 2, c?
c
Suppose -2*q - 2 = -t, 5*q + 0 + 5 = -t. Let u = 1381 + -1380.8. Which is the nearest to q? (a) 0.5 (b) 0.4 (c) u
c
Let k = 217/5 + -43. Let x = 0.15 + 0.85. Which is the closest to x? (a) 5 (b) k (c) 2
b
Let m = 5.97 + -5.77. Let a = 2 + -1.95. What is the closest to m in 1/7, a, -2?
1/7
Let w = -15 - -14.3. Let c = 0.677 + 2.323. What is the closest to c in w, -0.4, -0.3?
-0.3
Let k be ((-12)/(-168))/((-2)/(-4)). Let h = -45 - -44.8. Let y = -0.1 + 0.5. Which is the nearest to k? (a) 2/9 (b) y (c) h
a
Let j = 1.21 + 0.79. Which is the closest to -1.2? (a) -0.5 (b) j (c) -5
a
Let x be 476/77 + -6 + (-16)/44. What is the closest to 10 in -5, x, 0.1, 6?
6
Let h = 431 - 431.5. What is the closest to -1/16 in 0, h, -2/15, -3?
0
Let m(f) = -f**3 - 5*f**2 + 4*f + 2. Let h be m(-5). Let y be 3/h*(-2 - 1). Let t = -2.4 + 2. Which is the closest to y? (a) 4/7 (b) -4 (c) t
a
Let j = 5 + -10. Let v = -85 - -83. Let g = -0.36 - 0.14. What is the closest to 0.1 in g, j, v?
g
Let d be -152 - ((-6)/(-18))/(1/6). Let c = d + 154. What is the nearest to c in 4, 2/3, 19?
2/3
Let t = -2 + -8.5. Let f = -10 - t. What is the nearest to 1 in f, 3, -2?
f
Let h = -10/9 - -49/36. Let m = 1.1 - 0.4. Let j = 1.7 - m. Which is the closest to j? (a) h (b) -1/3 (c) -1/5
a
Suppose 0 = -i + s + 4, 0 = -3*i - 3*s - 2*s - 20. Suppose -4*j - 19 = 3*g + 13, -2*g + 5*j + 17 = i. Which is the nearest to -0.04? (a) -3 (b) g (c) 0.2
c
Let m = -0.39 - 0.41. Let j = m - -0.86. Let i = 0.1 - 0.1. Which is the nearest to i? (a) j (b) 1 (c) 3
a
Let n(m) = m**2 + 27*m + 106. Let x be n(-22). What is the closest to -2/5 in -2, 0.4, x, -1?
-1
Let n be 16/(-6) - (-2)/3. Suppose -6*r = 581 + 679. Let z be 1/(-2) + r/(-340). What is the nearest to n in z, 0.2, -2/7?
-2/7
Let p = -66.8 + 32.6. Let l = 29 + p. Let y = 1.2 + l. What is the closest to y in -0.4, -4, 4?
-4
Let g be ((-4)/(-20)*5)/3. Suppose -2*s + 13 = 3*s - 3*r, 2*r = -2*s + 2. Let v be 3 - (0 + s/2). What is the nearest to g in -2, -5, v?
v
Let o = -32360853/5 + 6438385. Let y = o + 33650. Let u = 136 + y. What is the nearest to -2/7 in 1/2, u, -5?
u
Let h be (-3)/4*(-2 - (-76)/30). Let w = h - -9/10. Which is the closest to w? (a) -0.5 (b) -8 (c) 5
a
Let u = 1.4 + -1.5. Let g = 13 + -12.92. Let j = g + -0.48. What is the nearest to -1 in u, -7, j?
j
Let q = -156/5 - -327/10. Which is the nearest to -0.1? (a) -0.5 (b) -0.16 (c) 1/8 (d) q
b
Let b = -278.9 - -279. What is the nearest to b in -3, -0.018, -0.5?
-0.018
Let p = 0.1 - 0.9. Let h = 1.4 + p. Let r = 0.9 - h. Which is the closest to -3/2? (a) 0.2 (b) 4/7 (c) r
a
Let v be -5 - -4 - (2 + (-15)/10). Which is the closest to 4? (a) 1 (b) v (c) -0.4 (d) -2
a
Let v = 0.938 - -1.062. Let o = 0.1 - -0.1. What is the nearest to o in v, -2, 4/7?
4/7
Suppose 4*n = -5*k - 17, n + 8 = -0*k - 2*k. Let t = -9 - -9.4. What is the closest to t in 2/5, -0.5, k?
2/5
Let s = 2.034 - -2.936. Which is the closest to -0.1? (a) s (b) 1/2 (c) -4
b
Let y = -60 - -57. Let l = -6.3 + -0.7. Which is the nearest to 1? (a) l (b) y (c) -2/5
c
Let n = 14 - 13.96. Let y = -13.96 - n. Let p = 18 + y. Which is the closest to 0? (a) p (b) 0.4 (c) 3
b
Let m = 0 + 0.2. Let r = -17 + 16.65. Let l = r - 0.05. Which is the closest to 0? (a) -5 (b) m (c) l
b
Let f = -65 - -108. Let s = 42.9 - f. Which is the closest to s? (a) 8/3 (b) -1/4 (c) 1
b
Let h = 54.183 + -0.183. What is the closest to 1 in 5, 2, h?
2
Let r = 0.044 + -0.544. Which is the nearest to 0.02? (a) -3 (b) -3/5 (c) r (d) 4
c
Let m = 1 + -7. Let l = 12 + m. What is the nearest to -2 in l, -0.1, 3/2?
-0.1
Suppose -46*h + 63*h = -68. Which is the closest to -4? (a) 6 (b) h (c) 5
b
Let r = 23131/25 - 925. Let n = -11/25 + r. Let s = 8.89 + 0.11. Which is the nearest to 1? (a) s (b) 0 (c) n
b
Let z = 3 - 5. Let c(t) be the third derivative of -5*t**4/24 + 35*t**3/6 + 14*t**2. Let m be c(8). What is the nearest to z in -1, 0, m?
-1
Let x = 0.498 + -0.53. Let h = x - 1.968. Which is the nearest to -2/7? (a) -5 (b) 1 (c) h
b
Let w = -0.186 + 0.386. Which is the closest to w? (a) 1/6 (b) 1.2 (c) -0.5
a
Let w = 946 - 939. Let l = -0.05 - -7.05. Let z = l - w. Which is the closest to z? (a) 4 (b) -1/3 (c) -1/4
c
Let f be (-10)/(-8)*320/12. Let a = 33 - f. Let i = -5 + 5.4. What is the nearest to -0.1 in a, -2/19, i?
-2/19
Let m = -5 - -2. Let n be 1*(-10)/25 - 4/(-35). What is the nearest to 1 in n, 7, m?
n
Let s = -0.04 + 0.02. Let m = 0.12 + s. Let l = 0.91 + 4.09. Which is the closest to -1? (a) m (b) l (c) -3
a
Let x = -433 + 427. What is the nearest to 1 in -0.01, x, -0.2, -3?
-0.01
Let v be -3 - ((-130)/42 - 0). Let u = -3/32 - 37/288. Which is the closest to 1? (a) -9 (b) v (c) u
b
Let k be (1/27)/(1/6). Suppose 9 = -2*q - 5*d, 5*d + 24 = 2*q + q. Suppose h - q = -2. What is the closest to h in 0.2, -0.2, k?
k
Let x be 6 - 0 - 10*(-6)/(-12). Which is the nearest to -2/3? (a) x (b) 4 (c) 3
a
Suppose -3*t - 4*u - 19 = 21, -3*t = -4*u + 8. Let z = t - -12. Let k = -0.4 + -0.1. What is the nearest to 0.1 in 1, z, k?
k
Let g = -99.5 + 99. What is the closest to 1/70 in -2/5, g, -0.2?
-0.2
Let x(a) = 12*a - 639. Let p be x(53). What is the closest to 11 in -5, 1, p?
1
Let y = -6 + 4. Let o = 1.84 - -1.16. What is the closest to o in -4, y, -2/7?
-2/7
Let i = -25 + 24.96. Let b = 11 + -11.24. Let c = i - b. What is the nearest to -1 in -0.3, c, 1?
-0.3
Let z = 11 - 16. Let j = -1.71 + -1.29. Which is the nearest to -0.1? (a) j (b) z (c) 4
a
Let f = 28 + -32. Let y be f - 1*(-4 + 5 + 0). Which is the nearest to 0? (a) 7 (b) 4 (c) y
b
Let f = -50.9 - -51. Which is the closest to f? (a) -1/3 (b) 5 (c) -11
a
Let k be (-5 - -3)*2/14. Let o = 547.8 - 548. What is the closest to o in 3, k, 1/4?
k
Let w = -3.04 - -3. Let u = w + -0.06. Let v = 89/21 - 25/7. What is the nearest to u in v, -1, -0.3?
-0.3
Let g = -0.24 + -4.76. Which is the nearest to -0.01? (a) 0.3 (b) g (c) 0.03
c
Let i = -6.946 - 0.054. What is the nearest to 3 in -2/3, i, -0.3?
-0.3
Let f(n) = -n**3 - 4*n**2 - n + 2. Let i = -8 - -4. Let w be f(i). Let k = -0.204 + -0.096. What is the nearest to w in k, 4, 0?
4
Let n be (4/(-60))/((-1)/(-2)). Let y be 12/(-20) + 8/10. Which is the nearest to y? (a) n (b) 1/3 (c) -5
b
Let q = 0.3 + 4.7. Let g = 4941 - 4946. What is the closest to 1 in g, -9, q?
q
Let m = 0.036 - -0.363. Let v = 1.291 + m. Let q = 0.31 + v. What is the closest to q in -1, 1, -2/7?
1
Let q = -4.5 + 4.3. Let m = 1.8 - 1.3. Let c = m - 3.5. What is the nearest to 1 in c, q, -1/2?
q
Suppose -l = 2*q - 32, -q - 25 - 112 = -4*l. What is the nearest to 0 in l, 2, 3/2?
3/2
Let c = 5.52 + -5.52. What is th |
Members of the Massachusetts' all-Democratic congressional delegation are urging the federal Department of Commerce to immediately begin the process of allocating $75 million in fishery disaster funding.
The funding was included in a government spending bill that passed in January.
In the letter to Commerce Secretary Penny Pritzker, U.S. Sens. Elizabeth Warren and Edward Markey and six U.S. House members argue that the impact of the fishing crisis on Massachusetts fishermen accounts for 90 percent of the economic disaster in the Northeast region.
They also argue the money should be distributed directly to the state so it can be more efficiently delivered to fishermen, an approach suggested by Gov. Deval Patrick.
In January 2014, a federal law passed providing $75 million in disaster assistance to struggling fishermen and fishing-related businesses. |
New York Gov. Andrew Cuomo Andrew CuomoNew York City bus driver knocked out by passenger he told to wear a mask 44 percent of high earners have considered leaving New York City: poll Media's anti-Trump coronavirus spin has real consequences MORE (D) said Wednesday morning that there's still no evidence that Tuesday's terror attack in lower Manhattan was part of a wider network or plan of attacks.
In an interview with "CBS This Morning," Cuomo said that "there's no evidence now" that the suspect in the truck attack that killed eight people "was part of a larger conspiracy [or a] larger plot."
"The investigation is ongoing," Cuomo said, "[but] the best evidence we have is that he was, quote-unquote a 'lone wolf' model. They're going through social media to see what connections he may have had. There are very few interactions with law enforcement; he was a truck driver."
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Eight people were killed and several others were injured when a rented Home Depot truck ran off the road onto a pedestrian bike path in lower Manhattan Tuesday.
Cuomo said that the suspect, 29-year-old truck driver Sayfullo Saipov, had a previous interaction with local police in New York state when they helped him get his truck out of a ditch, but had a clean record other than minor traffic violations.
Saipov was shot by police and taken to a nearby hospital after exiting the vehicle with "imitation firearms," according to multiple news reports.
"He had some vehicular violations, state police actually helped him get his truck out of a ditch at one time," Cuomo said. "But there's no evidence now that it was part of a larger conspiracy, larger plot."
Cuomo called Tuesday's attack an "evolution" of the tactics known to be used by the Islamic State in Iraq and Syria and other radical Islamist terror organizations.
"This is the evolution of the jihad tactics. It's no longer geographically isolated — the internet has given them a global platform," Cuomo added. "They have a very simple play: Rent a car, rent a truck, create mayhem. And try to disrupt society. And that's what yesterday was." |
A fire extinguisher is an apparatus for extinguishing fire utilizing cooling effect or oxygen cut-off effect of fire extinguishing agents.
Fire extinguisher is classified by its extinguishing capacity into a heavy duty extinguisher with an extinguishing capacity of 10 or 20 units or more, or a small extinguisher with an extinguishing capacity of one unit or more, but lower than that of a heavy duty extinguisher. A small extinguisher is often employed at households, work places, offices, etc. due to its convenience in carriage and transport.
A fire extinguisher can also be classified by the type of extinguishing agents filled in the main body thereof, into an acid-alkali extinguisher, an enforcement liquid extinguisher, a halogen extinguisher, a carbon dioxide extinguisher, or a powder extinguisher, and the like. Since fire extinguishing agents are in general of high price, fire extinguisher using extinguishing agents other than powder extinguisher are employed normally only at specific sites.
A fire extinguisher can further be classified by the type of pressure it employs, into a pressure extinguisher or a accumulate pressure extinguisher.
A pressure extinguisher, being a conventional technology, comprises a pressure gas container (also called, a “cartridge”) in the main body thereof where fire extinguishing agent is filled, as the container aims to press the extinguishing agent for injection. When a user presses two levers of the fire extinguisher until they are closely accessed to each other while the safety pin has been removed, the pressure gas container is opened, and the gas is released to press the extinguishing agent in the main body so that the extinguishing gas is injected out of the fire extinguisher.
However, a drawback of such pressure extinguisher is that its structure is complicated, because it requires a separate pressure gas container within the main body thereof, inclusive of a gas pipe for transmission of the pressure gas as well as an injection tube for the extinguishing agent.
Form this background, use of accumulate pressure extinguishers has been increased recently. For convenience of explanation, a fire extinguisher refers in the following description to a small powder fire extinguisher using accumulate pressure, if not mentioned otherwise.
An accumulate pressure type conventional fire extinguisher is consisted of a main body 110 with extinguishing agent and pressure gas filled in it, a head 120 installed at one end of the main body 110, two levers 122 fixed at the head 120, an extinguishing hose 130, one end of which is connected to the inside of the main body 110 while the other end is extended from the main body 110 to be exposed outward, and a nozzle fixed at one end of the extinguishing hose 130, as illustrated in FIG. 1.
At the two levers, a safety pin 124 is installed to prevent unintended access of the levers 122 to each other. Further, the head 120 is equipped with a pressure gauge 150 which indicates the pressure of the pressure gas consisted of nitrogen or carbon dioxide. The pressure gauge is one functioning mechanically with its indicator changing mechanically in accordance with the pressure changes inside of the main body 110.
In case fire occurs, a user removes the safety pin 124, presses the two levers firmly so that they are closely accessed, whereupon the extinguishing agent filled in the main body 110 is injected through the extinguishing hose 130 out of the nozzle 132, triggered by the pressure difference between high pressure in the tightly sealed main body 110 and low pressure atmosphere outside thereof.
However, since the main body of such conventional fire extinguisher is made of metal, it does not allow a user to confirm with naked eyes whether the extinguishing agent filled in is of prescribed quantity.
Another important factor for faultless functioning of such fire extinguisher is that the extinguishing agent filled in remain intact. In other words, the fire extinguisher fails to function when the extinguishing agent is hardened, even if the agent filled in is of sufficient quantity. A further problem with the conventional fire extinguisher is that it does not allow a user to confirm with his eyes whether the extinguishing agent filled in the main body thereof is in an intact state, i.e. not hardened.
Still another problem of the conventional fire extinguisher is that the pressure gauge installed at the lever part thereof to indicate the internal pressure of the main body is designed to function mechanically with a relatively high rate of malfunction, resulting in occasions when the fire extinguisher fails to function even if the inner pressure indicated by the gauge is normal. In addition, since such pressure gauge is exposed outward, it can easily be damaged by external force during carriage or transport. |
Tag: Emilia Romagna
Garganelli Pasta with Romagna Shallots and Guanciale Pasta with Romagna shallots is a traditional dish in Emilia-Romagna, where delicious Romagna shallots are cultivated. It’s easy to make and of course you can use other types of shallots too! Garganelli con scalogno di Romagna...
Garganelli pasta alla Zingara with bell peppers, mushrooms and cream. Pasta alla zingara is a creamy North Italian recipe full of colourful fresh ingredients cooked in different stages and them combined with garganelli pasta to create a mouthwatering and beautiful dish. (scroll down for recipe)...
Summer Tagliolini Pasta Recipe with marinated vegetables. This light summer tagliolini pasta recipe from a restaurant in Bologna is so tasty, fresh and healthy. It’s also has a no-cook sauce, meaning all you have to cook is the pasta. Tagliolini Estivi. I first came across this recipe in a...
Classic Lasagne al forno with Bolognese. Le lasagne alla bolognese Lasagne al forno with bolognese sauce is probably one of the best known and most popular Italian pasta dishes, alongside its cousin tagliatelle bolognese. Nowadays, there are many different kinds of baked lasagne recipes...
Baked Passatelli with Pancetta & Pine nuts. Passatelli con pancetta, pinoli e rucola. Passatelli are fresh pasta made with breadcrumbs, grana or Parmesan cheese, eggs and lemon or nutmeg. Traditionally, they were invented as a way to make soup more filling and to use stale bread leftovers...
Passatelli: an unusual type of pasta! Although I have lived in Italy for 14 years, I only discovered passatelli last year. Probably because they’re not typical in many parts of Italy. Although you can find them in Marche and Lazio, they are considered to be essentially Romagnolo... |
Poly(ethylene terephthalate) (“2GT”) and poly(butylene terephthalate) (“4GT”), generally referred to as “polyalkylene terephthalates”, are common commercial polyesters. Polyalkylene terephthalates have excellent physical and chemical properties, in particular chemical, heat and light stability, high melting points and high strength. As a result they have been widely used for resins, films and fibers.
Poly(trimethylene terephthalate) (“3GT”) has achieved growing commercial interest as a fiber because of the recent developments in lower cost routes to 1,3-propane diol (PDO), one of the polymer backbone monomer components. 3GT has long been desirable in fiber form for its disperse dyeability at atmospheric pressure, low bending modulus, elastic recovery and resilience.
Spinning and drawing the 3GT filament may be carried out continuously in a single combined operation. The yarn produced by such a process may be referred to as spin-draw yarn (SDY). However the yarn so produced has a tendency to shrink on the tube on which it is wound, causing a heavy bulge in the yarn package, or even crushing the tube. This problem is more severe when larger packages of yarn are made, such as packages containing more than about 4 kg of yarn, and when the spinning speed is greater than about 3500 m/min. As a result of tube crushing, the yarn packages are stuck on the spindles on the winder, and can not be readily removed. In some embodiments, e.g., in some multifilament yarns, the yarn has an IV from about 0.7 to about 1.1.
Several solutions have been proposed. For example, when winding a small package, the shrinkage force can be reduced, because much fewer yarn layers are wound on the tube. However, packaging with small packages becomes uneconomical. The use of a thicker and stronger tube creates an unacceptably heavy package even when the package size is small, and is inadequate in strength when the package size is large.
It is also well known that the use of a slow spinning speed in a spin-draw process minimizes this problem, and improves the bulge or windup tube crushing. When a low spinning speed is applied, the low speed allows a high overfeed between the draw roll and windup in a two godet process, or a high overfeed between the second and third godet in a three godet process. Together with the large overfeed, the low speed allows more time to relax the filaments during spinning. However, the low spinning speed results in low productivity and the process becomes uneconomical.
Japanese Kokai JP 9339502 discloses a spin-draw process for 3GT in which the extruded fiber is wound on a first roller at 300-3500 m/min. and 30-60° C., stretched to 1.3 to 4 times its length through a second roller at 100-160° C., and then wound and cooled on a third roller. However, this technology could not make packages with a weight of more than 2 kg, as pointed out in subsequent patent JP 99302919.
U.S. Pat. No. 6,284,370 discloses a spin-draw process for 3GT so as to obtain a cheese-like package. The molten multifilament enters a holdup zone at 30-200° C. to solidify the filaments. It then passes the first godet which is heated at 30-80° C. at a speed of 300-3500 m/min, is drawn at a draw ratio of 1.3-4 to a second godet at 100-160° C., before being wound into a package at a slower winding speed. The winding tension is preferably between 0.05 and 0.4 gram/denier. In two examples (Examples 11 and 12), the filaments are cooled on a third godet. Neither example shows a high spinning speed in combination with a suitable third godet overfeed. Package sizes ranged from 1 to 5 kg.
Japanese Kokai JP 99302919, by co-applicants to U.S. Pat. No. 6,284,370, discloses a similar process. After the molten 3GT multifilament is extruded and solidified as before, it passes the first godet which is heated at 40-70° C. at a speed of 300-3000 m/min, is drawn at a draw ratio of 1.5-3 to a second godet at 120-160° C., and is cooled down before being wound into a package at a slower winding speed. This final cooling was done by cooling on a third godet (Example 1), or by applying cold water (Example 3). The second and third godets were run at the same speed, i.e., with no third godet overfeed. The winding tension, although important, was not disclosed. Package sizes were up to 6 kg.
The above processes are limited in package size and winding speed. There is a need for a spin-draw process which enables spinning 3GT fibers at a speed of 4000 m/min or more at the second godet into a cheese-like package containing over 6 kg of fiber. |
There is so much I can say about this.
Of course there is, scientists have even invented a word for everything that comes out of your blog: retarded.
I can go on and on about how “Reverse racism” and “heterophobia” and “cisphobia” are laughable concepts,
No you can’t. All of the above are defined as discriminating someone on the basis of their x. The only way you can’t discriminate against someone on the basis of their x is if they don’t have the x that you’re talking about.
That means the only way you can’t discriminate against white people on the basis of them being white is if they’re not white. This is the stupidity your logic amounts to.
that the lack of institutionalized power immediately makes such power dynamics impossible.
Your “racism equals prejudice plus power” argument is based on the preconceived notion that everybody part of said group has institutional power and everybody of said other group does not. This is a fundamentally flawed view of the world for the fact that we do not live in a social caste, which is the only place where this ideology is remotely applicable.
Obama has the most institutional power in the United States at the moment. And guess what, he’s black. How does your argument uphold here? This is the second biggest fallacy in your argument - the sole existence of black people in positions of institutionalized power.
Your number one biggest fallacy is assuming that because somebody is white, straight, or cis, they somehow have institutionalized power. Somehow my vote counts for more than a gay, transgender, black person’s vote. Somehow I’ve had a position in political office my entire life without knowing about it. Somehow Obama has less institutional power than me because he’s black.
So to close this part off, let’s give a name to what generalizing based on race is called: racism.
I can go on and on about how the anger of the oppressed is inherently incomparable to the violence of the oppressor.
Same fallacies as your above argument. Somehow every single straight person treats gay people in a cruel and unjust way their entire life - even the ones campaigning for gay rights. Every single white person hates black people - including the ones still alive that marched to end segregation half a century ago.
But let me say this as loud as I can: It doesn’t MATTER, for example, if “Heterophobia” won’t end Homophobia. You want to know why? It’s not my job to make straight people stop hating me.
Well it’s not my job to make gay people stop hating me either. That means I can hate them for as much as I want until they stop hating me!
This is what we call circular logic:
I have to hate straight people. Why? Because they hate me.
Why do straight people hate me? Because I hate them.
You’re right in that it’s not your job to make others like you - but only because you’re making it your job for others to hate you.
I can not reach into some heteroweenie’s brain and make them see me as a person worthy of their respect by being nice to them. I don’t have mind control powers.
So the way you gain respect - by being seen as a worthy person - is actually mind control. Nice.
And it’s not my fault is straight people continue to be homophobic little shits because I didn’t lick their boots shiny enough.
I’m just gonna leave you with this:
Victim mentality is an acquired (learned) personality trait in which a person tends to regard him or herself as a victim of the negative actions of others, and to think, speak and act as if that were the case — even in the absence of clear evidence.
https://en.wikipedia.org/wiki/Victim_mentality
It might be a nice, introspective read into your psyche. |
Credit rating agencies (short presentation)
President
The next item is the report by Mr Klinz, on behalf of the Committee on Economic and Monetary Affairs, on credit rating agencies: future perspectives.
Wolf Klinz
Madam President, ladies and gentlemen, credit rating agencies certainly did not cause the global financial crisis, but, in my opinion, they were responsible to a significant extent for its severity. When the so-called structured financial products were developed in America on the basis of the subprime mortgages, the credit rating agencies supported this process by rating dozens, if not hundreds, of products each day in an almost conveyor-belt fashion. In so doing, they also accepted conflicts of interests, in that they supported the issuers with advice and help in designing these products.
They continued to claim that they were only expressing an opinion, although they knew very well that their ratings were, in fact, being used as a seal of approval. My report deals with numerous deficiencies and puts forward proposals in the hope that the Commission will perhaps be able to include some of them in its legislative proposal that it will be tabling in the autumn.
I put forward five proposals. The first is that the reliance on ratings must be reduced. In practice, we have found that the regulatory environment has led to the use of ratings being absolutely essential, by banks, insurance companies, pension funds etc. which invest their money. Basel II made this very clear and, in fact, the credit rating agencies have become regulatory certification bodies.
We need to make it possible once again for market operators, particularly institutional investors, which possess their own expertise to actually take responsibility themselves and not outsource the responsibility for investment decisions. It needs to be made clear that investors should only invest if they actually understand the product and cannot use the excuse that they can, to a certain extent, automatically make a triple A product the goal of their investment strategy.
Secondly, we must ensure that the information on which credit rating agencies base their decisions is made publicly available, that it is understood, and that the models used are also known. That will lead to transparency and will also make it easier for institutional investors seeking to invest to make their own decisions. It will also help to enable unsolicited ratings to be given. In this connection, we should also consider whether the proposal that the United States is considering is a sensible one, namely, that where only one credit rating agency is chosen by issuers, a second, independent body could be encouraged to give a rating and this second body could be allowed to work on the basis of the information that is publicly available.
Thirdly, we need more competition. We have a de facto oligopoly. The three credit rating agencies that exist and operate worldwide control 95% of the global business. They have a so-called monopoly income of 40% return on turnover, and therefore I am proposing that we set up a European credit rating agency. It should be based on a foundation model and the start-up financing should be provided by the finance sector by means of interest-bearing loans. After five years, we will know whether it is working and then this credit rating foundation will also have to pay back the funds that it has received.
However, I am sure that there are also other options. It would also make sense to perhaps allow national and regional credit rating agencies to operate in the form of a European network.
Fourthly, we still have an outstanding matter with regard to the payment model. Currently, we have an issuer-pays model. That is the model that essentially works throughout the world. Thus, the issuer pays, but clearly there is a conflict of interests here that we could reduce if there was no more advising of issuers and if the staff of the supervisory bodies was genuinely independent. Other possible models include a subscriber-pays model. Here, there is obviously the risk of conflicts of interest as well as of this being an invitation to freeloaders. Therefore, this needs consideration. The third option would be a performance-based payment, in other words, an up-front payment and then the final payment only once it is clear how good the rating is.
The last, but important, point is that we must introduce liability. Credit rating agencies must accept responsibility for what they actually do, and therefore I believe that we should make them liable, obviously not for the rating as such, but for failures and negligence in their work.
Elena Băsescu
(RO) Mr President, the credit rating industry has numerous shortcomings, the most important of which are the lack of competition and transparency, as well as the oligopolistic structures. Competition would be enhanced by creating a regulatory environment which will promote market entry. This would carry out an in-depth analysis of the current obstacles. I should emphasis how important it is to monitor the progress of the Basel III system and the process relating to Chapter 4 of the Capital Requirements Directive. There is a need to increase accountability and the powers for monitoring the internal models and imposing preventive measures. All rating agencies must abide by the highest standards relating to the publication of information, transparency and management of conflicts of interest.
At the moment, Romania's rating has a stable outlook. This could improve if the pace of structural reforms and the stability of the financial sector are maintained.
Georgios Papanikolaou
(EL) Mr President, the credit rating agencies lost their credibility a long time ago. Our rapporteur is absolutely right on that point. They upgrade and downgrade almost everything: countries, banks, municipalities, even public corporations, absolutely everything, but their ratings are based, for the most part, on undisclosed, unpublished and, hence, non-transparent information.
The issue of the lack of transparency and, hence, of the credibility of the data used by credit rating agencies raises an important question: is it fair, is it logical, is it morally correct for ratings that affect the economy and upset the lives of millions of our fellow citizens overnight to be non-transparent and possibly unreliable? Obviously it is not.
Jaroslav Paška
(SK) Mr President, in the wake of the financial meltdown, the credit rating agencies, which assess financial product safety, were criticised for their unprofessional and self-serving ratings of financial products.
Doubts arose over the fairness and professionalism of their evaluations after the transparency of their operating mechanisms was found to be wanting, and it is therefore time we looked for ways to improve the system for the constant assessment and rating of financial products.
In this light, I consider the report submitted by the rapporteur to be very important, and I think that the processes he has outlined will enable us to modify the apparatus used to assess financial products so that the conclusions that are offered, either by rating agencies or by other mechanisms, will result in more objective ratings of financial products.
Ilda Figueiredo
(PT) Mr President, experience has clearly shown that credit rating agencies are not credible and that their activities continue to be detrimental to certain countries, whether to their economies or to their sovereign debt. Today, this is particularly affecting countries that have relatively weak economies. That is why the intervention of credit rating agencies, which continue to be extremely harmful despite having lost all of their credibility, must be properly controlled. This control should not be limited to transparency rules, but should go further and exert complete control over the international financial system, while also putting an end to tax havens, properly regulating the financial sector with taxes on the movement of speculative capital, and preventing financial capital from continuing to ...
(The President cut off the speaker)
Nikolaos Salavrakos
(EL) Mr President, I absolutely agree with the rapporteur on all five points of his proposals on so-called rating agencies and the exaggerated impact which they have on the global economy and on the European economy. These firms cannot, at the same time, engage in commercial activities which are similar or relate to their supervisory or rating role.
We are calling for controls on reports by these agencies, for certain basic principles to be adopted, and for liability for compensation to be introduced for losses caused to states which were poorly evaluated or misleadingly evaluated. I also propose that basic accounting principles be introduced and applied in all the Member States of the European Union, so as to highlight the value, the official valuation of the property of these states, so that we have assets and liabilities and these states cannot be left prey to the whims of rating agencies and the parties they represent.
Viviane Reding
Vice-President of the Commission. - Mr President, Commissioner Barnier is currently in the United States meeting with his counterparts and he has asked me to convey to you the following statement in reply to Wolf Klinz's own-initiative report on rating agencies, which was adopted by the Committee on Economic and Monetary Affairs in March.
The Commissioner agrees that shortcomings in the working methods of credit rating agencies are widely recognised today as having contributed to the financial crisis. In order to address these concerns, and in accordance with G20 commitments, the EU reacted very quickly by adopting - already in 2009 - a regulation on credit rating agencies. This introduces strict requirements with which agencies must comply in order to eliminate potential conflicts of interest and to improve the quality of rating and methodologies as well as the transparency of the ratings.
As a second step, following the establishment of the three new European financial supervisory agencies, the regulation of credit rating agencies will be strengthened by the introduction of centralised supervision by the European Supervisory Markets Authority. The amending regulation became effective on 1 June 2011. We will pay very close attention to the correct application of this legislation.
Nowadays, the European regulatory framework is a model for other jurisdictions. However, the developments in the European markets following the sovereign debt crisis in spring 2010 make it clear that further review and strengthening is required. For this reason, the Commission undertook in June 2010 to analyse the topics in depth. A public consultation was carried out, the Commission services have evaluated the responses and are working on an impact assessment with a view to issuing legislative proposals in the course of this year. In this context, the Commission will examine measures to reduce excessive dependence on external ratings, improve transparency, promote competition, introduce the principle of liability and reduce the risk of potential conflicts of interest due to the issuer-pays payment model.
We know that these are very complex issues and we want to be sure that we address them correctly. In this context, we have looked with great interest at Mr Klinz's own-initiative report which covers the topics we are currently reviewing and makes a very big contribution to our legislative initiative.
Last but not least, at a global level, in October 2010, the Financial Stability Board issued a number of principles aimed at reducing the dependency of financial institutions on credit ratings. In accordance with these principles we intend to introduce measures against excessive dependence on ratings in our forthcoming legislative proposal for the banking sector, the so-called CRD4.
President
The debate is closed.
The vote will take place on Tuesday, 7 June at 12:00.
Written statements (Rule 149)
George Sabin Cutaş
Prior to the Lehman Brothers investment bank going bankrupt, it was given the highest rating by the main credit rating agencies. They also thought that Iceland's three biggest commercial banks were sound a few days before they collapsed. In addition, the downgrading of Greece's rating has not taken into account the launch of its economic recovery programme. The economic and financial crisis has highlighted credit rating agencies' oligopolistic structure, as well as their lack of competition, transparency and accountability. In a world dominated by three such institutions, greater diversity is needed, along with a new way of working. I therefore support the notion of creating a public European credit rating agency as an alternative to the private institutions of this kind. It would become compulsory to obtain a rating from the European agency, which would supplement the ratings offered by the traditional agencies, thereby boosting competition for the fairest rating.
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NASA
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SpaceX
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NASA TV
NASA has tried Bigelow's expandable habitat on its International Space Station, and the agency likes it. Installed now for more than a year on the station, the Bigelow Expandable Activity Module has passed key structural tests, and engineers now believe it will be capable of surviving in low Earth orbit for a longer period of time.
So this week, NASA announced that it intends to extend the lifetime of the station's new, expandable room. Initially, the module was to be attached to the station for two years, but NASA says it wants to extend the lifetime for three years from now, with two additional one-year options. The Bigelow habitat, therefore, could remain on-station well into the early 2020s.
For now, at least, the module won't exactly have a glamorous purpose on-station. NASA will use the additional space to store up to 130 "cargo transfer bags," bags of various sizes first used for storage in space shuttle mid-deck lockers and later used to transfer cargo to the space station. One of the real problems on the orbiting laboratory is excess stuff, such as these bags, that clutter up workspaces. Now astronauts will be able to stow dozens of them in the expandable module.
Over the longer term, it will benefit Bigelow Aerospace to have the module on-station for several more years. Not only can the Nevada-based company collect more data about the attachment's performance in microgravity, it can continue to demonstrate to NASA the viability of expandable habitats for longer-duration spaceflight.
Bigelow is part of a competition among a number of aerospace firms to develop a new in-space habitat for NASA, which the space agency may ultimately assemble in an orbit around the Moon as a base for deep-space exploration. Whereas a lot of the other concepts are theoretical, Bigelow has the advantage of a working prototype now serving NASA's needs.
Listing image by NASA |
Thursday, 26 June 2014
At a certain point in the next few months the recession in Britain will
officially be over as the real level of GDP will finally exceed its previous
peak in the 1st quarter of 2008. The media coverage will be generally
very favourable, in the hope that this will boost the Tory vote and vindicate
the austerity policy. In reality it will do neither. The economy was already
recovering modestly when the Coalition took office and the austerity policy
reversed that upturn. This is the weakest and most drawn out recovery since the
19th century.
Nor is the hoped-for political impact likely to materialise. One reason why
the Tory vote in opinion polls has hit a ceiling fractionally above 30 per cent
is precisely because of austerity. The policy is designed to transfer incomes
from labour and the poor to capital and the rich. At the same time, the
austerity policy of cutting state investment undermines any robust or
sustainable recovery. The economy overall continues to stagnate and only a
fraction of society feels any benefit from the recovery. During this ‘recovery’
most people’s living standards continue to decline. The political impact is that
the Tory Party can shore up its core vote, but not add to it.
It is important to be clear about the task that will face an incoming Labour
government. Labour will inherit a crisis, not a recovery. While the economy will
soon recover its pre-2008 level, this represents 6 years of lost output. Living
standards should have been rising, but they have not because of economic
stagnation. Instead, living standards for the overwhelming majority have fallen
as a direct result of austerity policies. A continuation of austerity policies
after 2015 would produce the same result of economic stagnation and falling
living standards for the majority.
Chart 1 below shows the medium-term trend growth for the British economy, and
its current performance. The economy is approximately 16% below its previous
trend level of growth. There is no evidence to suggest that this gap between
previous and actual growth rates will close in the foreseeable future.
Chart 1. Trend and Actual GDP Growth
This means the poverty created during the slump will become a semi-permanent
feature of the British economy. An incoming Labour government would need a
radically different policy in order to achieve a very different outcome. It
would need to address the cause of the crisis.
The fall in investment remains the main brake on recovery, led by the decline
in private sector investment. On current estimates, GDP in the 1st
quarter of 2014 was still £10bn below its peak level in the 1st
quarter of 2008, but investment (Gross Fixed Capital Formation, GFCF) remains
£50bn below its level at the same time. The slump in investment more than
accounts for the current stagnation. The private sector has been unwilling to
lead investment higher, so government policy must lead the way.
How to pay for investment?
Since Britain was not a high-investment economy even before the current
crisis, £50bn a year in additional investment over the lifetime of the next
Parliament is the minimum that would be required to resume trend growth.
Replacing lost output and investment would require a further £320bn to avoid the
loss incurred in the recession becoming permanent.
These are enormous sums, approaching the level of the bank bailout in 2009.
There is no appetite for borrowing on this scale, even though there is clearly a
case for some increased government borrowing to fund productive investment,
especially when government interest rates remain close to zero in real terms.
Therefore, the bulk of the funds must come from another source. If it were
really the case that ‘there is no money left’ then that would be the end of the
matter. But it has already been noted that sometime in the near future the
economy will recover its pre-crisis peak. Logically, this means there will soon
be more money, more resources available than was the case before the recession,
not less.
There is money left, it is simply not being invested. There is a yawning gap
which has emerged between the level of investment (GFCF) and the level of
profits. In 1990 the level of uninvested profits was £73bn. In 2013 it was
£307bn. Even if we take profits after the effects of taxes and subsidies, the
level of uninvested profits has risen from £5bn to £97bn in 2013. This is
because taxes on production have been cut repeatedly over the period. The trend
in uninvested profits is shown in Chart 2 below.
Chart 2. Profits & Investment, 1990 to 2013
What levers for a radical, reforming government?
Since the fall in investment accounts for the continued stagnation of the
economy and corporate profits are not being invested at an increasing rate, it
follows that any serious discussion on reversing the slump must be focused on
the mechanisms for directing those profits towards productive investment.
The key areas for that investment remain home building, infrastrucure,
energy, transport and education.
In passing, it should be noted that the uninvested profits themselves have
number of different destinations, all of them with negative consequences. The
main destinations for uninvested profits include increased executive pay and
returns to shareholders in the form of dividend payments and share buybacks,
which have all reached record levels. In addition, there is a growing cash
mountain held in the bank accounts of British non-financial companies. It
remains unused by them (and most is held in accounts yielding little or no
interest). But it is used by the banks partly to fund increased speculation in
financial assets, including housing, international stock markets and
commodities, including foodstuffs.
Levers for investment
I . Using the banks One unintended consequence of the financial crash
of 2008 to 2009 was to increase the role of the state in the economy, even, or
especially in countries where governments were committed to laissez fare
policies. In Britain a very large section of the banking industry remains in
public ownership in the form of RBS and Lloyds banks, through the body UKFI. At
the same time all banks operating here are subect to licensing, authorisation,
regulation and capital requirements from the Bank of England and other public
bodies.
Prior to deregulation and Thatcherism, the Bank of England used to engage in
‘credit direction’. This was largely done informally, but in some detail so that
banks would be instructed not only as to the amount of credit they should
provide to the economy, but to which sectors and in which proportions[i]. The formal
powers and associated bodies now are far greater and renewed credit direction
actually runs with the grain of current regulation, which favours lending to
governments as far safer than lending to corporations.[ii]
The government has a wide array of measures it can use to instruct the banks
to provide credit for productive investment. The government could create special
vehicles in order to channel that credit, or use existing ones (see below).
Where bank executives prove reluctant to follow those instructions, the summary
dismissals of Fred Goodwin from RBS and Bob Diamond from Barclays demonstrate
the public sector’s power over the banks, if it chooses to exercise it.
II . Transforming existing schemes In the post-World War II period all
economic recoveries have been led by government spending. In that sense, this
recovery is no exception. The crucial difference is the content of that
government intervention, which has increased current spending, but slashed
public investment. It has supplemented this with a series of subsidies for
investment to the private sector.
These schemes include, funding for lending, help to buy, guaranteed profits
for the builders of nuclear power stations and innumerable other schemes. One
part of the nuclear guarantee alone may cost government £17.6bn[iii].
Without incurring any additional costs, a reforming government could simply
reverse the priorities highlighted by these policies. For example, it could
transform the Help to Buy Scheme which boosts house prices but not home
building. Instead, it could offer the same £40bn in government guarantees to
local authorities to build homes, at no extra cost but from which there would be
an additional public sector revenue in the form both of income taxes from
newly-employed builders and rental income from public sector tenants, as well as
building desperately needed new homes.
The same logic applies to the whole panoply of government schemes. So, the
nuclear subsidy should be scrapped and the same subsidy provided to generate
renewable energy in which the state has a controlling revenue share.
III. Cutting waste All cash-strapped governments project huge savings
from cutting waste which often remain unrealised. This is frequently because the
biggest, most wasteful areas of expenditure are sacrosanct and not to be
touched.
In Britain one of the biggest areas of wasteful spending is on the Private
Finance Initiative and the generalised outsourcing of contracting and supplies by
the public sector. Even George Osborne began as a critic of PFI waste and promised
to replace it. Instead, in grasping how dependent private sector profits are
on this subsidy from taxpayers, the Coalition has maintained PFI and expanded
it. In the current and next Financial Year the level of private sector capital
spending under the PFI amounts to just £3.3bn, which is only a portion of the
total capital cost. Yet the private sector will be receiving £20bn in ongoing
current payments over the same two-year period[iv].
This is a colossal waste, amounting to a direct subsidy to the private sector
that the public sector could and has done more cheaply. New PFI could be ended,
all existing contracts scrutinised for their potential to be rescinded and a new
enforcement body established to apply the highest possible service conditions,
again with the threat of cancelling contracts.
IV . Cutting Trident and defence spending £100bn could be saved by a
decision not to renew the Trident missile system[v]. Clearly,
nuclear weapons of mass destruction cannot possibly provide any economic
benefit. Trident is not even an independent system, so could only be used under
US authorisation and then in all likelihood only as part of a global nuclear
conflagration which would have Britain as a prime target.
The notion of Britain ‘punching above its weight’ received an historic
reversal with the decision not to bomb Syria. Yet British defence spending
remains way above European countries, which have perfectly adequate defence.
Cutting British defence spending to their average would release nearly £20bn for
alternative purposes.
V. Taxation Government priorities were clear when increasing VAT but
cutting corporate taxes, costing the same amount. This was a direct transfer
from the poor to capital. Similarly, cutting the 50p tax rate while imposing
austerity on the majority was a clear example of the logic of austerity.
Less widely remarked, the government also removed tax incentives for genuine
investment while cutting the corporate tax rate. The effect was a higher rate of
tax for those that do invest, and a lower one for those who do not, including
the banks. All of this was done in the name of stimulating investment, which has
not materialised. This is because private investment is driven by the
rate of profit. Keeping a larger post-tax share of dwindling profits will
not drive up private investment.
These priorities could be reversed at no cost, and no loss of investment. The
tax system could be used to improve living standards and boost genuine
productive investment while at the same time penalising those firms who refuse
to invest but have high dividends, executive pay or share buybacks. Higher taxes
on unearned income, speculation and capital gains could be combined with tax
breaks for investment and lower taxes on the poor.
VI. Removing private sector subsidies A large number of private sector
firms receive government subsidies for running monopoly services that can, and
have been performed more efficiently in the public sector. These include, but is
not confined to areas such as the railways, utilities such as water, energy, and
even NHS procurement and provision.
A consequence of privatising natural monopolies is that the private firms
maximise revenues simply by raising prices and cutting costs by reducing the
quality of the service. At the same time, successive governments have created a
system where public funds are used to subsidise the private sector firms.
Removing these subsidies (guaranteed income, inflation-plus price rises, direct
grants, and so on) would save both government and service users enormous sums.
The most well-known example is the privatised rail franchises, where the
process of renationalising the franchises could be accelerated by a stricter
insistence on the terms of the franchise contracts in terms of service,
investment, fares, and so on. But a creeping privatisation has been under way
for the NHS under successive governments. In 2011/12 the private sector obtained
£8.7bn from the NHS for providing services, £8.3bn in secondary care[vi] and £2.8bn
in drugs and other procurement for a total of just under £20bn. Detailed data is
difficult to obtain, but the level of the private sector take of NHS spending
will have risen dramatically under this government[vii].
VII. Renationalisation There are clear benefits in renationalising the
privatised companies in terms of the government’s ability to direct investment.
Higher levels of investment in turn lead to better services, lower costs and
increased or better paid jobs for the workforce.
But there is also a fiscal and strategic economic benefit to
renationalisation that meets the objection that a cash-strapped government must
have other priorities for its limited resources. The real position is that
renationalisation increases government resources and allows them to be directed
to boost the economy.
This can be illustrated with the example of Royal Mail. Royal Mail pays a
dividend to its private shareholders from the profits it generates and the
dividend yield is 3.8% (for every £100 shares owned, the shareholder receives
£3.80 each year). This will rise each year if the company grows. But the
borrowing cost to the British government when it issues new debt to be repaid in
10 years’ time is currently 2.7%. Buying the entire shares of Royal Mail
(renationalisation) would cost the government less in interest than it would be
able to receive in dividends from the company itself. It would generate
additional resources, which could be used to reduce the deficit, or better
still, to increase investment on which there is an even greater return.
The same logic applies to the privatised energy and utility companies, whose
dividend yields are all even greater than Royal Mail’s. There is also a
strategic imperative. The energy companies have been creaming off profits since
they were privatised, and not invested in either additional energy capacity or
in renewables and carbon-reduction. Spare energy network capacity was
approximately 25% when they were privatised and different estimates now put it
at between 4% and 8%. In response to Ed Miliband’s promise of a temporary price
freeze, they threatened an all-out investment strike, that they would ‘turn the
lights out’. This may happen anyway in the near future, given the decline in
network capacity.
This is not a situation any government should allow. Ed Miliband has
committed the next Labour government to decarbonising the economy by 2030. Given
the resistance of the energy companies to even a modest price freeze, and their
complete unwillingness to invest on the scale necessary to meet energy
requirements, renationalisation is the only realistic option. Given the huge
dividend payments currently made to private shareholders (5.2% for Centrica,
5.3% for SSE) there would be a very large benefit to government finances from
their renationalisation.
VIII. Living standards The focus on living standards is the correct
one, and led to Labour rising sharply in the polls. Given that living standards
for the majority continue to decline, it remains the right theme to focus on.
The simplest way to restore living standards for those in work is to raise
the national minimum wage to the level of the living wage, and to strictly
enforce it. While boosting the living standards of millions of people, the
single biggest beneficiary would be government itself, since the bulk of those
in receipt of social security and other government payments are in work, not
unemployed. This highlights a general truth, that the interests of a radical
reforming government are aligned with those of workers and the poor.
The main objection is that firms find paying the living wage unaffordable.
But we have already noted the huge level of uninvested profits, executive pay
and returns to shareholders. These can be cut to make it affordable. Where there
are genuine cases of small, shoestring firms operating at the margin, there
could be some transitional arrangements to help preserve employment. But these
would only be temporary measures, and would still oblige all firms to pay the
living wage. Otherwise, the effect is to allow inefficient and
super-exploitative firms to compete with efficient firms that pay decent wages,
embedding the ‘race to the bottom’ in the economy.
IX . Equality A similarly robust policy should be adopted in pursuit
of genuine equality. The most scandalous treatment of women has been a hallmark
of the austerity drive, with the pay gap widening, reduced employment, greater
burdens of childcare and other household burdens, reduced public services, and
so on.
Without any cost to government it could strictly enforce equal pay provisions
for all firms. Again, government itself would be the largest single beneficiary
of this. There is too a recognition that investing in universal childcare
provides a wider economic benefit, which naturally has a positive fiscal impact.
But a similar approach should also apply to the issues of all social care and
reduced public services, where the burden of removing them has fallen mainly on
women. The public sector is more efficient provider of these services. If the
economy is being boosted by a large-scale investment programme, preventing women
from taking their equal place in the workforce on equal terms is a brake on the
optimal development of the whole of society and the economy.
A similar approach should inform policies in relation to the equality of
black people and ethnic minorities in the economy and wider society. Black youth
are living in a different country to their contemporaries, suffering Greek-style
levels of unemployment. Combatting unequal pay, and inequality in terms of
access to jobs, housing and education need to be central to an economic
programme that attempts to utilise all the talents of its citizens. In that
light, the perpetual campaign against immigration is wholly counter-productive.
The strong growth produced by an investment-based recovery will both attract and
require additional immigration to Britain. The alternative is to create a slum
which attracts no-one.
The discriminations based on sexual orientation and on disability need to be
confronted. Basic human rights are being denied causing untold misery and the
whole of society and the economy is poorer as a result.
Conclusion
The 9 points above are not designed to address every possible aspect of the
economic and social crisis that will confront a Labour government, and are far
from an exhaustive prescription. Instead, they are designed to highlight some of
the key steps a radical, reforming government could take to address the scale of
the economic crisis that will confront it.
Individually, none of the measures is very radical. All governments used to
engage in ‘credit direction’ before the 1970s, windfall taxes were imposed by
John Major and the postal system was nationalised by Gladstone. They only seem
very radical because the political spectrum has shifted so far in the direction
of those who caused the current crisis.
Taken together, these measures would allow the state to lead an
investment-based recovery using the main levers that are currently available to
it in Britain. That would be a major reform of the British economy and of
society. A more enduring transformation would require other levers and a
different alignment of social forces to be pulling on them.
Friday, 6 June 2014
The now notorious UKIP poster which suggested the entire population of the EU
might come to Britain for work is designed to whip up racism. But it contains
two fallacies that are unfortunately shared by many people who are not racists,
and are therefore worth rebutting.
Myth 1
The first myth is that Britain is a uniquely attractive place within Europe
in terms of pay or workers’ rights, or social security entitlements. The graphic
below was produced by the UNITE union in Ireland in their argument for higher
pay. But it is such a good graphic it is worth reproducing as it stands.
Compensation includes both pay and social wages such as pensions and other
benefits. The data is in Purchasing Power Parity terms, so that they account for
price differentials between European countries. The data is drawn from Eurostat
database here.
The compensation for British workers is among the lowest in Western Europe.
Britain is not a uniquely attractive destination for economic migration within
the EU. Therefore it should come as no surprise that Britain has one of the
lower levels of immigration of the Western European economies.
Another graphic, this time from the
Huffington Post, illustrates this point very neatly. It shows the level of
immigration (the total stock of migrants) as a proportion of the total
population. (The data source is also
Eurostat).
Graphic 2. Immigrants as a proportion of total population, %
Although there are a series of cultural, historical and legal factors which
are important, in general the higher the level of workers’ compensation, the
higher the level of immigration. Britain is nearer the bottom on both measures.
Myth 2
The second myth is that immigrants ‘take’ jobs or drive down wages. If that
were true, then the introduction of the single market in the EU and with it the
provision for the freedom of movement of labour would have led to a convergence
of both unemployment and pay rates across the EU.
But we have already noted that the highest pay is in many of those countries
with the highest levels of immigration. The same can be said of unemployment
too. Immigrants have neither increased unemployment nor driven down pay in those
countries. In fact, there has been a divergence
in rates of pay in the EU over a prolonged period despite increased mobility
of labour.
The argument about immigrants ‘taking jobs’ or driving down pay has strong
echoes of (male-dominated) labour
movement opposition to women’s entry into the workforce. Exactly the same
arguments were used. From an economic perspective the country of origin or the
gender of the worker is immaterial. What is relevant is the skills and
adaptability of the workforce as a whole.
This is because there is not a fixed ‘lump of labour’
in the economy, which immigrants, or women (or young workers) detract from. If
there was a fixed amount of available labour no economy would ever be able to
grow, even via the birthrate. Instead, economic activity grows and prosperity
increases with what Adam Smith identified as the division of labour and what
Marxists understand as the socialisation of production.
In the fastest-growing economies of the word, such as China and India,
workers frequently migrate internally over vastly greater distances than is
required in a move from one small corner of Western Europe to another. Sometimes
too, the cultural and even language barriers are also greater.
This migration is a key factor in the growth of all economies. It is
primarily responsible for the somewhat better performance of the US economy
compared to the EU over a prolonged period. The absence of immigration also
partly accounts
for Japan’s long-term stagnation.
This is because the movement of labour is a necessary counterpart to the
increase in the division of labour, or the socialisation of production. It
increases both the size and the capacity of the whole economy. This in turn
means that effects of the division of labour are magnified. As a result,
immigrants increase jobs as whole. In Britain, 14% of
new jobs are created by immigrants (approximately double their proportion of
the population).
Consequently, any restrictions on the freedom of movement of labour within
Europe will not create jobs but destroy them. They will not underpin pay, but
will serve to drive it down. Labour MP Frank Field, who is strongly
anti-immigration and in favour of restricting free movement of labour within the
EU is explicit on this matter. If migrants are stopped from entering Britain to
work, those
on benefits can be forced to do the work instead. His anti-immigration
agenda has nothing to do with protecting workers rights or pay. It is an agenda
which supports the interests of capital, not those of labour.
There are some who mistakenly believe there is a genuine left-wing case for
curbing immigration. But this is completely wrong. Immigration is a function of
increasing prosperity and tends to reinforce it. The only effective way to
reduce immigration in Britain is to lower living standards, reduce real pay and
increase poverty. It is Britain’s relative decline in living standards which
explains which it has lower immigration than most of Western Europe. There is no
genuine left-wing case for reducing immigration.
The alternative is a policy aimed at increasing prosperity which is
necessarily accompanied by increased immigration. Prosperity and immigration
versus poverty with immigration curbs. That is the real policy choice. |
Q:
Modify user-agent WP8
In my windows phone 8 app, I call to external APIs developed by client may be in PHP.
They told us that the user agent is showing NativeHost.
They want it to be Windows Phone so that they could better track the windows phone requests.
A:
Try setting the HttpWebRequest.UserAgent property.
|
#!/usr/bin/python
# -*- coding: utf-8 -*-
# Copyright: (c) 2017, Ansible Project
# GNU General Public License v3.0+ (see COPYING or https://www.gnu.org/licenses/gpl-3.0.txt)
# This is a virtual module that is entirely implemented as an action plugin and runs on the controller
from __future__ import absolute_import, division, print_function
__metaclass__ = type
DOCUMENTATION = r'''
---
module: fetch
short_description: Fetch files from remote nodes
description:
- This module works like M(ansible.builtin.copy), but in reverse.
- It is used for fetching files from remote machines and storing them locally in a file tree, organized by hostname.
- Files that already exist at I(dest) will be overwritten if they are different than the I(src).
- This module is also supported for Windows targets.
version_added: '0.2'
options:
src:
description:
- The file on the remote system to fetch.
- This I(must) be a file, not a directory.
- Recursive fetching may be supported in a later release.
required: yes
dest:
description:
- A directory to save the file into.
- For example, if the I(dest) directory is C(/backup) a I(src) file named C(/etc/profile) on host
C(host.example.com), would be saved into C(/backup/host.example.com/etc/profile).
The host name is based on the inventory name.
required: yes
fail_on_missing:
version_added: '1.1'
description:
- When set to C(yes), the task will fail if the remote file cannot be read for any reason.
- Prior to Ansible 2.5, setting this would only fail if the source file was missing.
- The default was changed to C(yes) in Ansible 2.5.
type: bool
default: yes
validate_checksum:
version_added: '1.4'
description:
- Verify that the source and destination checksums match after the files are fetched.
type: bool
default: yes
flat:
version_added: '1.2'
description:
- Allows you to override the default behavior of appending hostname/path/to/file to the destination.
- If C(dest) ends with '/', it will use the basename of the source file, similar to the copy module.
- This can be useful if working with a single host, or if retrieving files that are uniquely named per host.
- If using multiple hosts with the same filename, the file will be overwritten for each host.
type: bool
default: no
notes:
- When running fetch with C(become), the M(ansible.builtin.slurp) module will also be
used to fetch the contents of the file for determining the remote
checksum. This effectively doubles the transfer size, and
depending on the file size can consume all available memory on the
remote or local hosts causing a C(MemoryError). Due to this it is
advisable to run this module without C(become) whenever possible.
- Prior to Ansible 2.5 this module would not fail if reading the remote
file was impossible unless C(fail_on_missing) was set.
- In Ansible 2.5 or later, playbook authors are encouraged to use
C(fail_when) or C(ignore_errors) to get this ability. They may
also explicitly set C(fail_on_missing) to C(no) to get the
non-failing behaviour.
- This module is also supported for Windows targets.
seealso:
- module: ansible.builtin.copy
- module: ansible.builtin.slurp
author:
- Ansible Core Team
- Michael DeHaan
'''
EXAMPLES = r'''
- name: Store file into /tmp/fetched/host.example.com/tmp/somefile
fetch:
src: /tmp/somefile
dest: /tmp/fetched
- name: Specifying a path directly
fetch:
src: /tmp/somefile
dest: /tmp/prefix-{{ inventory_hostname }}
flat: yes
- name: Specifying a destination path
fetch:
src: /tmp/uniquefile
dest: /tmp/special/
flat: yes
- name: Storing in a path relative to the playbook
fetch:
src: /tmp/uniquefile
dest: special/prefix-{{ inventory_hostname }}
flat: yes
'''
|
The goal of this project is to utilize engineered forms of the enzyme cytochrome c peroxidase to demonstrate the feasibility of rational protein design towards the accomplishment of oxidative catalysis of specific organic reactions. The discovery that the active site Trp- 191 in the oxidized "ES" state of CCP is reversibly oxidized to a stable cation free radical has prompted an interest in exploiting the chemistry inherent at this site for the possible binding and/or oxidation of organic molecules. To this end, construction of the W191G mutant, in which the active site tryptophan was replaced with glycine, was recently reported, and the feasibility of small molecule binding to this site was clearly demonstrated. Part I of this proposal involves the systematic determination of the factors that control substrate specificity and binding within the cavity. Part II of this proposal involves an investigation of the oxidative chemistry of organic substrates, such as the aminothiazole anti-thyroid drugs, that are known to react with heme enzymes. Part III of this proposed study utilizes the information gleaned from Parts I and II of this proposal, and focuses on the feasibility of utilizing the W191G cavity mutant for the purposes of catalyzing general oxidation of organic substrates from within the cavity. |
Q:
Linear Programming, with slack variables
I'm trying to prove the following statement
Show that the set ${\{(x,w) \in \mathbb R^n\times \mathbb R^m \mid Ax \leq0, c^T x >0,w^TA=c, w\geq0 \}}$ is empty, where $A\in \mathbb R^{m\times n}$ and $ c \in \mathbb R^n$ are given.
A:
Suppose that it is non-empty and let $(x,w) \in \Bbb R^n \times \Bbb R^m$ satisfy the property. Then (where for a vector $v$, $(v)_i$ denotes the $i$-th component):
$$w^T A x= \sum_{i=1}^m (Ax)_i (w)_i$$
but $(Ax)_i \ge 0$ and $(w)_i \le 0$ for all $i$, so $w^TAx \le 0$.
On the other hand, $w^T Ax = cx > 0$.
|
January 31, 2009
Still, the American era in Iraq is nowhere near a final act. If this were an opera, it would be just past midway in the libretto. While both sides are disconnecting, neither can let go entirely.
The Iraqis need the Americans not just to dampen terrorist activities within the country but to protect them from rapacious neighbors. Syria and Iran have interfered here since the invasion, and while the Iraqis are often uncomfortable with how the American have reined in these powers, they are reluctant to stop them because they fear their neighbors more.
When American forces pursued insurgents over the Iraqi border into Syria in late October, it was an international incident. Iraq was embarrassed in front of the Arab world. Such incidents are likely to recur and could become much more fraught.
For the United States, Iraq remains a strategic prize close to the Middle East flash points of Israel, Lebanon and Syria as well as Iran and the oil-rich Persian Gulf countries. It is not by chance that the Central Intelligence Agency has its largest station in the world in Baghdad.
I think one of the major unanswered questions facing the U.S. in Iraq is whether the country is ultimately willing to tolerate a "South Korea" like encampment of U.S. forces for years and perhaps decades to come.
January 30, 2009
Michael Yon suggests that, despite 30 years of evidence to the contrary, what the Mullahs of Iran really want to do is commit mass suicide:
And when Iran has the capacity to launch rockets over to Europe or the United States, one can count on it happening. If they can manage to hatch nuclear weapons, we could see Israeli cities annihilated, leaving Israelis with little choice other than to respond with nuclear weapons, which could leave millions dead....If you want to see World War III unfold, just sit quietly about Iran. Iran could be the opening chapter of an apocalyptic era.
One should not discount the possibility that if Iran does acquire a nuclear weapon (and it's still an "if" at this point, as Stephen Walt explains here) the world will be dramatically less secure. We could very well have an arms race in the Gulf and a stepped up campaign of conventional terrorism by Hezbollah and Hamas against U.S., Israeli and Arab targets.
But the notion that Iran will, out of the blue, launch rockets at the U.S. or Europe or, worse, launch a nuclear-tipped rocket into Israel strains credulity.
As I've written earlier, Iran is widely suspected of having a chemical and biological weapons program for nearly 20 years. They have possessed the capacity to launch a mass casualty strike against Israel for a while now - and one that would be far harder to trace back to Iran than a nuclear bomb. And yet, they haven't launched one. Presumably because, contra Yon, they're not willing to sacrifice their entire country to strike a blow at Israel.
It is a mistake to treat Iran as an irrational state when they are in fact a belligerent one (which is bad enough).
Photo via Richard John Jones under a Creative Commons license.
January 28, 2009
Fouad Ajami and Peter Wehner argue that President Bush boldly broke with precedent to align the U.S. with liberty in the Middle East. Here's Ajami in the Wall Street Journal:
Say what you will about the style -- and practice -- of the Bush years, the autocracies were on notice for the first five or six years of George W. Bush's presidency. America had toppled Taliban rule and the tyranny of Saddam Hussein; it had frightened the Libyan ruler that a similar fate lay in store for him. It was not sweet persuasion that drove Syria out of Lebanon in 2005. That dominion of plunder and terror was given up under duress.
President Obama may be eager to return us to the days of Jimmy Carter, when we spoke about human rights on the one hand and bowed before autocrats and despots on the other; or the days of Bill Clinton, with Madeleine Albright frantically chasing after Yasir Arafat. Such an approach may appear to be less burdensome than advocating freedom, but it comes at a high cost - to the Arab world and, eventually, to our own.
To briefly review the record: the regimes directly responsible for fomenting radical Islamism - Pakistan and Saudi Arabia - were not "put on notice" by the Bush Administration after 9/11. They were embraced. The illiberal/autocratic/monarchical states of Egypt, Jordan, Kuwait, and the UAE weren't exactly given a cold shoulder either. Qaddafi's Libya was embraced not after political reforms but after a change in WMD policy. He still runs his country along the same despotic, cult-of-personality lines as before. And do we really have to say anything about Pakistan and General Musharraf?
So long as the Middle East produces oil in sufficient quantity to impact global markets (i.e. for as long as industrial economies rely on the stuff) and so long as the U.S. places the security of Israel among its key regional interests, the U.S. is not going to be on the side of liberty in the Middle East. Instead, it will be on the side of stability of the regimes that support the U.S. and Israel (however quietly) regardless of how they comport themselves internally. Indeed, as the containment of Iran becomes ever-more pressing, we will pay even less attention to the internal repressions of the various Sunni autocracies provided they align their foreign policies with ours. Why else did the Bush administration offer $20 billion in arms to Saudi Arabia and other Gulf states? For their human rights records?
This is Middle Eastern geo-politics 101 and the notion that President Bush broke from it simply won't wash. Yet at some point during the Bush years, certain segments of the conservative establishment decided they wanted to bathe America'smachtpolitic in the region in a miasma of do-gooderism and hokum. President Bush did indeed break from past U.S. practice by invading and militarily occupying a Middle Eastern country, but liberty had (and continues to have) very little to do with that particular endeavor, even if Iraq does consolidate its democratic gains into an enduring liberal government.
Stepping back, it's clear that what the George Bush presidency accomplished was not so much the advance of liberty in the Middle East but to shine a glaring spot-light on U.S. hypocrisy. This hypocrisy isn't a bad thing: the U.S. needs to cooperate with autocracies. But seeking that cooperation while proclaiming loudly that we are freedom's standard bearer in the Middle East is, at a minimum, counter productive.
There will always be a disconnect between a nation's professed values and its conduct abroad. The ideal is to minimize that disconnect where possible, and when not, to stop drawing attention to it with lavish rhetoric and hollow promises.
The Heritage Foundation's Baker Spring, Mackenzie Eaglen and James Jay Carafano argue that the U.S. should devote 4 percent of its GDP to defense en-perpetuity. Among the arguments they offer is this:
Pentagon spending is not the source of the federal government's current fiscal woes. Spending on the armed forces represents only about one-fifth of the federal budget and approximately half the average level of defense spending during the Cold War (as measured as a percentage of GDP). Defense has gradually declined as a percentage of GDP since the 1960s, while spending on the major entitlements (now about half the federal budget) have usually exceeded economic growth rates over the same period. Further, current projections show that spending on the major entitlements will far outpace economic growth and all components of government spending in the decades to come. Addressing entitlement spending, not defense expenditures, is the key long-term challenge for lawmakers.
When you consider the vast gulf between what America spends on her defense, and what every other nation does, it's pretty obvious that our defense spending is indeed entitlement spending. Only instead of American citizens enjoying the entitlement (after all, it is their money), it's South Korea, Taiwan, Europe, Israel, Saudi Arabia and a variety of other American strategic dependencies that get the benefit of taxpayer largess.
Maybe this wealth transfer is justified. Maybe it isn't. But let's at least be honest about it.
January 27, 2009
"I'm concerned about the level of frankly subversive activity that the Iranians are carrying on in a number of places in Latin America," Gates said in response to a question from Sen. Mel Martinez, a Florida Republican.
"They're opening a lot of offices and a lot of fronts behind which they interfere in what is going on in some of these countries," Gates said, without elaborating.
Gates has plenty of reason to be concerned.
Just last month Italian newspaper La Stampa reported that Iran is going through Venezuela to dodge UN sanctions and use Venezuelan aircraft to ship missile parts to Syria. La Stampa reported that Venezuelan airline Conviasa transports computers and engine components from the Iranian industrial group Shahid Bagheri, which is involved in Iran's ballistic missile program.
On January 6, Turkey was holding a suspicious shipment bound for Venezuela from Iran because it contained lab equipment capable of producing explosives. Over the past few years Chavez has allowed the opening in Venezuela of an Iranian ammunition factory, a car assembly plant, a cement factory, and Iran Air has direct air service between Tehran, Damascus and Caracas.
Bolivia's Evo Morales has raised visa restrictions on Iranian citizens, while Iran promised a $1 billion investment in the oil and gas industry.
Iran is holding several of its citizens from being tried in Argentina for planning the 1994 bombing of the Argentine AIMA Jewish center in Buenos Aires, which killed 85 people.
In Nicaragua's Caribbean shore, Iran - along with Venezuela - is helping to finance a $350 million deep-water port at Monkey Point, and they're also building a "dry canal" of pipelines, highways and rails to the Pacific shore. Iran recently opened an embassy in Managua.
Iran is lending Ecuador $200 million to finance trade, technology transfer "and many other things," according to Pres. Rafael Correa.
As Greg Scoblete was asking here, we would do well to ask what are Iran's national interests, and additionally, Iran's interest in our hemisphere.
President Obama gave an interview with Al-Aribiya where he said that the U.S. had made mistakes in the past but "that the same respect and partnership that America had with the Muslim world as recently as 20 or 30 years ago, there's no reason why we can't restore that."
My take away from that book is that America was indeed much beloved in the Middle East, prior to 1945. We were beloved when our interaction with the region was confined to civilian missionary work and a political posture that was supportive of self-determination but largely unwilling to interfere with the region's politics. That all changed following the retreat of French and British imperial power in the region, and the establishment of a "pax Americana" knitting together our anti-Communist allies.
Given that history, it will be very difficult (although not impossible) for President Obama to restore America's image in the region. Ultimately, that image is not tarnished by the words of our leaders but by the power politics they're forced to engage in because of the importance of oil and our support of Israel. And I highly doubt that President Obama is going to attempt to reset America's relationship with the region along pre-1945 lines.
But Obama gets to make his own reality at the moment -- and is imposing it -- in a respectful, humble, and powerful way.
His style matters -- just like Bush's swagger did -- and it is this act of humility towards the Muslim world which may animate hope in the nations around the world and in the Middle East specifically.
Everyone will have to adjust now. The Saudis will leave the peace deal on the table. The Israelis have to remake themselves -- even if Netanyahu succeeds Olmert. Hamas will have to find a way to become differently postured -- if not on Israel, then at least on some level of international acceptability with American partners. Arab stakeholders are going to have to snap out of positions shaped more by status quo thinking and inertia that things will never change and get with the Obama program.
What Obama did has provided a new punctuation point in American foreign policy, and it is not "continuous" foreign policy at all. This is a new game and a very impressive new leader.
While I think the speech was a worthy and important gesture, I really don't see how Clemons can imbue it with this God-like ("reality-creating") impact. I would argue that symbolism does not, in fact, matter nearly as much as Clemons suggests. Do we suppose that the Arab world really cannot discern the difference between rhetoric and policy? That they are going to be swept off their feet? I will happily stand corrected if there's any evidence that mere rhetoric will turn around America's image, but I suspect it won't be enough.
John Nagl is one of the more hard-headed proponents of "smart power" out there, so it's well worth reading his "The Expeditionary Imperative" in the Wilson Quarterly.
While the piece makes a lot of sense, I'm troubled by the conclusion:
Victory in this long struggle requires changes in the governments and educational systems of dozens of countries around the globe. This is the task of a new generation of information warriors, development experts, and diplomats; it is every bit as important as the fight being waged by our men and women in uniform, but nowhere near as well recognized or funded.
There is a growing body of commentary that suggests that the answer to terrorism is a form of neo-colonialism that injects the United States into every troubled country on the theory that we can - and will - successfully manage to reform them. This reformation, in turn, will reduce the threat of Islamic terrorism around the globe.
Like the theory of "democratic transformation" that provided much of the intellectual impetus behind the Iraq war, there's very little empirical evidence that this is indeed the answer. Shouldn't we have learned by now to be wary of sweeping claims of societal transformation, even if the instruments of said transformation are dollars and not bullets?
Secondly, the most obvious objection to the neo-colonial view is that the Federal Government does not have a mandate for global social work. With a national debt poised to soar over $2 trillion, we have not exactly demonstrated a capacity to successfully manage our own affairs. Just consider how hard it is for Americans (lobbyists, unions, politicians, etc.) to reform the U.S. education system. Now, throw in a culture they don't understand and a language they don't speak and explain to me how the U.S. reforms the education system in dozens of countries.
But more to the point, Nagl and his peers routinely ignore several fairly troubling facts about terrorism. The first is that many jihadists hail from Europe. None of the supposed ills of the world - illiberal educations, poverty, tribalism, autocracy, etc. - can account for Western citizens turning toward radical Islam. Nor can they account for men like bin Laden or Khalid Sheikh Mohammed. Yes, Europe does not provide the kind of safe havens that a failed state would afford. But a few enterprising youths could certainly devise a way to kill dozens, if not hundreds, of people without access to the Hindu Kush.
Finally, the political dimension of radical Islam's global insurgency is a reaction against Western interference in Islamic societies. "Interfering better," as proponents such as Nagl propose, doesn't change that basic dynamic.
None of this counsels against a rebalancing of America's national security investment. But it should be undertaken with a sufficient dose of humility and an awareness that even when we use all of the "tools" at our disposal, the world is not mere clay in our hands.
January 26, 2009
In the course of an interesting post on U.S.-Iran dialoging, Hillary Mann Leverett writes:
It will take not only sustained effort but also clear strategic vision for the Obama Administration to repair the damage to U.S. interests done by the Bush Administration's mishandling of relations with Iran.
Defining that clear strategic vision will require a willingness to question the all-too-prevalent image of Iran as an ideologically-driven and categorical supporter of an undifferentiated array of terrorist groups--from Hizballah to HAMAS to Al Qaida. Fundamentally, the Islamic Republic is a state that acts on the basis of what it perceives as its national interests.
This is all well and good, but what are Iran's national interests? Mann doesn't say, which is unfortunate because ultimately this is the whole enchilada.
We could very well find ourselves in a situation where the basic interests of the U.S. and Iran are simply never going align. The U.S. position on the Gulf is clear: no single power (save the U.S.) can dominate the region. Iran, we're told, similarly seeks to be the single power that dominates the Gulf.
No matter how conciliatory the Obama administration is toward Iran, this baseline divergence of interests is going to rear its head. Unless, of course, the U.S. or Iran renounces their hegemonic ambitions in the region. But what are the odds of that?
January 25, 2009
Two weeks ago the U.S. Joint Forces Command published its "Joint Operating Environment (JOE 2008)" report, which projects global threats and potential next wars. The report stated that Mexico and Pakistan are two countries that "bear consideration for a rapid and sudden collapse,"
"The Mexican possibility may seem less likely, but the government, its politicians, police and judicial infrastructure are all under sustained assault and press by criminal gangs and drug cartels. How that internal conflict turns out over the next several years will have a major impact on the stability of the Mexican state. Any descent by Mexico into chaos would demand an American response based on the serious implications for homeland security alone."
While Mexico's collapse may not be imminent, the report underlines the seriousness of the current drug wars in Mexico, which represent an urgent problem to the US.
This is not a new problem: Last May Stratfor had posed the question, Mexico: On the Road to a Failed State? in one of its Geopolitical Intelligence Reports that expressed the similar concerns to that of the JOE report. Stratfor also points out state failures in Mexico's past.
The most reliable and concise background study on the seriousness of the problem is the 2007 CRS Report for Congress on Mexico’s Drug Cartels, which provides an overview of Mexican drug cartels and their operations, their ties to gangs like the Mara Salvatrucha (MS-13), and Mexican cartel presence and their drug production in the US. The cartels - Juárez, Sinaloa, Gulf, Nuevo Laredo, Guerrero. Valencia and Michoacán - form alliances and work together (like Sinaloa-Juárez-Valencia Federation), but remain independent organizations, which operate throughout Mexico and branch into the United States.
Police corruption and the emergence of multiple, well-armed groups further complicate the problem.
Yesterday's AP article on the arrest of a dozen high-ranking officials with alleged ties to the Sinaloa Cartel (currently the most powerful of the cartels) illustrates the corruption problem :
Over the last five months, officials from the Mexican Attorney General's office, the federal police and even Mexico's representatives to Interpol have been detained on suspicion of acting as spies for Sinaloa or its one-time ally, the Beltran Leyva gang. An officer who served in Calderon's presidential guard was detained in December on suspicion of spying for Beltran Leyva.
Gerardo Garay, formerly the acting federal police chief, is accused of protecting the Beltran Leyva brothers and stealing money from a mansion during an October drug raid. Former drug czar Noe Ramirez, who was supposed to serve as point man in Calderon's anti-drug fight, is accused of taking $450,000 from Sinaloa.
Most of such tips are coming from a Mexican federal agent who infiltrated the U.S. embassy for the Beltran Leyva drug cartel. No such infiltrators have been found for the Gulf cartel, which controls most drug shipments in eastern Mexico and Central America. Sinaloa controls Pacific and western routes.
A year into the Calderon goverment's crackdown on the cartels, the Mexican government continues to increase its efforts against the cartels - for instance, sending 2,000 troops to Juárez this month - but the extent of the violence ravaging the country is immense.
El Universal has a webpage of drug war related articles; there have been 312 deaths in 2009 so far. This article from El Universal lists 34 killings in one day, all related to the drug wars. El Universal and the BBC report the arrest on Friday of Santiago Meza López, a.k.a. "Teo's wellman", No. 20 in the FBI's most-wanted list, who allegedly decomposed in acid 300 bodies of people murdered by the Sinaloa Cartel and Teodoro Eduardo García Simental, alias “El Teo”.
the killings have become more frequent, more brazen and more gruesome. One body was beheaded and hung from a bridge.
In contrast, the article describes
El Paso... is made up mostly of new immigrants or their children, who tend to be cautious, law-abiding and respectful of authority.
Many Mexicans who previously lived in small villages near the American border had to leave for the US or be killed. Another big difference between the two cities is that the Mexican military and police are understaffed and untrained, while in Texas Fort Bliss and the heavy police presence continue to make El Paso safe.
Anti-drug officials believe the uptick in clashes between the police and gunmen of the cartels is a sign that Mexico's long-running drug violence has entered a new phase. Until recently, most fighting had involved rival traffickers battling over turf, but today most of the violence is between the federal government and the gangsters. The year-long government crackdown has seriously rattled the cartels, the officials say, and they are making an orchestrated attempt to get the government to back off.
The scenario in which a breakdown of institutions where the state becomes an instrument of criminals in Mexico would bring millions of war refugees into the US, and neighboring Central American countries would also collapse. Mexico, the world's 14th largest economy, has over 100 million people.
The JOE 08 report, along with the 2007 CRS Report for Congress on Mexico’s Drug Cartels, should be the starting point for the discussion of what we need to do here in the US: Strenghthening the Merida Initiative (whose purpose is to train and professionalize Mexico's military and civil forces), paying special attention to immigration and drug enforcement in the border states, increasing the National Guard, making other defense contingency plans in the US, and educating the public on the level of threat are a few suggestions.
Mexico's descent into chaos, while not imminent, is a real possibility.
For Chinese communities around the world, this week marks the beginning of a week-long holiday to mark Chinese New Year, or Spring Festival as it is usually called. The significance of the holiday is on the same level as Christmas for the Western world and also involves family reunions in one’s hometown. One of the phenomena associated with the Spring Festival is the massive outflow of people from the cities where they work back to their hometowns. Even in an island as small as Taiwan, every time Chinese New Year rolled around there would be massive traffic jams on the highways with hundreds of thousands of people leaving Taipei for their hometowns down south. The scale of the travel situation in China is even more mind-boggling where you have an estimated 188 million people making the journey home, and that is only for the railways.
A blog posting in China comparing the differences between how holiday travel is handled in the U.S. and China has struck a chord, receiving over 100,000 views and 1,100 comments. Popular novelist and former Atlantic Council senior fellow Yang Hengjun attributes China’s travel problems to two main factors: 1. The inability of regular citizens to change their official residence (known as hukou in Mandarin) which greatly limits the social services that migrant workers and their families can access outside of their hometown. This often ends up separating parents from their children who can only receive schooling in their hometowns. 2. Train and airplane tickets are snatched up by those with special connections to the government.
Yang writes, “Unlimited authority, abuse of power, an unfair system, monopolistic corporations, social inequality, and corruption has made the Chinese New Year travel rush not a transportation problem, but a social and political one. That is what causes so many people to get angry! … In the U.S., apart from a small minority of government officials who are traveling for business dealing with national interests, those who are traveling for personal reasons are all treated the same in the purchasing of tickets. Even if you were traveling on business for your company or the government, you need to go through the same process as an illegal immigrant worker in a Chinese restaurant: purchase tickets online or line up at the counter, first come first serve. … In China, one’s level in society basically determines whether you are able to get a ticket, and the highest level is, obviously, the ‘servants of the people.’ Have you ever heard any public servant or their family members complain about not being able to get tickets?”
For Taiwanese businessmen working on the other side of the Strait, the new year usually means either getting on a plane back home or flying one’s wife and kids out to China. However, the global financial crisis has changed this dynamic this year. An article in Commonwealth, the leading general affairs magazine in Taiwan, explains how economic difficulties in China have affected cross-strait travel: “The Fu-hsing Travel Agency pointed out that in the past there would always be tons of people flying to the mainland to visit relatives or go on tours, and demand for seats outstripped supply. This year that demand has decreased significantly. ‘There are already airline companies that are selling direct flights to Shenzhen for an extremely low price of NT$7,000 [approx. US$212], but this still hasn’t attracted any buyers,’ a representative from the travel agency said.
This year, China-based Taiwanese businessmen will have a particularly cold Spring Festival. Those who are unlucky have been laid off and sent back to Taiwan. Some are temporarily unable to reunite with their family.
Mr. Chen, who has been ‘recalled’ to Taiwan, said with a note of sarcasm, ‘This year it’s my turn to go back to Taiwan to see my family. During the past decade, whether Taiwanese businessmen spent their Chinese new year in Taiwan or China was an indicator of which location was more attractive. Mr. Chen plans to see how things go in Taiwan for the next year or two, and then make a decision once the economy recovers.
‘It’s hard to say whether I’ll return to the mainland. After this shuffling of the deck, I think new opportunities will appear on both sides,’ Chen said optimistically.”
As Russia watched the historic inauguration of US President Barack Obama, there was plenty of commentary about the Jan. 20 event that took place in Washington - from positive and cautious optimism to pragmatic remarks about what the new American president means to Russia, its near abroad and Russia's relations with her neighbors.
Daily "Izvestia" published several opinions on the way Russian political observers saw the inauguration. Almost all of them commented on president-elect's mistake in saying the oath of office, as well as other interesting moments. Many writers quickly took the attention away from amusing moments to the grave concerns about the American economy and the fate of the global financial crisis. "The future is shrouded in darkness, and today's throngs of enthusiastic supporters screaming "Omaba!" will, once things turn for the worse, may be screaming something entirely different," writes political commentator Maksim Sokolov. He further remarked with skepticism that "emotions and effort are well-combined when it's clear how to use one's efforts for best results. But all that we now know about concrete plans of this new American President is boiled down to the slogan. "For all that is good, against all that is bad, and let no one be upset. Technically, he was elected as a wonderful, pleasant and harmless healer."
Turning to the on -going economic crisis, Sokolov writes that " ... in his defense, even more mature and experienced colleagues of the new president do not know the way out of the current economic hardship. The difference between them and Obama is that his colleagues were not elected to office on an emotional wave of hope and change and therefore are not really responsible to anyone for the results of their actions. But Obama is responsible."
Other articles also turned their attention to the Inauguration Day. An "Izvestia" article commented that "... in contrast to the overflowing streets of Washington on Jan. 20, one cannot help but think back to May 2008, when the the procession of the new Russian President Dmitry Medvedev moved towards the Kremlin on empty - almost dead - Moscow streets. But we should not compare the two events - after all, it [the Inauguration] is a typical American showboating. The harsh reality is already setting in - US Dollar, instead of rising on the wave of this presidential euphoria, instead fell against the Russian ruble - while our currency rose in the evaluation. Party is over, so to speak."
Russian political establishment continued to isolate Georgia and to limit any remaining trade with the Caucasus country. On Jan. 20, Russian President Medvedev signed a law that prohibited any deliveries of defense and dual-use materials to Georgia. Medvedev also requested the creation of official legislation that would limit or prohibit military-technical cooperation with countries that deliver Russian or Soviet military hardware to Georgia. The second initiative is clearly aimed at Ukraine, since Moscow accused it of aiding Georgian military during the August 2008 war. However, "it would not be possible to completely cut off military-technical cooperation with Ukraine, since the interdependence of military-industrial complexes of our two countries is too great, dating back to the Soviet times." In another not-so-subtle hint at Kiev, Russian daily "Vzglyad" accused Ukrainians of arming separatist Tamil Tigers movement that fought against the government of Sri Lanka. Quoting a former Tiger commander, the paper wrote that Tigers bought military hardware in Ukraine up until recently, at lowered prices. Such hardware included artillery systems, small arms and other equipment.
January 23, 2009
World Public Opinion found what it dubbed a "remarkably modest" self-assessment from the major nations of the world:
Asked to assess the morality of their nation's foreign policy, in 19 out of 21 nations the most common answer is that their nation is about average or below average.
In the United States, about half (49%) say the morality of US foreign policy is average with another 16 percent saying it is below average. Just 24 percent say it is above average.
I admit that I am guilty of bemoaning a certain element of self-righteousness and sanctimoniousness in our foreign policy. But look at the chart below and you'll see that we are by no means an outlier when it comes to how we view the morality of our approach to the world.
January 22, 2009
China's GDP for the fourth quarter of 2008 plunged, in the latest indication that the impact of the global financial crisis on China has worsened, AP reported. Economic growth came in at 6.8% compared to a year earlier, according to data released today by the National Bureau of Statistics (NBS). This compares to 9% growth in the previous quarter and 10.6% in the first quarter. The economy grew by 9% for the full year, marking the slowest annual growth since 2001, and down significantly from the 13% growth seen in 2007. Exports fell by 2.8% in December, following a 2.2% drop in November.
So, will a declining economy spur domestic unrest? If China's leadership is unable to deliver economic gains commensurate with the past few years, will they go abroad in search of demons to slay?
January 21, 2009
Thomas Ricks touts the brilliance of this article by Col. McMaster (the "brain behind Petraeus") in World Affairs Journal. It is essentially an extended attack on the technological hubris of American defense planners and well worth a read.
However, McMasters offers up this as a conclusion:
In the last paragraphs of his book, A Better War, Lewis Sorley relates a story from December 1975, about seven months after the fall of Saigon. New Secretary of Defense Donald Rumsfeld was away from the Pentagon. Workmen took advantage of the opportunity to refurbish the secretary’s office. In doing so, they removed a large relief map of Southeast Asia that had hung on the wall during much of the Vietnam War. Perhaps if the map were still hanging there when Secretary Rumsfeld returned to the Pentagon more than thirty years later, it might have inspired a healthy dose of skepticism about the latest orthodoxy predicting how U.S. technological advantages would make war fast, efficient, and decisive. That skepticism, in turn, might have generated a deeper understanding of the nature of the conflicts in which the United States and its partners remain engaged today.
I think McMaster's point about the dangerously seductive quality of defense technology, while valid, is being taken altogether too far. If we collectively decide that the problem with the Iraq war was that Donald Rumsfeld and company were insufficiently mindful of population security and overly optimistic about high-tech warfare, then we haven't actually learned anything. It never ceases to amaze me that critics of the invasion - such as the New York Times editorial board - nevertheless insist that we build an Army to wage future Iraq-style wars.
But why? If the war was a strategic mistake, as people such as Brent Scowcroft argued at the time, then the flaws that it exposed in our defense establishment are actually not flaws of force structure or doctrine, etc. but flaws in the strategic decision making of our civilian policy makers. The lesson we should learn from Iraq is not that we need to do a better job "next time" but that there should be no next time. I mean, what's easier: replacing strategically inept bureaucrats with astute ones, or reorienting the entire defense establishment on the theory that future blunders are simply inevitable?
Moreover there is nothing about the "nature of the threat that we face" that necessitates building a constabulary Army capable of pacifying unruly natives. Indeed, the nature of the threat of Islamic terrorism warns specifically against such a move, on the grounds that it would vindicate bin Laden's propaganda, tie down a disproportionate amount of U.S. combat power, and drain the economy of needed resources. The surest way to keep the threat of Islamic terrorism alive deep into the 21st century is to garrison ever larger contingents of U.S. troops on Muslim soil.
Yet the very people one would expect to acknowledge that fact are the same people insisting that we build an Army to do just that. It's very frustrating.
One further quibble. McMasters writes that "the way the United States went to war influenced everything that followed. A fixation on American technological superiority and an associated neglect of the human, psychological and political dimensions of war doomed one effort and very nearly the other."
The problem with "how we went to war" wasn't the undue focus on technological superiority, it was the legitimacy of the enterprise. A war without an obvious and compelling casus belli - a war viewed globally as grossly illegitimate - was going to have a much higher hurdle associated with the end state than one (like Afghanistan) where U.S. action was widely viewed as urgent and compelling. We simply couldn't leave behind an Iraq that was demonstrably worse than we found it.
That, again, suggests that the answer isn't to pay more attention to the human aspects of waging war, but to the legitimacy of initiating military conflict. I would argue that the more legitimacy the U.S. has in taking military action against a state, the less will be expected of us by way of nation building.
A new era has started for the United States and for the world: Barack Obama is now the North American country's 44th President to be sworn in at the Washington Capitol building in front of a huge crowd of people filled with emotion, excitement and hope.
The sun, which had been hiding during lunchtime, shone brightly again during the [Obamas'] trajectory celebrating the swearing in of the 44th President of the United States; sometimes he rode in his car, sometimes he walked.
This afternoon Barack Obama became the United States' first black President. And he did it in front of a crowd convening at the Capitol to witness the historic event. In a speech that was directed as much to the country as it was to the rest of the world, he talked about the challenges his country faces, which he said, "is ready to return to leadership." And insisted that his electoral victory was the triumph of "hope over fear."
January 20, 2009
While the world welcomes a new American President, Central American political observers also await the results from the first round of historic elections in El Salvador.
This is the first time since 1994 that Salvadorenos go to the polls to elect a new assembly, new mayors and a new president during the same year. Polls have varyingly shown the candidate of the leftist FMLN party, Mauricio Funes, with a steady and sometimes large lead.
Last week, the country went to the polls for municipal and legislative elections. With 75% of the votes counted, the results so far show FMLN moving into the lead in the assembly with 35 seats to ARENA’s 32 - which would essentially flip the current balance of power - leaving the right-wing PCN as kingmakers again. ARENA also expects to lose 30 mayoral seats in sum, although they scored the major headline of the day by retaking San Salvador, where Funes had campaigned last week in support of the FMLN.
The small Central American nation, and one-time Cold War flash point, has been ruled by the right-wing ARENA party since 1992 peace accords ended a 12-year civil war between the U.S.-backed dictatorship and leftist guerrillas. The war featured some of the most brutal and infamous episodes in recent history. Since ’92, though, the country has remained peaceful and ARENA has mostly dominated the country’s politics; maintaining power over a series of legitimate elections.
Electing a left-wing government for the first time would be a sign of political maturity for a young democracy, as the ruling party hands over power for the first time (although the threat to the party, it should be mentioned, stems largely from concerns about corruption and a steep rise in crime). Funes, who is going up against Rodrigo Avila, represents the moderate wing of FMLN. He is a former CNN freelancer, and he has no connection to the party's old days as a Marxist guerrilla group.
The potential for change has also had the predictable effect of placing El Salvador in the spotlight as possibly the latest in a block of Latin American countries to move away from alignment with the United States; opting instead to elect a leftist leadership. Funes has said he plans to keep market-friendly policies and close contacts with Washington, but the right-wing has not shied away from fear-based campaigning, in particular trying to tie FMLN to Hugo Chavez.
Take, for instance, this ad run by ARENA ally Fuerza Solidaria:
The ad begins with an image of President Obama. The narrator tells viewers that, while FMLN claims to be his "friend," "this man - Obama foreign policy advisor Dan Restrepo - says otherwise."
Restrepo: "Obama is very worried about the anti-American rhetoric and broken policies of Hugo Chavez, in Venezuela...or other places, like El Salvador."
Restrepo never explicitly mentions the local political context. But that's politics.
January 19, 2009
The spokesman for Brazil's President Luiz Inacio Lula da Silva says the Brazilian leader has invited Bush to come fishing.
Marcelo Baumbach says Bush made a farewell call to Silva on Monday and received the invitation. Bush also invited Silva to visit him in Texas.
Aside from being sociable and friendly, Lula, by publicly issuing this invitation, is further distancing himself from Hugo Chavez's highly inflammatory brand of politics. Just last week Chavez was saying that Obama has the "stench" of Bush; Lula is very much aware of Chavez's position.
To further drive his point, O Globo quotes Lula as saying that "it's been a privilege to have been among the presidents who are building good relationships with the United States."
January 18, 2009
During President Bush’s final press conference last week, he was asked indirectly about his views of America’s damaged “moral standing.” Bush defended himself spiritedly saying, “I strongly disagree with the assessment that our moral standing has been damaged. It may be damaged amongst some of the elite, but people still understand America stands for freedom, that America is a country that provides such great hope.” He went on to name some parts of the world where the U.S. was still held in high regard, and China was one of those countries.
So how does China, or, more specifically, members of the Chinese media feel about Bush’s legacy? A commentary in the Southern Metropolis Daily, one of China’s leading commercial newspapers, mentions how Truman left office with very low approval ratings, but his legacy was later on vindicated. The writer pins Bush’s place in history squarely upon the Iraq war and comes up with a measured assessment: “People say that history often repeats itself, and it’s hard to say that it will not do the same for Bush in how his stature may be revised the same way that Truman’s was. However, the difference is that the emergence of Europe and Japan along with the end of the Cold War serve as the basis for Truman’s place in history. The basis for Bush’s legacy has yet to be determined.
"Moreover, what makes it even more uncertain is the promotion of his Middle East democracy strategy in Muslim countries where there lies a wide gap between them and Western ideals. If Iraq is able to continue moving forward in the development of its democracy and rule of law and go on to influence other Middle Eastern countries, there will be greater hope of a comprehensive realization of Bush’s Middle East democracy project. However, if Iraq goes backwards in democracy and its sects are unable to cooperate, leading to widespread chaos with global effects, than history will render a judgment that Bush will not like. But that is the impartial judgment that he has no choice but to accept.”
The People’s Daily, the official newspaper of the Chinese government, casts U.S.-China relations in a guardedly optimistic light in an editorial titled, “Sino-U.S. Cooperation Leads to World Peace.” Although Bush is not mentioned directly, his administration’s policy of encouraging China to become a “responsible stakeholder” is discussed. The timing and nature of the article also indicates that it was written in response to Bush’s oncoming departure.
“In recent years, amidst the efforts of the international community to resolve problems of a global nature, the fruits of the Sino-U.S. ‘global relationship’ are gradually being seen. Room for cooperation and opportunity has continuously growing larger, and mutual trust has also been increasingly strengthened. It can be said that the harder the global problem, the more it shows the necessity and importance of Sino-U.S. cooperation. … The Sino-U.S. relationship is made up of the world’s largest developing country and the largest developed country. They have the common responsibility for the peace and development of mankind.”
The absence of criticism and forward-looking nature of this editorial seems to indicate that the Chinese government has been pleased with how the Bush administration has conducted its dealings with them and hopes that they will see the same from the Obama administration.
Russian news devoted time and attention to the current problems and concerns in its near abroad. Daily Izvestia published a report from Abkhazia, a break-away region of Georgia that achieved independence together with South Ossetia in the early 1990s. Just like its former Georgian counterpart, Abkhazia is at the epicenter of the continuing stand-off between Russia and Georgia over the international legitimacy of the territory's status. Russia recently launched a massive campaign to award Russian passports to the resident of Abkhazia, and currently more than 80% of the people living in the province have Russian citizenship. The article describes Abkhazia's strong pro-Russian sentiment, and its hopes for common borders and a customs union with Russia and Belarus.
The province's Foreign Minister Sergei Shamba told reporters that Abkhazia already designated two plots of land in Sukhumi, the capital city, for the constriction of the Russian Embassy and Russian Ambassador's future residence, with "... construction to be undertaken by the Russian Ministry of Foreign Affairs ... which should be completed in two years and the diplomatic mission will have 30 diplomats." Shamba noted that Abkhazia has a representative office in Moscow, staffed by 12 people and that "soon enough, our Ambassador will submit his credential to (Russian President) Medvedev. We were already offered several mansions for out future permanent embassy."
The article's description of fait accompli concerning Abkhazia's relationship with Russia is a cause of concern to the European Union and the United States. The international community has tried to resolve the status of Abkhazia for the last 15 years, with no apparent success. Georgia considers Abkhazia part of its territory, the international community - including the United States - supports the territorial integrity of Georgia that includes Abkhazia and South Ossetia (where war was fought in August 2008). On the other hand, Russia threw its full military and diplomatic support behind the breakaway states that are on track to joining the Russian Federation in one way or another - as a constituent republic, as a unionized territory, or a legal territorial entity. Given the fact that similar status issues regrading South Ossetia were settled by war, there is concern that Abkhazia may become another source of military conflict between Russia and pro-Western Georgia.
In Georgia proper, Izvestia reports on the political scandal involving television stations that are favorable in their coverage to President Mikhail Saakashvili. The TV stations reported that future US Secretary of State Hillary Clinton pledged to defend Georgia and Ukraine against Russia's "imperial ambitions." Pro-Saakashvili politicians and political experts tried to convince the population that such statements are a continuation of George W. Bush's foreign policy that maintains strategic partnership with Georgia. However, political opposition reported that Senator Clinton never pledged such policy in her Senate confirmation, and opposition media published the entire 16-page transcript of Clinton's congressional hearings. According to leading Georgian political opposition experts, "such attempts to state that "Obama cannot live without Saakashvili" is pure disinformation. Saakashvili is a great student of Brezhnev and Goebbels." Izvestia noted that President Saakashvili's press office did not refute oppositions' claims about Senator Clinton's actual words.
The question of separatism and breakaway tendencies received additional coverage in an interesting article that described the attempt by Russia's Sverdlovsky Oblast - which encompasses energy-rich Ural region - to secede from the Russian Federation in early 1990s. Online publication "Noviye Regioni" published a remarkable report on the exhibition devoted to the 75-year history of the Ural region. The exhibition featured "Ural Franks", printed in 1991 for use as official currency. Apparently, 56 million of these "franks" were printed in order to fight the inflation of the Soviet rubble that reached nearly 1,000% following years of economic liberalization launched in 1987. Following the deteriorating economic climate, Sverdlvosky Oblast held a popular referendum in early 1990s, in which more than 60% of the population supported the session of the Middle Ural region from the Russian Federation. The idea to use Ural franks as official currency alongside Soviet rubble was even floated to Egor Gaidar, then Economic and Finance Minister of the Russian Federation (still part of the USSR in 1991) and future Economic Minister of independent Russia. There are some uncomfortable parallels between the crashing Soviet economy that facilitated the breakup of the USSR in 1991 and the current worsening economic situation across Russia, which today affects many regions, including Sverdlovsky Oblast.
Turning to the incoming administration of the President-elect Barack Obama, business daily "Vzglyad" published a farewell review of Secretary of State Condoleeza Rice. The paper noted that Rice was one of Russia's strongest critics, especially during the August 2008 war between Georgia and Russian Federation over South Ossetia. The paper quotes Russian Foreign Minister Sergey Lavrov stating that he tried to ask Rice over the years to put pressure on Georgia in order to prevent military conflict, with Secretary of State failing to restrain her allies. He noted that for Moscow, the political dialogue with incoming Secretary of State Hillary Clinton will be much more cordial than with Rice.
The French World Beat is taking a break this week, as news are pretty slow on the other side of the Atlantic, aside from the Gaza crisis, that is. But some interesting issues have come from up north. Less than two full months after two elections (federal and provincial in Quebec), let's discuss the forces involved in Canadian and Quebecer politics for 2009.
Ten seats short of a majority in the House of Commons, Mr. Harper's government was almost overthrown by what Don Martin from the National Post describes as a "hodge-podge coalition led by the Liberals" just before the Christmas holidays. Drawing his last card of 2008, the Prime Minister suspended Parliament for a month in order to buy time and hoped for divisions within the Liberal Party over Mr. Dion's leadership to soar and disrupt plans for a coalition. Now, Mr. Harper's plan at least partially worked, as prospects for a coalition government overthrowing the Tories in the House are slimmer now than they were a month ago. How is that?
First, the Liberals have themselves a new leader in the person of Michael Ignatieff. It was widely known that while Mr. Dion, still the leader of the party, signed the coalition deal with the NDP and the Bloc, Mr. Ignatieff was the least enthusiastic of liberal heavyweights regarding this situation. Second, the liberal MPs, especially Ontarians, can read polling numbers: The idea of a Liberal-NDP coalition supported by the Bloc might get some traction in Quebec and liberal Toronto, but the majority of Canadians remain opposed to the idea. And who could blame them? In the ROC (Rest Of Canada, outside Quebec), electors favored the Tories over the Liberals or the NDP by a significant margin. Especially for Westerners, the idea of handing over the government to a Liberal-NDP coalition is tantamount to a coup d'etat. Third, Mr. Harper modified the initial budget propositions that started the fire. He backed down on cutting public financing for political parties and he is now promoting a stimulus package to jump start the economy in 2009.
Regarding this latest issue, it is interesting to note that Mr. Harper's right-wing ideological zeal, prominent at the end of 2008, has paved way to a more pragmatist approach. Indeed, Mr. Harper, instead of cutting a budget deal with the opposition, launched a series of discussion with the country's 10 provincial PMs. His guess was, and still is, that if he can satisfy the demands of most provinces with his budget, Ignatieff will have no choice but to back down and and vote with the government.
How did the provinces answer to Mr. Harper's economic stimulus package and plans to reorganize equalization* payments? Most did so positively, as PMs from British Columbia and Ontario labeled the discussions as productive and very constructive.
But, yet again, when you read the Quebec media, you get a whole different story.
"Charest hits a wall," titles Le Devoir. After the first few rounds of discussion, it became quite clear that Mr. Harper's equalization program changes did not cut it for PM Jean Charest's government, leading him to qualify the Tories' brand of federalism as "not so open" to traditional Quebec nationalist demands. Coming from a PM whose defense of federalism and Canadian unity in front of sovereigntists came in the form of enchantment by Mr. Harper's apparent "open federalism" just two years ago, this would be funny if it were not so sad.
Quebec will probably lose hundreds of millions of dollars every year in equalization payments with the new formula, which amounts for at least two preliminary conclusions:
First, after suffering a crippling defeat at the hands of the sovereigntist Bloc Québécois in Quebec in the latest federal elections, the Tories have mostly given up on Quebec. They bet that the 10 ridings they lack to form a majority government could be won in Ontario, B.C. and the Maritimes, but not in Quebec. The "open federalism" concept (an updated version of the "renewed federalism" from the '90s), praised by Tories and Quebec federalists just a few years ago, seems long gone.
Second, Quebec federalists, and especially Mr. Charest and his Liberal Party, have lost one of their main argument against sovereigntists. This amounts to the desert of ideas that is now crossing the federalist option in Quebec. While sovereignty as a political option is not showing upward or downward signs, federalism definitely lost the initiative in the last few months.
With a newly reinvigorated Parti Québécois and its 51 MPs in Quebec, sovereigntism and nationalism could be headed for a comeback in the coming months and years.
*Note : Equalization is a constitutional obligation of the federal government to redistribute revenue from wealthier provinces to poorer ones.
January 16, 2009
Pew Research finds remarkable similarity between American attitudes towards Israel's 2006 war in Lebanon and the current fighting in Gaza.
As in 2006, most Americans express a fairly non-interventionist sentiment regarding the fighting:
There is little support for a greater U.S. role in resolving the Gaza crisis. Just 17% believe the United States should be more involved than it is currently, 27% say the United States should be less involved, and nearly half (48%) say it is about as involved as it should be. Again, these opinions closely replicate views of U.S. involvement in the war in Lebanon in 2006.
Pew also found a partisan break-out, with Republicans identifying themselves more closely with government activism:
A majority of Republicans (56%) say that the United States should publicly support Israel, compared with 37% of independents and 34% of Democrats. The plurality view among independents and Democrats, shared by roughly four-in-ten in each group (42% of independents, 40% of Democrats) is that the United States should say or do nothing in this conflict.
There are smaller partisan differences in views about the U.S. role in resolving the conflict. Fewer than one-in-five Democrats (18%), independents (17%) and Republicans (15%) say that the United States should be more involved than it is now in resolving the conflict. However, more Democrats (31%) and independents (26%) than Republicans (20%) say the United States should be less involved than it is now.
January 15, 2009
I hope to have a lot more to say on this shortly, but suffice it to say that I think this is the wrong way to judge the merits of the invasion of Iraq:
To understand properly what the Bush administration’s legacy will be with regard to Iraq, one must comprehend the conditions Saddam Hussein subjected Iraq’s citizenry to prior to the country’s liberation in 2003. Moreover, one must compare those past conditions to the current condition of the newly forming democracy in the Middle East.
I would suggest that those questions are, in fact, irrelevant (not in an absolute moral sense, of course, but to the question at hand). Bush's legacy hinges on the question of whether the invasion improved American security at an acceptable cost. If President Bush had stood before the American people in 2002 and suggested we invade Iraq to improve the lives of Iraqis, there would be no war.
The war's remaining supporters have to answer a simple question, without recourse to absurd hypotheticals about what Saddam Hussein "might" have done (because any leader anywhere might do something crazy): has the invasion made us safer?
Nonetheless, Clinton's remarks were not those of someone eager to make choices or set priorities, even though she deployed clever new concepts like "smart power." Clinton did not say which of these problems merited the most resources or the most immediate attention, which problems were the most easily solved and which might be intractable, or how the United States might deploy its power strategically, so that our actions in one area made solving other problems easier, instead of operating (as we often do) at cross-purposes.
It was an impressive performance in some respects -- she's mastered her brief, showed admirable poise, and made it clear that she's on the same page with the president-elect. But taken as a whole, her testimony was entirely consistent with the well-engrained tendency for great powers to assume that what happens anywhere matters everywhere, and especially matters to them. I'm no isolationist, but it would be refreshing to hear a more rigorous assessment of our vital interests and a clearer acknowledgment of the limits of U.S. power, especially these days.
And I'd like to be named Secretary of Defense. Unfortunately (for me, at least) neither is going to happen.
Obviously, once in power the Obama administration, like any administration, will prioritize even if they pay rhetorical lip service to American omnipotence. But no one should be surprised that an administration staffed with former Clinton officials would wax hubristic.
Following up on this post, news on Venezuela: Hugo Chávez held a constitutional referendum on December 2007 that would have allowed him to remain in power without having to run for office.
That referendum was defeated.
However, since Chávez controls the National Assembly, he has never given up on his quest for permanence, and yesterday the National Assembly approved a constitutional amendment to remove term limits for all elected officials. The amendment is scheduled to go to the board of elections, which is also controlled by Chávez, and they'll probably schedule yet another referendum next month.
Not that this comes as any surprise; Chávez was talking about a February 2008 referendum last December.
Venezuela and Bolivia broke diplomatic ties with Israel over its deadly military offensive in the Gaza Strip and refusal to comply with international calls for a ceasefire, their leftist governments said.
Worthy of note is this,
[Evo] Morales' diplomatic announcement on Israel came shortly after he received a letter from Iranian President Mahmoud Ahmadinejad asking him to support an international agreement to resolve the Gaza crisis.
Iranian Cooperation Minister Mohammad Abbasi disclosed to reporters the contents of Ahmadinejad's letter after he met with the Bolivian president.
Iran's largest embassy in our hemisphere is located in La Paz, Bolivia.
Last week, there were two significant events relating on the African piracy front. First was the ransom payout for the Saudi supertanker reported to be $3 million, following initial demands of $25 million. Second was the creation of a multinational task force under the command of the US Fifth fleet. There were also several piracy attempts in the last three weeks and at least one success, according to International Maritime Bureau reports. A few piracy attempts were broken up by coalition forces, specifically helicopters based on ships.
Ransom collection continues to prove that piracy is a good business, but the use of the money remains a puzzle. Who gets it? Public statements from the pirates say that it is divided between the participants only. That’s hard to believe since other reports indicate much of the money moves to others. Even small portions contributed to Islamic extremist activities can fund major terrorists activity. I hope that someone is actively following the flow of this money, because the motivation to do it again must be high.
On the opposite side of the ledger is the creation of the multinational task force focused on anti-piracy actions. It is Combined Task Force 151, which was created to include only forces with national authorization for forceful engagement if necessary. This action is long overdue. It is to be fully operational this week.
Time will tell if sufficient forces will be included to make a difference and hopefully there will be adequate continuous air surveillance to spot the mother ships and pirate skiffs early. This will help anti-pirate ships get out of the emergency reaction mode and into the preventive mode.
While the news is not all good, there is a good signal of possible coordinated action by the ships of many countries now operating in the Gulf of Aden. Let’s hope it proves successful.
Everett Pyatt was Principal Deputy Assistant Secretary and Assistant Secretary of the Navy (USA) in the Carter and Reagan administrations.
January 14, 2009
Republicans now hold the biggest lead over Democrats on the issue of national security since early September. The latest Rasmussen Reports national telephone survey found that 48% of voters trust the GOP more to handle national security and the War on Terror, while only 40% trust Democrats more.
In December, the GOP held just a four-point lead on the issue. Trust in the Republicans hasn’t been this high since September 6, when they led the Democrats 50% to 40% on the issue.
Voters not affiliated with either party trust Republicans more to handle national security by a 51% to 31% margin.
Now imagine what these numbers would be if Obama had stacked his national security cabinet with actual progressives.
January 13, 2009
Much of the popular debate over Iran's nuclear program seems to neglect an important historical fact: Iran's nuclear ambitions predate the Islamic revolution. For all the apocalyptic talk that attends their nuclear pursuits, the Iranians were at work on nuclear technology while they were allied with the United States. This shouldn't necessarily make us breath any easier, but it should make us a bit more skeptical of assertions that Iran has been developing a doomsday weapon with the explicit purpose of eradicating Israel.
Either way, the National Security Archive has just published some recently declassified material on U.S./Iranian nuclear talks from the 1970s that makes for interesting reading.
Caribbean Net News had the story on Jan. 2, and today Bloomberg has it: Venezuela Begins Stealth Devaluation After Oil Price Plunge: In a move to preserve foreign currency reserves, Venezuela's government reduced by half the amount of of dollars it will let people spend when traveling abroad to $2,500. The Venezuelan Foreign Exchange Administration Commission, known as Cadivi, reduced the amount of cash at the fixed exchange rate that Venezuelans can withdraw from foreign banks by half, from $500 to $250 a month. The new rules require that travelers have airplane, bus or ship ticket abroad; new Cadivi cardholders can't get Cadivi dollars for six months.
Since Venezuelans need government permission to purchase dollars at the official rate, which was established in 2005, and the government is cutting down on its sales of dollars, Venezuelans increasingly are buying dollars in a a parallel, unofficial market where the US dollar trades at a 61% premium.
Call it a de facto devaluation.
The price of oil peaked at $147/barrel last July. As of the writing of this post, it is trading at $37.70. Venezuelan oil, which is of lesser quality, has dropped below $30 a barrel.
Venezuela is more dependent on oil now than it was when Mr Chávez took power. Oil brought in 92% of export revenues in the first nine months of 2008, compared with 64% in 1998.
Compounding the problem is the decrease in world oil demand, and Venezuela's decreasing oil production.
Because of this, the government cannot subsidize cheap dollars.
Adding to the economic ills is the rampant inflation, which last year reached 31.9% for consumer prices. Venezuela has the highest inflation out of the 82 world currencies tracked by Bloomberg.
There is talk of reducing the amount of dollars allotted to importers by limiting foreign currency to food, medicine and machinery, and other "priority goods". That would have the effect of cutting imports.
While to the foreign observer devaluation appears to be inevitable, rest assured that Chavez will struggle to avoid it, at least in the near future, since he's pushing for another constitutional referendum to remove the limit on further presidential terms.
Back in the early 1980s Venezuela's economy crashed after the oil boom of the 1970s. Sadly, it may happen again.
January 12, 2009
Jim Arkedis at the Progressive Policy Institute says that I'm missing the point when I expressed skepticism of General Petraeus' attempt to "regionalize" the challenge of Afghanistan.
Arkedis writes:
...linking Afghanistan to Pakistan isn’t an attempt at making the problem bigger; rather, it’s a simple strategic necessity. Achieving any modest goal in Afghanistan is more often than not tethered to Pakistan. NATO and the US could harden every target imaginable in Afghanistan, but if we don’t address the root of the problem - that militias in Afghanistan are drawing significant support from counterparts across the border in Pakistan - then we will bring at best fragile peace to Afghanistan.
As I understand it, and as Obama himself has said, the problems in Pakistan relate to its stand off with India. That is why they have cultivated the extremist elements now waging war against U.S. forces in Afghanistan.
So attempts to bring Pakistan around must hinge on bringing the Kashmir standoff to some kind of resolution. And that is a tall order to say the least. Understanding the solution and implementing it are two vastly different things. Exhibit A: Israel/Palestine. There is a fairly broad agreement about what a "final settlement" will look like, yet getting there has never been harder.
If we go off on a half-cocked effort to bring peace to India and Pakistan, we could find ourselves in a situation akin to the decades long effort to resolve the Israel/Palestine issue. We won't actually bring peace, but we will ensure that the parties to the conflict come to either resent the U.S. or come to depend on the U.S. for security and arms. Any settlement - should it come - would be years in the making while the al Qaeda and Taliban elements inside Afghanistan have to be dealt with immediately. Only a swift and significant change in the Pakistani military's cost/benefit analysis will do that - and if threats of being "bombed to the stone age" and billions in largely misappropriated U.S. aid haven't done it, I'm at a loss to think of what will.
This isn't to say that no effort should be made to relieve the fear in Pakistan that the U.S. is conspiring with India to splinter the country. But that effort should be modest and kept quiet.
As the conflict between Israel and Hamas continues, some analysts are addressing a valid concern, and that is whether Iran's relationship with Hamas is based on rhetoric or reality.
In his most recent Newsweek editorial, Fareez Zakaria stated that "Hamas is not Iran's pawn."
He goes on to quote the much respected Iran scholar Professor Vali Nasr as saying "Iran does not have tangible assets in Gaza or the Palestinian territories…It's a misunderstanding to think of its strength in that way. Its real influence in the Arab world comes from its soft power, the reputation it has built as the defender of the great Arab cause of Palestine."
If we look closely at the situation however we see that this analysis misses some extremely important evidence, which shows that Iran does indeed have tangible assets in Gaza, which includes the influence it wields over the Hamas leadership. And the evidence is not from Washington or Jerusalem. It is from the most powerful man in Iran, Supreme Leader Ayatollah Khamenei.
In his 2003 Grand Bargain offer to the United States, Khamenei specifically talked about ceasing support for Hamas as part of the bargain he was offering to the U.S. This was confirmed by Flynt Leverett, the former Middle East director of the U.S. National Security Council who received the offer from the Iranians in 2003. In an interview with PBS he specifically said:
"On the Iranian side, they acknowledged that they would need to be prepared to deal with our concerns about their WMD activities, their links to terrorist groups like Hezbollah and Hamas, and they said in there that they would be prepared to eliminate military support for these organizations and to work to turn Hezbollah, for example, into a purely political and social organization in Lebanon."
Khamenei did not offer his influence over Shiites in Pakistan, because he has very little or none. The fact that he included support for Hamas as part of the bargain shows that he has something at his disposal. When the words "military support" are included as part of the bargain, it clearly shows that there is something more than Iran's image in Gaza or merely its reputation as "defender of Palestine."
Nor would that be enough for Hamas. It would be illogical for Hamas - an Arab Sunni organization with political as well as military aspirations - to side with increasingly isolated Persian Shiite Iran, solely for the sake of living under its reputation and no financial or military support in return. The losses in relations to rewards would make such a decision completely irrational and counter productive. Hamas' leaders may be good at sending their soldiers on suicide missions. It is very unlikely that they would do that with their own political aspirations.
The current conflict in Gaza does not only serve Israel's interests and goals to reduce Iran's influence. It also serves U/S. interests, which is why Washington is not intervening in a forceful manner in the current conflict. Washington wants Jerusalem to weaken Hamas, not because of the deep love which Joe Biden professed for Israel during his vice presidential debate with Sarah Palin. Its because the Americans know that sooner or later they will have to sit at the negotiation table with Ayatollah Khamenei. If Israel can reduce the value of Hamas, then the Iranians will have one less bargaining chip at their disposal, and that will not be so bad for Obama. Especially since - much like Iran - the U.S. attained its goal through proxy; which, in this case, happens to be Israel.
January 11, 2009
Russian news have been dominated by the growing row with Ukraine over deliveries of natural gas. The entire dispute has been "economically politicized," with both sides blaming the other for non-compliance and belligerence at a time of dropping winter temperatures across Eastern and Western Europe.
Daily Izvestia blamed Ukraine for thwarting the creation of independent commission made up of Russian, Ukrainian and European technical observers in order to mediate the dispute. The newspaper stated that Ukrainians refused to let Russian in, while citing that Ukrainians continued 'till the last minute to illegally siphon off gas for their own use, as "recently, nearly 86 million cubic meters of other people's gas have disappeared in the Ukrainian steppes." Today, as exactly two years ago in a similar dispute, the Russian side blames the Ukrainians for stealing some of the gas intended for the markets in Central and Western Europe. Russian Gazprom chairman Aleksei Miller expressed his concern that since Ukraine blocked the creation of an international observation commission to oversee the end of the dispute, the only people who may be observing the situation are members of the European Commission - themselves career politicians and clerks who may have never seen gas pipeline equipment in their entire life. The newspaper stated that EC's conclusions about the dispute will be undoubtedly politically motivated. "All blame is on the Ukrainian side," Miller was quoted by the paper.
On Friday, the energy dispute took on another dimension, as Kiev Economic Court concluded that the terms of Russian gas transit through Ukrainian territory in 2006 and 2007 are deemed illegal. The five-year contract - signed in 2006 and set to expire on December 31, 2010 - was considered unlawful because the Ukrainian signee, Igor Voronin, former Assistant to the Chairman of national "Naftogas" company, had no government authorization to sign such a contract with the Russian side. As of now, the terms of Russian gas transit through the Ukrainian territory are still undefined.
Izvestia reported on the "persecution" of Russian sailors in the Black Sea port of Sevastopol. Ukrainian Interior Ministry arrested several sailors of the Russian Fleet for "lack of proper registration." The paper commented that such "hunt for the Russian sailors always resumes at the onset of another crisis between Russia and Ukraine." Last time such action was undertaken by the Ukrainian authorities in August 2008, following Russia-Georgia war, when Russian Black Sea fleet returned from a mission to Abkhazia, a break-away region of Georgia.
Russian President Dmitry Medvedev called for greater military-technical cooperation for the Commonwealth of Independent States Members (former Soviet republics) with Russia. "The majority of defense industries across Russia and FSU were based on a single Soviet complex, and still depend on each other to a great degree," stated Medvedev. "The maintenance of such ties increases mutual combat readiness and guarantees collective security in the face of rising threats." The article comments that the strength of today's Russian Army is the result of work of hundreds of defense industries across former Soviet Union. Therefore, future success of the Russian military is not possible without close cooperation with former Soviet partners.
President Medvedev also announced the plan to make purchases of Russian military equipment easier for the CIS members, starting with the ease of delivery of spare parts. This would simplify the purchasing process by former Soviet countries and their militaries - all part of the continuing push by Moscow to become the top defense exporter in the world.
In line with its desire for stability both at home and in the international system in order to foster its ongoing “peaceful development,” the Chinese government has been generally opposed to Israel’s recent actions in Gaza. When Israel began launching airstrikes two weeks ago, the initial reaction from the Chinese foreign ministry was an expression of “serious concern” and a condemnation of “actions that have caused civilian casualties.” After ground operations commenced, Chinese President Hu Jintao addressed the situation in Gaza as a “humanitarian crisis” and called for all sides to “immediately stop their military activities.” On Jan. 7, China was one of the 14 UN Security Council members who voted in favor of the resolution calling for a ceasefire and the full withdrawal of Israeli military forces from Gaza.
The Southern Metropolis Daily, one of the leading commercial newspapers in China, draws attention to a Jan. 5 blog posting by Renmin University professor Zhou Xiaozheng in which he proclaims that Israel is a “good country” and praises various aspects of Jewish culture and civilization. The sociology professor does not address the Gaza situation, but the timing of his post seems to be a response to the discourse taking place over it, most of it presumably negative towards Israel. Zhou writes, “Chinese are apt to describe their modern history as ‘full of disasters and tragedies.’ Much of that was due to causes originating from ourselves. For the Jewish people, however, the causes are almost all external. All of the enormous calamities they have encountered for the past thousands of years have been solely due to their religious faith. These suffering people who have endured years of wars, who have long wandered in exile, and who have gone through a crucible of famine, torture, killings, and humiliation, have held on to their faith from beginning to end. They prospered in adversity and exhibited stubborn resolve in their growth and development. Not only did they keep from falling down, they were even able to miraculously garner worldwide recognition for their great achievements in technology, military, education, modern agriculture, and other fields.”
Zhou’s blog post has attracted over 350,000 views and nearly 5,000 comments which range from harsh condemnation to unabashed praise. The Southern Metropolis Daily article states that Zhou’s post has given rise to “pro-Zhou” and “anti-Zhou” camps in the blogosphere. The anti-Zhou blogger highlighted by the article writes, “Your defense [of Israel] brings to mind the behavior and actions of Japan and its people. If you choose to ignore their perpetration of inhuman massacres and pillaging, there are also many things you can praise about the various achievements of their culture and civilization. … The problem is that this admiration of Japan’s achievements and my understanding of its crimes of invasion against China, Asia, and the world are two different things!”
The pro-Zhou blogger featured in the Southern Metropolis Daily article writes, “During the War of Resistance against Japan in Shanghai, kindhearted sons and daughters of China, while under attack from the Japanese devils, welcomed Jewish refugees who were fleeing a murderous German Fascist regime. Half a century later, no matter whether China adopted a radical Leftist policy or a pragmatic policy, the Israeli people have always felt a deep gratitude towards the Chinese people. Even after being misunderstood by China for 30 years, this country and its people had still quietly done so much for China. To be frank, as a Chinese citizen, I hold positive feelings towards Israel and the Jewish people. A people that understand gratitude are the true friends of the Chinese people.”
In the absence of strong historical, ideological, or religious connections to the Middle East, Chinese views of the Israeli-Palestinian issue are all over the map as the different viewpoints above illustrate. However, what is notable is that in spite of nearly universal condemnation of Israel’s actions in Gaza and the Chinese government’s critical remarks, there still exists a significant vocal contingent of Israel supporters and admirers in China.
Two subjects were on top of the list in the French media this week: The hot war in Gaza and the cold war between Kiev and Moscow over natural gas supplies.
Let's start with Gaza. Up until Nicolas Sarkozy's successful bid for the presidency in 2007, the French position on the Palestinian question seemed, at least from this shore of the Atlantic, mostly pro-Palestine. In fact, former president Jacques Chirac was widely perceived as pro-Arab. I need not mention the fact that among Israeli political elites, president Chirac's decision not to run for reelection in 2007 was greeted with sighs of relief. They knew that Sarkozy, the emerging leader of the UMP, was a lot more pro-western and that he had a very good shot at winning the presidency.
Even if I have yet to find a single piece of significant legislation passed by this French government regarding internal affairs, I must admit that Mr. Sarkozy's record on the foreign policy front is impressive. He harnessed France solidly into the Western bloc and it shows in the very moderate comments put forward by the Elysée regarding the situation in Gaza.
But this did not discourage left-wing parties and associations to organize rallies against what they call the "Israeli massacre". On Saturday, the biggest of these rallies so far too place, as organizers claimed the presence of up to 100,000 protesters. A lot of these rallies are taking place in other European countries, as it seems that pro-Palestinian groups are speaking much louder than pro-Israeli ones. But all in all, the only interesting story here is the change of tone that the Sarkozy foreign policy has imposed upon the debate. France can definitely be written off the pro-Arab list of countries.
Aside from the crisis in Gaza, the showdown between Moscow and Kiev regarding gas supplies was the other big story this week. As reported by Le Figaro, Ukraine and Russia did sign on Saturday an agreement regarding gas prices and accumulated debts by Kiev.
I would like to remind our readers that this is not the first time that Moscow has tried to bully Western Europe with its natural gas pipelines. The crisis did get jump-started by Kiev's decision to shut down deliveries to Western Europe, but this is mainly noise. We need to keep our eyes on the ball; the main narrative for this crisis is Moscow's will to bully neighbor countries. From a French perspective, we cannot say that president Sarkozy spoke in full force on this issue. As outspoken as he has been regarding the situation in Gaza, the crisis in Georgia in August 2008 or other topics, he has been remarkably mute regarding Moscow's actions and intentions.
Does the Elysée have a plan to diversify its energy sources in order to rely less upon Russian gas deliveries? Not sure; but if they do have one, we have not heard much of it yet.
Public transportation tariffs (buses, trains, and subway) will rise by 20%-25% on Monday.
The measure is driven by the government’s desire to lower costly budget subsides as government revenue is staring to erode on the back of lower commodity prices and the overall sharp deceleration of economic activity.
This is the second tariff increase in six years; the measure is expected to save the government ARS800 million.
Over the last few years Argentina's neighbor, Chile, used the windfall in copper revenues towards a $21 billion special fund that can bankroll future budgets for nearly a decade. Instead, Argentina used the money from high commodity and agricultural export prices (including soybeans) to increase government spending. Both Néstor Kirchner (president from 2003 to 2007) and his wife, Cristina Fernández (president since December 2007) have vowed to reverse free-market policies, and the economy reflects their approach.
Argentina also embarked on market-unfriendly moves, boosting government revenue by taking control of private pension funds and raising taxes on agricultural exports. Protesting farmers blocked highways throughout the year. Argentinians began withdrawing money from private bank accounts, fearing government seizure.
The farmers were protesting a proposed sliding-scale taxation system for agricultural exports which eventually didn't pass. A pension nationalization law did pass and was made into law on December 2008. Ten bank-owned pension funds worth over $26 billion were taken over by the government, in an attempt to bolster its finances and prevent a second default in a decade.
The Fernández administration denies that motive, claming instead that the pension funds were mismanaged, and that the global financial crisis made it necessary for the government to step in to protect investors.
Credit-default-swap spreads on its government debt have surged to horrifying levels, signalling that investors see a high risk of default.
The specter of a default has not vanished, in spite of the pension takeover, since its $21bn in debt-servicing obligations is due this year. Jittery investors are also worried that Ecuador's voluntary default on its debt last month might embolden Fernández to follow Ecuador's precedent.
Setting aside the emotional and financial impact to Argentine workers as they contemplate their futures, the government has ensnared itself in an accounting dilemma. If spending continues in the face of falling revenue and limited credit, Buenos Aires eventually will hit a wall. And so far, its only recourse has been to liquidate what few financial assets remain in-country. Although there could yet be a grand scheme that will compensate for this problem, the government has shown no evidence thus far that one exists. The odds of an outright debt default and a return to the economic crisis of 2002 are growing.
January 9, 2009
Petraeus linked Afghanistan's fortunes directly to Pakistan's, where a U.S.-backed civilian government is struggling and the country's ability to control militants along its border with Afghanistan is in doubt.
"Afghanistan and Pakistan have, in many ways, merged into a single problem set, and the way forward in Afghanistan is incomplete without a strategy that includes and assists Pakistan," and also takes into account Pakistan's troubled relationship with rival India, Petraeus said.
This is certainly true, but think about the implications. The U.S. and NATO have not been able to shore up Afghanistan seven years after invading. They're now asserting that they can only solve that problem by tackling a much larger, immensely more complicated one in India/Pakistan.
But why should we have any confidence that this gambit can succeed, if the smaller problem of Afghanistan has proven so difficult? Wouldn't setting more modest goals for Afghanistan make more sense?
Stephen Walt picks up a line you hear frequently in the debate over Israeli military action – that those who oppose the action are actually Israel’s true friends, because stopping a friend from making a mistake is better than reflex cheer leading (which our political leaders engage in unrepentantly).
It’s a valid sentiment to be sure, but it strikes me as essentially conceding the argument to Israel’s reflex boosters. The question isn’t fundamentally “what is or is not good for Israel” because Walt – like me – is not a citizen of Israel. Nor are members of Congress. The proper question is, is their course of action good for American interests. That – and not questions of relative degrees of fidelity to Israel – needs to the be locus of the debate.
Indeed, framing your criticism as coming from a friend of Israel, already concedes the important premise that the proper lens to view these events are Israel’s – not America’s. It makes the important assumption that American and Israeli interests (and enemies) are identical.
But if you don't like that "thought experiment," here's another, offered by philosophy professor Joseph Levine at University of Massachusetts: what if Hamas was hiding out among the civilian population of Tel Aviv, and attacking Israel from within? Would the IDF be using massive force to eradicate them? Unless you think that Palestinian and Israeli civilian lives are not equal, what justifies the current policy?
Israel is hardly unique in placing a higher value on its own citizens' lives than it places on the lives of others, and we should not forget that U.S. forces have caused plenty of civilian casualties in places like Iraq and Afghanistan. "The strong do what they can, and the weak suffer what they must." But that doesn't make it right, and there are good reasons to question whether it will even be effective in this instance.
There's so much that's very wrong with this hypothetical scenario. First, as a well regarded realist, you'd think Walt could appreciate the fact that the Israeli government - or any government, for that matter - is first and foremost responsible for the well-being of its own citizenry. If Hamas were embedded within an Israeli city it would of course change the retaliatory options. The IDF is charged with the security of Israelis, not the citizens of the world. Walt admits as much.
I'm inclined to agree with Ross Douthat on this, who rightly argues for a new kind of realism in the realm of foreign policy. What often passes as such in contemporary forums is nothing more than misplaced and misguided contrarianism.
January 6, 2009
Israel's "right to defend herself" has taken the lives of over 500 Palestinians and up to 120 (roughly over 20 percent) of those are children. Home-made rockets from Hamas have killed 20 Israelis in eight years and approximately four Israelis have been killed during the current conflict. Robert Fisk sums it up nicely in his piece for the Independent:
We've got so used to the carnage of the Middle East that we don't care any more – providing we don't offend the Israelis. It's not clear how many of the Gaza dead are civilians, but the response of the Bush administration, not to mention the pusillanimous reaction of Gordon Brown, reaffirm for Arabs what they have known for decades: however they struggle against their antagonists, the West will take Israel's side. As usual, the bloodbath was the fault of the Arabs – who, as we all know, only understand force. ... And we demand security for Israel – rightly – but overlook this massive and utterly disproportionate slaughter by Israel. It was Madeleine Albright who once said that Israel was "under siege" – as if Palestinian tanks were in the streets of Tel Aviv.
The fact remains that Israel has carried out its response to Hamas rocket fire with unbridled brutality and it is the Gazans who bear the brunt of this response. Those same Gazans who have been suffering under Israel's economic and aid embargo over the past year. It is safe to say that the Palestinians in Gaza have known nothing but misery over the past year and the so-called "international community" has remained impotent in the face of suffering. During the past few days, according to a Palestinian legislator on CNN's Rick Sanchez, 17 entire families have been wiped out in Gaza.
The international press is banned from entering Gaza so the stories we are getting out of the conflict can only be half the picture. In fact, if one looks at Freedom House's World Press Rankings 2008 Israel flies by with a ranking of "Free." Israel banned journalists from entering Gaza well before the Israeli siege, opened it up again, and then placed a ban when the current conflict started. How they get a ranking of "Free" is beyond me but falls perfectly in line with the point that Robert Fisk makes; the west grants Israel a free ride. And unfortunately it is only the west that have any bargaining power with Israel while they also supply them with the weapons to unleash in their heavy-handed responses.
Furthermore, the Israelis have now started targeting houses, mosques and not-so hidden tunnels where they suspect Hamas militants are hiding out. All the while, Palestinians have no means for warning their citizens of impending air strikes because they do not have the resources for air-raid sirens, according to ABC chief foreign correspondent Richard Engel. But then again who knows if that's true considering the Israelis wont allow foreign press into Gaza.
Hospitals in Gaza, as predicted, are overflowing with patients and will continue to have trouble dealing with casualties adding to the suffering and chaos in Gaza. Witnesses report they have already seen Israeli tanks in Gaza City, which can only add to Gaza's hospital crisis.
President-Elect Barack Obama has stayed largely silent concerning the conflict in Gaza. Whether any "change" in the American stance towards the Palestinians and Israelis begins under his administration is still highly unlikely. He himself has repeated the apologist and open-ended statement that Israel has the right to defend itself, yet the American's do not have the political will to define exactly what that entails.
At the moment Israel interprets it to mean that they can take military action, whenever, wherever and by whichever means they find suitable. Obama should help to craft some tangible guidelines for what "the defense of Israel" actually means if he hopes to make any leeway with the Arab and Muslim world. America's policy towards Israel is like that of a mother to her child: Unconditional love. If America wants to be a just power in the world she should learn that she has other children in the region.
Forty rocket attacks over the past few days is evidence that Hamas still has ample capability when it comes to light rocket fire. Israel has stated that its intentions are to "create the conditions" where Hamas does not have the capability to fire rockets into Israel. This means the alleged flow of arms from Iran through Egypt is to be contained. Even if the flow is contained for the next few months, it is almost certain Hamas will find new means.
The Israelis have greatly harmed their efforts to de-legitimize Hamas, who were said to have a 14% approval rating before the current conflict. The Palestinians understand that Hamas has provoked the Israelis, but the bombs that fall around them are coming from Israel fired from weapons provided by the Americans. It is logical that Palestinians rally behind those that are resisting an invading army. Logical, yet unfortunate, because this support is likely to perpetuate the miserable rule of Hamas in Gaza.
Israel has made it clear that it is not targeting civilians but nonetheless it is civilians who are suffering. When a state uses heavy artillery and air strikes on one of the most densely populated areas on earth it is near impossible to distinguish fighters from a civilian population. It may be too far to state that the Israeli government is committing repeated acts of terror. But being fully aware of the horror their military will inevitably unleash upon the civilians in Gaza, the Israeli strategy is willful ignorance at best.
January 5, 2009
Stephen Walt - sporting his new blog over at Foreign Policy - asks his readers to consider the following:
Imagine that Egypt, Jordan, and Syria had won the Six Day War, leading to a massive exodus of Jews from the territory of Israel. Imagine that the victorious Arab states had eventually decided to permit the Palestinians to establish a state of their own on the territory of the former Jewish state. (That's unlikely, of course, but this is a thought experiment). Imagine that a million or so Jews had ended up as stateless refugees confined to that narrow enclave known as the Gaza Strip. Then imagine that a group of hardline Orthodox Jews took over control of that territory and organized a resistance movement. They also steadfastly refused to recognize the new Palestinian state, arguing that its creation was illegal and that their expulsion from Israel was unjust. Imagine that they obtained backing from sympathizers around the world and that they began to smuggle weapons into the territory. Then imagine that they started firing at Palestinian towns and villages and refused to stop despite continued reprisals and civilian casualties.
Here's the question: would the United States be denouncing those Jews in Gaza as "terrorists" and encouraging the Palestinian state to use overwhelming force against them?
Here's another: would the United States have even allowed such a situation to arise and persist in the first place?
This hypothetical strikes me as a bit odd and simplistic. First off, we needn't start with an unrealistic mental experiment in 1967, since there had always been a group of "hardline Orthodox Jews" living in the Gaza Strip. This small, ancient group - which preceded the first Aliyah (major wave of Jewish immigration) by many, many years - didn't form large militias and kill innocent civilians (this is, of course, a cursory glance at the history, but we're already dealing with a rather unlikely and sweeping hypothetical anyway).
There's too much historical oversight to even begin considering Walt's questions. If the Palestinians were handed all of the land then they'd have been in violation of multiple UN edicts and mandates. Why would the international community even let it get to the point where a group of "hardline Orthodox Jews" were conducting acts of terror against the ruling state? Wouldn't said state be made illegitimate by the partition of 1947? Doesn't the UN seek a return to the '67 borders, thus acknowledging a sovereign Israeli state?
I suspect Max Boot and Juan Cole don't agree on much, but reading their respective takes on Israel's war in Gaza does bring you to the same conclusion: Israel is in a deep bind, both in the short term but especially over the long term.
There has been talk lately that Israel was doing the incoming Obama administration a "favor" by taking Hamas out of the equation, thereby paving the road to a renewed peace process. It could be the exact opposite. By taking military action now, Israel may be demonstrating how untenable its long term prospects are and affirming in the minds of her enemies that time is on their side (see Cole on the demographic details).
Israel cannot extirpate every Hamas member in Gaza without, as Boot writes, resorting to tactics that it and the world would rightly find abhorrent. But they can cause enough damage to ensure that the residents of Gaza are even less amenable to a negotiated settlement than before - a settlement that everyone recognizes is the ultimate path toward security for Israel and statehood for the Palestinians. Gaza - the security problem for Israel and the governance problem for the 1.5 million Palestinians that reside there - does not go away when (or if) the IDF withdraws.
something you need to look at here is the risk that weakening Hamas will only lead to the rise of more extreme groups. The high level of power that Hamas had achieved as of last week was, after all, precisely the result of a deliberate Israeli campaign to weaken Fatah. The hope was that this would bring some more accommodationist Palestinians to the fore, but instead the reverse happened. And now that Israel is going about trying the same thing with Hamas, one needs to worry that Hamas will be displaced by Salafist groups who think Hamas is too weak-kneed.
This is a fair concern, but I find this Salafist argument to be highly unlikely. Hamas, after all, was put in power for very pragmatic purposes. The idea that Gazans elected Hamas to power as one component in the reinstatement of a creeping 'global caliphate' has been grossly exaggerated. At the end of the day, it's a question of administration and honesty. Hamas is a vast network of politicians, militants and social servants. They were ultimately given power because Fatah had proven too corrupt and too divisive to govern (which, incidentally, they are).
This is what differentiates Hamas from Palestinian Islamic Jihad (PIJ), and PIJ from radical Salafists hellbent on strict Koranic doctrine. They all share a level of extremism, but Hamas is the only one of the three that has presented a governing platform that actually enjoyed popular support.
As we've learned in Afghanistan, Iraq, and even Somalia, it's stability and steady governance that often make Islamic radicals an attractive option to their usually more corrupt and autocratic alternatives. But radical groups without legitimate means to administer such government are doomed to failure (as we saw in the horrid form of "governance" Al-Qaeda implemented in Ramadi).
Israel has held to pretty limited goals since initiating the Gaza assault, and I've seen no indication that it expects to completely scrub Hamas from the territory. Clearly, there will be leaders and militants left behind to pick up the pieces and rebuild. I highly doubt, however, that Gaza will be left to an even further fringe.
For a more thoughtful analysis on the political implications of supplanting Hamas, please check out our friend and RCW contributor Meir Javedanfar.
I was doing a roundup of posts for my blog's Monday Carnival of Latin America and the Caribbean when I came across this image:
The rusted wrought-iron balconies and fading handcrafted doors look back to an older era of artisanship and pride of ownership, now gone. Paint colors from decades ago, stucco coming apart from the wall, graffiti and mold, signal decay and pain.
Hope has bypassed that wall.
The photograph is in an article about Steven Soderbergh's latest movie, Che, but it is emblematic of today's Cuba: the only recent paint that building has seen is the iconic figure of Che (most prominently the Korda photo), whose myth and fiction override the reality of the hundreds of people he killed:
But a glance beneath the surface glamour of Alberto Korda's 1960 beret-and-curls photograph of Guevara is enough to expose the less-than-romantic reality. At the time he posed for Korda's camera, Guevara was jailer and executioner-in-chief of Castro's dictatorship. As boss of the notorious La Cabaña prison in Havana, he supervised the detention, interrogation, summary trials and executions of hundreds of "class enemies".
We know from Ernest Hemingway – then a Cuban resident – what Che was up to. Hemingway, who had looked kindly on leftist revolutions since the Spanish civil war, invited his friend George Plimpton, editor of the Paris Review, to witness the shooting of prisoners condemned by the tribunals under Guevara's control. They watched as the men were trucked in, unloaded, shot, and taken away. As a result, Plimpton later refused to publish Guevara's memoir, The Motorcycle Diaries.
There have been some 16,000 such executions since the Castro brothers, Guevara and their merry men swept into Havana in January 1959. About 100,000 Cubans who have fallen foul of the regime have been jailed. Two million others have succeeded in escaping Castro's socialist paradise, while an estimated 30,000 have died in the attempt.
The woman in front of the building looks at the contents of a small shopping bag, where she may be carrying the meager rations that Fidel Castro introduced in the country in 1962, rations that compare to that which Cuban slaves received in the 1840s.
A month's rations would fit in that bag.
Of course there's a propaganda aspect, and the Cuban government places the blame for nearly everything on the USA and the embargo, el bloqueo, even when the US is Cuba's #5 trading partner according to the Cuban government's own figures:
Trade data for 2007 posted on the website of Cuba's National Statistics Office placed the U.S. fifth at $582 million, compared with $484 million in 2006, including shipping costs.
January 3, 2009
Whatever you think of the merits of this step, I think we can take it as implicit acknowledgment by the IDF that the past week’s worth of air strikes were, though deadly to the people killed or maimed by high explosive and flying rubble, basically useless and undertaken without real strategy.
January 2, 2009
The recent flare up in Gaza is causing more anger in the Iranian government. There have been several demonstrations, including the burning down of the Benetton shop in Tehran and recruitment of suicide bombers. The Iranian government has also embarked on setting up a tribunal to try Israeli officials and has called for more stringent boycotting of companies who do business with Israel.
These demonstrations and calls for help are directed by Iran's Supreme Leader, Ayatollah Khamenei. He is ultimately in charge of Iran's policy, and as such acts would not be under taken without his permission. There are a number of reasons behind his current strategy:
1. To pressure Western governments to put an end to Hamas's destruction. Khamenei is trying to say to them that we don't have a border with Israel, but our anger should be taken into consideration, because we are a new power in the region and our opinion should be taken seriously.
2. There is also the question of Egypt and Saudi Arabia. Iran sees both of them as trying to muscle in on Gaza, an area which Tehran considers as its sole sphere of influence. To Tehran's anger, the Egyptians are not budging. Khamenei is hoping that through public gestures such as setting up courts to try Israeli officials, the Egyptian public would feel encouraged, and thus would place pressure on Mubarak to help Hamas.
3. Iran is an Islamic Republic. Compared to all of the chants we used to shout as children (Death to America, USSR, Saddam,) the only one Iran is still holding true to is 'Death to Israel.' Without it, the regime would lose the last revolutionary DNA which holds its identity together.
4. Iran is trying to be the leader of the Islamic world. Khamenei believes that the majority of the Islamic world is angry about what is happening in Gaza, and he is right. He sees the Muslim government's silence as being against the wishes of locals. By saying what he believes Muslims feel world wide, he is trying to be their representative. There is of course no free lunch. In return his hope is that they will get their government to back Iran's nuclear program.
The one person who has the most to gain is President Ahmadinejad. He has just submitted a controversial bill to the Majlis to cut state subsidies. This will make him even more unpopular. The Gaza affair is a gift to him, which he will use to distract the Iranian people from the economic pain which is about to hit them.
Meir Javedanfar also blogs at The Middle East Analyst. |
Presentation of Toulouse
The municipality of Toulouse (437,715 inhabitants in 2006 [urban area, 1,102,882 inh.]; 11,830 ha) is the préfecture of the Department of Haute-Garonne,
préfecture of the Region Midi-Pyrénées and the capital of the traditional province of Languedoc.
Municipal flag of Toulouse
The flag of Toulouse, featuring the yellow Cross of Toulouse on a red field, is the banner of arms of the Counts of Toulouse.
The first known Cross of Toulouse is shown on Count Raimond VI's
seal, dated from 1211. Then widely used all over
Languedoc, the Cross of Toulouse appeared on the municipal arms of Toulouse and the
provincial arms of Languedoc in the 14th century.
Pierre Saliès (Archistra, December 1994) claims that the
Cross of Toulouse is a modification of the Latin Cross, attributed to
Count Raimond VI. In 1099, Raimond VI took part to the reconquest of
Jerusalem with the Crusaders. As a Crusaders' chief, Raimond would
have adapted a cross slightly different from the Latin Cross bore by
the low-rank Crusaders. According to this theory, the edges of the
arms of the cross were cut into two pieces and curved. To be fixed on
a shield, such a cross required twelve rivets. The design would have
progressively evolved towards the Cross of Toulouse.
Roger Camboulives believes that the origin of the Cross of
Toulouse is pre-Christian. Its origin could have been a twelve-ray
solar wheel. Such a cross has been found in Saint-Michel-de-Lanes, in
Lauragais, not far from Toulouse. The twelve discs, possibly symbolizing
the twelve zodiacal mansions, were in the 13th century rather
associated with the twelve apostles. A remote origin of the cross is
possible, and Camboulives mentions the Turfan cross, in
Eastern Turkestan, as a possible
archetype of the Cross of Toulouse. According to this theory, the
emblem would have traveled from East to West and materialized the
migration of the Wisigoths from the Black Sea to Toulouse. Similar
crosses have been found in northern Italy (Pisa and Venice),
Provence (Venasque and Forcalquier) and
Spanish Catalonia (Santa María de l'Estany).
The cross could have been brought to Count Guillaume Taillefer
(951-1037) by his wife, Emme de Venasque, Marchionness of Provence.
Ivan Sache, 24 April 2003
Stade Toulousain
Flag of Stade Toulousain - Image by Ivan Sache, 17 October 1999
Stade Toulousain is one of the leading French rugby
teams.
The club's flag, vertically divided red-black, the club's colours, is hoisted in the stadium. |
The US Department of Transportation (DOT) has granted controversial airline Norwegian Air International (D8, Dublin Int'l) a Foreign Air Carrier Permit (FACP) thus bringing to a close a drawn-out, and often acrimonious, authorization process.
In its decision finalizing a tentative ruling issued in April of this year, the regulator said the case was among the most "novel and complex" it had ever undertaken.
"We have taken the necessary amount of time to review and consider the comments from a wide range of stakeholders," it said justifying the three-year review process.
The DOT said that among the most difficult aspects of the case was the interpretation of Article 17 bis contained within the EU-US Open Skies Treaty. The clause governs labour standards.
Opponents to NAI's application had argued that its plan to employ cabin crew outsourced from a third-party company domiciled in Singapore, rather than directly employing personnel itself, undermined the terms of the Article and would violate the DOT’s statutory public interest goal of encouraging fair wages and working conditions. They argued this was sufficient grounds for the DOT to reject NAI's application, an argument the US Attorney General's office later refuted in its analysis of the treaty. It upheld the Department of State and the DOT's conclusion that so long as an applicant airline satisfied all the requirements for an FACP as prescribed under the treaty, Article 17 bis did not provide an independent basis upon which the US may deny the carrier’s application
"Regardless of our appreciation of the public policy arguments raised by opponents, we have been advised that the law and our bilateral obligations leave us no avenue to reject this application," the DOT said. "Therefore, ..., we have decided to make final our tentative decision to grant the request of NAI for a foreign air carrier permit."
The approval now sets a precedent for the issuance of an FACP to another of Norwegian's units, Norwegian UK (DI, London Gatwick). In July, the DOT denied the UK-based carrier exemption authority in the face of strong resistance from airlines, trade unions, and lobby groups on either side of the Atlantic.
“We welcome the long overdue news that Norwegian Air International (NAI) has been awarded a foreign carrier permit by the US Department of Transportation," a Norwegian (DY, Oslo Gardermoen) spokesman said. “This approval finally makes it possible for us to plan the Cork to the U.S. routes we, and many others, have been looking forward to. We also now look forward to our foreign carrier permit for Norwegian Air UK (NUK) being approved next." |
Introduction {#Sec1}
============
HLA is the earliest and most widespread example of personalised medicine, in relation to transplantation biology. It is also the region of the genome associated genetically with more diseases than any other, including infectious conditions, but particularly autoimmunity. Resistance to disease is thought to drive the extreme polymorphism of HLA, but other mechanisms have been proposed. In the last two decades, attention has turned to unexpected roles for MHC molecules such as in modelling of synapses (Shatz [@CR66]) and, as discussed in this volume by Colucci and by Persson et al., pregnancy. In support of the former, many different microbial species, particularly viruses and bacteria, elaborate proteins that block antigen processing and presentation. The human MHC encompasses over 200 genes, at least 50 of which have functions in immune defence. They include the following: three classical and three non-classical class I loci, plus several pseudogenes; four classical and two non-classical class II loci, each comprising two genes (A and B chains); four complement components; two immune regulators; 10 genes involved in inflammation or activation of NK cells; three genes involved in stress responses; six genes to do with leukocyte maturation; five genes encoding antigen processing elements; and two other IgSF molecules. Transplantation is discussed in this volume in relation to allorecognition and viruses by Frans Claas.
Class I processing and presentation {#Sec2}
-----------------------------------
MHC class I molecules have evolved mainly to present peptides from pathogens that replicate within host cells, in particular viruses. The presence of three classical class I isotypes HLA-A, HLA-B and HLA-C, with different peptide-binding characteristics, ensures that pathogens with different protein coding capacity remain visible to the immune system. Alleles of all three isotypes utilise a common pathway for peptide loading. In brief, protein from the pathogen is first degraded in the cytosol, and the resulting peptides are then translocated into the endoplasmic reticulum. Here, they are loaded onto class I molecules before transit to the cell surface for presentation to cytotoxic CD8 T cells.
The proteasome, a cytosolic protease, is largely responsible for generating the peptides that eventually bind class I molecules. It comes in various forms. In many cell types, MHC peptide presentation is linked to constitutive protein turnover and is undertaken by a proteasome that utilises three catalytic subunits termed β1, β2 and β5. In professional antigen presenting cells, or in the presence of interferon, these subunits can be exchanged for βi, β2i and β5i to produce an immunoproteasome, which tailors peptides for MHC binding (Gaczynska et al. [@CR27]). The immunoproteasome has altered specificity and preferentially generates peptides with C-terminal hydrophobic or basic residues. These amino acids are used by the majority of class I alleles to anchor the C-terminus of the peptide into the MHC molecule (Gaczynska et al. [@CR27]; Young et al. [@CR78]). The subunit composition of the immunoproteasome can be further modified by substitution of β5i with β5t to generate the thymoproteasome. The β5t subunit confers reduced chymotrypsin-like activity thereby influencing the generation of peptides with hydrophobic C-terminal residues, amino acids favoured by 90% of MHC alleles (Takahama et al. [@CR67]). Expression of the thymoproteasome by thymic cortical epithelial cells may assist thymic education by generating fewer high affinity peptides and in doing so prevent excessive loss of T cells through negative selection (Takahama et al. [@CR67]; Tomaru et al. [@CR68]).
Once generated by the proteasome, peptides must be rapidly transported into the endoplasmic reticulum to escape the activity of cytosolic aminopeptidases, which would otherwise lead to their rapid degradation (Reits et al. [@CR61]). This is mediated by the transporter associated with antigen processing (TAP), a heterodimer of TAP1 and TAP2 that is encoded in the MHC (Kelly et al. [@CR36]). Human TAP preferentially transports peptides that are 8--12 aa in length (Androlewicz and Cresswell [@CR4]). In contrast to other species, it is promiscuous in the diversity of peptides translocated, and so for humans, the class I molecule itself largely determines which peptides are ultimately presented to the immune system (Androlewicz and Cresswell [@CR4]). Although there is limited flexibility in the length of peptide that MHC I molecules can accommodate, those that are too long to bind particular alleles can be trimmed at the amino-terminus by ER resident peptidases ERAP1 and ERAP2 (Chen et al. [@CR16]). A related enzyme, insulin-regulated aminopeptidase (IRAP), performs a similar function in endosomal compartments and is important in cross-presentation (Saveanu et al. [@CR64]). In addition to its transport function, TAP forms the central pillar of the peptide-loading complex, an assembly of proteins that ensure efficient loading of peptide onto MHC class I (Blum et al. [@CR9]; Cresswell et al. [@CR22]; Neefjes et al. [@CR54]). After initial association with calnexin, empty MHC I/β2 enters a complex comprising TAP, two general folding chaperones, ERp57 and calreticulin, and tapasin, a dedicated class I chaperone (Cresswell et al. [@CR22]). Tapasin functions to bridge class I molecules awaiting peptide with TAP and is essential for the efficient optimization of class I peptide selection (Williams et al. [@CR77]). A molecular tug-of-war between peptide and tapasin is the basis of the selection process (Fisette et al. [@CR26]). Tapasin exerts force upon the peptide-binding domain resulting in opening of the grove and release of low affinity peptide. High affinity peptide binds strongly to the MHC molecule and is able to overcome the force exerted by tapasin resulting in closure of the groove and release of tapasin (Fisette et al. [@CR26]). Interestingly, some class I alleles optimise peptide selection in the complete absence of tapasin, possibly as a mechanism to counter pathogen subversion (Williams et al. [@CR77]). For these tapasin-independent alleles, peptide optimization is poorly enhanced when tapasin is present (Williams et al. [@CR77]). More recently TAPBPR, a second tapasin-related MHC I chaperone, has been shown to enhance peptide optimisation and also reduce the diversity of peptides presented by MHC class I (Hermann et al. [@CR30]). How these two chaperones cooperate is yet to be determined, but ultimately class I with its peptide cargo arrives at the cell surface for presentation to T cells. Recently, attention has focused on the association of certain HLA-B and HLA-C alleles and resistance to disease (Carrington et al. [@CR14]). Whilst this might be predictable given their role in immune surveillance, an unexpected correlation with the level of cell surface expression of HLA-C and prevalence of cytotoxic T cell responses to HIV was observed (Apps et al. [@CR7]). Increased surface expression may correlate with a more focused peptide repertoire and may be a more general feature of MHC biology than previously appreciated (Chappell et al. [@CR15]).
The MHC also encodes three non-classical molecules HLA-E, HLA-F and HLA-G that show limited polymorphism, covered here by Persson et al. The best defined of these is HLA-E which interacts with inhibitory receptors present on the surface of NK cells to prevent killing but may also present peptides from microorganisms to T cells (Braud et al. [@CR10]; van Meijgaarden et al. [@CR47]). It is limited in the diversity of peptides it can bind, preferentially accommodating peptides that originate from signal sequences derived from classical HLA-A, HLA-B and HLA-C (Miller et al. [@CR49]). Interference in the expression of classical class I molecules, such as occurs during viral infection, may be detected by 'missing-self', or lack of surface HLA-E expression. The functions of HLA-F and HLA-G are less well-characterised. HLA-G expression was first reported in placental trophoblast cells and a role in acceptance of the foetus 'allograph' proposed. Here, HLA-G may influence the function of NK cells directly by interaction with receptors on NK cells, monocytes in the form of an HLA-G dimer (Clements et al. [@CR18]), or indirectly by supporting the expression of surface HLA-E. Caution has been suggested in interpreting reports of functions in other settings where consensus on basic issues such as confirmation of expression is lacking (Apps et al. [@CR6]). The function of HLA-F is even more enigmatic with proposed roles in cross-presentation and NK receptor binding (Burian et al. [@CR12]).
MHC class II processing and presentation {#Sec3}
----------------------------------------
MHC class II molecules represent a second group of surface receptors whose function is to present peptides to T cells, in this case various CD4 subsets. There are three classical isotypes, HLA-DP, HLA-DQ and HLA-DR, each composed of an alpha and a beta chain, which, with the exception of DR alpha, show extensive polymorphism. The exact number of alpha beta pairs expressed by an individual will vary depending on the number of alleles inherited from parents and their ability to pair in *trans*. MHC class II molecules show limited distribution and constitutive expression is largely limited to dendritic cells, B cells and cells of the monocyte/macrophage lineage but can be induced in other cell types (Unanue et al. [@CR71]). During biosynthesis, alpha and beta chains assemble in the endoplasmic reticulum with a folding chaperone, invariant chain (Cresswell [@CR21]). Targeting motifs encoded in the cytoplasmic tail of invariant chain direct the complex towards loading compartments termed MIIC (Neefjes [@CR53]). During trafficking, Ii is sequentially degraded by proteases leaving a small peptide fragment, CLIP, in the binding groove. CLIP is exchanged for peptide that is generated by proteolysis of antigen that enters the endocytic pathway. Partial unfolding of protein is favoured by the reduction of inter or intra-molecular disulphide bonds by GILT, a thiol reductase and more generally by the low pH environment (Arunachalam et al. [@CR8]). The protein is exposed to proteolysis, by a range of endopeptidases and exopeptidases, many of which show broad cleavage specificity (Lennon-Dumenil et al. [@CR39]). Members of the cathepsin family are important not only for generating antigenic peptide but also for the degradation of invariant chain (Riese et al. [@CR62]). Studies involving an asparginal endopeptidase suggest that key cleavage events may control subsequent generation of peptide epitopes and that proteolysis may not be as redundant as once thought (Antoniou et al. [@CR5]).
Once generated, antigenic peptide can replace the surrogate peptide CLIP. This exchange process is facilitated by HLA-DM, a non-classical class II-related molecule (Kelly et al. [@CR35]; Mellins and Stern [@CR47]). Crystallographic studies have captured stages in this exchange process (Pos et al. [@CR58]). Large conformational changes in DR alpha facilitate peptide dissociation and force incoming peptides to compete with repositioned DR residues for access to the P2 position and P1 pocket (Pos et al. [@CR58]). Different alleles show varying degrees of DM dependency, suggesting pathways for DM-dependent and DM-independent CLIP exchange (Wieczorek et al. [@CR76]). Additionally, polymorphic variants of DM show differential catalytic activity upon different class II substrates adding further complexity to the system (Alvaro-Benito et al. [@CR3]). DM likely interacts with a natural transition state of class II, as it samples different conformations and is essential for efficient peptide loading by some alleles and less so for others (Wieczorek et al. [@CR76]). As observed in computer-driven simulations, a natural plasticity in class II underpins both the DM-dependent and DM-independent exchange mechanisms (Wieczorek et al. [@CR76]). Peptides loaded onto MHC class II in the presence and absence of HLA-DM may adopt different conformations that are recognised by non-overlapping T cell subsets (Mohan and Unanue [@CR50]). The latter may escape thymic editing and predispose to autoimmunity (Mohan et al. [@CR51]).
The activity of DM is controlled by DO, a molecule bearing close amino acid and structural similarity to DP, DQ and DR (Guce et al. [@CR29]; Trowsdale and Kelly [@CR69]). DO requires association with DM to prevent its degradation and to allow egress from the ER (Liljedahl et al. [@CR44]). It adopts a conformation similar to HLA-DR when in association with DM, acting as a substrate mimic to block DM activity until it reaches a low pH environment (Guce et al. [@CR29]). Under late endosomal/lysosomal conditions, acid-promoted destruction of DO occurs releasing free DM (Jiang et al. [@CR34]). The role of HLA-DO is still controversial but likely involves fine-tuning of the peptide repertoire presented by MHC II, possibly by limiting the location of DM activity within the endocytic pathway or more specifically within the sub-domains of the multivesicular peptide loading compartment (Denzin and Cresswell [@CR24]; Jiang et al. [@CR34]; van Lith et al. [@CR45]).
Haplotypes and LD {#Sec4}
=================
The HLA region is under extensive linkage disequilibrium, leading to suggestions that the sets of polymorphic genes on haplotypes act in concert to coordinate presentation of the health of cells to the immune system. Just as it may be argued that by maintaining polymorphic TAP transporters near to class I genes allows for functional coordination on haplotypes, alleles of other genes within the MHC may be tuned as a set to balance immune responses. In relation to function of NK receptors, MHC haplotypes form two schools in which alleles are coordinated (Horowitz et al. [@CR31])). Other candidate genes for coordinated functional linkage include TNF, LTA, C2, C4, BF, MICA and MICB. This phenomenon may account at least in part for the extensive linkage disequilibrium over the region (Dawkins et al. [@CR23]; Yunis et al. [@CR79]). As new techniques for rapidly compiling complete MHC sequences replace laborious cloning and assembly more haplotypic relationships between genes will become evident (Horton et al. [@CR32]; Lenz et al. [@CR40]; Norman et al. [@CR56]; Norman et al. [@CR55]).
Disease association {#Sec5}
===================
More diseases are associated with the MHC than with any other region of the genome (Lenz et al. [@CR41]; Trowsdale and Knight [@CR70]). The majority of these are autoimmune conditions. Two conditions where the MHC has been particularly informative are included in this volume, namely, Celiac disease (Sollid) and Arthritis (Kampstra and Toes). However, since the HLA region is so gene dense, polymorphic and spans 4Mbp, it is understandable that other disorders will be genetically associated. Included are several Mendelian disorders, associations of which are explained as linkage disequilibrium with HLA alleles. An example is congenital adrenal hyperplasia, which is due to alleles of the CYP21 genes, in the class III region (White et al. [@CR75]). It is widely assumed that resistance to infection is driving the extreme MHC variation, although direct evidence for this is limited. Escape variants of HIV-1 are consistent with the need for continual novelty in peptide-binding grooves (Moore et al. [@CR52]). Several viruses down-modulate HLA expression to escape T cell or NK cell recognition, which attests to its importance for disease resistance.
Genome-wide association studies (GWAS) for autoimmune conditions implicate contributions throughout the genome, but the MHC remains the most important link, with a greater effect size (Lenz et al. [@CR41]). These disorders are generally associated with discrete class I or class II alleles. This is consistent with involvement of specific peptides. For example, narcolepsy, the sleeping disorder, is associated with HLA-DQB1\*006:02 in at least two different populations (Mignot [@CR48]). The recent finding that a specific flu vaccine gives rise to narcolepsy in a small group of young individuals is consistent with a complication of immune response to the vaccine (Ahmed et al. [@CR1]). Narcolepsy is one of the best examples of a clear MHC association. It has been difficult to identify key MHC loci association in other disorders. This is likely because they may be influenced by more than one HLA locus. In addition, the gene density over the MHC and the strong LD make analysis very difficult, unless extremely large cohorts of patients and controls are studied to generate sufficient statistical power. For example, sarcoidosis is an autoimmune disease associated with HLA-DRB1\*003. There are reports of an additional, independent association with BTNL2, but these are difficult to confirm, since the two genes DRB1 and BTNL2 are adjacent (Valentonyte et al. [@CR72]). Most autoimmune conditions are multifactorial and appear to involve many gene variants as well as environmental effects. Clearly, more reliable data may be obtained by larger studies. This has been facilitated recently by imputation of HLA type to 4-digit resolution based on high density SNP genotyping (Leslie et al. [@CR42]). Infectious diseases associated with the MHCs of a variety of species are covered in detail in this volume.
There has been progress in understanding one set of MHC-associated conditions, namely drug sensitivities (Illing et al. [@CR33]). This topic is reviewed here by the key contributors to understanding the molecular mechanisms behind the pharmacogenomics; McClusky this volume. Abacavir sensitivity is strongly associated with *HLA-B\*057:01*. Purification of HLA-B\*057:01 from cells treated with abacavir indicated that the drug bound to the antigen-binding cleft, pushing up peptides and thereby leading to stimulation of a set of T cells. The drug non-covalently bound to the B\*057:01 molecule, breaking tolerance (Illing et al. [@CR33]).
Other conditions linked to the MHC region include cancers of a suspected viral aetiology, such as nasopharyngeal carcinoma and Hodgkin's lymphoma. There are reports of a variety of other condition such as schizophrenia and complement C4 genes, embedded in the MHC (Sekar et al. [@CR65]).
Receptors {#Sec6}
=========
As discussed above, antigen presentation is probably the main raison d'etre of class I and class II molecules. Both classes I and II interact with T cells, through their receptors, which result in modulation of immune responses in a peptide-dependent fashion. But, there are a variety of ways in which the information from these molecules may be interpreted. Other sets of receptors may detect differences in MHC classes I and II in peptide-dependent and peptide-independent ways resulting in 'missing-self', releasing inhibition by inhibitory receptors on NK or other cells, as discussed in this issue.
KIRs bind sets of HLA molecules generally assumed to be associated with peptide (Saunders et al. [@CR63]). Changes in the peptide associated with class I molecules can prevent inhibition of NK activation (Fadda et al. [@CR25]). In this regard, they have peptide:HLA specificity, which may be associated with effects on infections with viruses. Examples include the inhibitory receptor KIR2DL3 and hepatitis C and the activating receptor KIR3DS1 and HIV (Buchanan et al. [@CR11]; Martin and Carrington [@CR46]). The main paradigm for Natural Killer cells detecting the presence of class I molecules is encapsulated in the missing self hypothesis, whereby loss of class I or failure to bind to inhibitory receptors signifies that the cell has been compromised. Canaries were taken down coalmines as a warning system for toxic gasses, particularly carbon monoxide. In a similar way, class I molecules are sentinels of unhealthy or infected cells. Some KIR-related receptors on cells of monocyte lineages (LILR, ILR, ILT) also influence immune responses.
Cancer immunosurveillance {#Sec7}
=========================
There is some evidence that the immune system naturally protects against cancer (Corthay [@CR19]). However, the incidence of cancer only increases marginally when acquired immunity is disabled, and it has also been proposed that inflammation may promote tumour growth (Mantovani et al. [@CR45]).
In spite of this, initiatives to direct adaptive T cell immunity to cancer cells are starting to show promise. There has been some clinical success with three approaches: (a) cancer vaccination; (b) with antibodies that stimulate T cells by blocking inhibitory receptor interactions, such as anti-CTLA4, PD1 or PDL1; and (c) with adoptive transfer of anti-tumour T cells. These techniques depend on exploiting T cells from the patients that specifically recognise tumour antigens through MHC molecules. They may be combined to produce greater efficacy.
Before discussing issues associated with MHC and immunosurveillance, it is worth considering the scope of HLA expression. The textbook view is that class I is expressed on all nucleated cells, with a few notable exceptions, and that class II molecules are restricted in expression to professional antigen presenting cells unless induced by cytokines such as gamma-interferon. This simplistic view has been questioned as there is evidence for considerable variation in HLA levels in different tissues. There is debate over whether loss of HLA expression in tumours is governed by immunoselection or whether it is simply a by-product of genomic instability (Campoli et al. [@CR13]).
There are at least three major problems in terms of specificity:Loss of HLA class I or peptide epitope expression---immunoediting
There is abundant evidence for loss of expression of HLA class I as an escape mechanism on a variety of tumours (Garrido et al. [@CR28]). A number of strategies have been suggested to overcome HLA class I defects if they are due to reversible mechanisms and not permanent gene deletion (Lampen and van Hall [@CR37]). These include addition of cytokines or the use of epigenetic modifiers such as inhibitors of DNA methyl transferase or histone deacetylase. However, \~30--40% of tumours appear to have a more permanent loss of HLA class I, due for example to loss of β2microglobulin. In principle, NK cells may be capable of targeting HLA-negative tumours, if they are stimulated by IL-12/IL-18 treatment. It has been proposed that tumours with a more complex genome have a higher frequency of total HLA class I loss (Rashidi [@CR60]). There are also data suggesting that there may not be a simple relationship between class I and cancer survival (Powell et al. [@CR59]).2.Identification of epitopes
After some early work identifying mouse tumour antigens, pioneering work from Thierry Boon's laboratory revealed novel epitopes in human cancers (Coulie et al. [@CR20]). The first of these, derived from the MAGEA1 gene, was a normal cellular component from a gene family. Other anti-tumour cytotoxic T cells (CTLs) were shown to recognise peptides from antigens that were mutated in the tumour cells. In melanoma, some CTLs and some CD4 T cells recognised peptides from proteins specifically expressed in the melanoma cells. It was realised that numerous genes are likely to be mutated in cancer, producing neo-epitopes that could be presented by the specific MHC allele in the patient. Computer algorithms were generated to identify likely peptide sequences that could be presented by the host's MHC molecules. In essence, there are four types of tumour antigen recognised by T cells: (a) viral antigens, in cervical carcinoma or hepato-carcinoma, where there is a clear viral aetiology; (b) antigens from mutated genes, by a variety of mechanisms, including frame-shift, single amino acid changes or protein extension due to loss of the correct stop codon; (c) cancer-germline genes, that also used to be called oncofetal antigens. These are normal proteins expressed in tumours but not in normal somatic tissues. They may have become activated in tumours due to demethylation of their promoter. (d) Proteins over-expressed in tumours. An example of this is MUC1, a protein over-expressed on most adenocarcinomas.
Recent work indicates that peptide targets for CTLs are not randomly distributed amongst the whole range of cellular proteins but rather are focussed onto less than 50% of genes, from selective regions of the genome (Pearson et al. [@CR57]). Some proteins are responsible for several different peptide antigens, and peptides may be derived from non-canonical reading frames (Laumont et al. [@CR38]). Algorithms are being developed to facilitate prediction of relevant self peptides. Another complication is the finding that a large number of HLA-associated peptides are 'spliced' products of the proteasome (Liepe et al. [@CR43]). There are data that suggest tumours that respond best to immunosurveillance have the highest mutagenic load (Alexandrov et al. [@CR2]).3.Autoimmune side effects
It is difficult to predict whether T cell immunotherapy to a specific antigen will be harmful, but several cases have been documented (Coulie et al. [@CR20]). Most immunotherapeutic approaches to cancer have concentrated on T cells, but there is emerging interest in NK cells in the last few years (Childs and Carlsten [@CR17]). Clearly, there is a long way to go in developing better tumour immunotherapy. There is evidence that the local tumour environment is immunosuppressive. It is possible that therapeutic intervention invokes immunostimulation, awakening quiescent T cells already in the tumour environment (Coulie et al. [@CR20]). Introducing inhibitors of immunosuppression may help to complement some of the approaches.
Contributions to the subject of HLA and cancer are included in this volume.
Peptide databases: iedb (<http://www.iedb.org>/); SYFPEITHI (<http://www.syfpeithi.de/)>; [http://www.imtech.res.in/raghava/mhcbn/](http://www.imtech.res.in/raghava/mhcbn).
This article is published in the Special Issue *MHC Genes and Their Ligands in Health and Disease* with Editor Prof. Ronald Bontrop.
This work was supported by grants from the MRC (G0901682) and Wellcome Trust (089821) with partial support from the NIHR BTU Cambridge Biomedical Research Centre. The project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 695551).
|
Q:
Delocalization of positive charge
How is positive charge delocalized? I understand how negative charge can be delocalized. Electrons are mobile and they can move around. But what about positive charge? For example, consider this resonance structure and its composite:
How exactly is that positive charge delocalized? Protons aren't mobile. I can't see any protons moving through the remaining pi-system.
A:
There are no protons moving - protons cannot move in resonance structures. In resonance structures all nuclei must remain fixed, only electrons can move. As you progress from the top-left resonance structure to the top-middle resonance structure you have taken the two pi electrons in what I'll call the 3-4 bond (position 1 being where the bromine is attached) and moved them between carbons 2 and 3, creating a pi bond between carbons 2 and 3 and simultaneously moving the electron vacancy (the positive charge, what a physicist would call a "hole") to carbon 4.
|
/*
Copyright 2019 The Matrix.org Foundation C.I.C.
Licensed under the Apache License, Version 2.0 (the "License");
you may not use this file except in compliance with the License.
You may obtain a copy of the License at
http://www.apache.org/licenses/LICENSE-2.0
Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.
*/
import { Main } from "../../Main";
import { expect } from "chai";
import { constructHarness } from "../utils/harness";
import { FakeDatastore } from "../utils/fakeDatastore";
let harness: { main: Main };
describe("AdminCommandTest", () => {
beforeEach(async () => {
harness = constructHarness();
await harness.main.run(57000);
harness.main.datastore = new FakeDatastore();
});
it("will not respond to itself", async () => {
let called = false;
harness.main.onMatrixAdminMessage = async () => {
called = true;
};
await harness.main.onMatrixEvent({
event_id: "foo",
room_id: "!admin_room:foobar",
sender: harness.main.botUserId,
content: {
body: "help",
},
type: "m.room.message",
});
expect(called).to.be.false;
});
afterEach(async () => {
await harness.main.killBridge();
});
});
|
Urinary tract infection caused by anaerobic bacteria in children.
Anaerobic bacteria were recovered from 5 children with urinary tract infection (UTI). Three had pyelonephritis and 2 cystitis. Two of the patients had a history of prior recurrent UTI. Urine samples were collected using suprapubic aspiration. The anaerobic organism recovered were 3 isolates of Bacteroides fragilis and one each of B. melaninogenicus, Peptococcus asaccharolyticus, and Bifidobacterium adolescentis. Mixed infection was present in 3 children. In 2 cases B. fragilis were present with Escherichia coli, and in the other case two anaerobes were present. All patients were treated with antimicrobial agents for ten to fourteen days and responded well to therapy. Two of the children had a recurrence of UTI with aerobic organisms recovered from their urine within six to eight months. This report demonstrates the association of anaerobic organisms with UTI in children. It is suggested that cultures for anaerobic organisms be performed in symptomatic children whose aerobic cultures show no bacterial growth. |
Baker's Billion Dollar Casino Idea Draws Early Opposition
Steven Snyder, Penn National senior vice president of corporate development, in testimony before a legislative committee last month in Annapolis, said of the National Harbor plan, "Their proposed $1billion project is conditioned [on] a 'competitive tax structure' that can support their investment. So the developers who have already been the beneficiaries of nearly a half billion dollars of taxpayer support for National Harbor and who have allegedly been opposed to the concept of gaming there, now are seeking a tax break to support this 11th hour proposal for a billion dollar resort.
"Alternatively, Penn's $300 million privately financed development at current tax rates at Rosecroft [that] would create a brand new, state of the art integrated gaming and racing facility is not conditioned on the tax rollback outlined in the study commissioned by the County Executive."
Snyder added that Penn National thinks Rosecroft would be the best location for the state's sixth gaming license "for a number of different reasons including ... It would help to revitalize one of Prince George's oldest communities, helping lift what has been a failing business to one that creates prosperity and opportunity in the community around us."
A spokesperson for Baker said, on Penn National's comments, "We acknowledge that there might have to be a different tax structure [than what the state has mandated for existing gaming facilities] for this project, in order to do the kind of high end gaming resort facility that the County Executive wants to have for the county. But that would be up to the state to decide, our position is based on what we would support in the county and that is a high end destination facility that can attract out of state visitors."
Concerns over "favoritism" raised by Gaskins
Joseph Gaskins, chairman of the Prince George's County Contractors Association, questions Baker's plan from another perspective, regarding safeguards for a competitive bidding process for the award of a gaming contract.
Gaskins said in a statement, "We are concerned about the most recent announcement by the County Executive and his continuing marketing efforts on behalf of the Peterson Companies for a casino at National Harbor ... The action of the County Executive gives the appearance of the possibility of collusion, favoritism and unfair bid practices by seemingly steering or sole sourcing' slots to one location within the county.
"Because of the past history of our prior County Executive ... we feel that the County can ill afford to have its image further damaged by another County Executive. We are concerned that the County Executive actions to date, suggests that he is attempting to bypass or circumvent the bid process and influence a decision that appears to favor one bidder and creates an unlevel playing field for other bidders at Rosecroft, Largo Town Center or other locations."
In response to Gaskins' statement, a spokesperson for the county executive said in an email, "Any characterizations that there is an attempt to bypass the bid process or that there was anything improper with Mr. Baker's proposal concerning gaming in Prince Georges County is completely false. What Mr. Baker has done, in fact, is deliver a clear and concise recommendation as well as conditions in the form of a high end destination casino resort in order for him to support gaming in Prince George's County. The County Executive has indicated his preference for the National Harbor site based on the harbor already being a travel destination, the infrastructure and the minimum impact it would have on surrounding communities. |
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- 4/21/10 |
Friendswood Rips Texas City 69-49
It appears that District 24-4A is going to be another race to the final game if Friendswood’s win over Texas City is any indication.
Texas City nipped defending district champion Dawson 83-82 just a few nights before the Stings traveled to face the Mustangs. But the outcome was quite different as Texas City proved to be colder inside the gym than outside in the weather.
The Stings hit only 3-of-21 from beyond the 3-point arc while the Mustangs had the hot hand from downtown hitting 7-of-11 including four by Chris Collins who led the way with 20 points. Collins got scoring help from senior power forward Adam Hinchcliffe who hit one bomb at the end of the third quarter to give the Mustangs a 45-40 lead after Texas City had pulled within two points.
Hinchcliffe added a little topping to the shot as he gave Texas City “the stare” following the clutch shot which ignited the crowd and team.
“I was just having a little fun,” Hinchcliffe said following the shot. Hinchcliffe hit 18 points, grabbed 10 rebounds, and blocked three shots.
Kelby Schimming was also instrumental in the big win as he finished with 14 points, 10 boards, and four blocked shots.
Friendswood led 14-12 at the end of the first quarter, but took advantage of the cold shooting by Texas City to outscore the visitors 17-9 in the second period for a comfortable 31-21 lead at intermission.
But Texas City found the range in the third quarter to outscore the ‘Stangs 20-14 to pull within two-points before Hinchcliffe hit his timely bomb at the buzzer for a five-point lead entering the final eight minutes of play.
That’s when Friendswood got really hot on offense to outscore the Stings 24-9 down the stretch to grab the lopsided 69-49 victory.
The Mustangs are now 14-4 overall and 2-0 in district. Texas City falls to 14-6 overall and 1-1 in league play.
“We shot really well,” Friendswood head coach Jeff Keener said. “And when we shoot well, we are kind of tough to beat if we don’t beat ourselves.”
It appears that Friendswood will be one of the teams to beat if someone wants the district title this season. |
Relapsed and refractory Hodgkin lymphoma: transplantation strategies and novel therapeutic options.
Many patients with Hodgkin lymphoma are cured with initial therapy, although a portion of patients will experience primary induction failure or disease relapse. Pathologic confirmation of refractory or relapsed Hodgkin lymphoma is important. Following two to four cycles of non-cross-resistant salvage chemotherapy, the standard of care is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), which is associated with long-term event-free survival rates of 45-68%. Of note, survival rates for studies integrating total lymphoid irradiation into the autologous HSCT-conditioning regimen are among the highest reported for relapsed/refractory Hodgkin lymphoma. Further treatment options are available for patients not fit to proceed to HSCT, for relapsed disease after autologous HSCT, and for 'high-risk' Hodgkin lymphoma including chemotherapy-resistant disease. Allogeneic HSCT is a valid treatment option, as a graft-vs.-Hodgkin-lymphoma effect has been demonstrated. In addition, novel targeted treatments are being investigated such as receptor-specific antibodies, radiolabeled antibodies, antiapoptotic agents including inhibitors of the nuclear factor-kappaB complex or X-linked inhibitor of apoptosis proteins, transcription pathway modulators such as histone deacetylase and mTOR inhibitors, and Epstein-Barr virus-directed therapy. Continued translational and collaborative prospective clinical research efforts are needed in order to continue to increase the survival rates for Hodgkin lymphoma and to lessen the toxicities associated with lymphoma-related therapy. |
IN THE COMMONWEALTH COURT OF PENNSYLVANIA
Pennsylvania Liquor Control Board, :
Petitioner :
:
v. :
:
David Perretta, : No. 1470 C.D. 2018
Respondent : Submitted: May 17, 2019
BEFORE: HONORABLE MARY HANNAH LEAVITT, President Judge
HONORABLE RENÉE COHN JUBELIRER, Judge
HONORABLE CHRISTINE FIZZANO CANNON, Judge
OPINION NOT REPORTED
MEMORANDUM OPINION
BY JUDGE FIZZANO CANNON FILED: November 18, 2019
The Pennsylvania Liquor Control Board (PLCB) petitions for review
of the October 5, 2018 final determination of the Pennsylvania Office of Open
Records (OOR) concluding that the Right-to-Know Law (RTKL)1 request (Request)
submitted by David Perretta (Requester) to the PLCB seeking a copy of a complaint
allegedly filed by a particular individual, whom Requester identified by name, was
not exempt from disclosure as a record relating to a noncriminal investigation under
RTKL Section 708(b)(17)(i), 65 P.S. § 67.708(b)(17)(i). OOR’s Final
Determination at 5-10, Reproduced Record (R.R.) at 68a-73a. The PLCB requests
that this Court reverse the final determination of the OOR and find that the requested
1
Act of February 14, 2008, P.L. 6, 65 P.S. §§ 67.101–67.3104.
complaint, if it exists, is exempt from disclosure under the RTKL. Petition for
Review at 5. Upon review, we reverse.
On August 8, 2018, Requester submitted his Request to the PLCB,
seeking a copy of a complaint allegedly filed against him with the PLCB by a liquor
store employee, whom Requester identified by name, around May 2015 when
Requester was still a PLCB employee. Request, R.R. at 24a; Requester’s Appeal at
1, R.R. at 31a. On August 15, 2018, the PLCB sent Requester a final response
denying his Request because, among other reasons, the requested complaint was
exempt from disclosure pursuant to the noncriminal investigation exemption
contained in Section 708(b)(17) of the RTKL, 65 P.S. § 67.708(b)(17). PLCB Final
Response at 1, R.R. at 2a.
On September 6, 2018, Requester filed an appeal with the OOR.
Requester’s Appeal at 1, R.R. at 8a. On September 7, 2018, the OOR e-mailed
Requester and the PLCB a letter to advise them regarding the appeals process. OOR
Letter, 9/7/18 at 1, R.R. at 4a. The OOR advised the parties as follows:
Statements of fact must be supported by an affidavit or
attestation made under penalty of perjury by a person
with actual knowledge. Any factual statements or
allegations submitted without an affidavit will not be
considered. The agency has the burden of proving that
records are exempt from public access (see 65 P.S. §
67.708(a)(1)). To meet this burden, the agency must
provide evidence to the OOR. The law requires the
agency’s position to be supported by sufficient facts and
citation to all relevant sections of the RTKL, case law and
OOR Final Determinations.
Id. (emphasis in original). The PLCB submitted a position statement, contending
that it properly denied the Request pursuant to the RTKL’s noncriminal investigation
2
exemption because, “assuming for the sake of argument that a discrimination or
sexual harassment complaint was filed against [Requester], that complaint would
have been investigated by the PLCB as part of its legislatively granted official
duties.” PLCB Position Statement at 5-7, R.R. at 19a-21a (citing RTKL Section
708(b)(17), 65 P.S. § 67.708(b)(17)).
The PLCB submitted the affidavits of Jennifer Haas, Director of the
PLCB’s Department of Human Resources, and M. Kathryn Blatt, Human Resource
Analyst 3 with the PLCB’s Equal Opportunity Office. See Haas Affidavit, R.R. at
37a-38a; Blatt Affidavit, R.R. at 39a-40a. Haas attested that her duties include
overseeing the Equal Opportunity Office and the Labor Relations Division. Haas
Affidavit at 1, ¶ 2, R.R. at 37a. Haas further attested:
3. When complaints are made by or about PLCB
employees, such complaints are investigated by either the
[PLCB’s] Labor Relations Division or the Equal
Opportunity Office, depending on the specific nature of
the complaints.
4. Complaints involving allegations of
discrimination or sexual harassment are investigated by
the Equal Opportunity Office in accordance with
Commonwealth Management Directive 410.10
(Amended) and as required by, among other provisions of
law, 42 U.S.C. §§ 2000e [to 2000e-17] and 43 P.S. §§
951[to 963].
5. Complaints involving all other allegations of
misconduct or wrongdoing by PLCB employees are
investigated by the Labor Relations Division.
6. Any complaints that are received by either the
[PLCB’s] Labor Relations Division or the Equal
Opportunity Office are thoroughly investigated and, if
evidence supports the allegations, appropriate disciplinary
or other corrective action is taken.
3
Haas Affidavit at 1-2, ¶¶ 3-6, R.R. at 37a-38a.
Blatt attested that she is “responsible for administering the PLCB’s
equal opportunity and disability services functions” and that, “[t]o that end, [she]
. . . investigate[s] discrimination and sexual harassment complaints[.]” Blatt
Affidavit at 1, ¶ 2, R.R. at 39a. Blatt stated that when she “receives complaints
involving allegations of discrimination or sexual harassment, such complaints are
investigated by the Equal Opportunity Office in accordance with Commonwealth
Management Directive 410.10 (Amended) and as required by, among other
provisions of law, [federal equal employment opportunity law,] 42 U.S.C. §§ 2000e
[to 2000e-17] and [the Pennsylvania Human Relations Act2], 43 P.S. §§ 951 [to
963].” Blatt Affidavit at 1, ¶ 3, R.R. at 39a. Blatt further attested that
Commonwealth Management Directive 410.10 outlines the steps that must be taken
by the Equal Opportunity Office in investigating complaints of discrimination or
sexual harassment and specifies which materials the investigative file must include.
Id., ¶ 4, R.R. at 39a. Blatt stated that “[a]ny documents that are maintained as part
of the investigative file, including the complaint itself, are used solely for the
purposes of conducting the investigation and are otherwise treated as sensitive and
confidential,” partly in order “to encourage cooperation with investigations and
prevent [] possible retaliation.” Id., ¶ 5, R.R. at 39a. Blatt stated that “[a]ny
complaints that are received by [the Equal Opportunity Office] are thoroughly
investigated and, if any evidence supports the allegations, appropriate disciplinary
or other corrective action is taken.” Id., ¶ 6, R.R. at 39a. Blatt further attested that
“[i]f disciplinary action [was] warranted in any given case, the matter would be
2
Act of October 27, 1955, P.L. 744, as amended, 43 P.S. §§ 951 – 963.
4
referred to the Labor Relations Division for further action.” Blatt Affidavit at 2, ¶
7, R.R. at 40a.
On September 27, 2018, the OOR requested that the PLCB provide a
supplemental submission addressing “whether an investigation took place in relation
to the [requested] complaint and what entity conducted the investigation.” OOR E-
mail, 9/27/18, R.R. at 51a. That same day, the PLCB responded, asking the OOR to
reconsider its request. PLCB E-mail, 9/27/18 at 1, R.R. at 55a. The PLCB
contended that, because the Request identifies the name of a specific individual,
confirming whether an investigation took place would have the result of publicly
confirming whether this particular complainant actually submitted a complaint. Id.
The PLCB further asserted that complying with the OOR’s request would
contravene Stein v. Plymouth Township, 994 A.2d 1179 (Pa. Cmwlth. 2010), in
which this Court held that complaints submitted to an agency that are exempt from
access pursuant to the RTKL’s noncriminal investigation exemption are exempt in
their entirety, including the name or identity of the complainant. PLCB E-mail,
9/27/18 at 1, R.R. at 55a. The PLCB maintained that the affidavits it previously
provided to the OOR sufficed to demonstrate that any complaints of misconduct
received from or about a PLCB employee would have been investigated by the
PLCB’s Equal Opportunity Office or Labor Relations Division in accordance with
the PLCB’s official duties. Id.
On October 5, 2018, the OOR issued a final determination granting
Requester’s appeal and instructing the PLCB to provide a copy of the requested
complaint to Requester within 30 days. OOR Final Determination at 11, R.R. at 74a.
The OOR concluded that the PLCB failed to prove that the requested record is
exempt as a record relating to a noncriminal investigation under RTKL Section
5
708(b)(17), 65 P.S. § 67.708(b)(17). OOR Final Determination at 8, R.R. at 71a.
Relying on Brown v. Pennsylvania Office of Inspector General (Pa. Cmwlth., No.
730 C.D. 2016, filed Oct. 27, 2017), and Black v. Pennsylvania State Police (Pa.
Cmwlth., No. 676 C.D. 2016, filed Nov. 23, 2016),3 the OOR found that while the
PLCB established that it has the legislatively granted authority under the Liquor
Code4 and Commonwealth Management Directive 410.10 to investigate complaints
lodged against its employees, the PLCB failed to establish that an investigation
regarding the requested complaint was actually conducted. OOR Final
Determination at 7-8 & 10, R.R. at 70a-71a & 73a. The PLCB then appealed to this
Court.5
Before this Court,6 the PLCB argues that the OOR erred in determining
that the requested complaint was not exempt from disclosure as an agency record
relating to a noncriminal investigation under RTKL Section 708(b)(17), 65 P.S. §
67.708(b)(17). PLCB’s Brief at 22. The PLCB contends that the complaint sought
by Requester, assuming it exists, would be exempt from disclosure in its entirety,
including the name of the complainant. See id. at 15 (citing Stein, 994 A.2d at 1182).
The PLCB maintains that it had explained its legal obligations to investigate
allegations of discrimination or sexual harassment, and asserts the affidavits it
provided clearly indicate that all complaints made by or about PLCB employees are
This Court’s unreported memorandum opinions may be cited for persuasive value.
3
Commonwealth Court Internal Operating Procedure § 414(a), 210 Pa. Code § 69.414(a).
4
Act of April 12, 1951, P.L. 90, as amended, 47 P.S. § 1-101 to 10-1001.
5
Requester failed to file a brief as ordered by this Court, and consequently, this Court
precluded him from filing a brief. Cmwlth. Ct. Order dated 5/10/19.
6
This Court’s review of a final determination of the OOR is de novo and our scope of
review is plenary. Hunsicker v. Pa. State Police, 93 A.3d 911, 913 n.7 (Pa. Cmwlth. 2014).
6
investigated by either the Labor Relations Division or the Equal Opportunity Office,
depending on the specific nature of the complaint. Id. at 17 & 21. The PLCB
contends that the OOR erred in focusing on the fact that the PLCB did not provide
an affidavit indicating that the requested complaint was actually received and
investigated. Id. Further, the PLCB asserts that the OOR erred in relying upon Black
and Brown, as those cases are distinguishable given the wording of those requests.
The PLCB claims that, unlike Black and Brown, “there was no opportunity here for
[it] to prove that a responsive complaint was received and investigated without also
publicly revealing or confirming the identity of the alleged complainant.” Id. at 19.
The PLCB maintains that revealing or confirming the identity of a complainant
“would defy logic and ignore the obvious and recognized purposes for which the
‘complaint’ provision within the noncriminal investigation exemption exists in the
first place—to prevent retaliation and avoid discouraging persons from making
complaints concerning alleged wrongs.” Id. at 20 (citing Dep’t of Health v. Office
of Open Records, 4 A.3d 803, 811-12 (Pa. Cmwlth. 2010)).7
7
The PLCB also argues that Requester’s failure to include a copy of his August 8, 2018
RTKL Request with his OOR appeal warrants dismissal in accordance with the OOR’s Procedural
Guidelines. PLCB’s Brief at 35 & 36 (citing OOR Procedural Guidelines §§ IV(B)(1)(a) &
IV(C)(1)(a)). The PLCB notes that after it received Requester’s OOR appeal documents,
Requester supplied a handwritten document purportedly summarizing, yet differing from, his
initial Request. See id. at 36; see also Requester’s Handwritten Appeal Document, R.R. at 12a.
The OOR rejected the PLCB’s argument that Requester’s appeal was deficient, noting that the
PLCB provided a copy of the August 8, 2018 Request with its submission, such that the OOR had
a copy of the correct request language for purposes of review on appeal. OOR Final Determination
at 2 n.1, R.R. at 65a (citing RTKL Section 1102(b)(3), 65 P.S. § 67.1102(b)(3) (stating that “[i]n
the absence of a regulation, policy or procedure governing appeals under this chapter, the appeals
officer shall rule on procedural matters on the basis of justice, fairness and the expeditious
resolution of the dispute”)). We have previously noted that “[t]he OOR[] has not adopted
regulations similar to the provisions found in Chapter 5 of Title 2 [of the Administrative Agency
Law, relating to practice and procedure of Commonwealth agencies]; rather, it has only adopted
‘Interim Guidelines’ that do not constitute duly promulgated regulations.” Bowling v. Office of
Open Records, 75 A.3d 453, 471 n.20 (Pa. 2013). “It is well settled that regulations not
7
We begin with an overview of the RTKL. “The objective of . . . [the
RTKL] . . . is to empower citizens by affording them access to information
concerning the activities of their government.” SWB Yankees LLC v. Wintermantel,
45 A.3d 1029, 1042 (Pa. 2012). Further, the RTKL is remedial in nature and is
“designed to promote access to official government information in order to prohibit
secrets, scrutinize the actions of public officials and make public officials
accountable for their actions.” Pa. Dep’t of Educ. v. Bagwell, 114 A.3d 1113, 1122
(Pa. Cmwlth. 2015). “[C]ourts should liberally construe the RTKL to effectuate its
purpose[.]” Barnett v. Pa. Dep’t of Pub. Welfare, 71 A.3d 399, 403 (Pa. Cmwlth.
2013).
A record in the possession of a Commonwealth agency shall be
presumed to be a public record. RTKL Section 305(a), 65 P.S. § 67.305(a). This
presumption shall not apply if the requested record is exempt under the RTKL, is
exempt from disclosure under any other federal or state law or is protected by a
privilege. Id. “An agency bears the burden of proving, by a preponderance of the
evidence, that a record is exempt from disclosure under one of the enumerated
exceptions.” Brown v. Pa. Dep’t of State, 123 A.3d 801, 804 (Pa. Cmwlth. 2015).
“A preponderance of the evidence standard, the lowest evidentiary standard, is
tantamount to a more likely than not inquiry.” Delaware County v. Schaefer ex rel.
promulgated pursuant to the Commonwealth Documents Law[,] [Act of July 31, 1968, P.L. 769,
as amended, 45 P.S. §§ 1102-1602, 45 Pa.C.S. §§ 501-907,] have no force or effect and may not
form the basis of an agency’s action.” Cmty. Country Day Sch. v. Dep’t of Educ., 414 A.2d 428,
431 (Pa. Cmwlth. 1980). Thus, we find that the OOR did not err in denying the PLCB’s request
that it dismiss Requester’s appeal for failure to include a copy of the Request. See Kokinda v.
County of Lehigh (Pa. Cmwlth., No. 1146 C.D. 2013, filed Feb. 25, 2014), slip op. at 4 (holding
that the “OOR’s dismissal of [the] [r]equester’s appeal on the ground that he failed to follow the
OOR’s Interim Guidelines” by neglecting to include a copy of the RTKL request and/or agency
response “was without any legal basis”).
8
Phila. Inquirer, 45 A.3d 1149, 1156 (Pa. Cmwlth. 2012). However, “[e]xemptions
from disclosure must be narrowly construed due to the RTKL’s remedial nature
. . . .” Office of the Governor v. Scolforo, 65 A.3d 1095, 1100 (Pa. Cmwlth. 2013).
RTKL Section 708(b)(17)(i) exempts from disclosure “record[s] of an
agency relating to a noncriminal investigation, including . . . [c]omplaints submitted
to an agency.” 65 P.S. § 67.708(b)(17)(i). In order to invoke the exemption, the
agency must conduct the noncriminal investigation as part of its official duties—that
is, while “acting within its legislatively-granted fact-finding and investigative
powers.” Johnson v. Pa. Convention Ctr. Auth., 49 A.3d 920, 925 (Pa. Cmwlth.
2012). The noncriminal investigation exemption is intended to encourage
information sharing and promote cooperation with investigations, recognizing that
persons are less likely to provide valuable information out of fear of retaliation or
public embarrassment absent certain safeguards against disclosure. See Pa. Pub.
Util. Comm’n v. Gilbert, 40 A.3d 755, 761 (Pa. Cmwlth. 2012); Dep’t of Health, 4
A.3d at 811-12. This Court has specifically held that this exemption protects “the
names of individuals who filed the complaint that prompted the investigation.”
Stein, 994 A.2d at 1182.
Here, the OOR found that the PLCB failed to meet its burden to
establish that the requested complaint, if it existed, was exempt from disclosure
pursuant to the RTKL’s noncriminal investigation exemption. OOR Final
Determination at 9-10, R.R. at 72a-73a (citing RTKL Section 708(b)(17)(i), 65 P.S.
§ 67.708(b)(17)(i)). For the following reasons, we disagree.
Requester requested the complaint that was filed against him by an
employee of the PLCB while Requester was also an employee of the PLCB. The
Haas and the Blatt affidavits make clear that when complaints are made by or about
9
PLCB employees, all such complaints are investigated by either the PLCB’s Labor
Relations Division or the Equal Opportunity Office, depending on the specific nature
of the complaints, pursuant to Commonwealth Management Directive 410.10
(Amended) and as required by, among other provisions of law, 42 U.S.C. §§ 2000e
to 2000e-17 and 43 P.S. §§ 951 to 963. Haas Affidavit at 1, ¶¶ 3-4, R.R. at 37a,
Blatt Affidavit at 1, ¶ 3, R.R. at 39a. As such, the requested record, the employee
complaint against the Requester, falls squarely within the exemption described in
RTKL Section 708(b)(17)(i), 65 P.S. § 67.708(b)(17)(i), exempting records “relating
to a noncriminal investigation, including . . . [c]omplaints submitted to an agency.”
As stated, in order to establish an exemption from disclosure under the
RTKL, an agency need only satisfy the preponderance of the evidence standard,
which is the lowest evidentiary standard and “has been defined as ‘such proof as
leads the fact-finder . . . to find that the existence of a contested fact is more probable
than its nonexistence.’” Pa. State Troopers Ass’n v. Scolforo, 18 A.3d 435, 439 (Pa.
Cmwlth. 2011) (quoting Pa. Dep’t of Transp. v. Agric. Lands Condemnation
Approval Bd., 5 A.3d 821, 827 (Pa. Cmwlth. 2010)). Further, to satisfy its burden
of proof, an agency may submit an affidavit. See Moore v. Office of Open Records,
992 A.2d 907, 909 (Pa. Cmwlth. 2010). Here, we conclude that the sworn affidavits
submitted by the PLCB were legally sufficient to establish that, “more likely than
not,” it conducted a noncriminal investigation of the complaint.8 See Delaware
8
Although the OOR cites to our unreported decisions of Black and Brown for the
proposition that an agency must demonstrate that an investigation was in fact conducted with
respect to the requested complaint in order to claim the noncriminal investigation exemption, we
agree with the PLCB that these cases are distinguishable, as both involved RTKL requests that did
not identify the alleged complainants by name. Thus, in those cases, the agencies were able to
provide affidavits specifically establishing that investigations had been conducted with respect to
the requested complaints in order to establish the noncriminal investigation exemption without
automatically divulging the complainants’ names.
10
County, 45 A.3d at 1156. Thus, we find that the OOR erred in determining that the
PLCB failed to prove that the requested complaint, assuming it exists, was exempt
from disclosure as a record relating to a noncriminal investigation under RTKL
Section 708(b)(17)(i), 65 P.S. § 67.708(b)(17)(i).9
Accordingly, we reverse.
__________________________________
CHRISTINE FIZZANO CANNON, Judge
9
Due to our disposition, we need not address the PLCB’s remaining arguments regarding:
(1) exemption from disclosure for records containing written criticisms of an agency employee,
see RTKL Section 708(b)(7)(vi), 65 P.S. § 67.708(b)(7)(vi); (2) exemption from disclosure for
records containing grievance material pertaining to an agency employee, see RTKL Section
708(b)(7)(vii), 65 P.S. § 67.708(b)(7)(vii); (3) that the OOR erred in failing to address the
procedural due process implications of its failure to provide the alleged third-party complainant an
opportunity to participate; and (4) that the OOR erred by failing to rule on or otherwise
acknowledge the PLCB’s response to the OOR’s request that the PLCB supplement the record.
See PLCB’s Brief at 22, 30 & 33.
11
IN THE COMMONWEALTH COURT OF PENNSYLVANIA
Pennsylvania Liquor Control Board, :
Petitioner :
:
v. :
:
David Perretta, : No. 1470 C.D. 2018
Respondent :
ORDER
AND NOW, this 18th day of November, 2019, the October 5, 2018
final determination of the Office of Open Records is REVERSED.
__________________________________
CHRISTINE FIZZANO CANNON, Judge
|
//
// Copyright (C) 2004-2006 Maciej Sobczak, Stephen Hutton
// MySQL backend copyright (C) 2006 Pawel Aleksander Fedorynski
// Distributed under the Boost Software License, Version 1.0.
// (See accompanying file LICENSE_1_0.txt or copy at
// http://www.boost.org/LICENSE_1_0.txt)
//
#ifndef SOCI_MYSQL_H_INCLUDED
#define SOCI_MYSQL_H_INCLUDED
#ifdef _WIN32
# ifdef SOCI_DLL
# ifdef SOCI_MYSQL_SOURCE
# define SOCI_MYSQL_DECL __declspec(dllexport)
# else
# define SOCI_MYSQL_DECL __declspec(dllimport)
# endif // SOCI_DLL
# endif // SOCI_MYSQL_SOURCE
#endif // _WIN32
//
// If SOCI_MYSQL_DECL isn't defined yet define it now
#ifndef SOCI_MYSQL_DECL
# define SOCI_MYSQL_DECL
#endif
#include <soci/soci-backend.h>
#ifdef _WIN32
#include <winsock.h> // SOCKET
#endif // _WIN32
#include <mysql.h> // MySQL Client
#include <vector>
namespace soci
{
class SOCI_MYSQL_DECL mysql_soci_error : public soci_error
{
public:
mysql_soci_error(std::string const & msg, int errNum)
: soci_error(msg), err_num_(errNum) {}
unsigned int err_num_;
};
struct mysql_statement_backend;
struct mysql_standard_into_type_backend : details::standard_into_type_backend
{
mysql_standard_into_type_backend(mysql_statement_backend &st)
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void define_by_pos(int &position,
void *data, details::exchange_type type) SOCI_OVERRIDE;
void pre_fetch() SOCI_OVERRIDE;
void post_fetch(bool gotData, bool calledFromFetch,
indicator *ind) SOCI_OVERRIDE;
void clean_up() SOCI_OVERRIDE;
mysql_statement_backend &statement_;
void *data_;
details::exchange_type type_;
int position_;
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struct mysql_vector_into_type_backend : details::vector_into_type_backend
{
mysql_vector_into_type_backend(mysql_statement_backend &st)
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void define_by_pos(int &position,
void *data, details::exchange_type type) SOCI_OVERRIDE;
void pre_fetch() SOCI_OVERRIDE;
void post_fetch(bool gotData, indicator *ind) SOCI_OVERRIDE;
void resize(std::size_t sz) SOCI_OVERRIDE;
std::size_t size() SOCI_OVERRIDE;
void clean_up() SOCI_OVERRIDE;
mysql_statement_backend &statement_;
void *data_;
details::exchange_type type_;
int position_;
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struct mysql_standard_use_type_backend : details::standard_use_type_backend
{
mysql_standard_use_type_backend(mysql_statement_backend &st)
: statement_(st), position_(0), buf_(NULL) {}
void bind_by_pos(int &position,
void *data, details::exchange_type type, bool readOnly) SOCI_OVERRIDE;
void bind_by_name(std::string const &name,
void *data, details::exchange_type type, bool readOnly) SOCI_OVERRIDE;
void pre_use(indicator const *ind) SOCI_OVERRIDE;
void post_use(bool gotData, indicator *ind) SOCI_OVERRIDE;
void clean_up() SOCI_OVERRIDE;
mysql_statement_backend &statement_;
void *data_;
details::exchange_type type_;
int position_;
std::string name_;
char *buf_;
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struct mysql_vector_use_type_backend : details::vector_use_type_backend
{
mysql_vector_use_type_backend(mysql_statement_backend &st)
: statement_(st), position_(0) {}
void bind_by_pos(int &position,
void *data, details::exchange_type type) SOCI_OVERRIDE;
void bind_by_name(std::string const &name,
void *data, details::exchange_type type) SOCI_OVERRIDE;
void pre_use(indicator const *ind) SOCI_OVERRIDE;
std::size_t size() SOCI_OVERRIDE;
void clean_up() SOCI_OVERRIDE;
mysql_statement_backend &statement_;
void *data_;
details::exchange_type type_;
int position_;
std::string name_;
std::vector<char *> buffers_;
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struct mysql_session_backend;
struct mysql_statement_backend : details::statement_backend
{
mysql_statement_backend(mysql_session_backend &session);
void alloc() SOCI_OVERRIDE;
void clean_up() SOCI_OVERRIDE;
void prepare(std::string const &query,
details::statement_type eType) SOCI_OVERRIDE;
exec_fetch_result execute(int number) SOCI_OVERRIDE;
exec_fetch_result fetch(int number) SOCI_OVERRIDE;
long long get_affected_rows() SOCI_OVERRIDE;
int get_number_of_rows() SOCI_OVERRIDE;
std::string get_parameter_name(int index) const SOCI_OVERRIDE;
std::string rewrite_for_procedure_call(std::string const &query) SOCI_OVERRIDE;
int prepare_for_describe() SOCI_OVERRIDE;
void describe_column(int colNum, data_type &dtype,
std::string &columnName) SOCI_OVERRIDE;
mysql_standard_into_type_backend * make_into_type_backend() SOCI_OVERRIDE;
mysql_standard_use_type_backend * make_use_type_backend() SOCI_OVERRIDE;
mysql_vector_into_type_backend * make_vector_into_type_backend() SOCI_OVERRIDE;
mysql_vector_use_type_backend * make_vector_use_type_backend() SOCI_OVERRIDE;
mysql_session_backend &session_;
MYSQL_RES *result_;
// The query is split into chunks, separated by the named parameters;
// e.g. for "SELECT id FROM ttt WHERE name = :foo AND gender = :bar"
// we will have query chunks "SELECT id FROM ttt WHERE name = ",
// "AND gender = " and names "foo", "bar".
std::vector<std::string> queryChunks_;
std::vector<std::string> names_; // list of names for named binds
long long rowsAffectedBulk_; // number of rows affected by the last bulk operation
int numberOfRows_; // number of rows retrieved from the server
int currentRow_; // "current" row number to consume in postFetch
int rowsToConsume_; // number of rows to be consumed in postFetch
bool justDescribed_; // to optimize row description with immediately
// following actual statement execution
// Prefetch the row offsets in order to use mysql_row_seek() for
// random access to rows, since mysql_data_seek() is expensive.
std::vector<MYSQL_ROW_OFFSET> resultRowOffsets_;
bool hasIntoElements_;
bool hasVectorIntoElements_;
bool hasUseElements_;
bool hasVectorUseElements_;
// the following maps are used for finding data buffers according to
// use elements specified by the user
typedef std::map<int, char **> UseByPosBuffersMap;
UseByPosBuffersMap useByPosBuffers_;
typedef std::map<std::string, char **> UseByNameBuffersMap;
UseByNameBuffersMap useByNameBuffers_;
};
struct mysql_rowid_backend : details::rowid_backend
{
mysql_rowid_backend(mysql_session_backend &session);
~mysql_rowid_backend() SOCI_OVERRIDE;
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struct mysql_blob_backend : details::blob_backend
{
mysql_blob_backend(mysql_session_backend &session);
~mysql_blob_backend() SOCI_OVERRIDE;
std::size_t get_len() SOCI_OVERRIDE;
std::size_t read(std::size_t offset, char *buf,
std::size_t toRead) SOCI_OVERRIDE;
std::size_t write(std::size_t offset, char const *buf,
std::size_t toWrite) SOCI_OVERRIDE;
std::size_t append(char const *buf, std::size_t toWrite) SOCI_OVERRIDE;
void trim(std::size_t newLen) SOCI_OVERRIDE;
mysql_session_backend &session_;
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struct mysql_session_backend : details::session_backend
{
mysql_session_backend(connection_parameters const & parameters);
~mysql_session_backend() SOCI_OVERRIDE;
void begin() SOCI_OVERRIDE;
void commit() SOCI_OVERRIDE;
void rollback() SOCI_OVERRIDE;
bool get_last_insert_id(session&, std::string const&, long long&) SOCI_OVERRIDE;
// Note that MySQL supports both "SELECT 2+2" and "SELECT 2+2 FROM DUAL"
// syntaxes, but there doesn't seem to be any reason to use the longer one.
std::string get_dummy_from_table() const SOCI_OVERRIDE { return std::string(); }
std::string get_backend_name() const SOCI_OVERRIDE { return "mysql"; }
void clean_up();
mysql_statement_backend * make_statement_backend() SOCI_OVERRIDE;
mysql_rowid_backend * make_rowid_backend() SOCI_OVERRIDE;
mysql_blob_backend * make_blob_backend() SOCI_OVERRIDE;
MYSQL *conn_;
};
struct mysql_backend_factory : backend_factory
{
mysql_backend_factory() {}
mysql_session_backend * make_session(
connection_parameters const & parameters) const SOCI_OVERRIDE;
};
extern SOCI_MYSQL_DECL mysql_backend_factory const mysql;
extern "C"
{
// for dynamic backend loading
SOCI_MYSQL_DECL backend_factory const * factory_mysql();
SOCI_MYSQL_DECL void register_factory_mysql();
} // extern "C"
} // namespace soci
#endif // SOCI_MYSQL_H_INCLUDED
|
1. Introduction {#sec1-molecules-22-01796}
===============
Natural peptide products are one of the most dynamic sources of medicinally significant compounds \[[@B1-molecules-22-01796]\]. Cyclic dipeptides or cyclodipeptides (CDPs), also called 2,5-diketopiperazines, are the smallest cyclic peptides frequently found in nature, and are mainly synthesized by microorganisms \[[@B2-molecules-22-01796]\]. CDPs are a class of cyclic organic compounds in which the two nitrogen atoms of a piperazine 6-membered ring form amide linkages. The mainframe structure of CDPs is a CDP scaffold generated by the condensation of two α-amino acids. The nomenclature of CDPs is indicated by the three letter code for each of the two amino acids, plus a prefix to designate the absolute configuration, e.g., cyclo([l]{.smallcaps}-Xaa-[l]{.smallcaps}-Yaa). CDPs can be configured as both *cis* and *trans* isoforms, but *cis* configurations are predominant \[[@B3-molecules-22-01796]\].Various amino acid modifications confer diversified chemical and biological functions. CDPs exhibit better biological activity than their linear counterparts due to their higher stability, protease resistance, and conformational rigidity, all factors that increase their ability to specifically interact with biological targets \[[@B4-molecules-22-01796],[@B5-molecules-22-01796]\]. They constitute a large class of secondary metabolites produced by bacteria, fungi, plants, and animals \[[@B1-molecules-22-01796],[@B2-molecules-22-01796],[@B6-molecules-22-01796],[@B7-molecules-22-01796]\]. The available data indicate that approximately 90% of CDP producers are bacterial \[[@B7-molecules-22-01796]\]. CDPs and their derivatives exhibit a broad range of biological activities, such as bacterial quorum sensing, and antibacterial, antimicrobial, anticancer, and radical-scavenging properties. They have also been developed to carry biologically active molecules across the blood-brain barrier \[[@B1-molecules-22-01796],[@B8-molecules-22-01796],[@B9-molecules-22-01796]\].
The CDP scaffold can be synthesized either by purely chemically means using different solid-phases or under reflux conditions in solution \[[@B1-molecules-22-01796],[@B10-molecules-22-01796]\] or more naturally, by biosynthetic enzymes called non-ribosomal peptide synthetases (NRPSs) and CDP synthases (CDPSs; \[[@B7-molecules-22-01796],[@B11-molecules-22-01796]\]) ([Figure 1](#molecules-22-01796-f001){ref-type="fig"}). Common chemical synthesis of CDPs includes the condensation of individual amino acids at high temperature. Dipeptides substituted with an amine at one terminus and an ester at the other can also spontaneously cyclize to form a 2,5-DKP. However, conditions must be optimized carefully in order to force a cyclization reaction and to limit racemization. This is the procedure most commonly used for the chemical synthesis of CDP. Cyclization of amino dipeptide esters can also be carried out under thermal conditions, normally by refluxing them in high boiling solvents such as toluene or xylene for 24 h \[[@B1-molecules-22-01796]\]. In addition, CDPs are often products of unwanted side reactions or degradation products of oligo- and polypeptides in processed food and beverages \[[@B2-molecules-22-01796],[@B12-molecules-22-01796]\]. They are frequently formed during the chemical degradation of products in roasted coffee \[[@B13-molecules-22-01796]\], stewed beef \[[@B14-molecules-22-01796]\], and beer \[[@B15-molecules-22-01796]\]. Non-enzymatic processes can also lead to the formation of functional CDPs in various organisms, for example, cyclo([l]{.smallcaps}-His-[l]{.smallcaps}-Pro) is found throughout the central nervous systems of mammals \[[@B16-molecules-22-01796]\]. This, cyclo([l]{.smallcaps}-His-[l]{.smallcaps}-Pro) was the first active CDP and detected in human urine in 1965 \[[@B17-molecules-22-01796]\]. In this review, we will highlight the CDP biosynthetic machinery and the associated modifying enzymes crucial for their biological activities.
2. Biological Mechanisms of CDP Formation {#sec2-molecules-22-01796}
=========================================
CDPs are commonly synthesized from amino acids by various organisms, including mammals, and are considered secondary functional metabolites or side products of terminal peptide cleavage. Several CDP biosynthetic pathways have been elucidated, and in general, they can be classified into non-enzymatic and enzymatic pathways.
2.1. Non-Enzymatic Pathways of CDP Formation {#sec2dot1-molecules-22-01796}
--------------------------------------------
Cyclo(His-Pro) is an endogenous cyclic dipeptide that exists throughout the central nervous systems of various organisms, including mammals, and plays roles in a number of regulatory processes \[[@B16-molecules-22-01796]\]. In mammals, cyclo(His-Pro) is derived from the precursor to thyrotropin-releasing hormone (TRH, pGlu-His-Pro). The TRH precursor, called TRH-Gly (pGlu-His-Pro-Gly), is first cleaved by pyroglutamate aminopeptidase, producing His-Pro-Gly, which is then non-enzymatically cyclized to cyclo(His-Pro). The proline induces constraints that promote the *cis*-conformation of the peptide bond between the histidine and the proline, thereby facilitating cyclization which generates the CDP scaffold. This mammalian CDP imparts the cytoprotective effect during NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Nrf2 (nuclear factor like 2) signaling \[[@B16-molecules-22-01796]\].
2.2. Enzymatic Pathways of CDP Formation {#sec2dot2-molecules-22-01796}
----------------------------------------
CDPs are commonly considered to be secondary metabolites. Some protease enzymes, such as dipeptidyl peptidases, cleave the terminal ends of proteins into generate dipeptides, which can naturally cyclize to form CDPs. Two unrelated biosynthetic enzyme families catalyze the formation of CDPs: NRPSs and CDPSs.
### 2.2.1. NRPS-Mediated CDP Biosynthesis {#sec2dot2dot1-molecules-22-01796}
CDPscaffolds can be synthesized by one or more specialized NRPSs, either through dedicated biosynthetic pathways or through the premature release of dipeptidyl intermediates during the chain elongation process. The NRPS genes for a certain peptide are usually organized in one operon in prokaryotes, and in a gene cluster in eukaryotes \[[@B18-molecules-22-01796]\]. NRPSs are large modular enzymes, which simultaneously act as a template and as biosynthetic machinery. Each module is responsible for the incorporation of one amino acid into the final peptide, and can be further subdivided into the catalytic domains responsible for specific synthetic steps during peptide synthesis \[[@B19-molecules-22-01796]\]. In each module, NRPSs consist of three necessary domains: an adenylation (A) domain; a thiolation (T) domain post-translationally modified with a 4′-phosphopantetheinyl (4′-Ppant) arm, also termed the peptidyl carrier protein (PCP) domain; and a condensation (C) domain, separated by short spacer regions of approximately 15 amino acids. The A domain selects, activates, and loads the monomer onto the PCP domain. Here, the thiol group of the 4′-Ppantarm of the T domain mediates the nucleophilic attack of the adenylated amino acid. Subsequent peptide bond formation between two adjacent T-bound aminoacyl intermediates is catalyzed by the C domains \[[@B11-molecules-22-01796]\]. Another essential NRPS catalytic unit is the thioesterase (TE) domain, which is located in the C-terminus and catalyzes peptide release by either hydrolysis or macrocyclization. In addition, modification domains can be integrated into NRPS modules at different locations to modify the incorporated amino acids. Epimerization and N-methyltransferase domains are examples, which catalyze the generation of D- and methylated amino acids, respectively \[[@B20-molecules-22-01796],[@B21-molecules-22-01796]\]. NRPSs rely not only on the 20 canonical amino acids, but also use several different building blocks, including non-proteinogenic amino acids, and this contributes to the structural diversity of non-ribosomal peptides and their differential biological activities \[[@B20-molecules-22-01796]\]. CDPs synthesized by NRPSs can be further modified by tailoring enzymes, usually encoded by genes clustered with the NRPS genes. The majority of known NRPS-derived CDPs are produced by fungi, whereas few bacteria are recognized as NRPS-derived CDP producers.
Many CDPs can be formed by dedicated NRPS pathways, such as brevianamide F \[[@B22-molecules-22-01796]\], erythrochelin \[[@B23-molecules-22-01796]\], ergotamine \[[@B24-molecules-22-01796]\], roquefortine C \[[@B25-molecules-22-01796]\], acetylaszonalenin \[[@B26-molecules-22-01796]\], thaxtomin A \[[@B27-molecules-22-01796]\], gliotoxin \[[@B28-molecules-22-01796]\], and sirodesmin PL \[[@B29-molecules-22-01796]\]. In a few cases, CDPs can be formed by NRPSs during the synthesis of longer peptides, as truncated side products, as in the biosynthesis of cyclo([d]{.smallcaps}-Phe-[l]{.smallcaps}-Pro) and cyclomarazine A \[[@B30-molecules-22-01796],[@B31-molecules-22-01796]\].
### 2.2.2. CDPS-Mediated CDP Biosynthesis {#sec2dot2dot2-molecules-22-01796}
CDPSs are a new family of tRNA-dependent peptide bond-forming enzymes that do not require amino acid charging. CDPSs share a common architecture reminiscent of the catalytic domain of class-Ic amino acid tRNAsynthetases (aaRSs), for example TyrRS and TrpRS \[[@B32-molecules-22-01796]\]. Both CDPSs and class-IcaaRSs comprise well conserved Rossmannfold domains along with a helical connective polypeptide 1 (CP1) subdomain. However, Class-IcaaRSs possess signature motifs involved in ATP binding (HIGH and KMSKS sequences) that are not present in CDPSs. In addition, CDPSs do not possess a distinct tRNA-binding domain, but rather contain a large patch of positively charged residues located in helix α4, which are important for the binding of aminoacyl-tRNA substrates. All these observed differences between CDPSs and their ancestral aaRSs result in unique enzymes for CDP biosynthesis.
CDPSs use amino acid tRNAs as substrates to catalyze the formation of CDP peptide bonds \[[@B11-molecules-22-01796],[@B33-molecules-22-01796],[@B34-molecules-22-01796],[@B35-molecules-22-01796]\], diverting two aminoacyl-tRNAs from their essential role in ribosomal protein synthesis for use as substrates and catalyzing the formation of the two peptide bonds required for CDP formation \[[@B36-molecules-22-01796]\]. The synthesis process is initiated by the binding of the first aminoacyl substrate, likely involving ionic interactions between the negatively-charged ribose--phosphate tRNA backbone and the positive charges in helix α4 \[[@B32-molecules-22-01796],[@B37-molecules-22-01796]\]. Hence, by using aminoacyl-tRNAs as substrates, CDPSs represent a direct link between primary and secondary metabolism. The catalytic mechanism of CDPSs can be described using a ping--pong model ([Figure 2](#molecules-22-01796-f002){ref-type="fig"}). All CDPSs possess two surface-accessible pockets that contain active site residues important for substrate selection and catalysis. The different aminoacyl binding sites for the two aa-tRNA substrates are termed pocket 1 (P1) and pocket 2 (P2). Upon specific recognition of the first substrate, the first aminoacyl group is transferred to the conserved serine residue of P1. Here, interaction between the tRNA moiety and basic residues in the α4 helix generates an aminoacyl--enzyme intermediate \[[@B34-molecules-22-01796],[@B38-molecules-22-01796]\]. In the meantime, the aminoacyl moiety of the second aa-tRNA interacts with P2 through the α6--α7 loop. Ultimately, the aminoacyl--enzyme intermediate reacts with the second aa-tRNA to generate a dipeptidyl--enzyme intermediate, which undergoes intramolecular cyclization through the involvement of a conserved tyrosine, leading to the CDP scaffold as the final product. These CDPs can also be modified by closely associated tailoring enzymes.
There are approximately 163 putative CDPS genes identified so far, and of these, 150 are reported in bacteria, distributed among six phyla (Actinobacteria, Bacteroidetes, Chlamydiae, Cyanobacteria, Firmicutes, and Proteobacteria). Most known CDPSs are found in Actinobacteria, with 77 CDPSs reported to date. Twelve CDPSs were distributed among four eukaryotic phyla (Ascomycota, Annelida, Ciliophora, and Cnidaria), and one archaeon (*Haloterrigena hispanica*) CDPS has also been reported \[[@B7-molecules-22-01796],[@B11-molecules-22-01796],[@B39-molecules-22-01796]\]. Some bacterial CDPSs have been fully characterized, such as albonoursin in *Streptomyces noursei*, pulcherrimin in *Bacillus subtilis*, and mycocyclosin in *Mycobacterium tuberculosis* \[[@B11-molecules-22-01796],[@B40-molecules-22-01796]\].
3. Comparison of CDPS- and NRPS-Dependent Pathways {#sec3-molecules-22-01796}
==================================================
Both the CDPS and NRPS systems are used to synthesize CDP metabolites in nature. CDPSs are small enzymes (\~26 kDa), while NRPSs are large modular enzymes (\>100 kDa) \[[@B11-molecules-22-01796]\]. This size difference probably reflects the different strategies used to activate the amino acid carboxyl group required for peptide bond formation: NRPSs use A and PCP domains to recognize and activate amino acids in the form of PCP-bound aminoacyl thioesters, whereas CDPSs hijack aminoacyl-tRNAs, thereby eliminating the need to activate amino acids. The substrates of CDPSs are therefore limited to the 20 [l]{.smallcaps}-amino acids charged on tRNAs, whereas the range of amino acids that can be incorporated by NRPSs is much wider, including non-proteinogenic amino acids such as anthranilic acid in the synthesis of acetylaszonalenin, and 4-nitrotryptophan in thaxtomin biosynthesis \[[@B26-molecules-22-01796],[@B41-molecules-22-01796]\]. Moreover, NRPS substrates can be altered on the enzyme by accessory domains, which introduce chemical modifications such as methylation (methylation domains, thaxtominsynthetase) or configuration changes (epimerization domains, erythrochelin synthetase), while in CDPS pathways, chemical modifications can only be introduced after CDP formation. Hence, wider structural complexity is found in CDPs synthesized via NRPS pathways (e.g., roquefortine, siderosmin, ergotamine) than in those synthesized via CDPS pathways. Moreover, NRPS-dependent pathways are prevalent in bacteria and fungi (but have not yet been identified in plants or animals), while CDPS-dependent pathways have been identified in bacteria (*Bacillus* sp., *Pseudomonas* sp.), fungi (*Gibberella zeae*, *Fusarium oxysporum*), protozoa (*Ichthyophthirius multifiliis*), and animals (*Nematostella vectensis*, *Platynereis dumerilii*).
4. CDP-Tailoring Enzymes and Their Functions {#sec4-molecules-22-01796}
============================================
Tailoring enzymes that specifically modify CDP-containing natural products are usually associated with biosynthetic enzymes. Putative tailoring enzymes that modify the initially assembled CDPscaffold can be found in almost all NRPS and CDPS gene clusters, and are responsible for installing functional groups crucial for the biological activities of CDPs. In CDPS-dependent pathways, a large variety of different modification enzymes are found in close association with the respective CDPS genes \[[@B7-molecules-22-01796],[@B11-molecules-22-01796]\], including different types of oxidoreductases, hydrolases, transferases, and ligases. The most prevalent putative tailoring enzymes in CDPS clusters are cyclic dipeptide oxidases (CDOs). CDOs are composed of two distinct small subunits that assemble into an apparent mega-dalton protein complex. Depending on the substrate, the CDO can sequentially perform one or two dehydrogenation reactions. The precise reaction mechanism for this has not been elucidated, although three different scenarios have been proposed: direct dehydrogenation, α-hydroxylation followed by loss of water, and imine formation with subsequent rearrangement of the enamine \[[@B42-molecules-22-01796]\]. Known CDOs include at least seven distinct P450 enzymes, five different types of α-ketoglutarate/Fe^II^-dependent oxygenases, and three distinct flavin-containing mono-oxygenases.
In addition to oxidoreductases, a large number of different C-, N-, and *O*-methyltransferases, α/β-hydrolases, peptide ligases, and acyl-CoA transferases have been found in CDPS gene clusters in which different transcription factors belonging to the LuxR and MarR families, among others, are observed. They are usually involved in regulating various processes in response to environmental stimuli like toxic chemicals and antibiotics, which may hint at the biological functions of CDPS-dependent modified CDPs \[[@B43-molecules-22-01796]\]. Regarding NRPS-dependent pathways, a similar variety of modification enzymes has been reported, and again, enzymes that modulate the oxidation of the CDP scaffold and side chains are the most numerous \[[@B11-molecules-22-01796]\]. One distinguishing feature of fungal NRPS gene clusters is the prevalence of different prenyltransferases, which perform prenylations and reverse prenylations at various positions of tryptophan-containing CDP scaffolds \[[@B44-molecules-22-01796]\]. Judging by the diverse set of putative modification enzymes found within NRPS and CDPS gene clusters ([Table 1](#molecules-22-01796-t001){ref-type="table"}), it is assumed that highly modified CDPs represent a diverse family of microbial natural products with varied functions.
Both chemical synthesis and enzyme-catalyzed assembly are valid ways of providing suitable substrates for CDP tailoring enzymes. When using chemically synthesized substrates, CDP modification enzymes can be employed in chemoenzymatic and cell-free in vitro settings, as well as in feeding experiments, while whole-cell in vivo biosynthesis based on in situ substrate generation by NRPS or CDPS enzymes represents an alternative approach to obtain modified CDPs \[[@B52-molecules-22-01796]\].
5. Rational Design of CDPs for Structurally Diverse Peptides {#sec5-molecules-22-01796}
============================================================
There are two common methods for rationally altering the structure of natural peptides currently in practice. First, the peptide backbone itself can be altered by changing the identity, number, or connectivity of the constitutive amino acids. Second, tailoring enzymes can be introduced to catalyze specific chemical modifications into already assembled peptide scaffolds, leading to the synthesis of functionally altered peptides \[[@B34-molecules-22-01796]\].
DPs are normally quite limited with regards to peptide backbone modification, as they are composed of only two amino acid residues arranged with a predefined connectivity. Hence, the only possible diversification method is the alteration of monomer identity. Moreover, CDPS-derived CDPs have an additional limitation, because they use charged tRNAs as substrates, which means that they only contain 20--22 proteinogenic amino acids. CDPS specificity mainly depends on the identity of the aminoacyl moiety bound to the tRNA. Hence, diversification of the CDP scaffold can be achieved by changing either the building block carried by a certain tRNA or the sequence of a tRNA that is specific for a particular amino acid. In vitro transcription or standard mutagenesis techniques can be employed to introduce small specific sequence changes into tRNAs that do not affect their overall structure or aminoacylation \[[@B53-molecules-22-01796]\].
Additionally, altering the proteinogenic amino acids loaded onto specific tRNAs to produce non-proteinogenic amino acids could be used to produce CDPs containing non-standard monomers. For this, a residue-specific incorporation strategy can be employed by omitting the natural amino acid of choice in the growth medium while providing a non-canonical analog. By combining this with the use of auxotrophs as expression hosts, it is possible to obtain high-level replacement \[[@B54-molecules-22-01796]\]. Another strategy to alter the structure of natural peptide products is the tailoring of an already assembled peptide scaffold by specific modification enzymes \[[@B34-molecules-22-01796]\]. This approach can be employed in CDPs derived from both pathways, and increases the feasibility of constructing artificial hybrid pathways for the production of highly modified CDPs.
6. Biological Activities {#sec6-molecules-22-01796}
========================
Due to their rigid cyclic structure, CDPs, unlike their linear counterparts, can withstand enzymatic degradation, and this has further prompted the development of CDP-based systems for biomedical applications \[[@B4-molecules-22-01796]\]. In medicinal chemistry, CDPs are considered to be promising scaffolds for the design of a variety of active compounds for diverse biological functions because of the versatility associated with CDP functionalization \[[@B1-molecules-22-01796]\]. These compounds display diverse and noteworthy biological effects, such as antibacterial \[[@B55-molecules-22-01796]\], antitumor \[[@B56-molecules-22-01796]\], antifungal \[[@B57-molecules-22-01796]\], and antiviral \[[@B58-molecules-22-01796]\] activity. For instance, cyclo([l]{.smallcaps}-Phe-[l]{.smallcaps}-Pro) and cyclo([l]{.smallcaps}-Phe-trans-4-OH-[l]{.smallcaps}-Pro) are antifungal compounds \[[@B59-molecules-22-01796]\]. Erythrochelin, coprogen, and dimerumic acid are siderophores \[[@B23-molecules-22-01796],[@B60-molecules-22-01796],[@B61-molecules-22-01796]\], while roquefortine C and acetylaszonalenin are mycotoxins \[[@B25-molecules-22-01796],[@B26-molecules-22-01796]\]. Bicyclomycin and albonoursin are antibacterial agents \[[@B62-molecules-22-01796],[@B63-molecules-22-01796]\], and thaxtomin A acts as a phytotoxin \[[@B27-molecules-22-01796],[@B64-molecules-22-01796]\]. Brevianamide S exhibits selective antibacterial activity against *Mycobacterium bovis* bacillus Calmette-Guérin, suggestive of antitubercular potential \[[@B65-molecules-22-01796]\]. Ambewelamides A and B, phenylahistin, and verticillin A exhibit antitumor properties \[[@B66-molecules-22-01796],[@B67-molecules-22-01796]\]. Gliotoxin, a type of mycotoxin, and sirodesmin PL, a type of phytotoxin, have antibacterial, antiviral, and immune suppressive properties \[[@B68-molecules-22-01796],[@B69-molecules-22-01796]\]. In addition, gliotoxin is also a potent inducer of apoptotic and necrotic cell death \[[@B70-molecules-22-01796],[@B71-molecules-22-01796]\].
Some CDPs act as diffusible molecules involved in cell-to-cell communication, and may constitute a new class of quorum-sensing signals \[[@B72-molecules-22-01796],[@B73-molecules-22-01796]\] or interspecies signals \[[@B74-molecules-22-01796]\] in bacteria. Moreover, the CDP-based compound plasminogen activator inhibitor-1 (PAI-1) acts as a main serine protease inhibitor in humans \[[@B75-molecules-22-01796],[@B76-molecules-22-01796]\], and the above mentioned cyclo(His-Pro), a metabolite of TRH precursor is directly involved in the control of high blood glucose levels \[[@B77-molecules-22-01796]\]. Other CDP derivatives play important roles in cardiovascular and blood-clotting functions \[[@B77-molecules-22-01796]\].
Further, CDPs have bioactive effects on their plant or animal hosts, and a role in trans-kingdom signalling has also been proposed. Three CDPs, cyclo([l]{.smallcaps}-Pro-[l]{.smallcaps}-Val), cyclo([l]{.smallcaps}-Pro-[l]{.smallcaps}-Phe), and cyclo([l]{.smallcaps}-Pro-[l]{.smallcaps}-Tyr), are involved in the quorum-sensing-mediated promotion of plant growth by *Pseudomonas aeruginosa* \[[@B78-molecules-22-01796]\]. Additionally, Chen et al. \[[@B79-molecules-22-01796]\] have recently shown that cyclic dipeptides produced by the fungus *Eupenicillium brefeldianum* HMP-F96 induce extracellular alkalinization and H~2~O~2~ production in tobacco cell suspensions. Moreover, Wu et al. \[[@B80-molecules-22-01796]\] reported that two CDPs, named cyclo([l]{.smallcaps}-Pro-[l]{.smallcaps}-Pro) and cyclo([d]{.smallcaps}-Pro-[d]{.smallcaps}-Pro), induced systemic disease resistance in *Nicotiana benthamiana* against *Phytophthora nicotianae* infections by activating a salicylic acid-dependent defence pathway.
7. Concluding Remarks {#sec7-molecules-22-01796}
=====================
In conclusion, CDPs are usually biosynthesized from amino acids by tRNA-dependent cyclodipeptide synthases or non-ribosomal peptide synthetases. These represent complex mechanisms for secondary metabolism production. CDPs have attracted immense attention because they possess unique chemical and diverse biological properties such as antitumor, antifungal, antibacterial, and radical-scavenging activities. Further, CDPs are characterized by their resistance to proteolysis and improved interactions with biological targets, prompting the use of CDP-modified compounds in many pharmaceutical ingredients. In vivo or in vitro, a combination of biological and chemical pathways can generate specific hybrid target compounds, and this can enhance the natural diversity of CDPs. Although much is known about CDPs, many questions remain unanswered. For what purpose, and under which conditions, are specific modified CDPs produced in nature? Functional diversity is imparted by tailoring enzymes, but what kinds of modifications are introduced in which situations? In addition, we expect more CDPs will be identified in the near future, and could be employed in diverse biological applications.
This work was supported by a grant from Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
A.K.M., J.C. and K.-H.B. conceived of and designed the paper. S.-J.C. provided suggestions and modified the language the paper.
The authors declare no conflicts of interest.
![Structure and synthesis of the cyclodipeptide (CDP). CDP is synthesized chemically through (**A**) self-condensation of amino acids and (**B**) intramolecular cyclization of linear dipeptides. R, R1 and R2 represents a side chain, specific to each amino acid; (**C**) Biosynthesis of CDPs by CDP synthases (CDPSs) and subsequent modification by associated tailoring enzyme. Albonoursin \[Cyclo(∆Phe-∆Leu)\] (AlbC), is an antibacterial peptide produced by cyclo([l]{.smallcaps}-Phe-[l]{.smallcaps}-Leu) and tailoring enzyme CDO (cyclicdipeptide oxidase). AlbC is a CDPS and Δ represents the dehydrated form of CDP.](molecules-22-01796-g001){#molecules-22-01796-f001}
![Biosynthesis of the CDP scaffold by the CDPS-dependent pathway (modified from Belin et al. \[[@B11-molecules-22-01796]\]). Here, AA represents the amino acid.](molecules-22-01796-g002){#molecules-22-01796-f002}
molecules-22-01796-t001_Table 1
######
Overview of different tailoring enzymes associated with gene clusters of the non-ribosomal peptide synthetase (1--7) and cyclodipeptide synthase (8--13) pathways, their putative functions, and the substrate CDPscaffold used by those enzymes.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Serial Number Biosynthetic Pathway Tailoring Enzymes Putative Function CDP Substrate Reference
--------------- ------------------------------------------------------------------ ------------------------- -------------------------------------------------------- --------------- ---------------------------------------------------------
1 Thaxtomin A (*Streptomyces scabies*) Cytochrome P450TxtC Hydroxylation c(WF) \[[@B27-molecules-22-01796],[@B45-molecules-22-01796]\]
2 Brevianamide (*Aspergillus fumigatus*) Afu8g00240\ Oxidative cyclization\ c(WP) \[[@B22-molecules-22-01796]\]
Afu8g00230\ Oxidative cyclization\
Afu8g00220\ Hydroxylation\
Afu8g00200\ *O*-methylation\
Afu8g00190 Hydroxylation
3 Ergotamine (*Claviceps purpurae*) CpP4501\ Hydroxylation\ c(FP) \[[@B24-molecules-22-01796]\]
CpCAT2\ Hydro peroxidation\
CpOX3 Oxidative cyclization
4 Meleagrin (*Penicillium chrysogenum*) Pc21g15430\ C3-reverse-prenylation\ c(WH) \[[@B25-molecules-22-01796]\]
Pc21g15440\ *O*-methylation\
Pc21g15450\ Oxidative cyclization\
Pc21g15460\ *N*-hydroxylation\
Pc21g15470 α,β-dehydrogenation
5 Acetylazonalenin (*Neosartorya fischeri*) AnaPT\ *C3*-reverse-prenylation\ c(WF) \[[@B26-molecules-22-01796]\]
AnaAT *N*-acetylation
6 Gliotoxin (*Aspergillus* spp.) GliC\ Oxidation\ c(FS) \[[@B46-molecules-22-01796]\]
GliF\ Oxidation\
GliG\ Sulfurization\
GliI\ Cyclopropane-formation\
GliM\ *O*-methylation\
GliN *N*-methylation
7 CDP-alkaloids biosynthetic pathway (Fumitremorgin biosynthesis)\ Prenyltransferases Prenylation c(WW) \[[@B44-molecules-22-01796]\]
(Aspergillus and Penicillium)
8 Ditryptophenaline (*Aspergillus fumigatus)* Cytochrome P450 DtpC Dimerization c(WF) \[[@B47-molecules-22-01796]\]
9 Nocazine pathway (Dehydrophenylahistin)\ Cytochrome P450 α,β-dehydrogenation c(ΔLF)/c(LΔF) \[[@B48-molecules-22-01796]\]
(*Nocardipsis* spp.)
10 Albonoursin (*Streptomyces noursei)* Cytochrome P450 α,β-dehydrogenation c(FL) \[[@B49-molecules-22-01796]\]
11 Pulcherriminic acid (*Bacillus subtilis)* Cytochrome P450Cyp134A1 Fe-dependent Oxidation c(LL) \[[@B37-molecules-22-01796],[@B50-molecules-22-01796]\]
12 Mycocyclosin (*Mycobacterium tuberculosis*) Cytochrome P450Cyp121 Dimerization c(YY) \[[@B33-molecules-22-01796],[@B42-molecules-22-01796]\]
13 Neihumicin (*Nocardiopsis* spp.) Ndas-1145 S-adenosyl-methionoine dependent *O*-methyltransferase c(FF) \[[@B51-molecules-22-01796]\]
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Substrate amino acids are represented by single letters; Δ represents the dehydrated form of CDP.
[^1]: These authors contributed equally to this work.
|
Here are the advantages of the method: No reliance on the hazardous poisons The users can easily determine whether the rat has been killed or not The rat carcasses can be disposed of and thus there is the odour problems get totally eliminated which might have occurred with the use of poison Trapping of the Rodent is only useful provided the process of re-infestation has been followed properly.
In buildings, these rats take shelter in the places which are elevated or enclosed like walls, attics, cabinets and false ceilings.
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RodentControl Dubai Rodents: Rattusnorvegicus is the rat of Norway which is also known by the name of sewer rat or brown rat. It is quite a destructive pest which is found mainly in the suburban and urban areas. They cause harm to the properties and buildings and also contaminate the food items. This type of Rodent can also spread several dangerous diseases which can badly affect pets and human beings. Detection Of Rat Infestations: One can easily detect the presence of the past by the droppings of gnawing here and there. You can also find their tracks on dusty and muddy surfaces. Burrows and runways can be found along the fences, buildings, railway tracks, or even in debris. Some Facts On Rats: This type of Norway rate is usually brownish or husky in colour. The Rodent weighs almost eleven ounces. Its tail is six to 8inches tall and the body is approximately thirteen to 18inches long. It has coarse fur and the underside of the body id yellowish-white to grey in colour. 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Does the suit make the man or the does the man make the suit? That's the question Tony Stark, a.k.a. Iron Man, wrestles with in the latest installment of Marvel's superhero film franchise.
For a summer popcorn movie, Iron Man 3 definitely has some interesting things to say about dealing with the past, along with its usual fare—sci-fi action and comedy. A more introspective film, this third addition to the Iron Man cinematic catalog looks at the "demons" we create and the cost of fear and unbridled ambition.
THE MOVIE IN A MINUTE
Billionaire mechanical genius Tony Stark's very foundation is shaken when an elusive villain named the Mandarin begins terrorizing America. Iron Man challenges his new enemy, hoping the devious criminal will show himself. But the malicious terrorist remains cloaked in mystery, even as he continues to destroy Stark's life, a task almost too easy as Iron Man wars against his own past demons and crippling fears.
THE GOOD AND BAD IN IRON MAN 3
Robert Downey Jr. dons the perfectly-fitted Iron Man suit once again. But it's not long before the Mandarin (played by Ben Kingsley) begins to unravel the hero's world. Both seasoned actors are great as these commanding figures. Gwyneth Paltrow returns as Pepper Potts (Stark's love interest), and Don Cheadle appears again as friend and co-fighter Col. James Rhodes. Joining the fray are promising young actor named Ty Simpkins, Guy Pearce as Aldrich Killian, and Rebecca Hall as Maya Hansen, both brilliant scientists.
In Iron Man 3, Tony's past comes back to haunt him. In fact, the entire film centers on him confronting his fears and discovering his true identity. Is he merely man or truly a superhero? The movie also speaks to how quickly good intentions can be manipulated. Something that begins with pure intentions, though possibilities are exciting, will inevitably run into problems. Mistakes arise, and sometimes compromises follow.
The film fails to pack a punch because of its occasional plot holes. Some of its twists catch you off guard, while others aren't hard to see coming.
Rated PG-13 for sequences of intense sci-fi action and violence throughout, and brief suggestive content, Iron Man 3 is not an appropriate movie for children to see. With the level of violence (including scenes depicting assassinations and terrorism), foul language and sexually suggestive situations, caution is advised. Also, at one point, Tony describes the Mandarin's dramatic mannerisms as that of a Baptist preacher.
IN THE END
This sequel to the sequel will likely thrill action movie and Iron Man fans with its high-flying stunts and Tony Stark humor. However, plot holes and predictability keep Iron Man 3 from taking the franchise to new heights.
Note: As with all Marvel movies, audiences will want to stay until after the credits end for an extended clip. |
---
abstract: 'Structures of X-ray emitting magnetic polar regions on neutron stars in X-ray pulsars are studied in a range of the accretion rate, 10$^{17}$ g s$^{-1} \sim 10^{18}$ g s$^{-1}$. It is shown that a thin but tall, radiation energy dominated, X-ray emitting polar cone appears at each of the polar regions. The height of the polar cone is several times as large as the neutron star radius. The energy gain due to the gravity of the neutron star in the polar cone exceeds the energy loss due to photon diffusion in the azimuthal direction of the cone, and a significant amount of energy is advected to the neutron star surface. Then, the radiation energy carried with the flow should become so large for the radiation pressure to overcome the magnetic pressure at the bottom of the cone. As a result, the matter should expand in the tangential direction along the neutron star surface, dragging the magnetic lines of force, and form a mound-like structure. The advected energy to the bottom of the cone should finally be radiated away from the surface of the polar mound and the matter should be settled on the neutron star surface there. From such configurations, we can expect an X-ray spectrum composed of a multi-color blackbody spectrum from the polar cone region and a quasi-single blackbody spectrum from the polar mound region. These spectral properties agree with observations. A combination of a fairly sharp pencil beam and a broad fan beam is expected from the polar cone region, while a broad pencil beam is expected from the polar mound region. With these X-ray beam properties, basic patterns of pulse profiles of X-ray pulsars can be explained too.'
author:
- 'Hajime <span style="font-variant:small-caps;">Inoue</span>'
title: 'X-ray emissions from magnetic polar regions of neutron stars'
---
Introduction {#Introduction}
============
Soon after periodic X-ray variations were discovered from Cen X-3 (Giacconi et al. 1971) and Her X-1 (Tananbaum et al. 1972), accretion environments of such sources were theoretically discussed by Pringle and Rees (1972); Lamb, Pethick and Pines (1973). Since then, a large number of X-ray pulsars have been found and theoretical attempts have continuously been being done to explain the observational appearances of X-ray pulsars. We have now the general consensus on situations of X-ray pulsars, settings of which could sequentially be summarized as follows,
- a close binary of a strongly magnetized neutron star + a “normal" companion star,
- an accretion flow from the companion star to the neutron star,
- a magneto-boundary surface at $\sim 10^{8}$ cm from the neutron star where the magnetic pressure once stops the accretion flow,
- two channeled flows along magnetic funnels towards the magnetic poles on the neutron star surface,
- very hot regions at the bottoms of the channeled flows, after energy conversions of the kinetic energies to thermal energies through standing shocks,
- X-ray emissions from the polar regions near the neutron star surface,
- an oblique rotation of the magnetic axis, causing X-ray pulsations.
Pioneer studies on properties of the X-ray emitting regions were already done by some authors by the mid of 1970’s. Davidson (1973) proposed a situation that a hot, dense mound should be formed above each magnetic pole and that infalling material would be decelerated by the radiation pressure of photons trapped inside the mound. He further argued that energy released above the mound should diffuse out as moderately hard X-rays and that energy released within the mound should emerge as soft X-rays from the whole surface of the neutron star. By extending the idea of the radiation-pressure dominant polar mound to cases of high accretion rate, Inoue (1975) studied a structure of a radiation-pressure dominant polar cone above each magnetic pole by taking account of the effect of the gravity there. He discussed that the gravitational energy released in the polar cone should be radiated away from the surface of the cone as a multi-color blackbody emission. Basco and Sunyaev (1975), on the other hand, discussed the generation and diffusion of radiation in a plasma with a strong magnetic field at the bottom of a magnetic funnel, supposing a fairly low accretion rate corresponding to the X-ray luminosity $\ll 10^{37}$ erg s$^{-1}$.
Even at this early moment in the mid of 1970’s, a general picture on X-ray emission regions on each magnetic pole of X-ray pulsars was suggested. It was that there should exist two regions, the primary region where the kinematic energy of the infalling matter is converted the thermal energy and photons generated there or from the bottom side diffuse out upward suffering various interactions with matter in a magnetized plasma, and the secondary region where the accreted matter still gradually falls being braked by the radiation pressure and the gravitational energy gained there finally diffuses out from its surface and/or the adjacent neutron star surface as blackbody emissions. Studies on the primary region have since been being done by several authors (e.g. Becker & Wolff 2007; Wolff et al. 2016) but the secondary region has not been studied in more detail than done by Inoue (1975).
Davidson (1973) first introduced the secondary region as the dense mound at the base of the magnetic funnel. This mound should be surrounded by the magnetic funnel and the infalling matter through the magnetic funnel is considered to finally accumulate there. In the mound, a hydrostatic equilibrium should be established as $$\frac{dP}{dz} = \rho \frac{GM}{R^{2}},
\label{eqn:MoundStr}$$ where $P$ is the pressure at a position with a distance, $z$, from the mound bottom in the direction perpendicular to the stellar surface, $\rho$ is the matter density, $G$ is the gravitational constant, $M$ is the neutron star mass and $R$ is the neutron star radius. Here, we have assumed the height of the mound, $h_{\rm M}$, is sufficiently smaller than the stellar radius. Equation (\[eqn:MoundStr\]) can be solved as $$P_{*} = m \frac{GM}{R^{2}},
\label{eqn:P_*}$$ where $P_{*}$ is the pressure at the bottom of the mound and that at the top has been approximated to be zero. $m$ is the column density of the accreted matter in the mound defined as $$m = \int_{0}^{h} \rho dz.
\label{eqn:Def_m}$$ The total mass of the mound, $M_{\rm M}$, is approximately given by introducing the average radius of the mound cross section, $x_{\rm M}$, as $$M_{\rm M} = \pi x_{\rm M}^{2} m.
\label{eqn:M_M-m}$$ Let $t$ be time from the start of the accretion, then $M_{\rm M}$ should increase with $t$ as $$M_{\rm M} = \frac{\dot{M}}{2} \; t.
\label{eqn:M_M-Mdot}$$ $\dot{M}$ is the total accretion rate onto the neutron star and the factor (1/2) comes from an assumption that the flow should be equally divided into the two funnel flows to the respective N or S magnetic poles. From these equations above, we see that the column density, $m$, should increase in time and the bottom pressure, $P_{*}$ should do so. Then, at some moment, the pressure should overcome the magnetic pressure of the magnetic funnel and the matter should start to flow out from the mound bottom to the entire surface of the neutron star. Thus, a steady state of the mass flow in the mound should be realized when the bottom pressure slightly exceeds the magnetic pressure.
The column density in the steady state, $m_{\rm M}$, is approximately gotten by equating the bottom pressure, $P_{*}$, to the bottom magnetic pressure, $(B^{2}/8\pi)_{*}$ in equation (\[eqn:P\_\*\]) as $$m_{\rm M} = \frac{(B^{2}/8\pi)_{*}} {GM/R^{2}},
\label{eqn:m_M}$$ and the accumulation time of the matter in the mound, $t_{\rm A}$, is roughly estimated as $$t_{\rm A} = \frac{m_{\rm M} \pi x_{\rm M}^{2}}{\dot{M} /2}.
\label{eqn:t_A}$$ In the mound, the gravitational energy should still be released as the matter flows downwards and the energy generation rate should balance with the matter cooling rate in the steady state. The matter cooling rate should be given by the photon diffusion in the azimuthal direction of the mound as far as $x_{\rm M} \ll h_{\rm M}$. The side-way diffusion time, $t_{\rm D, M}$, is approximately given as $$t_{\rm D, M} = \frac{3\kappa_{\rm T} \rho_{\rm M} x_{\rm M}^{2}}{4c}
\label{eqn:t_D}$$ (see Inoue 1975), where $\kappa_{\rm T}$ is the Thomson scattering opacity, and $c$ is the light velocity. $\rho_{\rm M}$ is the average density of the mound and can be approximated as $$\rho_{\rm M} \simeq \frac{m_{\rm M}}{h_{\rm M}}.
\label{eqn:rho_M}$$ For the steady energy flow to realize, we set $t_{\rm A} = t_{\rm D}$ and get, from equations (\[eqn:t\_A\]), (\[eqn:t\_D\]) and (\[eqn:rho\_M\]), $$h_{\rm M} \simeq \frac{3\kappa_{\rm T} }{8\pi c} \dot{M} = 1.4 \times 10^{5} \left( \frac{\dot{M}}{10^{17}\; \rm{g s}^{-1}} \right) \; \rm{cm}.
\label{eqn:h-Mdot}$$ The above simple considerations indicate that the height of the mound, $h_{\rm M}$, could increase as the accretion rate, $\dot{M}$, increases and become comparable to or even larger than the stellar radius when $\dot{M}$ approaches to 10$^{18}$ g s$^{-1}$. If $h_{\rm M}$ gets larger than $R$, X-ray luminosity from the secondary region could be dominant to that from the primary region, since the energy release rate from the primary region and that from the secondary region are approximately given as ($\dot{M}$/2)$GM/(R+h_{\rm M})$ and ($\dot{M}$/2)\[$(GM/R)-(GM/(R+h_{\rm M}))$\] respectively.
In this paper, we study nature and structure of the secondary region as a function of $\dot{M}$ more precisely than such simple arguments as done above. Based on the results, then, we discuss observational appearances of X-ray emissions from there, focusing on cases of fairly high accretion rates corresponding to X-ray luminosities of 10$^{37} \sim 10^{38}$ erg s$^{-1}$. In section 2, the basic assumptions to study the accretion flow along the magnetic funnel are presented and structures of the X-ray emitting regions around the magnetic pole are solved through approximate equations. In section 3, we discuss observational appearances of X-ray spectra and pulse profiles expected from the magnetic polar regions as studied in section 2. Summary and discussions are given in section 4.
Structures of magnetic polar regions
====================================
Magneto-boundary surface
------------------------
Following the general consensus summarized in the previous section, we consider a situation that matter flows from a companion star into a region governed by gravitational field of a neutron star with magnetic field as strong as $10^{12} \sim 10^{13}$ gauss at its surface. The magnetic field once halts the matter from further falling around the magneto-boundary surface at the distance $\sim 10^{8}$ cm from the neutron star. The matter, then, flows along the magneto-boundary surface towards the magnetic poler regions and falls onto the neutron star through two funnel-like tubes guided by the magnetic lines of force.
The picture of the magneto-boundary surface was historically first studied in the case of roughly spherical accretion by a strongly magnetized compact star (e.g. Lamb, Pethick & Pines 1973; Inoue & Hōshi 1975; Arons & Lea 1976; Elsner & Lamb 1977), where the magnetic field is considered to be confined inside the magneto-spheric cavity because of complete screening of the stellar magnetic field from the outside plasma by currents in the transition region between the magneto-boundary surface and the plasma.
In the case that a thin disk extends down to the magneto-bounding surface, which should be more realistic in most of X-ray pulsars than the spherical flow, the accretion flow from the disk to the neutron star surface was studied in detail by Gosh, Lamb & Pethick (1977); Gosh & Lamb (1978, 1979). It is shown that the stellar magnetic field penetrates the inner part of the disk through the Kelvin-Helmholtz instability, turbulent diffusion and so on, and that a transition zone arises in which magnetic coupling between the star and the disk transfers the angular momentum from the disk to the star. The accreted matter is, then, considered to flow from the innermost region of the disk along the lines of force of the stellar magnetic field onto the polar regions of the stellar surface by getting over the barrier of the centrifugal force through the angular momentum transfer.
In the scheme of Gosh & Lamb (1978; 1979), only a thin disk is assumed to extend down to the magneto-boundary region and $\sim$ 20% of the stellar magnetic field is discussed to remain outside the inner edge of the disk. Recent observations, however, indicate that a geometrically thick flow could exist in parallel to the thin disk from the outermost part of the accretion disk (Churazov et al. 2001;Sugimoto et al. 2016; Inoue in preparation). If so, the thick flow should completely screen the remaining magnetic field and thus such a configuration as in figure \[MagnetoBoundarySurface\] could be expected. As discussed by Ghosh & Lamb (1978; 1979), a fraction of the magnetic field should penetrate the inner part of the thin disk and the matter flows along the lines of force of the filed threaded in the disk by losing its angular momentum through the magnetic stress force. A small fraction of the magnetic field could remain outside the transition layer in which the matter is flowing from the thin disk but should completely be compressed and screened by the plasma in the thick disk. The matter in the thick disk could go into the transition layer through instabilities such as the Reyleigh-Taylor instability (Arons & Lea 1976; Elsner & Lamb 1977), and flow together with the matter from the thick disk onto the neutron star surface. As a result, the outer surface of the transition layer could have a shape similar to those obtained by Arons & Lea (1976); Elsner & Lamb (1977), as schematically drawn in figure \[MagnetoBoundarySurface\], where two cusps appear on the magnetic axis. Here, we assume for simplicity that the magnetic axis and the rotational axis of the neutron star are aligned with each other and are perpendicular to the disk plane, as done in the above literatures.
![Schematic cross section of magneto-boundary surface considered in this paper. []{data-label="MagnetoBoundarySurface"}](MagnetoBoundarySurface.jpg){width="12cm"}
Let $r_{\rm M, e}$ and $r_{\rm M, p}$ be the distances of the inner surface of the transition layer in the magneto-boundary surface on the equatorial plane and on the magnetic axis, respectively. We assume $$r_{\rm{M,e}} = 0.4 \; r_{\rm{M,0}},
\label{eqn_Rel_r_p-r_e}$$ adopting the result from Gosh & Lamb (1978), where $r_{\rm{M,0}}$ is the characteristic radius of the magneto-boundary surface for spherical accretion, and $$\begin{aligned}
r_{\rm{M,p}} &=& 0.5 \; r_{\rm {M,e}} \nonumber \\ &\simeq& 6.4 \times 10^{7} \left(\frac{\dot{M}}{10^{17} \; \rm{g \; s}^{-1}} \right)^{-2/7} \left(\frac{M}{M_{\odot}} \right)^{-1/7} \left( \frac{\mu_{\rm M}}{10^{30} \; \rm{gauss \; cm^{3}}} \right)^{4/7},
\label{eqn:r_Me}\end{aligned}$$ adopting the value by Arons & Lea (1976). $\mu_{\rm M}$ is the magnetic moment of the neutron star. Considering a situation that the accreted matter with the density, $\rho_{\rm T}$, falls with the velocity, $v_{\rm T}$, in the transition layer with the thickness, $h_{\rm T}$, from the equatorial side to the polar side, the mass continuity is approximately expressed as $$\frac{\dot{M}}{2} \simeq \rho_{\rm T} v_{\rm T} h_{\rm T} 2\pi r \sin \theta,
\label{eqn:CntEq_TL}$$ where the factor of 1/2 comes from the presence of the two separate streams toward the two respective poles, and $\theta$ is the tangential angle of a relevant position from the polar axis. Here and hereafter, we assume that the identical things happen in both sides of the magnetic poles.
The pressure of the matter in the transition layer, $P_{\rm T}$, is expressed with help of equation (\[eqn:CntEq\_TL\]) as $$\begin{aligned}
P_{\rm T} &=& \frac{2 \rho_{\rm T}}{m_{\rm p}} kT_{\rm T} \nonumber \\ &\simeq& \frac{\dot{M} kT_{\rm T}}{m_{\rm p}v_{\rm T} h_{\rm T} 2 \pi r \sin \theta},
\label{eqn:P_TL}\end{aligned}$$ where $m_{p}$ is the proton mass, $k$ is the Boltzmann constant and $T_{\rm T}$ is the temperature of the flowing matter. The flow velocity, $v_{\rm T}$, should be given as a result of the angular momentum transfer in the transition layer and thus be proportional to the Alfven velocity there. In the present situation, the Alfven velocity should roughly equal to the sound velocity and hence $v_{\rm T}$ should be constant if the temperature is constant throughout the transition layer. Under the isothermal approximation, $P_{\rm T}$ can be written in terms of that around the equatorial plane, $P_{\rm T,e}$ as $$P_{\rm T} \simeq P_{\rm T,e} \left( \frac{r}{r_{\rm M,e}} \right)^{-1} \sin^{-1} \theta.
\label{eqn:P_M}$$ The magnetic pressure in the transition layer, $P_{\rm B}$, is, on the other hand, governed mainly by the magnetic field in the $\theta$ direction, which could be proportional to $r^{-3} \sin \theta$. Hence, $P_{\rm B}$ is approximately given, referring to the value around the equatorial plane, $P_{\rm B, e}$, as $$P_{\rm B} \simeq P_{\rm B,e} \left(\frac{r}{r_{\rm M,e}}\right)^{-6} \sin^{2} \theta.
\label{eqn:P_B}$$ Since $P_{\rm T} \simeq P_{\rm B}$ and $P_{\rm T,e} \simeq P_{\rm B,e}$, we get an approximate relation between $\theta$ and $r$ as $$\sin \theta \simeq \left( \frac{r}{r_{\rm M,e}} \right)^{5/3}.
\label{eqn:Rel_theta-r}$$ From this relation, we can see that there should be no solution near the cusp, where $r \simeq r_{\rm M,p}$ and $\theta < 1$, for the magnetic pressure of the magneto-boundary surface to balance with the matter pressure. The opening angle, $\Theta_{0}$, of the region, in which the matter tends to radially fall onto the stellar surface without halted by the magnetic pressure, is approximately calculated from equation (\[eqn:Rel\_theta-r\]) with help of equation (\[eqn:r\_Me\]) as $$\begin{aligned}
\Theta_{0} &\simeq& \left(\frac{r_{\rm M,p}}{r_{\rm M,e}}\right)^{5/3} \nonumber \\
&\simeq& 0.32.
\label{eqn:Theta_0}\end{aligned}$$
We assume that the magnetic field tends to be dipole-like and the matter should infall to the stellar surface along the lines of force in this region with $\theta \leq \Theta_{0}$, and call this region as the magnetic funnel, hereafter. We, then, approximate the opening angle of the magnetic funnel, $\Theta$, to be a function of $r$, as $$\Theta = \Theta_{0} \left(\frac{r}{r_{\rm M,p}} \right)^{1/2},
\label{eqn:Theta}$$ guided by the dipole-field lines of force. This equation can be rewritten with help of equations (\[eqn\_Rel\_r\_p-r\_e\]), (\[eqn:r\_Me\]) and (\[eqn:Theta\_0\]) as $$\Theta = \Theta_{*} \left(\frac{r}{R} \right)^{1/2},
\label{eqn:Theta_r/R}$$ where $\Theta_{*}$ is the opening angle of the funnel on the surface of the neutron star and is as $$\Theta_{*} = 4.0 \times 10^{-2} \left(\frac{R}{10^{6} \; \rm{cm}} \right)^{1/2} \left(\frac{\dot{M}}{10^{17} \; \rm{g \; s}^{-1}} \right)^{1/7} \left(\frac{M}{M_{\odot}} \right)^{1/14} \left( \frac{\mu_{\rm M}}{10^{30} \; \rm{gauss \; cm^{3}}} \right)^{-2/7}.
\label{eqn:Theta_*}$$
Overall picture of the magnetic polar regions
---------------------------------------------
Since the matter falling in the magnetic funnel, finally hits the neutron star surface, a standing shock should appear at a certain height from the stellar surface. The matter can be approximated to flow with the free fall velocity on the upper-stream side of the shock. We call this region as the free fall region.
The kinetic energy of the inflowing matter should be converted to the thermal energy through the shock. Thermal emissions are expected mainly in the X-ray band from the region between the shock and the stellar surface. We call this X-ray emitting region as the polar cone. The thermal pressure is lower than the magnetic pressure in the polar cone, and the matter falls inwards along the magnetic lines of force there.
At the bottom of the polar cone, however, the matter pressure comes to exceed the magnetic pressure and the matter flows out along the stellar surface from the polar cone by dragging the magnetic lines of force. A mound-like structure appears at each of the two polar surface regions and additional X-ray emissions are expected from there. We call these mound-like structures as the polar mounds hereafter.
Figure \[MagneticPolarRegions\] shows the schematic diagram of the magnetic polar regions, considered in this paper.
![Schematic diagram of magnetic polar regions considered in this paper. []{data-label="MagneticPolarRegions"}](MagneticPolarRegions.jpg){width="8cm"}
Free fall region
----------------
The matter is assumed to flow with the free fall velocity in the free fall region and then the radial inflow velocity, $v_{\rm F}$, at a position with a distance, $r$, from the center of the neutron star is given as $$v_{\rm F} = \left(\frac{2GM}{r} \right)^{1/2}.
\label{eqn:v_r}$$ The continuity equation is written as $$\rho_{\rm F} v_{\rm r} \pi (r \Theta)^{2} = \frac{\dot{M}}{2},
\label{eqn:ContEq}$$ where $\rho_{\rm F}$ is the density of the matter in the free fall region and is gotten as $$\rho_{\rm F} = \frac{\dot{M}}{2\pi \Theta_{*}^{2} (2GM)^{1/2} R^{3/2}} \left(\frac{r}{R} \right)^{-5/2}.
\label{eqn:rho_F}$$
The optical depth for Thomson scatterings, $\tau_{\rm F}$, in the azimuthal direction in the free fall region is calculated with equations (\[eqn:Theta\_r/R\]) and (\[eqn:rho\_F\]) as $$\begin{aligned}
\tau_{\rm F} &=& \kappa_{\rm T} \rho_{\rm F} r \Theta \nonumber \\ &\simeq& 9.9 \left( \frac{\dot{M}}{10^{17} \, \rm{ g \, s}^{-1}} \right)^{6/7} \left(\frac{M}{M_{\odot}} \right)^{-4/7} \left(\frac{\mu_{\rm M}}{10^{30} \, \rm{gauss \, cm}^{3}} \right)^{-2/7} \left( \frac{r}{10^{6} \rm{cm}} \right)^{-1},
\label{eqn:tau}\end{aligned}$$ where $\kappa_{\rm T}$ is the opacity of the Thomson scattering. From this equation, we see that the flow within the magnetic funnel above the shock front is optical thick for the Thomson scattering in case of $\dot{M} \gtrsim 10^{17}$ g s$^{-1}$ unless $r \gg 10^{7}$ cm.
X-ray emitting polar cone region {#XEPC}
--------------------------------
### Dominance of the radiation energy in the polar cone {#RadEnDominance}
As shown in equation (\[eqn:tau\]), the optical depth is larger than unity even in the free fall region in front of the shock. The density behind the shock front must be larger than the density in the free fall region and the density gets larger and larger as the matter in-falls in the polar cone. Thus, we can say that polar cone is sufficiently optically thick.
The density behind the shock, $\rho_{\rm S}$, is given as $$\rho_{\rm S} = \frac{\gamma+1}{\gamma-1} \rho_{\rm F} (r_{\rm S}),
\label{eqn:rhoS}$$ where $\gamma$ is the specific heat ratio. If we initially assume that the gaseous energy is dominant to the radiation energy, $\gamma$ should be 5/3 and then $\rho_{\rm S} = 4 \rho_{\rm F} (r_{\rm S})$. The ion temperature behind the shock, $T_{\rm i, S}$, is given as $$T_{\rm i, S} = \frac{3}{8} \frac{m_{\rm p}}{k} \frac{GM}{ r_{\rm S}}.
\label{eqn:T_iS}$$ The electron temperature, $T_{\rm e, S}$ should be determined by a balance between energy input through collisions with protons and energy loss through photon emissions and Compton scatterings. The energy input rate per mass, $\varepsilon_{+}$, is expressed as $$\dot{\varepsilon}_{+} = \frac{3 kT_{\rm i,S}/ 2m_{\rm p}} {t_{\rm ie}},
\label{eqn:epsilon_+}$$ when $T_{\rm i,S} \gg T_{\rm e,S}$. $t_{\rm ie}$ is the ion-electron equipartition time and is given by Spitzer (1962) as $$t_{\rm ie} = 4.2 \times 10^{-22} (\ln \Lambda)^{-1} \rho_{\rm S}^{-1} T_{\rm e,S}^{3/2}
\label{eqn:t_ie}$$ in cgs unit, where $\ln \Lambda$ is the Coulomb logarithm. The energy loss rate per mass, $\dot{\varepsilon}_{-}$ is, on the other hand, written as $$\dot{\varepsilon}_{-} = A \dot{\varepsilon}_{0} \rho_{\rm S} T_{\rm e, S}^{1/2},
\label{eqn:epsilon_-}$$ where $\dot{\varepsilon}_{0} \rho_{\rm S} T_{\rm e, S}^{1/2}$ is the free-free emission rate per mass and $A$ is an amplification factor through inverse Compton scatterings. From $\dot{\varepsilon}_{+} = \dot{\varepsilon}_{-}$ with help of equations (\[eqn:T\_iS\]) $\sim$ (\[eqn:epsilon\_-\]), we get, independently of the density, $$T_{\rm e,S} = 1.9 \times 10^{10} \left(\frac{M}{M_{\odot}}\right)^{1/2} \left(\frac{r_{\rm S}}{10^{6} \; \rm cm}\right)^{-1/2} \rm K,
\label{eqn:T_eS}$$ where we have assumed $\ln \Lambda = 10$ and $A = 10$ (Illarionov and Sunyaev 1972).
Since $\dot{\varepsilon}_{-}$ is thought to be the radiation energy generation rate per mass, we can approximately calculate the radiation energy density per mass, $\varepsilon_{\rm Rad,S}$, expected when the electron temperature is as in equation (\[eqn:T\_eS\]), as $$\varepsilon_{\rm Rad,S} \simeq \dot{\varepsilon}_{-} \; t_{\rm D,S}.
\label{eqn:Def_epsilon_Rad}$$ Here, $t_{\rm D, S}$ is a time scale, during which the generated photons diffuse out in the azimuthal direction of the polar cone, and is approximately represented as $$t_{\rm D, S} = \frac{3 \kappa_{\rm T} \rho_{\rm S} (r_{\rm S} \Theta_{\rm S})^{2}}{4 c}.
\label{eqn:tDS}$$
If $\varepsilon_{\rm Rad, S}$ is as large as or larger than the gaseous energy per mass behind the shock, which is given as $$\varepsilon_{\rm Gas, S} = \frac{9}{16} \frac{GM}{r_{\rm S}},
\label{eqn:epsilon_GasS}$$ with the specific heat ratio of 5/3, we can assure that the radiation energy is sufficiently established to be dominant to the gaseous energy in the polar cone.
Let $\zeta$ be the ratio of $\varepsilon_{\rm Rad, S}$ to $\varepsilon_{\rm Gas, S}$, and it is given from above equations as $$\begin{aligned}
\zeta &=& \frac{\varepsilon_{\rm Rad,S}}{\varepsilon_{\rm Gas,S}} \nonumber \\
&=& 0.9 \, \left(\frac{\dot{M}}{10^{17} \rm \, g \, s^{-1}} \right)^{12/7} \left(\frac{\mu_{\rm M}}{10^{30} \rm \,gauss \, cm^{3}} \right)^{4/7} \left(\frac{M}{M_{\odot}} \right)^{-53/28} \left(\frac{r_{\rm S}}{10^{6} \rm{\, cm}} \right)^{-5/4},
\label{eqn:zeta}\end{aligned}$$ where we have assumed $A=10$ and $\ln \Lambda = 10$ again. By using the $r_{\rm S}$ and $\dot{M}$ relation for the polar cone as given in figure \[Mdot-Height\_Relations\] in \[Structure\], we can calculate $\zeta$ as a function of $\dot{M}$ for two cases of $\mu_{\rm M}$ and the result is shown in figure \[Mdot-zeta\]. We see that $\zeta \gtrsim 1$, when $\dot{M} \gtrsim 10^{17}$ g s$^{-1}$. Since our concern mainly exists on the bright X-ray pulsars with $\dot{M} \gtrsim 10^{17}$ g s$^{-1}$ here, we approximate the thermal energy as being governed by the radiation energy, and neglect the gaseous energy in the polar cone.
![$\zeta$-value, which indicate the dominance of the radiation energy density behind the shock, as a function of $\dot{M}$. The thick and thin lines correspond to cases of $\mu_{\rm M} = 10^{30}$ gauss cm$^{3}$ and $\mu_{\rm M} = 10^{31}$ gauss cm$^{3}$ respectively.[]{data-label="Mdot-zeta"}](RadEnergyEstablishment.jpg){width="8cm"}
### Energy loss due to side-say diffusion of photons
Since $\Theta \ll 1$, photons in the polar cone tend to diffuse out in the azimuthal direction of the cone. Thus, we approximate that the energy loss of the inflowing matter in the polar cone is governed by the side-way diffusion of photons. In that case, the energy loss rate per unit volume, $q$, is approximately given as $$q = \frac{u}{t_{\rm D}},
\label{eqn:Def_q}$$ where $u$ is the typical radiative energy density in the polar cone, and $t_{\rm D}$ is the diffusion time as in equation (\[eqn:tDS\]). The equation for the energy flow in the polar cone is then given as $$\begin{aligned}
\frac{\dot{M}}{2} \frac{d}{dr}\left(\frac{v^{2}}{2} + \frac{4}{3} \varepsilon - \frac{GM_{\rm X}}{r} \right) &=& \pi (r \Theta)^{2} q \nonumber \\
&=& \frac{4 \pi c}{3 \kappa_{\rm T}} \varepsilon,
\label{eqn:BernoulliEq}\end{aligned}$$ with help of equation (\[eqn:Def\_q\]), equation $u = \rho \varepsilon$, and equation (\[eqn:tDS\]), where $v$ and $\varepsilon$ are respectively the inflow velocity and the radiative energy per unit mass in the polar cone.
### Structure of the polar cone {#Structure}
Based on the above arguments, equations determining structures of the polar cone are as follows.
The first is the continuity equation which is given in equation (\[eqn:ContEq\]) by replacing $v_{\rm T}$ with $v$. Here, we assume for simplicity that $\rho$ and $v$ are uniform on a cross section in the azimuthal direction of the polar cone.
The second is the dynamical equation, on an assumption that the flow in the polar cone is sufficiently subsonic to neglect the velocity gradient term, $$\frac{dP}{dr} = - \rho \frac{GM}{r^{2}}.
\label{eqn:DB_Eq}$$
The third is the energy equation, modified from equation (\[eqn:BernoulliEq\]) by neglecting the kinetic energy of the matter flow, as $$\frac{d}{dr} (\frac{4}{3} \varepsilon - \frac{GM}{r}) = \frac{\varepsilon}{r_{\rm D}},
\label{eqn:EnEq}$$ where $r_{\rm D}$ is a parameter defined as $$r_{\rm D} = \frac{3 \kappa_{\rm T} \dot{M}}{8 \pi c} = 1.4 \times 10^{5} \left(\frac{\dot{M}}{10^{17} \rm{g \; s}^{-1}} \right) \; \rm{cm}.
\label{eqn:Def_rD}$$
In the above two equations, we have assumed that $P$ and $\varepsilon$ are radiation pressure and radiation energy per mass, neglecting gaseous pressure and energy, and that both are representative quantities over a cross section of the polar cone. Then, we can set $$P = \frac{u}{3} = \frac{\rho \varepsilon}{3}.
\label{eqn:EqState}$$
From equations (\[eqn:DB\_Eq\]), (\[eqn:EnEq\]) and (\[eqn:EqState\]), we get two equations to determine $\varepsilon$ and $\rho$ as functions of $r$ as $$\frac{d\varepsilon}{dr} = \frac{3}{4} ( \frac{\varepsilon}{r_{\rm D}} - \frac{GM}{r^{2}} )、
\label{eqn:DifEq1}$$ and $$\frac{d\rho}{dr} = -\frac{3\rho}{4\varepsilon} ( \frac{\varepsilon}{r_{\rm D}} + 3 \frac{GM}{r^{2}} ).
\label{eqn:DifEq2}$$
The top boundary of polar cone is the shock front. The density at the top boundary should be given by equation (\[eqn:rhoS\]). Since the radiation energy density is considered to be dominant in the polar cone, we set $\gamma = 4/3$ in the polar cone and then $\rho_{\rm S} = 7 \rho_{\rm F} (r_{\rm S})$. By also approximating that the kinetic energy of the inflow matter in front of the shock is all converted to the radiative energy (enthalpy) behind the shock, $\varepsilon_{\rm S}$ is expressed as $$\varepsilon_{\rm S} = \frac{3}{4} \frac{GM}{r_{\rm S}}.
\label{eqn:OuterBC}$$
These boundary values are functions of $r_{\rm S}$, and thus we numerically solve equations (\[eqn:DifEq1\]) and (\[eqn:DifEq2\]) from an assumed position, $r_{\rm S}$, successively decreasing $r$ inward to the bottom boundary at the neutron star surface where $r = R$. As shown later, the radiative pressure steeply increases as $r$ decreases and comes to exceed the magnetic pressure of the funnel at some position. The magnetic funnel should be pushed out, when the radiative pressure exceeds the magnetic pressure, and the matter should flow out along the neutron star surface by dragging the magnetic lines of force from the funnel-like magnetic column. Thus, the following condition should be satisfied at the bottom of the polar cone as $$P_{*} = \frac{\rho_{*} \varepsilon_{*}}{3} = \frac{B_{r, *}^{2}}{8 \pi},
\label{eqn:BtmBC}$$ where we represent the physical quantities at the bottom of the polar cone with the subscript \*. The distance of the top boundary of the polar cone, $r_{\rm S}$, has been searched to satisfy this bottom boundary condition.
Solutions of equations (\[eqn:DifEq1\]) and (\[eqn:DifEq2\]) have been gotten with the procedures described above in various cases of $\dot{M}$, where we have adopted $M = M_{\odot}$, $R = 10^{6}$ cm and two cases of $B_{\rm r, *}$ as 10$^{12}$ G and 10$^{13}$ G. The obtained $\varepsilon$, $\rho$, $P$, $v$, $\tau$ and $T_{\rm C}$ as functions of $r$ are shown on five cases of $\dot{M}$ for $B_{\rm r, *} = 10^{12}$ G in figure \[Solutions\_B1\] and for $B_{\rm r, *} = 10^{13}$ G in figure \[Solutions\_B10\], respectively. Here, $v$ has been calculated from the continuity equation. $\tau$ is the optical depth for the Thomson scattering in the tangential direction of the polar cone. $T_{\rm C}$ is the typical temperature of the matter in the polar cone and has been calculated by an equation as $T_{\rm C} = (\rho \; \varepsilon/a)^{1/4}$, where $a$ is the first radiation constant. The normalization parameters in the figures are defined as $\varepsilon_{0} = GM/R$, $\rho_{0} = 3 B_{\rm r, *}^{2} R / (8 \pi GM) \sim 9 \times 10^{2} (B_{\rm r, *}/10^{12}$ G)$^{2} (M/M_{\odot})^{-1} (R/10^{6}$ cm) g cm$^{-3}$, and $P_{0} = P_{*}$ in equation (\[eqn:BtmBC\]).
![Solved distributions of $\varepsilon$, $\rho$, $P$, $v$, $\tau$ and $T_{\rm C}$ as functions of $r$ in five $\dot{M}$ cases for $B_{\rm r, *} = 10^{12}$ G. Columns (A), (B), (C), (D) and (E) correspond to cases of $\dot{M} = 3 \times 10^{16}$ g s$^{-1}$, $10^{17}$ g s$^{-1}$, $3 \times 10^{17}$ g s$^{-1}$, $10^{18}$ g s$^{-1}$, and $3 \times 10^{18}$ g s$^{-1}$, respectively. Dashed lines in the row of $P$ represent the $r$ dependence of the magnetic pressure as $\propto r^{-6}$. []{data-label="Solutions_B1"}](B1_Solution_Figures.jpg){width="15cm"}
![The same as figure \[Solutions\_B1\] but for $B_{\rm r, *} = 10^{13}$ G.[]{data-label="Solutions_B10"}](B10_Solution_Figures.jpg){width="15cm"}
The height of the polar cone, $h$, defined as $$h = r_{\rm S} - R,
\label{eqn:Eq_h}$$ is plotted as a function of $\dot{M}$ in figure \[Mdot-Height\_Relations\]. As seen from this figure, $h$ increases roughly in proportion to $\dot{M}$. When $\dot{M}$ is $\sim 10^{16}$ g s$^{-1}$, $h$ is about a tenth as small as the neutron star radius. When $\dot{M}$ is $\sim 10^{18}$ g s$^{-1}$, however, $h$ gets about ten times as large as the neutron star radius.
![Height of of the polar cone region as a function of $\dot{M}$ (solid lines). Dotted lines indicate positions of $r_{\rm M,p}$. The thick and thin lines correspond to cases of $B_{\rm r, *} = 10^{12}$ G and $10^{13}$ G respectively.[]{data-label="Mdot-Height_Relations"}](Mdot-Height_Relations.jpg){width="8cm"}
### Energy loss from the polar cone {#ELossPC}
From figures \[Solutions\_B1\] and \[Solutions\_B10\], we see, irrespectively of $\dot{M}$, that $\varepsilon$ once decreases as $r$ decreases from $r_{\rm S}$ but that it turns to increase after $r$ gets smaller than a certain value. The variation of $\varepsilon$ is determined by equation (\[eqn:DifEq1\]) in which the first term and the second term in the right hand side are the energy loss rate through the radiative diffusion and the energy gain rate from the gravitational energy, respectively. In the upper region near the shock, the radiative cooling rate is dominant to the energy gain rate and $\varepsilon$ decreases as the matter flows downwards. The energy gain rate through the gravitational acceleration, however, becomes dominant to the energy loss rate and $\varepsilon$ starts increasing with $r$-decrease when $r$ gets smaller than the boundary distance, $r_{\rm B}$, where $d\varepsilon/dr = 0$. Hereafter, the region where $r > r_{\rm B}$ and that where $r < r_{\rm B}$ are called as the upper polar cone region and the lower polar cone region respectively.
Let the total energy per mass of the inflow matter in the polar cone be $u$, it is expressed as $$u = \frac{4}{3} \; \varepsilon - \frac{GM}{r},
\label{eqn:Def_u}$$ where the first term in the right side is the enthalpy per mass under the situation in which the radiative energy density is largely dominant to the gaseous energy density. Since the top boundary condition of $\varepsilon$ is given as in equation (\[eqn:OuterBC\]), we have $$u_{\rm S} = 0,
\label{eqn:uS}$$ just behind the shock front. This is the result from an approximation that the specific total energy, $u$ is just zero at infinity. Then, if $u$ decreases to $u_{\rm B}$ as the matter falls down to the position, $r_{\rm B}$, the inflow matter should lose an amount of energy per mass, $w_{\rm U}$ in the upper region as $$w_{\rm U} = u_{\rm S}-u_{\rm B}=-u_{\rm B}.
\label{eqn:w_U}$$ Similarly, another amount of energy per mass, $w_{\rm L}$, which is lost from the inflow matter in the lower polar cone region, is given as $$w_{\rm L} = u_{\rm B}-u_{*},
\label{eqn:w_L}$$ where $u_{*}$ is the $u$ value at the bottom of the polar cone. The inflow matter should finally spread over the neutron star surface and assimilate with the interior matter of the neutron star. In order to do that, however, the inflow matter should throw away the radiative thermal energy, $\varepsilon_{*}$, which has remained at the bottom of the polar cone. This $\varepsilon_{*}$ should be conveyed to the polar mound region as discussed in the next sub-section and finally be radiated away from its surface. The amount of the thermal energy, $w_{*}$, which has been carried without radiated away even to the bottom of the polar cone, is given as $$w_{*} = \frac{4}{3}\; \varepsilon_{*}.
\label{eqn:w_*}$$
Figure \[EnergyLossPortions\] shows respective portions of the three amounts of the energy, $w_{\rm U}$, $w_{\rm L}$ and $w_{*}$ to the sum of the three, as functions of $\dot{M}$ in case of $B_{\rm r, *} = 10^{12}$ G. The result is about the same in case of $B_{\rm r, *} = 10^{13}$ G. We see that $w_{\rm H}$ is dominant when $\dot{M} \lesssim 10^{17}$ g s$^{-1}$, the three are comparable to one another when $10^{17}$ g s$^{-1}$ $\lesssim \dot{M} \lesssim 10^{18}$ g s$^{-1}$, and $w_{*}$ is dominant when $\dot{M} \gtrsim 10^{18}$ g s$^{-1}$.
![Portions of energy loss in the upper polar cone region (dotted line), the lower polar cone region (dashed line) and in the mound region (thick line) as functions of $\dot{M}$ in case of $B_{\rm r, *} = 10^{12}$ G.[]{data-label="EnergyLossPortions"}](EnergyReleasePortions.jpg){width="8cm"}
X-ray emitting polar mound region {#XEPM}
---------------------------------
The accreted matter still tends to flow downwards with significant amount of thermal energy at the bottom of the polar cone, but the thermal pressure should get stronger than the magnetic pressure of the surrounding magnetic funnel if the matter flows further below the bottom boundary. Thus, the matter should start expanding along the surface of neutron star, dragging the magnetic lines of force. We call this tangentially expanding region as the polar mound region. The schematic cross section of the polar mound is drawn in figure \[PolarMoundFigure\].
![Schmatic cross section of the polar mound. The shape is approximated by a low cone, as indicated with dashed lines, with a radius, $x_{\rm PM}$ of the base and a height, $z_{\rm PM}$, at the center, in order to roughly estimate the sizes of the polar mound.[]{data-label="PolarMoundFigure"}](PolarMoundFigure.jpg){width="8"}
The structure of the polar mound should be determined from the following two conditions.
The first is that the matter flowing in the polar mound should radiate away the residual thermal energy which has remained at the bottom of the polar cone before settling on the surface of the neutron star. This condition can be represented by a simple equation as $$\frac{\dot{M}}{2} = \frac{M_{\rm PM}}{t_{\rm D, PM}}.
\label{eqn:EnEq_PM}$$ $M_{\rm PM}$ is the total mass in the polar mound, approximately given as $$M_{\rm PM} = \frac{1}{3} \pi x_{\rm PM}^{2} z_{\rm PM} \rho_{\rm PM},
\label{eqn:M_PM}$$ and $t_{\rm D, PM}$ is the photon diffusion time in the direction perpendicular to the stellar surface, roughly written as $$t_{\rm D, PM} = \frac{\kappa_{\rm T} \rho_{\rm PM} z_{\rm PM}^{2}}{3c}.
\label{eqn:t_DPM}$$ Here, we have assumed the shape of the polar mound to be a very low cone with a radius, $x_{\rm PM}$ of the base and a height, $z_{\rm PM}$. It is simply assumed that the density is uniform in the polar mound and that $t_{\rm D, PM}$ is represented with the value in the envelope of the cone with the average thickness, $z_{\rm PM}/3$. From above three equations we get $$x_{\rm PM}^{2} = \frac{\dot{M} \kappa_{\rm T}}{2\pi c} z_{\rm PM}.
\label{eqn:x-z_Rel_1}$$
The second condition is a pressure balance between the radiation pressure pushing out the magnetic lines of force and the magnetic pressure intensified by being dragged by the expanding flow in the polar mound. The radiation pressure, $P$, could be approximately obtained by extending the $P$ - $r$ relation in the polar cone to a position slightly lower than the bottom of the polar cone. If we express it as $P \propto r^{-\alpha}$, $P$ which pushes out the magnetic lines of force is roughly given as $$P = P_{*} \left( \frac{R}{R + z_{\rm PM}} \right)^{-\alpha},
\label{eqn:P_PM}$$ where $P_{*}$ is the pressure at the bottom of the polar cone as is given in equation (\[eqn:BtmBC\]). The magnetic pressure which pushes back the matter pressure could be approximated as $$\left( \frac{B^{2}}{8\pi} \right)_{\theta} = \left( \frac{B^{2}}{8\pi} \right) \frac{z_{\rm PM}}{(x_{\rm PM}^{2} + z_{\rm PM}^{2})^{1/2}} = P_{*} \frac{(x_{\rm PM}^{2} + z_{\rm PM}^{2})^{1/2}}{z_{\rm PM}},
\label{eqn:MagP_PM}$$ where we have assumed $$B = B_{\rm r, *} \frac{(x_{\rm PM}^{2} + z_{\rm PM}^{2})^{1/2}}{z_{\rm PM}}.
\label{eqn:B-Br*}$$ By equating two equations (\[eqn:P\_PM\]) and (\[eqn:MagP\_PM\]), we get $$\left( \frac{R}{R + z_{\rm PM}} \right)^{-\alpha} = \frac{(x_{\rm PM}^{2} + z_{\rm PM}^{2})^{1/2}}{z_{\rm PM}}.
\label{eqn:x-z_Rel_2}$$
By seeing $\alpha$ from the $P$ distribution in the polar cone as a function of $\dot{M}$, shown in figures \[Solutions\_B1\] and \[Solutions\_B10\], and solving simultaneous equations (\[eqn:x-z\_Rel\_1\]) and (\[eqn:x-z\_Rel\_2\]), we obtain $x_{\rm PM}$ and $z_{\rm PM}$ as functions of $\dot{M}$ in two cases of $B_{*}$. The results in case of $B_{*} = 10^{12}$ gauss are plotted in figure \[MoundParameters\]. Those in case of $B_{*} = 10^{13}$ gauss are almost identical. When $\dot{M}$ becomes larger than $10^{18}$ g s$^{-1}$, $x_{\rm PM}$ comes to be as large as or even larger than $R$ and simple arguments as done above become inapplicable.
![Base radius (the thick line) and height (the thin line) of the polar mound, in unit of the stellar radius, as a function of $\dot{M}$. []{data-label="MoundParameters"}](MoundParameters_R.jpg){width="8cm"}
X-ray emissions from the magnetic polar regions {#X-ray_Emissions}
===============================================
We have seen the portions of energy loss from the upper polar cone region, the lower polar cone region and the polar mound region in \[ELossPC\]. Since the energy lost from these regions should be emitted mainly in X-rays from their surfaces, the portions of the energy loss from the three regions as shown in figure \[EnergyLossPortions\] correspond to those of the local X-ray luminosities.
In the polar cone region, photons are considered to diffuse out from the side surface of the cone. The differential X-ray luminosity emitted from the polar cone surface per unit radial-length is given from equation (\[eqn:BernoulliEq\]) as $$\frac{dL}{dr} = \frac{4\pi c}{3 \kappa_{\rm T}} \varepsilon.
\label{eqn:dLdr}$$ It should be noted that this quantity is proportional to $\varepsilon$ and does not directly depend on $\dot{M}$ nor $\Theta$.
Since thermal equilibrium between matter and radiation is considered to be well established in the polar cone, emission from the surface of the polar cone should be basically blackbody emission. In that case, the effective temperature, $T_{\rm e}$, of a surface of the polar cone at a distance, $r$, is estimated from the following equation as $$\frac{dL}{dr} = 2 \pi r \Theta \sigma T_{\rm e}^{4},
\label{eqn:RltnTe^4}$$ where $\sigma$ is the Stephan Boltzmann constant.
However, we should take account of the dilution effect of the blackbody photons, since scattering is considered to be dominant to absorption in such an atmosphere with a temperature as high as 10$^{7}$ K as the surface of the polar cone. In such a situation, we can approximate that the thermal equilibrium between matter and radiation is established within a region with an optical depth for the scattering, $\tau_{\rm a} \gg 1$, and only elastic scatterings take place in the atmosphere with $\tau < \tau_{\rm a}$. Under this approximation, the observed spectrum can be approximated with the blackbody spectrum with the apparent temperature, $T_{\rm a}$, at the bottom of the scattering atmosphere with $\tau_{\rm a}$. In the atmosphere with $\tau \lesssim \tau_{\rm a}$, a radiation energy flux should be conserved and we can approximate that $$\frac{T_{\rm a}^{4}}{\tau_{\rm a}} = T_{\rm e}^{4}.
\label{eqn:Rltn_Ta&Te}$$
From equations (\[eqn:dLdr\]) and (\[eqn:RltnTe\^4\]) with help of equation (\[eqn:Rltn\_Ta&Te\]), the observed blackbody (apparent) temperature, $T_{\rm a}$, is written as $$T_{\rm a} = \left( \frac{2c}{3\kappa_{\rm T} \sigma} \frac{\tau_{\rm a} \varepsilon}{r \Theta} \right)^{1/4}.
\label{eqn:Ta}$$
If we introduce the following relations in general as $$\begin{aligned}
T_{\rm a} &\propto& r^{-p}, \label{eqn:T-r} \\
\varepsilon &\propto& r^{\nu}, \label{eqn:epsilon-r} \\
\Theta &\propto& r^{\eta}, \label{eqn:theta-r} \\
\tau_{\rm a} &\propto& T_{\rm a}^{\omega}, \label{eqn:tau-Tc} \end{aligned}$$ we get $$p = \frac{-\nu + \eta + 1}{4 - \omega}.
\label{eqn:Rltn_p}$$ Note that differential equations (\[eqn:DifEq1\]) and (\[eqn:DifEq2\]) in \[Structure\] does not include the parameter $\Theta$. Thus, the solutions as shown in figures \[Solutions\_B1\] and \[Solutions\_B10\] allow such a freedom of $r$ dependence of $\Theta$ as in equation (\[eqn:theta-r\]), as far as $\Theta \ll 1$. In this study, we have assumed $\eta = 0.5$ as in equation (\[eqn:Theta\_r/R\]).
As seen in top panels of figures \[Solutions\_B1\] and \[Solutions\_B10\], two local maximums of $\varepsilon$ appear, and the locally most luminous positions in the polar cone are the top of the polar cone just behind the shock and the bottom of the polar cone just on the neutron star surface. The most luminous place, however, depends on $\dot{M}$. When $\dot{M} \lesssim 10^{17}$ g s$^{-1}$, the top of the polar cone is the most luminous, when $\dot{M} \simeq 3 \times 10^{17}$ g s$^{-1}$, the top and the bottom of the polar cone are comparably luminous, and when $\dot{M} \gtrsim 10^{18}$ g s$^{-1}$, the bottom is the most luminous.
The relative amount of the differential luminosity between the top and bottom of the polar cone is seen to depend on $\dot{M}$ in figure \[EnergyLossPortions\] too. This figure further reminds us that the polar mound region is the most luminous when $\dot{M} \gtrsim 3 \times 10^{17}$ g s$^{-1}$.
The X-ray luminosity from the polar mound region, $L_{\rm PM}$, is given as $$L_{\rm PM} = \frac{\dot{M}}{2} w_{*},
\label{eqn]L_PM}$$ where $w_{*}$ has been defined in \[ELossPC\]. In the polar mound region, the matter should successively sink into the surface layer of the neutron star as it expands tangentially on the stellar surface. Because of the matter sinking and the area-extension, the column density should decreases and it get easier for photons to diffuse out as the distance from the mound center increases. Furthermore, since the magnetic lines of force are dragged tangentially along the surface of the polar mound, photons easily go outward, without scattered by ambient electrons which cannot move across the dragged lines of force. As a result, we can expect that the X-ray emission could be largely weighted on the outermost area of the polar mound and be approximated by a single blackbody emission with an apparent temperature, $T_{\rm a, PM}$, which could be calculated from the following equation as $$L_{\rm PM} = \chi \pi x_{\rm PM}^{2} \sigma T_{\rm a, PM}^{4}.
\label{eqn:T_aPM^4}$$ Here, $\chi$ is a parameter which represents both a reducing factor of the effective emission area from the whole surface area of the mound and a dilution factor of the scattering dominant atmosphere, and should be $\ll 1$.
Properties of X-ray spectrum {#X-ray_spectrum}
----------------------------
When $\dot{M} \lesssim 10^{17}$ g s$^{-1}$, X-ray emission from the upper polar cone is the most luminous. As seen from the top panels of figures \[Solutions\_B1\] and \[Solutions\_B10\], the logarithmic slope of $\varepsilon$ against $r$, $\nu$, is much larger than unity, and thus a single blackbody spectrum is expected in this $\dot{M}$ range within the simplified arguments in this study. Since establishment of the radiation field is thought to be insufficient behind the shock as in figure \[Mdot-zeta\], however, Comptonization of bremsstrahlung photons and blackbody photons produced around there should be taken into account to consider properties of X-ray spectrum from there, which was already studied by Becker and Wolff (2007) and Wolff et al. (2016). We do not go into detail on this low $\dot{M}$ range here.
When $\dot{M} \gg 10^{17}$ g s$^{-1}$, on the other hand, the X-ray emission from the upper polar cone region get less luminous than those from the lower polar cone region and the polar mound region. Furthermore, since the distance of the shock front, $r_{\rm S}$, is several times as large as the neutron star radius in case of $\dot{M} \simeq 10^{18}$ g s$^{-1}$ (see figure \[Mdot-Height\_Relations\]), the temperature of the emission from the upper polar cone region should be much lower than those from the two regions near the neutron star surface. Thus, we neglect contribution of the emission from the upper polar cone region here because our present concern exists on properties of X-ray spectrum in the energy range above a few keV in the $\dot{M}$ range around 10$^{18}$ g s$^{-1}$.
From the lower polar cone region, we can expect a multi-color blackbody spectrum, which should be expressed with the $p$-free disk model (Kubota & Makishima 2004). This model was developed to reproduce X-ray spectra from accretion disks and the surface blackbody temperature is assumed to distribute as a function of an orbital radius in a disk as in equation (\[eqn:T-r\]). In the present case considered here, the $p$ parameter is given by equation (\[eqn:Rltn\_p\]). The value of $\nu$, which is defined as the logarithmic slope of $\varepsilon$ against $r$ in equation (\[eqn:epsilon-r\]), can be calculated from the radial distribution of $\varepsilon$ solved in \[Structure\], and is $\sim$ -1.3 near the bottom of the polar cone when $\dot{M}$ is around 10$^{18}$ g s$^{-1}$. Then, $p$ is estimated to be $\sim$ 0.7, taking account of $\eta$ = 0.5 as assumed in equation (\[eqn:Theta\_r/R\]) and setting $\omega$ = 0 for simplicity. The highest apparent temperature in the multi-color component can be estimated from equation (\[eqn:Ta\]) by setting $\varepsilon = \varepsilon_{*}$, $r = R$ and $\Theta = \Theta_{*}$, and assuming $\tau_{\rm a}^{1/4} \simeq 2$ (e.g. Shimura & Takahara 1995). Since $\varepsilon_{*} \simeq 0.4 \varepsilon_{0}$ when $\dot{M} = 10^{18}$ g s$^{-1}$ as seen both in figures \[Solutions\_B1\] and \[Solutions\_B10\], we get the highest apparent temperature $\sim$ 5 keV around that accretion rate.
From the polar mound region, a quasi-single blackbody spectrum should be detected. The apparent temperature, $T_{\rm a,PM}$, is calculated from equation (\[eqn:T\_aPM\^4\]) to be again $\sim$ 5 keV when $L_{\rm PM} \simeq 10^{38}$ erg s$^{-1}$ and $\chi^{-1/4} (x_{\rm PM}/R)^{-1/2} \simeq 2$.
According to above arguments, we can expect a hybrid spectrum composing of the multi-color blackbody spectrum from the lower polar cone region and the quasi-single blackbody spectrum from the polar mound region, for X-ray emissions in the energy range above a few keV, in case of $\dot{M} \gg 10^{17}$ g s$^{-1}$.
Observationally, Makishima et al. (1999) showed that continuum X-ray spectra of X-ray pulsars in 2 - 50 keV can generally be reproduced with the NPEX model, in which the model spectrum, $F(E)$, is assumed as $$F(E) = ( G_{1} E^{-\lambda} + G_{2} E^{2} ) \exp \left( - \frac{E}{kT} \right),
\label{eqn:NPEX}$$ where $E$ is a photon energy and $G_{1}$ and $G_{2}$ are normalization factors. In the present framework, the first and second components could be understood to be the multi-color blackbody spectrum from the bottom polar cone region and the quasi-single blackbody spectrum from the polar mound region respectively. The multi-color blackbody spectrum from the polar cone has a power-law like spectrum in the medium energy range and an exponential decay determined by the highest surface temperature of the polar cone in the high energy range. This could well be reproduced by the first component of the NPEX model. The second component of the NPEX model has the Rayleigh-Jeans spectrum in the low energy range and the Wien spectrum in the high energy range, and could be considered to represent the quasi-single blackbody spectrum from the polar mound surface. Although there is no reason why the first and second components have the common temperature in these considerations, the NPEX model is the phenomenological model to reproduce the observed spectra and it would not be required to separate the common temperature into two in practical spectral fits.
From these considerations, the fact that the NPEX model consisting of the two spectral components, the cut-off power law spectrum and the single blackbody-like spectrum, can well reproduce the continuum spectra observed from many X-ray pulsars could be considered to strongly support the present model which predicts presences of the two spectral components, the multi-color blackbody spectrum from the polar cone region and the quasi-single blackbody spectrum from the polar mound region. It should be noted that the temperatures obtained with the NPEX model fits to X-ray spectra observed from several sources by Makishima et al. (1999) distribute around 5 keV, which agree to the values estimated above in the present study.
Furthermore, Kondo, Dotani & Inoue (in preparation) have recently analyzed phase-resolved spectra observed from Her X-1 with Suzaku and have successfully resolved the continuum spectra into three components, each of which keeps its respective spectral shape constant and varies only its normalization factor in association with the pulse-phase change, independently of the other components. A remarkable thing is that the two components resolved in the energy range above $\sim$ 2 keV are well reproduced with the multi-color blackbody spectrum and the single blackbody spectrum respectively, although they have been obtained in a model-independent way.
Properties of X-ray pulse profile {#X-ray_pulse_profiles}
---------------------------------
Here, we discuss pulse profiles expected from the presently considered configurations in the magnetic polar regions in case of $\dot{M} \gg 10^{17}$ g s$^{-1}$.
As seen in figure 12-(c) in Makishima et al. (1999), the crossover energy, where the two components in the NPEX model in equation (\[eqn:NPEX\]) cross over, generally exists around 10 keV. Thus, we can consider that the multi-color blackbody component, identical to the first component in the NPEX model, from the lower polar cone should mainly govern the pulse profile in an energy range, say, 2 to 6 or 7 keV. On the other hand, in an energy range above say 15 or 20 keV, the single blackbody component, identical to the second component in the NPEX model, from the polar mound region should be the main component in the pulse profile.
We discuss pulse profiles expected for X-rays from the polar cone and the polar mound respectively, below. In calculating the pulse profiles, we take into account two effects deforming the profiles, occultation of the emission regions by the neutron star body and influences of relativistic light bending. They are explained in appendix.
### Directional distributions of X-ray emissions from the polar cone
X-rays from the polar cone mainly forms the pulse profile in 2 - 6 $\sim$ 7 keV.
Several X-ray pulsars exhibit absorption features at Cyclotron resonance energies around 20 $\sim$ 40 keV in their X-ray spectra (e.g. Makishima et al. 1999). Since X-ray energies of 2 to 6 $\sim$ 7 keV considered now are significantly lower than these Cyclotron energies, X-rays in this energy range cannot move electrons in the direction perpendicular to the magnetic lines of force sufficiently. Hence, when X-rays diffuse out in the azimuthal direction of the polar cone, those having a linear polarization perpendicular to the magnetic lines of force (“ordinary photons”) can easily go out of the surface layer without suffering from electron scattering, but those having another polarization in direction to the line of forces (“extraordinary photons”) cannot escape without a number of electron scatterings from the surface layer. Even the extraordinary photons, however, become free from electron scattering, if they are scattered in the direction to the magnetic lines of force. Therefore, the extraordinary photons should gradually be focused in the direction to the magnetic lines of force through a number of electron scatterings. This beaming effect was first pointed out by Basko and Sunyaev (1975).
As a result, photons diffusing out in the azimuthal direction from the central region of the polar cone could be divided into two groups in the surface layer: One is the ordinary photon group and could be emitted with a constant intensity per a solid angle to every direction from the surface. Then, a differential flux per unit length of the polar cone, $dF_{\rm O}/dr$, detected by an observer in a direction with an angle, $\phi$, from the outward direction of the central axis of the polar cone at a distance of $D$ can be expressed as $$\frac{dF_{\rm O}}{dr} = \frac{4}{\pi} \frac{dL_{\rm PC, O}/dr}{4\pi D^{2}} \; \sin \phi,
\label{eqn:Def_F_O}$$ where $dL_{\rm O}/dr$ is a differential luminosity of this ordinary component emitted from the surface per unit length.
The other half is the extraordinary photon group and should be focused in the direction of the surface magnetic lines of force. If the beam pattern is assumed to have a form as $\exp [-(\phi/\sigma_{\rm E})^{2}]$ with a parameter, $\sigma_{\rm E}$, representing a beam width, the differential flux per unit length of the polar cone, $dF_{\rm E}/dr$ can be approximated under a condition $\sigma_{\rm E} \ll 1$ as $$\frac{dF_{\rm E}}{dr} = \frac{dF_{\rm E, 0}}{dr} \; exp[-(\frac{\phi}{\sigma_{\rm E}})^{2}] \; \sin \phi ,
\label{eqn_F_E}$$ where $$\frac{dF_{\rm E, 0}}{dr} = \frac{4}{\pi^{1/2} \sigma_{\rm E}^{3}} \frac{dL_{\rm PC, E}/dr}{4 \pi D^{2}}.
\label{eqn_F_E0}$$ $dL_{\rm PC, E}/dr$ is the differential luminosity of this extraordinary component. Calculated from equation (\[eqn\_F\_E\]), $dF_{\rm E}/dE$ has a peak at $\phi_{\rm P}$ given as $$\phi_{\rm P} = \frac{\sigma_{\rm E}}{\pi^{1/2}}.
\label{eqn:phi_P}$$
Let us introduce $dL_{\rm PC}/dr$ as the total differential luminosity per unit length of the polar cone and set $dL_{\rm PC, O}/dr = dL_{\rm PC, E}/dr = (dL_{\rm PC}/dr)/2$, then we get the total differential flux $dF_{\rm PC}/dr$ as $$\frac{dF_{\rm PC}}{dr} = \frac{dL_{\rm PC}/dr}{4 \pi D^{2}} \left( \frac{2}{\pi^{1/2} \sigma_{\rm E}^{3}} \; exp[-(\frac{\phi}{\sigma_{\rm E}})^{2}] \; + \; \frac{2}{\pi} \; \right) \; \sin \phi.
\label{eqn:dF_PC}$$
### Directional distributions of X-ray emissions from the polar mound
X-rays from the polar mound mainly forms a pulse profile in the energy range above $\sim$ 20 keV.
In the polar mound, the accreted matter produces a mound-like structure by dragging the magnetic lines of force and finally lands on the stellar surface there. The remaining thermal energy at the bottom of the polar cone should be carried in the polar mound as radiation energy and the photons should diffuse out in the direction to the surface of the mound. The X-ray emission from the polar mound could be expected to be largely weighted on the outermost area as discussed earlier in this section. Since magnetic lines of force cover this mound region, the same thing happens to the diffusing-out-photons in the surface layer as in the polar cone. Namely, ordinary photons can easily go out in every directions without suffering from electron scattering, while extraordinary photons tend to escape, after a number of electron scatterings, in the direction along the magnetic lines of force. In the case of the polar mound, however, the surface magnetic lines of force should gradually curve to be normal to the stellar surface towards the outermost side of the polar mound (see figure \[PolarMoundFigure\]) and the extraordinary photons should tend to go out in directions around the normal axis to the stellar surface. The ordinal photons should, on the other hand, be radiated away, independently of the directions of the magnetic lines of force, around the normal axis to the stellar surface simply by the projection effect. We approximate, therefore, that an intensity per solid angle from the polar mound surface is isotropic and that the observed flux, $F_{\rm PM}$, is written as $$F_{\rm PM} = 4 \frac{L_{\rm PM}}{4 \pi D^{2}} \cos \phi,
\label{eqn:F_PM}$$ where $L_{\rm PM}$ is the X-ray luminosity radiated from the polar mound and $\phi$ is an angle between the line of sight and the central axis of the mound.
### Expected pulse profiles {#Expected_Pulse_Profiles}
A pulse profile of X-rays from the polar cone and the polar mound can be obtained from equation (\[eqn:dF\_PC\]) and equation (\[eqn:F\_PM\]) respectively by substituting $\phi$ derived from $\phi$’, which periodically varies in association with the neutron star rotation, taking account of the light bending effect as shown in appendix. $\phi$’ is calculated with an inclination angle, $i$, of the line of sight to the rotational axis, an angle, $\theta_{\rm R}$, of the magnetic axis of the neutron star to the rotational axis, and a rotational angle, $\psi$, of the magnetic axis around the rotational axis. Figure \[AngularGeometries\] indicates (A) angular relations among the rotational axis, the magnetic axis and the line of sight, and (B) a relation between $\phi$ and $\phi$’ reflecting the light bending effect. Note that the opening angle of the polar cone and the height of the polar mound are both assumed to be negligibly small in the pulse-profile computations and that all the angular distributions of the emissions from them are given as functions of $\phi$ referring to the magnetic axis.
![ (A) Angular relations among the rotational axis, the magnetic axis and the line of sight, and (B) a relation between $\phi$ and $\phi$’ reflecting the light bending effect. []{data-label="AngularGeometries"}](AngularGeometries.jpg){width="8cm"}
Figure \[PulseProfileMap\] show two dimensional distributions of the flux from the polar cone and the polar mound respectively as functions of $i$ and $\psi$, in three cases of $\theta_{\rm R}$. Fluxes in figures \[PulseProfileMap\] through \[PLS\_PRFL\_ParameterDependence\_3\] are given as relative fluxes to those in cases of isotropic emission, by normalizing $dF_{\rm PC}/dr$ in equation (\[eqn:dF\_PC\]) by $(dL_{\rm PC}/dr)/(4 \pi D^{2})$ for the polar cone component, and $F_{\rm PM}$ in equation (\[eqn:F\_PM\]) by $L_{\rm PM}/(4 \pi D^{2})$ for the polar mound component, respectively.
Since both emissions from the polar cone and the polar mound are mainly focused in directions to the two magnetic axes corresponding to the N- and S-poles, two enhancements of the flux appear in each of these maps. In case of emissions from the polar mound, each enhancement has a flux-peak at a position where the line of sight just directs to the N or S pole. In case of those from the polar cone, however, each enhancement has a crator-like hole at its center surrounded by a circular wall with the angular radius of $\phi_{\rm P}$ as defined in equation (\[eqn:phi\_P\]).
![Two dimensional distributions of flux from the polar cone (left) and the polar mound (right) on pulse phases and inclinations in three cases of $\theta_{\rm R}$. $\xi$ = 5, $\theta_{\rm R} = 30^{\circ}$, and $\phi_{\rm C} = 60^{\circ}$ are assumed.[]{data-label="PulseProfileMap"}](PLS_PRFL_CntMap.jpg){width="16cm"}
Hereafter, we discuss properties of the pulse profiles only in the range of $i \leq 90^{\circ}$ and let the magnetic axis closer to the line of sight be the N-pole.
In case of those from the polar mound, pulse profiles in terms of $i$ is somewhat simpler than that of the polar cone. When $i$ is larger than a boundary value, two peaks are exhibited, a stronger peak from the N-pole side and a weaker peak from the S-pole side. When $i$ is smaller than the boundary value, on the other hand, we see only one peak from the N-pole side. The boundary $i$-value depends on $\theta_{\rm R}$ and gets larger as $\theta_{\rm R}$ gets smaller.
The similar trend of the overall flux-enhancements is seen in pulse profiles of X-rays from the polar cone. Sub-peaks, however, appear in some ranges of $i$ on these cases.
Let us introduce, here, $\theta_{\rm L, N}$ and $\theta_{\rm L, S}$ as $$\theta_{\rm L, N} = |\theta_{\rm R}-i|
\label{eqn:theta_LN}$$ and $$\theta_{\rm L, S} = |\pi - \theta_{\rm R}-i|.
\label{eqn:theta_LS}$$ Then, we observe two sub-peaks around the top of the flux enhancement associated with the N-pole, in case of $$\theta_{\rm L,N} < \phi_{\rm P},
\label{eqn:thetaLN<phiP}$$ while another couple of sub-peaks appears in the flux enhancement associated with the S-pole, in case of $$\theta_{\rm L,S} < \phi_{\rm P},
\label{eqn:thetaLS<phiP}$$ From above four equations (\[eqn:theta\_LN\]) $\sim$ (\[eqn:thetaLS<phiP\]), we see that both enhancements with N- and S- poles exhibit respective two sub-peaks only when both $i$ and $\theta_{\rm R}$ are close to $\pi/2$ satisfying a condition $i + \theta_{\rm R} < \pi - \phi_{\rm R}$. In the other $i$ - $\theta_{\rm R}$ range, the enhancement with the S-pole never show two sub-peaks, while that with the N-pole exhibits two sub-peaks in a range of $i$ as $$\theta_{\rm R} - \phi_{\rm P} < i < \theta_{\rm R} + \phi_{\rm P},
\label{eqn:SP_Cond_i}$$ calculated from equations (\[eqn:theta\_LN\]) and (\[eqn:thetaLN<phiP\]).
Figure \[PulseProfileFigures\] shows some examples of pulse profiles of emissions expected from the present model configurations for different combinations of $i$ and $\theta_{\rm R}$. Those of emissions from the polar cone and the polar mound are respectively presented in parallel there. In a relatively soft X-ray band, say, in 2 - 5 kev, X-rays from the polar cone is dominant, while those from the polar mound is so in a relatively hard X-ray band, say, in 20 - 50 keV. Thus, the left and right panels in figure \[PulseProfileFigures\] can be considered to represent pulse profiles expected in the soft and hard band respectively.
![Pulse profiles of fluxes from the polar cone (left) and the polar mound (right) in five cases for the combination of $i$ and $\theta_{\rm R}$. (a) through (e) corresponds to cases of (50$^{\circ}$, 20$^{\circ}$), (80$^{\circ}$, 50$^{\circ}$), (60$^{\circ}$, 30$^{\circ}$), (50$^{\circ}$, 50$^{\circ}$) and (90$^{\circ}$, 80$^{\circ}$), respectively. If we replace the values of $i$ and $\theta_{\rm R}$ with each other, the profile is the same. $\xi = 5$, $\sigma_{\rm E} = 30^{\circ}$ and $\phi_{\rm C} = 60^{\circ}$ are assumed. The red, purple, blue and green lines in the polar cone component are profiles of the pencil beam component from the N-pole, that from the S-pole, the fan-beam component from the N-pole and that from the S-pole, respectively. The red and purple lines in the polar mound component are the profiles from the N-pole and S-pole, respectively.[]{data-label="PulseProfileFigures"}](PulseProfileFigures.jpg){width="15cm"}
Pulse profiles observed from X-ray pulsars are classified into five groups by Nagase (1989). His classifications are shown, slightly changing the original wording, as follows,
1. single sinusoidal-like shapes both in the soft and hard bands,
2. sinusoidal-like double peaks with little energy dependence, where the amplitudes of the two peaks are usually different,
3. an asymmetric single peak with some features,
4. a single sinusoidal-like peak in the high energy band and close adjacent double peaks in the soft energy band, and
5. double sinusoidal-like peaks in the high energy band and complex five peaks in the soft energy band.
Although sources on which the Nagase’s classifications are based have a wide range of X-ray luminosities, we can identify sources with X-ray luminosities $\gtrsim 10^{37}$ erg s$^{-1}$ to groups (a) $\sim$ (d), as LMC X-4 (e.g. Hung et al. 2010) to (a), SMC X-1 (e.g. Raichur & Paul 2010) to (b), Cen X-3 (e.g. Raichur & Paul 2010) to (c) and Her X-1 (e.g. Deeter et al. 1998) to (d). Vela X-1 (e.g. Makishima et al. 1999) is the representative source of the group (e) but its luminosity is as low as $\sim$ 10$^{36}$ erg s$^{-1}$.
The present model can explain the basic features of the profiles (a) through (d), as seen from figure \[PulseProfileFigures\], where each pair of profiles (a) through (d) is shown as a typical example for the respective group (a) through (d). Even for the group (e), we see presence of multiple peaks in the profile of the polar cone component in figure \[PulseProfileFigures\] - (e), although the number of peaks is not five but four.
Even though the pulse profiles are mainly reproduced by adjusting two parameters, $\theta_{\rm R}$ and $i$, simultaneous adjusting of the other model parameters should be necessary in order to have the model profile fit to the observed profile as accurately as possible.
The beam width parameter, $\sigma_{\rm E}$, determines the width of the main peak in the pulse profile of the polar cone component. Figure \[PLS\_PRFL\_ParameterDependence\_1\] shows the pulse profiles of the polar cone component when we change only the value of $\sigma_{\rm E}$ from 30$^{\circ}$ to 20$^{\circ}$ to 40$^{\circ}$ keeping the other parameters in the case of figure \[PulseProfileFigures\] (c). We can see that the peak profile gets significantly sharper with the $\sigma_{\rm E}$ decrease. In rough comparisons of the models with the observations, $\sigma_{\rm E}$ around 30$^{\circ}$ seems appropriate.
![Examples of pulse profile variations in terms of $\sigma_{\rm E}$. The pulse profile of the polar cone component in figure \[PulseProfileFigures\]-(c) in which $\sigma_{\rm E} = 30^{\circ}$ changes to the left and right profiles in this figure by replacing $\sigma_{\rm E}$ to 20$^{\circ}$ and 40$^{\circ}$ respectively.[]{data-label="PLS_PRFL_ParameterDependence_1"}](PLS_PRFL_ParameterDependences_1.jpg){width="15cm"}
The relative distance, $\xi$, of the X-ray emitting position, normalized by the Schwarzshild radius of the neutron star mass, determines effects of the relativistic light-bending on pulse profiles. One of the effects appears in depth of hollows between pulse peaks of the polar mound component. Figure \[PLS\_PRFL\_ParameterDependence\_2\] shows respective pulse profiles of the polar mound component in cases of $\xi$ = 10 and 2.5 when the other parameters are the same as those in figure \[PulseProfileFigures\] - (e) in which $\xi$ = 5. We see that the smaller $\xi$ makes the hollow shallower, suffering the larger light bending.
![Examples of pulse profile variations in terms of $\xi$. The pulse profile of the polar cone component in figure \[PulseProfileFigures\]-(e) in which $\xi = 5$ changes to the left and right profiles in this figure by replacing $\xi$ to 10 and 2.5 respectively.[]{data-label="PLS_PRFL_ParameterDependence_2"}](PLS_PRFL_ParameterDependences_2.jpg){width="15cm"}
The other effect produces small humps between main peaks in combination with the parameter, $\phi_{\rm C}$, which expresses the degree of the obscuration of X-rays by the neutron star body, defined in appendix. Two examples are shown in figures \[PLS\_PRFL\_ParameterDependence\_3\]. A low plateau begins to appear between two adjacent peaks when we change $\xi$ from 5 to 10 for the profile of the polar cone component in figure \[PulseProfileFigures\] - (c), as in figure \[PLS\_PRFL\_ParameterDependence\_3\] - (A) - (left). It gets more significant if we add a change of $\phi_{\rm C}$ from 60$^{\circ}$ to 30$^{\circ}$, as in figure \[PLS\_PRFL\_ParameterDependence\_3\] - (A) - (right). This feature could explain the presence of a small hump only in the soft band in the observed pulse profile of Cen X-3 (see figure 12 in Raichur & Paul 2009).
![Two examples of pulse profile variations in terms of a combination of $\xi_{\rm S}$ and $\phi_{\rm C}$. (A) The pulse profile of the polar cone component in figure \[PulseProfileFigures\]-(c) in which $\xi$ = 5 and $\phi_{\rm C} = 60^{\circ}$ changes to the left profiles by replacing $\xi$ to 10, and further changes to the right profile by replacing $\phi_{\rm C}$ to 30$^{\circ}$. (B) The pulse profile of the polar cone component in figure \[PulseProfileFigures\]-(e) in which $\xi$ = 5 and $\phi_{\rm C} = 60^{\circ}$ changes to the left and right profiles by replacing ($\xi$, $\phi_{\rm C}$) to (10, 30$^{\circ}$) and further to (10, 15$^{\circ}$), respectively.[]{data-label="PLS_PRFL_ParameterDependence_3"}](PLS_PRFL_ParameterDependences_3.jpg){width="15cm"}
If we change the combination of $\xi$ and $\phi_{\rm C}$ from (5, 60$^{\circ}$) to (10, 30$^{\circ}$), the pulse profile of the polar cone component in figure \[PulseProfileFigures\] - (e) also converts to figure \[PLS\_PRFL\_ParameterDependence\_3\] - (B) - (left) and a small peak start to be exhibited. It gets higher when we further change $\phi_{\rm C}$ to 15$^{\circ}$ as seen in figure \[PLS\_PRFL\_ParameterDependence\_3\] - (B) - (right), where we can now produce six peaks in the model pulse profile.
As seen above, various combinations of the model-parameters can produce variety of pulse profiles but cannot form an asymmetry of a pulse-peak around the center of the peak. Such asymmetries are often seen in observed pulse profiles and the typical example is the pulse profile of Cen X-3. The similar asymmetry is seen in the pulse profile of Her X-1. It is known, in case of Her X-1, that the pulse profile changes between the main-on phase and the mid-on phase of the 35-day on-off cycles. Deeter et al. (1998) and Scott, Leahy and Wilson (2000) propose that the central X-ray emission regions are periodically obscured by the outer boundary of the magnetic funnels located at the inner edge of a precessing accretion disk, and that the pulse phase of the obscuration varies in association with geometry changes due to the disk precession. By introducing such periodic obscuration by the outer boundaries of the magnetic funnels co-rotating with the central neutron star, we could interpret the asymmetries seen in the pulse profiles from Cen X-3 and Her X-1 in the present model frame.
Obscuration could be done even by matter flowing along the magnetic funnels toward the neutron star surface, since optical depth for the electron scattering of the free fall region in the magnetic funnel is calculated in equation (\[eqn:tau\]) to be larger than unity unless $r \gg 10^{7}$ cm. In this case, the obscuration could be observed as an absorption dip in a pulse profile and be able to interpret some features in the complex multiple peaks as seen in the group (e).
Summary and discussions
=======================
Structures of X-ray emitting magnetic polar regions of neutron stars in X-ray pulsars are studied, and expected properties of X-ray emissions from them are compared with observations.
The matter flow in the polar cone is solved on such several assumptions as follow:
- The flow is one-dimensional in the radial direction, steady and sufficiently subsonic.
- The opening angle of the cone is sufficiently smaller than unity and the physical quantities can be represented by respective typical values over the cross section of the cone.
- The optical depth in the tangential direction of the cone is sufficiently large and the radiation energy density is greatly dominant to the gaseous one.
- The energy loss of the flow is governed by photon diffusion in the tangential direction of the cone.
We discuss the validities of these assumptions below.
Equations (\[eqn:DifEq1\]) and (\[eqn:DifEq2\]) do not include the opening angle parameter, $\Theta$, and thus the solutions on the basic structure of the polar cone do not depend on the assumption of $\Theta$ in equation (\[eqn:Theta\_r/R\]). That assumption is necessary only to calculate the inflow velocity and the optical depth in the azimuthal direction.
As seen in figure \[Mdot-Height\_Relations\], the height of the polar cone is close to the position of the magneto-boundary surface with the distance of $r_{\rm M,p}$, when $\dot{M}$ gets as large as several times 10$^{18}$ g s$^{-1}$. Since $\Theta$ = 0.32 at $r_{\rm M,p}$ as obtained in equation (\[eqn:Theta\_0\]), $\Theta \ll 1$ can be assured in the polar cone unless $\dot{M}$ is close to 10$^{19}$ g s$^{-1}$. The solved infall velocities are displayed in figures \[Solutions\_B1\] and \[Solutions\_B10\], while the sound velocities in the polar cones should be 10$^{9} \sim 10^{10}$ cm s$^{-1}$. These confirm that the flow in the polar cone is sufficiently subsonic. The sufficiently large optical depth can be recognized in figures \[Solutions\_B1\] and \[Solutions\_B10\].
The radiation temperatures of the polar cone are plotted in figures \[Solutions\_B1\] and \[Solutions\_B10\], while the gaseous temperature should be 10$^{11} \sim 10^{12}$ K in order for the gaseous energy density to comparable to the radiation energy density. Thus we see that the radiation energy is greatly dominant to the gaseous one in the polar cone. The establishment of the radiation field just behind the shock front (the upper boundary) has been discussed in \[RadEnDominance\].
The temperature at the bottom of the polar cone is simply calculated by the lower boundary condition as $P = B_{\rm r, *}^{2} / 8\pi$ to be 2.0 $\times 10^{9}$ for $B_{\rm r, *} = 10^{12}$ G, and the average energy of photons is $\sim$ 170 keV. Since this energy is much larger than the cyclotron energy, $\sim$ 12 keV for $B_{\rm r, *} = 10^{12}$ G, the reduction of the electron-scattering opacity for photons passing along the magnetic lines force should not take place in the main part of the polar cone. Thus, we can say that the simple geometry with $\Theta \ll 1$ determines the direction of the photon-diffusion, which should be the side-way direction.
Solutions show that the height of of the polar cone has a large dependence on the accretion rate. When $\dot{M} \simeq 10^{16}$ g s$^{-1}$, the height is a tenth as low as the neutron star radius. On the other hand, when $\dot{M} \simeq 10^{18}$ g s$^{-1}$, the height is about 10 times as large as the neutron star radius. This large dependence of the height on the accretion rate originates from the proportionality of $r_{\rm D}$ to the accretion rate, $\dot{M}$ as seen in equation (\[eqn:Def\_rD\]). If we introduce the time scale for photons to diffuse out in the azimuthal direction, $t_{\rm D}$, it is given by replacing $r_{\rm S}$, $\rho_{\rm S}$ and $\Theta_{\rm S}$ in equation (\[eqn:tDS\]) with $r$, $\rho$ and $\Theta$ for a general position in the polar cone. Then, with the help of equation (\[eqn:ContEq\]), the following relation is achieved: $$r_{\rm D} = v \; t_{\rm D}.
\label{eqn:rD-tD_Rel}$$ This means that $r_{\rm D}$ expresses the distance by which the infalling matter advances in the diffusion time. Since the photon diffusion time is considered to be the cooling time of the radiation energy in the polar cone, $r_{\rm D}$ represents the cooling length in which the infalling matter significantly loses its energy unless a heating exists. In fact, if we neglect the heating term, $GM/r^{2}$, in the right side of equation (\[eqn:DifEq1\]), we get such a solution as an exponential decay of $\varepsilon$ with the scale length of (4/3) $r_{\rm D}$. The rough proportionality of the height of the polar cone to $\dot{M}$ as seen in figure \[Mdot-Height\_Relations\] is basically explained by the proportionality of $r_{\rm D}$ to $\dot{M}$.
In practice, however, the term of $GM/r$ in the right side of equation (\[eqn:DifEq1\]) cannot be neglected and rather plays the more important role with the larger accretion rate. When $\dot{M}$ is as low as $10^{16}$ g s$^{-1}$, the energy carried with the free-fall matter is almost released soon after the shock. However, when $\dot{M}$ is as large as $10^{18}$ g s$^{-1}$ or larger, the gravitational energy gain exceeds the energy loss due to the photon diffusion and a significant amount of energy piles up on the bottom side of the polar cone. In section \[Introduction\] it has been mentioned that the presences of the two regions, the primary and secondary regions, were already introduced even in the mid of 1970’s. This paper quantitatively clarifies that X-ray emissions from the primary region is dominant when $\dot{M} \lesssim 10^{17}$ g s$^{-1}$, and that those from the secondary region becomes dominant when $\dot{M}$ exceeds 10$^{17}$ g s$^{-1}$.
As the accretion rate increases to 10$^{17} \sim 10^{18}$ g s$^{-1}$, the specific radiation energy remaining at the bottom of the polar cone increases. Then, the radiation pressure should increase and exceed the magnetic pressure which holds the flow within the polar cone. As a result, the matter should expand in the tangential direction along the neutron star surface, dragging the magnetic lines of force, and form a mound-like structure (the polar mound region). By assuming that the matter settles on the neutron star surface after losing its remaining energy through photon-diffusion in the polar mound and the excess radiation pressure balances with magnetic pressure enhanced by dragging, the structure of the polar mound is simply calculated and the results are reasonable unless $\dot{M} \gg 10^{18}$ g s$^{-1}$. Davidson (1973) originally introduced the concept of the mound as the optically thick region at the bottom of the magnetic funnel. It is here generalized to be composed of the polar cone and the polar mound, structures of which vary with the accretion rate.
From such configurations as discussed above, we can expect an X-ray spectrum composed of a multi-color black-body spectrum from the polar cone region and a quasi-single black-body spectrum from the polar mound region from X-ray pulsars with $\dot{M} \gtrsim 10^{17}$ g s$^{-1}$. These spectral properties basically agree with observations as discussed in \[X-ray\_spectrum\]. For further confirmations of validities of the present model, the following two analyses are expected. One is analyses of spectral variations linked with the pulse phase, as done by Kondo, Dotani & Inoue (in preparation) for Her X-1. It could be able to resolve the overall spectrum of an X-ray pulsar into several components, which keep the constant spectral shapes but change their normalization factors with the pulse phase. The other is to see a spectral change of a X-ray pulsar associated with the flux. The spectrum should get harder as the accretion rate increases, since the relative flux of the quasi-single blackbody component to the multi-color blackbody component increases with the accretion rate.
A fairly sharp pencil beam is expected together with a broad fan beam from the polar cone region, while a broad pencil beam from the polar mound region. With these X-ray beam properties, basic patterns in X-ray pulse profiles observed from X-ray pulsars can be explained too.
The fairly sharp pencil beam is formed when the emitted photon energy is well lower than the cyclotron energy at the surface of the pencil beam. The cyclotron energies observed from several X-ray pulsars are around 20 keV (e.g. Makishima et al. 2000), while the typical X-ray energies from the polar cone are around a few keV. This confirms the above condition for the fairly sharp pencil beam to appear. If we see the softer X-rays from an X-ray emitting place in the polar cone far from the stellar surface, however, the cyclotron energy rapidly decreases in proportion to $r^{-3}$ while the surface temperature does not so largely. Hence, the beaming effect should tend to weaken in the spectral range below 1 keV.
We have a number of freedoms in the present phenomenological model for the pulse profiles to make fine tuning the model pulse profile to reproduce an observed pulse profile. In particular, there could be large uncertainties in the periodic obscuration by the outer-boundary and the lower side of the free fall region of the magnetic funnel. The magnetic funnel should be bent in the rotational direction around the axis of the total angular momentum of the accreted matter at the magneto-boundary surface, since the angular momentum should be transferred though the magnetic stress to the neutron star within the magneto-boundary surface. The degree of the bend of the magnetic lines of force depends on the amount of the angular momentum to be transfered (see e.g. Inoue 1976). Thus, if the amount of the angular momentum changes, the pulse phase at which obscuration by the magnetic funnel takes place should change. In fact, Her X-1 exhibits the pulse-profile change linked with the 35 day on-off cycle. The super-orbital modulation of the X-ray flux can well be explained by the precession of the accretion disk (Inoue 2019). If so, the angular momentum axis of the accreted matter changes with the precession and the periodic phase shift of the obscuration place in the pulse profile could be understandable. It could be possible to resolve the practical configurations of the magnetic funnel by adjusting the model pulse profile to an observed profile.
This model can explain basic features in the pulse-profiles of many X-ray pulsars as discussed in \[Expected\_Pulse\_Profiles\] but it has not been done yet to show a good evidence for the present model to reproduce an observed pulse profile precisely. It should be done in future.\
In this paper, we have basically dealt with cases of the accretion rate in the range of 10$^{17} \sim 10^{18}$ g s$^{-1}$. In this accretion rate range, we have seen that the fairly tall polar cone stands and the fairly wide polar mound extends from the bottom of the polar cone on each of the magnetic polar region of the neutron star. The strength of the magnetic field of the neutron star has been assumed to be 10$^{12} \sim 10^{13}$ gauss at its surface and the obtained configurations of the X-ray emitting polar region do not largely depend on it around this magnetic field range.
When the accretion rate is as low as 10$^{16}$ g s$^{-1}$ or less, the height of the polar cone becomes as low as or lower than a tenth of the neutron star radius. Thus, such cases do not fit to the main assumption of the present study that the photon diffusion in the tangential direction plays the main role to construct the polar cone structure. Several studies have, however, been being done on this low accretion rate case by several authors (e.g. Becker & Wolff 2007, Wolff et al. 2016, and references therein) since the pioneer works done by Davidson (1973) and Basko & Sunyaev (1975).
When the accretion rate is as high as 10$^{19}$ g s$^{-1}$ or higher, on the other hand, the luminosity largely exceeds the Eddington luminosity of 1 $M_{\odot}$ star. Although the solution can exist in the present scheme of the magnetic polar regions even in the case of $\dot{M} \simeq 10^{19}$ g s$^{-1}$, some obtained parameters are inconsistent with the approximations in this study.
The first issue is on the base radius of the polar mound, $x_{\rm PM}$, as shown in figure \[MoundParameters\]. We see that it exceeds the stellar radius when $\dot{M}$ gets close to 10$^{19}$ g s$^{-1}$. Although this is the result from the very simplified treatment, the tendency could be understandable for the polar mound to extend over the entire surface of the neutron star as the accretion rate increases. Taking account of it that the portion of the energy loss rate from the polar mound gets close to unity when $\dot{M}$ gets close to 10$^{19}$ g s$^{-1}$, as seen in figure \[EnergyLossPortions\], most of the super-Eddington luminosity should quasi-spherically be emitted from the entire surface of the neutron star with this accretion rate. It could, then, be difficult for the polar mound to maintain the steady state under the super-Eddington radiation pressure. The effect of the radiation pressure might, however, be weakened due to the reduction of the Thomson scattering cross section under the strong magnetic field on the surface of the neutron star.
The second is on the height of polar cone. It becomes as high as or higher than that of the magneto boundary surface when $\dot{M} \gtrsim 10^{19}$ g s$^{-1}$ as shown in figure \[Mdot-Height\_Relations\]. If the upper boundary of the polar cone reaches the magneto-boundary surface, the matter trying to flow into the magnetic funnel should flood over the magneto-boundary surface. In that case, the approximations around the upper boundary of the polar cone in the present study become inapplicable and we will need some new treatments on them.
In addition to them, the optical depth of the accreted matter surrounding the central X-ray source could be a problem. The optical depth of the transition layer of the magneto-boundary surface, $\tau_{\rm T}$, is roughly calculated from equation (\[eqn:CntEq\_TL\]) as $$\begin{aligned}
\tau_{\rm T} &\simeq& \kappa_{\rm T} \rho_{\rm T} h_{\rm T} \nonumber \\ &\simeq& \frac{\dot{M}}{4\pi r v_{\rm T} \sin \theta} \nonumber \\
&=& 3.3 \; \beta^{-1} \sin^{-1} \theta \left(\frac{r}{r_{\rm M,e}}\right)^{-1/2} \left(\frac{\dot{M}}{10^{19}\; \rm{g \; s}^{-1}}\right)^{8/7} \left(\frac{M}{M_{\odot}}\right)^{-1/14} \left(\frac{\mu_{\rm M}}{10^{30} \rm{gauss cm}^{3}}\right)^{2/7},
\label{eqn:tau_M}\end{aligned}$$ where we have expressed $v_{\rm T} = \beta (2 GM/r)^{1/2}$. Since $\beta$ must be significantly smaller than unity, the matter in the transition layer is considered to be optically thick everywhere in the case of $\dot{M} \gtrsim 10^{19}$ g s$^{-1}$. If so, the super-Eddington radiation pressure should interfere with steady accretion.
This estimation is, however, on the assumption that the magnetic axis aligns with the rotational axis of the neutron star and both axes are perpendicular to the equatorial plane of the accretion disk. In practical cases of X-ray pulsars, the magnetic axis must be oblique to the rotational axes, and thus the matter distribution in the transition layer should be biased to the equatorial plane of the disk. In those cases, a part of the transition layer could be optically thin and steady accretion, in which the matter inflow and the photon outflow segregate from each other, might be possible even if the luminosity exceeds the Eddington limit.
These issues in the case of $\dot{M} \gtrsim 10^{19}$ g s$^{-1}$ as discussed above are quite interesting in relation to ultra-luminous X-ray pulsars recently discovered one after another (Bachetti et al. 2014; F$\ddot{\rm u}$rst et al. 2016; Israel et al. 2017; Carpano et al. 2018), and wait for future studies.\
This study presents several clues to resolve observational evidences of X-ray pulsars from various viewpoints, but is still based on several simplified assumptions and approximations. Further theoretical and observational studies of X-ray pulsars are largely expected.
The author greatly appreciates the referee for his or her critical comment on the original manuscript.
Deformations of pulse profiles by the central neutron star
==========================================================
We discuss two effects deforming the pulse profile of X-ray pulsars owing to the central neutron star.
One is an occultation of X-rays emitted from the polar cone by the neutron star body. When the line of sight of those X-rays from the polar cone crosses the neutron star body, they cannot be observed. A critical direction within which emitted X-rays suffer from this effect depends on the height of the X-ray emitting position on the polar cone, but we simultaneously observe X-rays from the polar cone in a fairly wide range of the height. Thus, we introduce the following deformation factor, $A$, in calculating expected pulse profiles as $$A = \left\{
\begin{array} {ll}
1 & \rm{when} \; \; \phi \leq \pi/2 \\
\exp \left (- \left[\frac{(\phi - \pi/2)}{\phi_{\rm c}} \right]^{2} \right) & \rm{when} \; \; \phi > \pi/2,
\end{array}
\right.
\label{eqn:F_cf_obs}$$ where $\phi_{\rm C}$ is the average critical angle over the region of the polar cone emitting relevant X-rays.
Another is the relativistic light bending effect by the gravitational field of the neutron star. To include this effect, we adopt the simple analytic formula to describe it which was introduced by Leahy & Li (1995). The applicable range of their original formula is limited in $2 \leq \xi \leq 5$, supposing the photon emitting place is on the surface of the neutron star. Here, $\xi$ is a relative distance of a photon emitting place to the Schwarzschild radius. In the present study, our interests are also in emissions from fairly far places of the polar cone from the neutron star surface and thus we have expanded the applicable range of $\xi$ up to $\sim 10$ or more by recalculating the necessary parameters in the same way as used in Leahy & Li (1995). The formula we have used is as follows. $$\cos \phi' = a \cos \phi + b,
\label{eqn:LightBend}$$ where $$a = \frac{2.304}{\xi^{2}} + \frac{0.653}{\xi} + 1.017,
\label{eqn:Prm_a}$$ $$b = -\frac{2.490}{\xi^{2}} - \frac{0.584}{\xi} - 0.021.
\label{eqn:Prm_a}$$ Here, $\phi$ is an angle, at which the light is emitted from a place with a relative distance, $\xi$, to the radial direction from the gravity center, and $\phi'$ is an angle at which the light is observed at infinity, to the original radial direction.
Arons, J., & Lea, S.M. 1976, , 207, 914 Bachetti, M., et al. 2014, , 514, 202 Basco, M.M., & Sunyaev, R.A. 1975, , 311, 321 Becker, P.A., & Wolff, M.T. 2007, , 654, 435 Carpano, S., Haberl, F., Maitra, G., & Vasilopoulos, G. 2018, , 476, L45 Churazov, E., Gilfanov, M., & Revnivtsev, M. 2001, , 321, 759 Davidson, K. 1973, Nature Phys. Sci., 246, 1 Deeter., J.E., Scott, D.M., Boynton, P.E., Miyamoto, S., Kitamoto, S., Takahama, S., & Nagase, F. 1998, , 502, 802 Elsner, R.F., & Lamb, F.K. 1977, , 215, 897 F$\ddot{\rm u}$rst, F., et al. 2016, , 831, L14 Giaconi, R., Gursky, H., Kellogg, E., Schreier, E., & Tananbaum, H. 1971, , 167, L67 Ghosh, P., Lamb, F.K., & Pethick, C.J. 1977, , 217, 578 Ghosh, P., & Lamb, F.K. 1978, , 223, L83 Ghosh, P., & Lamb, F.K. 1979, , 232, 259 Hung, L., Hickox, R.C., Boroson, B.S., & Vrtilek, S.D. 2010, , 720, 1202 Illarionov, A.F., & Syunyaev, R.A. 1972, , 16, 45 Inoue, H. 1975, , 27, 311 Inoue, H., & Hōshi, R. 1975, Progress of Theoretical Physics, 54, 415 Inoue, H. 1976, , 28, 293 Inoue, H. 2019, , 71, 36 Israel, G.L., et al. 2017, Science, 355, 817 Leahy, D.A., & Li, L. 1995, , 277, 1177 Kubota, A., & Makishima, K. 2004, , 601, 428 Lamb, F.K., Pethick, C.J., & Pines, D. 1973, , 184, 271 Makishima, K., Mihara, T., Nagase, F., & Tanaka, Y. 1999, , 525, 978 Nagase, F. 1989, , 41, 1 Pringle, J.E., & Rees, M.J. 1972, , 21, 1 Raichur, H., & Paul, B. 2010, , 401, 1532 Scott, D.M., Leahy, D.A., & Wilson, R.B. 2000, , 539, 392 Shimura, T., & Takahara, F. 1995, , 445, 780 Spitzer, L.Jr. 1962, Physics of Fully Ionized Gases (New York; John Wiley & Sons) Sugimoto, J., Mihara, T., Kitamoto, S., Matsuoka, M., Sugizaki, M., Negoro, H., Nakahira< S., & Makishima, K. 2016, , 68, S17 Tananbaum, H., Gursky, H., Kellogg, E.M., Levinson, R., Shreier, E., & Giacconi, R. 1972, , 174, L143 Wolff, T.W., et al. 2016, , 831, 194
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Troubled politics in Taiwan
TAIPEI, TAIWAN
— An opposition motion to recall President Chen Shui-bian, whose family is accused of profiting from their proximity to power, failed Tuesday to pass in the legislature, giving breathing space to the embattled president.
But the heat generated by the thwarted recall, which needed a two-thirds majority to force a national referendum, seems unlikely to diminish, leaving Taiwan with a lame-duck president until 2008.
President Chen has denied any hand in a corruption case that has snagged his son-in-law, who was arrested last month, and touched his wife, who is accused of receiving payoffs from a company but has not been charged. A senior aide has also been implicated, though not charged.
Chen apologized Tuesday for the political upheaval and appealed to lawmakers to let the legal inquiry into the corruption charges run its course, but his opponents continued to call on him to step down. His fiercest critics in the legislature, which is controlled by an opposition coalition, threatened to launch a censure motion against his cabinet, which requires a simple majority to pass.
A blow to Chen would appear to pave the way for the Taipei mayor, Ma Ying-jeou, to lead his once-invincible Kuomintang Party (KMT) back into power.
As Chen's star has faded, undone by policy setbacks and scandals, so Mr. Ma's has risen, to the point where he's already seen as heir apparent to the presidency. Opponents admit that he's the candidate to beat.
That could be welcome news to China, which is keeping a close eye on how the turmoil plays out, analysts say. Chen's pro- independence camp has soured cross-straits relations. Mayor Ma, by contrast, is considered more likely to extend an olive branch to the mainland should he step into the top slot. Ma has said that he favors eventual reunification if it is supported by a majority of Taiwanese.
"Beijing is watching very carefully to see what kind of leader Ma is, and will be in the future. It's important for cross-straits relations," says Professor Lo.
The Chen recall vote "is all about who will be the next leader of the country. Forget Chen. He's finished, a lame duck," says Lo Chih-Cheng, a political scientist at Soochow University in Taipei. "People are looking to judge who they will vote for in 2008."
With a two-term limit on the presidency, Chen's Democratic Progressive Party (DPP) is likely to throw its weight behind Premier Su Tseng-Chang, who recently was given a greater role in policymaking. But Chen's erratic handling of the corruption probe has hurt its chances of holding the presidency and regaining the legislature, say analysts.
Some of Chen's supporters are worrying aloud about the party's future. "The DPP is committing political suicide. We're not taking a strong stance on corruption – and it's becoming impossible for us to succeed in 2008," says Lee Wen-chung, a three-term DPP legislator.
A Harvard-educated lawyer and former justice minister, Ma has put his stamp on Taipei since he became mayor in 1998, when his opponent was then-opposition party leader Chen. The city's humming economy and swish buildings, most of them wired for the Internet, are seen as a sign that Ma can deliver. Unlikely many of the old-timers in the KMT, which ruled Taiwan for decades under martial law, Ma has a reputation as being graft-free, methodical, and socially progressive.
But the heated row over the presidential recall hasn't necessarily played to Ma's strengths. He initially resisted the idea when it was first proposed by James Soong, the firebrand leader of an allied party.
Ma later reversed course, while trying to strike a more conciliatory tone, leaving some KMT legislators wondering if he had the stomach for Taiwan's brand of full-blooded political sport.
Chen's supporters say that Ma was forced to take an extreme position that will lose him votes among fed upTaiwanese who want to see the legislature get back to business. A logjam between the executive and opposition-run legislature has left many bills on hold, including a landmark package to shrink the number of seats in the house and redraw electoral boundaries. A weapons deal with the US, valued between $10 billion ans $19 billion, also continues to languish.
"As a presidential candidate, Ma should have a vision and see the national perspective. What he's doing right now is destroying the DPP, and not in the right way," says Ker Chien-ming, head of the DPP legislative caucus.
Viewed from the outside, Taiwan's divisive politics might appear to be an aspect of its perennial identity crisis as a "renegade province" of China, the giant across the straits. Chen made his name as a pro-independence diehard who stood up to the ruling KMT, which favors eventual reunification with the mainland. But such divisions don't figure much in the current sparrings, which focus on Chen's alleged misconduct and the ability of the ruling party to keep the economy ticking. |
Jessica Alba Covers 'InStyle' February 2013
Jessica Alba shows off her gorgeous smile on the cover of InStyle magazine’s February 2013 issue, on newsstands this Friday (January 11).
Here’s what the 31-year-old actress had to share with the mag:
On knowing husbandCash Warrenwas “the one”: “I just knew when I met him that I was going to know him forever. It was weird; he instantly felt like family. It was so easy. I’d never felt like that with anyone. I was usually pretty self-conscious, minding my p’s and q’s, very aware of every time my fork hit the plate when I was having dinner on a date. With him, there was none of that. We got each other. We’re kindred spirits.”
On what she’s learned from motherhood: “Before I had kids, I was very responsible and serious. I used to be all about controlling my environment; everything had to be just so. Now my idea of perfection is different. You can label bins and have a place for stuff, but when the kids go into the playroom, you’re not going to say, ‘We can’t paint, because how are we going to clean it up?’”
On her style sense: “My style is more adventurous since I became a mom. In the past, I was into my uniform of leggings and a sweater. Now I’m willing to try bold prints, bright colors, and different cuts. Never say never, but I probably won’t ever wear booty shorts. I feel pretty confident about that.” |
Blackfish SQL Community
Welcome to the JDataStore Community
Here in the JDataStore Community weve placed white papers, FAQs, code snippets and other technical information that can help developers achieve their development goals faster and easier. Borland engineers and members of the JDataStore user community author the information provided. The JDataStore Community also provides access to the JDataStore newsgroup where you can interact with other users and the JDataStore development team. We welcome your participation and contributions to the JDataStore Community. |
1. Field of the Invention
The present invention generally relates to lines, leaders, tippet material, or tapered leaders (for sake of brevity hereinafter called xe2x80x9cfishing line or linesxe2x80x9d), used in various types of fishing applications and, more particularly, is concerned with an enhanced fishing line having a unique combination of properties in terms of breaking strength, elongation, knot breaking strength, breaking toughness, and flexibility stiffness.
2. Description of the Prior Art
Synthetic monofilament fishing lines, comprised of synthetic polymeric materials such as polyamides, polyesters, polyethylenes, or fluoropolymers, have long been used in fishing applications. The synthetic monofilament fishing lines employed in the prior art have traditionally attempted to achieve the highest possible breaking strength with the smallest possible diameter. The objective of creating fishing lines with the smallest possible diameter is to make the fishing line as inconspicuous as possible so as to increase the potential for attracting the fish to the bait or fly, while also providing as high a strength as possible in order to hook-up and land the larger fish.
This traditional way of making fishing lines has several disadvantages associated with it that have not yet been overcome in the design and construction of fishing lines. Due to the nature of the polymeric materials used to make the monofilament fishing lines, the material becomes increasingly stiffer in order to achieve a high ultimate breaking strength. The stiffness of the material is related to its elongation, or the ratio of the extension of the material to the initial length of the material prior to stretching. The increased stiffness of the material results in the line becoming less flexible which tends to make tying knots in the line more difficult and also tends to dramatically reduce the breaking strength of the line at the knot.
In addition, stiffer, stronger lines have less capacity to resist shock or rapid impact loading conditions before breaking, such as when a fish is hooked-up and rapidly swims in a direction away from the rod and reel to place a rapid loading on the line. The capacity to resist rapid loading conditions is referred to as the breaking toughness of the line. Lines that have a high breaking strength will generally have a lower ultimate elongation and a correspondingly low breaking toughness. The lower breaking toughness is what causes the instantaneous breakage of the line under the rapid impact conditions. Since the line breaks almost instantaneously, the fisherman does not have ample time to react and relieve the pressure in the line by either raising the tip of the rod or allowing the line to come off the reel. Therefore, more fish are lost after the initial hook-up due to breaking of the line from these rapid loading conditions as a result of its lower breaking toughness.
By observing and studying prior art fishing lines and statements that are made with regard to the benefits of the so-called high-performance fishing lines, one concludes that current state-of-the-art practices employed to improve performance of fishing lines primarily involve making fishing lines that have higher ultimate breaking strength and correspondingly thinner diameters. The apparent intent is to achieve a higher ultimate knot breaking strength while the critical property of breaking toughness is ignored.
Tests conducted on prior art fishing lines demonstrate this assertion. The so-called high performance fishing lines do generally have higher ultimate breaking strength and thinner diameters. However, there is generally only a marginal benefit, if any, in terms of a higher ultimate knot breaking strength. They also have relatively lower ultimate elongation, significantly lower breaking toughness and significantly less flexibility by virtue of their higher flexibility stiffness.
The test equipment used to measure the aforesaid properties of fishing lines is a conventional universal testing machine, such as those under the Instron name, and the tests are conducted in accordance with test procedures outlined in ASTM D-2101-91 where a constant rate of extension of ten inches per minute and a specimen gauge length of 10 inches were used.
As referred to herein, the various properties are defined as follows. The Ultimate Breaking Strength is defined as the force required to break the line divided by its cross sectional area, whose value is presented with units of pounds per square inch (also referred to as psi herein). The Ultimate Knot Breaking Strength is defined as the force required to break the line divided by its cross sectional area, with an overhand knot tied into the line, whose value is presented with units of pounds per square inch. The Ultimate Elongation is defined as the ratio of the extension of a material at the breaking point, to the length of the material prior to stretching, whose value is presented as a percentage. The Breaking Toughness is defined as the actual work per unit volume of material that is required to break the material, whose value is presented with units of inch-pounds per cubic inch. The Flexibility Stiffness is defined as the stiffness of the material measured between 5% and 10% elongation and is determined by subtracting the stress in the monofilament at which 5% elongation is achieved from the stress in the monofilament at which 10% elongation is achieved, and dividing this difference by the 5% difference in elongation. The lower the Flexibility Stiffness, the more flexible the monofilament.
Due to the adverse effects on performance from the tradeoffs associated with prior art fishing lines, there exists a need for an enhanced fishing line having a unique combination of the aforementioned properties which improves performance.
The present invention provides an enhanced fishing line designed to satisfy the aforementioned need. The enhanced fishing line of the present invention is adapted for use in various types of fishing applications and provides a product having superior properties over those presently on the market which improves performance. In particular, the enhanced fishing line of the present invention has a unique combination of ultimate breaking strength and ultimate elongation properties so as to provide a fishing line with a significantly higher breaking toughness and with an optimal ultimate knot breaking strength, and lower flexibility stiffness, so as to provide a fishing line with significantly higher performance.
Accordingly, the present invention is directed to a fishing line which comprises: (a) a monofilament made of a polymer, such as a polyamide, such as nylon 6, nylon 66, nylon 612, nylon 11, and nylon 12; or a fluoropolymer, such as polyvinylidene fluoride; or a polyolephine, such as polypropylene; (b) the monofilament having an ultimate breaking strength of a minimum of about 150,000 psi, an ultimate elongation of a minimum of about 30%, an ultimate knot breaking strength of a minimum of about 130,000 psi, a breaking toughness of a minimum of about 25,000 inch-pounds per cubic inch, and a flexibility stiffness of no greater than about 500,000 pounds per square inch.
More particularly, the monofilament has a diameter of between about 0.003 inches to 0.045 inches, and is manufactured by an extrusion process followed by a drawing process, such that the monofilament has an extruded diameter between about 1.1 and 1.4 times the finished diameter after drawing.
Further, the ultimate breaking strength of the monofilament is within a range of about 150,000 to 180,000 psi. The ultimate elongation of the monofilament is within a range of about 30% to 100%. The ultimate knot breaking strength of the monofilament is within a range of about 130,000 to 170,000 psi. The breaking toughness of the monofilament is within a range of about 25,000 to 35,000 inch-pounds per cubic inch. Also, the monofilament has a flexibility stiffness of about 225,000 to 500,000 pounds per square inch.
These and other features and advantages of the present invention will become apparent to those skilled in the art upon a reading of the following detailed description of the invention.
The enhance fishing line of the present invention is a monofilament made of a polymer, preferably a polyamide, such as nylon 6, nylon 66, nylon 612, nylon 11, and nylon 12; or a fluoropolymer, such as polyvinylidene fluoride; or a polyolephine, such as polypropylene. The monofilament has a finished diameter of between about 0.003 inches to 0.045 inches.
The monofilament preferably is made by an extrusion process, followed by a drawing process where the extruded diameter is between 1.1 and 1.4 times the diameter of the finished monofilament after stretching or drawing. Specifically, in a set of representative examples, a quantity of the polymer, as described above, is extruded using conventional extruding equipment to provide an extruded monofilament of between 1.1 and 1.4 times the finished diameter of the monofilament. The extruded monofilament is then subjected to a drawing process where the monofilament is stretched out along its length and results in a corresponding reduction in the diameter of the monofilament until the finished diameter is achieved. The drawing process aligns the molecular chains in a direction parallel to the long axis of the monofilament thereby increasing the ultimate breaking strength of the material along with its stiffness. After the drawing process, the monofilament is heat treated to relieve the high stresses, which can exist near the surface of the monofilament as a result of the drawing process. This heat treatment subjects the monofilament to a temperature range of between 40 and 150 degrees Celsius for a time period of between 30 minutes and 4 hrs. After heat treating the monofilament can further be subjected to an irradiation process, wherein the monofilament is exposed to gamma irradiation or electron beam to achieve an accumulation of 0.5 to 100 mega rads of exposure. The irradiation process promotes cross linkage of the molecules and results in lower flexibility stiffness and greater ultimate elongation while maintaining a high ultimate breaking strength.
The aforementioned extrusion, drawing, treatment processes are set to instill the enhanced fishing line with a unique combination of properties which include the following. The enhanced fishing line will generally have a minimum ultimate breaking strength of 150,000 psi (pounds per square inch) or within a range of about 150,000 to 180,000 psi, a minimum ultimate elongation of 30% or within a range of about 30% to 100%, a minimum ultimate knot breaking strength of 130,000 psi or within a range of about 130,000 to 170,000 psi, a minimum breaking toughness of 25,000 inch-pounds per cubic inch or within a range of about 25,000 to 35,000 inch-pounds per cubic inch, and a flexibility stiffness of no more than 500,000 psi or within a range of about 225,000 to 500,000 psi, based on averaging the test results for a total of five specimens from the same production lot being tested using a universal testing machine in accordance with test procedures outlined in ASTM D-2101-91 at a constant rate of extension of ten inches per minute and a specimen gauge length of 10 inches. |
[Sodium Selenite Regulates Growth and Uptake of Se,As and Heavy Metals of Trillium tschonoskii].
To study the influence of different concentrations of selenium on the growth and absorbing of Se,Cd,Pb,Hg and As in Trillium tschonoskii. Trillium tschonoskii was treated with different concentrations of exogenous selenium, arsenic and heavy metals,and then the mass growth, leaf area,root number and other indicators reflecting its growth rule were calculated. Atomic fluorescence method was used to measure the absorption contents of Se,Cd,Pb,Hg and As. The relative mass growth,leaf area and root number of Trillium tschonoskii increased at first and then decreased with the increasing of exogenous selenium concentrations. When the concentration of selenium was 25 mg / kg,the relative mass growth,leaf area and root number of Trillium tschonoskii reached a maximum. When selenium concentrations was over than 30 mg / kg,it inhibited the growth and development of Trillium tschonoskii. Trillium tschonoskii absorbing Cd,Pb,Hg and As had a regular of first decreasing then increasing and last decreasing. It reached the lowest when selenium concentrations at the range of 10 ~ 15 mg / kg. . Selenium had both stimulating effect and inhibiting effect on the growth and development of Trillium tschonoskii. Different selenium concentrations have different effects in absorbing Cd,Pb,Hg and As of Trillium tschonoskii |
Q:
Typescript: Any way to define object shape within a class?
I would like to specify an object shape. I think this is normally done with an Interface:
interface DesiredResponseShape {
status: string
, optionalMessage: string|null
}
class Example {
callApi() : Promise<object> {
const response = fetch(...)
const json: DesiredResponseShape = response.json();
}
}
This example is small enough that clarity isn't hurt by the interface definition being outside the class. From my reading, interfaces can not be defined inside classes without resorting to undesirable patterns. Is there any other way to define the desired shape of a variable inside the class close to its point of use?
A:
You can inline your interface:
const json: {
status: string
, optionalMessage: string|null
}
= response.json();
|
/**
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
* See the License for the specific language governing permissions and
* limitations under the License.
*/
package org.apache.aurora.scheduler.config.validators;
import com.beust.jcommander.IValueValidator;
import com.beust.jcommander.ParameterException;
public class NotEmptyString implements IValueValidator<String> {
@Override
public void validate(String name, String value) throws ParameterException {
if (value.isEmpty()) {
throw new ParameterException(String.format("%s must not be empty", name));
}
}
}
|
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Following the Twins 6-1 win on Saturday afternoon against the Tampa Bay Rays, manager Ron Gardenhire announced another member of his starting rotation. Gardy said that Nick Blackburn, who threw three no-hit innings against the Rays, was one of “his guys.” Francisco Liriano and Carl Pavano are givens. Gardy announced earlier in the week that Brian Duensing would be a starter as well. It would appear that the fifth spot in the rotation will be between Kevin Slowey and Scott Baker, although Gardy wants Kyle Gibson to also be given a shot to earn the role. One can only assume that he would say such a thing to potentially light a fire under the two right-handed veterans.
Many Twins fans, myself included, were calling for the removal of Blackburn from the starting rotation last year when he was really struggling. Rightfully, he was removed from the rotation shortly after the All Star break and sent to the minor leagues. He came back and pitched well down the stretch for the team. However, in the offseason, when discussion of which of the six starts should move to the bullpen, Blackburn was the easy choice for me. He had struggled in 2010, but in my mind, the right-hander’s cutter makes him a good bullpen option.
But maybe we are not giving Blackburn the appropriate due. The assumption was always that his extremely low strikeout rate would catch up with him. In 2008, he struck out just 4.5 batters per nine innings. That number dropped to 4.3 per nine in 2009. And as you would expect from watching last year, he missed even fewer bats in 2010 and struck out just 3.8 per nine innings. Check out the correlation between his declining strikeout rate and his hits per inning pitched.
Year
K/9
H/9
2008
4.5
10.4
2009
4.3
10.5
2010
3.8
10.8
But let’s even look at his 2010 season. It started out bad, and he left the team to go to a family emergency. When he came back, he was tremendous in May. In fact, he was runner-up for AL Pitcher of the Month. Then things went bad. Really bad in June and July. Everything he threw toward the plate was hit, and hit hard, and often hit a long way. Blackburn would be replaced in the rotation by mid-July by Brian Duensing. He went to the bullpen and soon after was sent back to Rochester. He pitched well there and soon he was back with the Twins. He then pitched at least seven innings in seven of his eight starts before the end of the season. He ended the season with 14 quality starts. It’s incredible how up and down his season was.
Month
W-L
ERA
WHIP
OPS
BABIP
April
1-1
6.85
1.73
1.058
.325
May
5-0
2.65
1.21
0.677
.288
June
1-4
10.17
2.18
1.079
.394
July
0-2
9.87
1.90
1.081
.362
August
1-1
1.72
0.77
.455
.233
Sept
2-4
3.70
1.14
.679
.236
After identical 11-11 seasons in 2008 and 2009 with nearly identical 4.05 and 4.03 ERAs, it’s hard to believe that with the movement he gets on his pitches, the sinker and the cutter, that he can’t return to those types of numbers again in 2011. Equally important, Blackburn combined to throw 399 innings between those two seasons.
The comparisons to Carlos Silva can be scary. Silva, in fact, struck out even fewer than Blackburn has. He has certainly had his struggles since leaving the Twins. However, he was a terrific starter for the Twins three of his four seasons. His one bad year, his third with the team, he posted a 5.94 ERA. Silva was at 1.6 walks per nine innings in three of his four seasons, and we all remember the season where he walked just nine batters in 188 innings. Blackburn was at 1.8 walks per nine innings his first two seasons, and that number jumped to 2.2 last year. Of course, Silva struggled in his two seasons with the Mariners after they gave him 4 years and $48 million. He was better last year with the Cubs and of course is already in the news this year for he went after teammate Aramis Ramirez in the dugout after the Cubs 3B had an error in Silva’s first spring outing.
Nick Blackburn PREDICTIONS for 2011:
So, let’s make some predictions. What are your thoughts on Blackburn starting the season in the Twins rotation? Can he stay healthy and production and in the rotation the full season? And how well will he produce? Here are my predictions… what are yours?
W-L (which of course are impossible to predict, but we will anyway): 16-11
8 Responses to “Blackburn Named Twins Starter (Predictions)”
W-L 5-11
ERA 5.31
WHIP 1.56
IP 147
H 176
BB 47
K 65
K/9 3.9 I think the only reason he gets the starter job out of spring training is that he is signed long term and they really don’t know what to do with him. He’s not a fit out of the bullpen. And he is not a very good pitcher. Slowey is a winner and he should be starting. But he is a bette fit for the bullpen. I just have little faith in Mr.Blackburn. He was smart to sign for all that money when he did. Because otherwise he would be a non tender candidate in my opinion. Just a righthanded version of Glen Perkins.
People, even people who should know better, persist in thinking that spring training is a tryout camp. This is not true in a general sense and is seldom even true in a specific sense. The Twins staff and front office have been looking at their current 6 starters for a long time. Most have come through the farm system and they have all had a lot of exposure to Gardy and Anderson. The idea that the Twins should wait until the end of spring training to decide on who the starters are, is silly. The biggest factor is health, and of course if one of the 6 is not completely healthy, he won’t start the year in the rotation.
Clearly, the 4 best starters at the end of last year were Liriano, Pavano, Duensing and Blackburn. Since all appear healthy, all 4 get to start the year in the rotation. If Baker and Slowey are both healthy at the end of spring training Baker will probably get the nod because he has a slightly longer and better resume. There is no Gardy favorites or anything of the sort, just a perfectly logical and normal way of deciding on your starters.
Regular season performance will determine the starters after that. If one falters or is injured, then if no. 6 is still with the team (not traded) he will likely get another shot at starting. Obviously Gibson, Bromberg, Guerra or others could factor in with strong minor league performances.
I still don’t understand why so many bloggers are so down on Blackburn. He had 2 solid years as a starter and actually pitched solidly last except when he was hurt(apparently ). While his margin for error is smaller than other pitchers because he lacks dominant stuff, he seems to get more out what he has than many pitchers with more raw stuff. I find myself rooting for people who seem to stay more consistent and get the most out of their tools.
Hi Seth,
I’m very bullish on Blackie.
Wins: 16-9
ERA: 3.80
IP: 200
HITS: 190
BB: 45
K: 120
WHIP: 1.18
A very under appreciated pitcher for the Twins. He is healthy, and driven. With a good knowledge of the league and he understands his strong points and what it takes to compete. I’ll take a healthy Blackburn anyday.
I find it interesting Seth. I like Blackburn and see the upside but think he should have been the odd man out to start the season and that he will likely be the 5th best starter. In John Bonnes article he says the Twins are a solid pick to win 86.5 and yet you have our 5th best starter at 16-11. I would bank 16-11 right now if offered. I hope you are right. I also hope the other 4 guys win at least 16 as well. They all seem capable of it.
I expect a healthier, sinkier Blackburn in 2011. If he can figure out how to pitch within his parameters and get some sink on the fastball, he has proven that he can be successful at the major league level. |
//===--- HeaderGuardCheck.cpp - clang-tidy --------------------------------===//
//
// The LLVM Compiler Infrastructure
//
// This file is distributed under the University of Illinois Open Source
// License. See LICENSE.TXT for details.
//
//===----------------------------------------------------------------------===//
#include "HeaderGuardCheck.h"
namespace clang {
namespace tidy {
namespace llvm {
LLVMHeaderGuardCheck::LLVMHeaderGuardCheck(StringRef Name,
ClangTidyContext *Context)
: HeaderGuardCheck(Name, Context) {}
std::string LLVMHeaderGuardCheck::getHeaderGuard(StringRef Filename,
StringRef OldGuard) {
std::string Guard = tooling::getAbsolutePath(Filename);
// Sanitize the path. There are some rules for compatibility with the historic
// style in include/llvm and include/clang which we want to preserve.
// We don't want _INCLUDE_ in our guards.
size_t PosInclude = Guard.rfind("include/");
if (PosInclude != StringRef::npos)
Guard = Guard.substr(PosInclude + std::strlen("include/"));
// For clang we drop the _TOOLS_.
size_t PosToolsClang = Guard.rfind("tools/clang/");
if (PosToolsClang != StringRef::npos)
Guard = Guard.substr(PosToolsClang + std::strlen("tools/"));
// The remainder is LLVM_FULL_PATH_TO_HEADER_H
size_t PosLLVM = Guard.rfind("llvm/");
if (PosLLVM != StringRef::npos)
Guard = Guard.substr(PosLLVM);
std::replace(Guard.begin(), Guard.end(), '/', '_');
std::replace(Guard.begin(), Guard.end(), '.', '_');
std::replace(Guard.begin(), Guard.end(), '-', '_');
// The prevalent style in clang is LLVM_CLANG_FOO_BAR_H
if (StringRef(Guard).startswith("clang"))
Guard = "LLVM_" + Guard;
return StringRef(Guard).upper();
}
} // namespace llvm
} // namespace tidy
} // namespace clang
|
St Michael's School, Llanelli
St. Michael's School (Welsh: ) is an independent boarding and day school for children aged from 3 to 18 years old in Llanelli, Wales.
The school is divided into four sections, comprising the Pre-Preparatory School, Preparatory School, Senior School and Sixth Form. The current head teacher is Benson Ferrari.
History
The school was first established in 1923 and has been situated in the east Llanelli village of Bryn since 1928. The school was originally established by the Rees brothers, with Percy Rees as the founding Headmaster. Upon retirement of the Rees' brothers, former head boy Mr Vaughan-Evans was appointed Headmaster in 1962.
The school's main building, St. David's House, dates back to the 19th century and was originally a large house belonging to a local industrialist. The school's Pre-Preparatory School is housed in a converted former public house, The Royal Oak, which was purchased by the school in 2012
Ownership
The school was acquired in 2019 by Chinese company Bright Scholar, as part of a £150m purchase of colleges in the UK. Bright Scholar is also the largest operator of international and bilingual schools in China. The deal for St Michael's, along with Bosworth Independent College, specifically cost the company a sum of £38m.
Results
The school offers GCSE and A-Level qualifications, with 60.9% of all A-Level entries graded A* or A in 2018, winning the Sunday Times 2018 Welsh Independent Secondary School of the Year award.
Incidents
In 2012 the school appeared in national headlines after accusations arose that education officers at Cognita UK, a rival education company, had posed as parents at St Michael's in order to obtain commercial information. Cognita operate nearby Ffynone House school in Swansea but deny all of the allegations.
In 2016 the school was twice the victim of hoax calls warning of a bomb on the school estate. The school twice evacuated its premises, and a heavy police presence was required to confirm the communications were both in fact a hoax. The threat was linked to a number of other hoaxes around that time including threats to schools in Kent and Newcastle.
Notable former pupils
Notable former pupils of St Michaels' include:
Robert Buckland MP
Cerys Matthews
Kirsty Williams
Ivor Richard
Siân Gwenllian AM
St Michael's alumna and singer Cerys Matthews has acknowledged in interviews that her career benefited from attending St. Michael's, because "through the public school system, you've had so many leg ups", and avoids playing music by privately-educated acts on her 6 Music show. She is subsequently an advocate for state educated acts in the music industry.
References
External links
Official website
Category:Boarding schools in Wales
Category:Llanelli
Category:1923 establishments in Wales
Category:Schools in Carmarthenshire |
Creech Air Force Base
A Las Vegas judge on Thursday handed down a decision that got a mixed reaction from protesters of drone warfare who were arrested for trespassing nearly two years ago at Creech Air Force Base in Southern Nevada.
Judge William Jansen, in a 20-page decision, ruled that the "Creech 14" who protested April 9, 2009, at the base, were guilty of the crime of trespassing.
"Go in peace," were Jansen's final words to the defendants after an hour-long court proceeding this morning in Las Vegas Justice Court.
The judge also urged them to use diplomacy, rather than trespassing, in their attempts to get U.S. drone warfare policy changed.
There was some scattered applause in the crowded courtroom upon hearing the defendants wouldn't get jail time — but the defendants weren't pleased about the judge's guilty verdict.
The protesters had argued there was "necessity" that compelled them to act. As someone might trespass onto private property to save a child from a burning building, they said they were trying to stop drone warfare from killing civilians thousands of miles away in Afghanistan.
However, in his conclusion, Jansen said that "Defendants' motivation for why they committed the offense is irrelevant and does not constitute a defense to the charge. Moreover, defendants are unable to show that their conduct was compelled by true 'necessity' as that doctrine has been defined by various courts."
Those found guilty of the misdemeanor charge are the Rev. John Dear, a Jesuit priest; Dennis DuVall; Renee Espeland; Judy Homanich; Kathy Kelly; the Rev. Steve Kelly, a Jesuit priest; Mariah Klusmire; Brad Lyttle; Libby Pappalardo; Sister Megan Rice, a member of the Sisters of the Holy Child Jesus; Brian Terrell; Eve Tetaz; and the Revs. Louie Vitali and Jerry Zawada, both Franciscan priests.
Vitali, a friar who at one time worked in a Las Vegas Catholic parish, was not at the hearing because he is currently serving a six-month sentence in the federal prison in Lompoc, Calif., for protesting at the Ft. Benning, Ga., 'School of the Americas," which peace activists say has taught foreign military leaders interrogation techniques they use in torturing political prisoners in their home countries.
Thursday's hearing drew about 40 supporters for the defendants from around the country, who filled the courtroom.
Jansen gave each of the defendants a copy of his decision and asked them if they could also give copies to former Johnson Administration Attorney General Ramsey Clark, retired Air Force Col. Ann Wright, and Bill Quigley, a Loyal University professor. Those three had provided testimony for the defendants at the September trial. Jansen said after reviewing the transcript of that trial, he and law clerk spent four months analyzing the case in federal and state law regarding the use of the defense of "necessity."
Before Jansen sentenced them, he allowed them to make statements. Each of those who spoke said they disagreed that what they were doing wasn't out of necessity.
Sister Megan Rice told the judge that the protesters entered Creech on April 9, 2009, intending to speak to and advise the commanding officer.
"I had to speak then and I do now," Rice said. "The evil of killing and destroying people in lands 8,000 miles away, of using bombs targeted by Air Force technicians who control computer-programmed joysticks was and is emblazoned upon my awareness. I see this form of warfare as an evolution toward human execution fostered in the psyche of a nation by immoral, addictive, excessive and illegal practice of developing more and more nuclear weapons."
Rice said Nobel Peace Prize winner Desmond Tutu has said "to remain neutral in situations of injustice is to be complicit in that injustice."
Rice said she had written letters and sought meetings with the base commander to warn him about the need to disobey orders that conflict with U.S. and international laws. She said she had to enter the base in order to obey "higher orders."
"I have listened to the victims of drone warfare," she said. Lebanon victims told her they had been treated like insects.
"My non-violent resistance was an is an absolute necessity," she said.
Brian Terrel, a defendant from Maloy, Iowa, said he "respectfully disagreed" with the judge there was no imminent harm occurring at Creech Air Force Base. Terrel said that after the September trial he had spent three weeks in December in Afghanistan and saw the victims of the drone attacks, including a 9-year-old child who lost an arm in an air attack,
He also said he had read an article about post-traumatic distress being suffered by soldiers carrying out drone attacks on computer screens at Creech.
"One thing that really is haunting me is that one operator said 'I am 7,000 miles away from the killing. I am 18 inches away from the killing.' One, being the distance between Creech Air Force Base and Afghanistan and the other the distance between his nose and the computer screen and the video he was seeing of human beings being dismembered," Terrel said.
He said the drones "are giving an illusion of distance. The 7,000 miles between Creech Air Force Base and Kandahar (the second largest city of Afghanistan) is an illusion. We are very, very close. The harm is imminent. The harm is real. "
Terrel said the analogy that was first mentioned by Ramsey Clark in September about disregarding a no-trespassing sign to enter into a burning building to save a child "is so close to the reality, it is the reality. "
Dennis DuVall criticized the judge's decision that the trespassing didn't fall under the argument of necessity, calling it "outrageous."
DuVall also said drones don't prevent or eliminate terrorism, but instead incite more hatred, revenge and retaliation against American military.
Every time there's a drone strike and innocent people are killed, more IEDs are built to try to harm U.S. soldiers, he said.
DuVall said a year after the protesters were arrested for trespassing at Creech, he was in New York City at a nuclear disarmament march on Times Square where a car bomb was almost detonated.
"The builder of the car bomb, this young man, Faisal Shahzad, in the New York Post the next day says why he did it: revenge for drone attacks in Pakistan," DuVall said, pointing out that those attacks originated at Creech, where the defendants trespassed. "If that isn't necessity, then what the hell is?" |
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Can we save this marriage?
Our political system often reminds me of a marriage. The Republicans and Democrats are married. They are in it together and an effective marriage depends on compromise and collaboration because two people will never want exactly the same thing.
Every four years there’s a big fight and the winner gets to set the priorities of the couple for the next 4 years.
In a marriage, when you fight you have to fight knowing that a) you are ultimately on the same team, and b) you ultimately need to make peace and work together for the good of the family (the electorate) and the marriage (good governance).
If you remember these two things you fight with civility and always attempt to maintain respect. You don’t break certain rules. You don’t fight to kill. You don’t raise the stakes with too much aggression because this will lead to wounds that may bring retaliation and make peacemaking harder.
When disrespect, rudeness, excessive aggression, violence and threats of violence, personal insults, and all decency and decorum goes out the window, at best you end up in a divorce, at worst you end up in a war of the roses, a battle to the death, which is obviously bad for the family and likely the end of the marriage.
These divisions lead to each spouse taking actions that are in their selfish interests but which compromise the relationship. And at some point, all hell breaks lose unless someone finds a way to make peace.
Unfortunately there are no marriage counselors, no priests to turn to. You have to be the adults in the room and police yourselves or else risk creating divisions that are impossible to overcome.
To me, that is the tragedy of the last 8 years and this last election. We’ve allowed toxic rhetoric and disrespect and extreme animus, and hateful rhetoric and behavior to become almost normal. This has destroyed our trust in one another and people aren’t looking for ways to make peace, we’re looking for ways to score points and win short term battles.
And that we mostly interact through an online filter is just driving us further and further apart.
The only way out is mutual respect, empathy and understanding which are critical to rebuilding trust. But these things are in short supply and I’m not sure I see the light at the end of the tunnel. Honestly, at times I don’t even see the fucking tunnel anymore.
But I try to remember that the moral arc of the universe bends towards justice. And I try to have hope that decent people on both sides will come to their senses and demand civility and will come together to find common solutions and won’t cave in to the seductive appeals of bigotry, blame of others and defensiveness. How much I’d wager this is a likely outcome depends on my mood each day and how much negativity I’ve had to deal with. But I still have hope. |
Last updated on .From the section Football
Emmanuel Emenike signs for Al Ain
UAE side Al Ain have completed the loan signing of Nigeria striker Emmanuel Emenike from Turkish giants Fenerbahce.
Emenike replaces Ghana striker Asamoah Gyan who has joined Chinese Super League side Shanghai SIPG on a two-year deal.
The deal includes an option for Al Ain to buy Emenike at the end of the loan.
The 28-year-old, who scored 4 league goals in 27 matches last season, knows he has much to live up to after Gyan's 128 goals in four years in the UAE.
quote On a personal note this is a fresh challenge that I need in my career and I hope to make a great contribution at Al Ain Emmanuel Emenike Al Ain and Nigeria striker
"This is a big club with high expectations and I promise to give my best," he told BBC Sport.
"It is true that [Asamoah] Gyan has done a remarkable job here so I understand there will be expectations.
"But I also want to succeed alongside the fantastic players here and win trophies because that is what the club is all about.
"On a personal note this is a fresh challenge that I need in my career and I hope to make a great contribution at Al Ain.
"I've been given an amazing welcome by the club and my focus now is to deliver on the pitch."
Emenike endured a turbulent period at Fenerbahce having initially transferred to the Turkish side in 2011.
However, a match-fixing scandal, for which he was later cleared, prompted the Istanbul club to sell him to Russian side Spartak Moscow less than two months later.
He re-joined Fenerbahce in 2013 and helped propel them to the 2013/14 Super Lig title and the 2014 Turkish Cup crown.
But Emenike, who made his Nigeria debut in 2011 and was top scorer at the 2013 African Cup of Nations, suffered a dramatic dip in form last season which attracted negative reactions from Fenerbahce fans.
He demanded to be substituted after he was booed by his own fans during their 1-0 home win over rivals Besiktas in March.
A Nations Cup winner with Nigeria in 2013, Emenike started all four of the Super Eagles' matches at last summer's World Cup in Brazil. |
As the evolution of infrastructure/architecture moves to universal hardware with software defined functions, it is possible that the software defined functions migrate significantly from one piece of universal hardware to another. As such the software defined functions will necessarily be tracked (and subsequently mapped for addressing purposes) in a manner different than what is presently done with single function hardware (i.e., a piece of hardware (a router) typically has a network media access control address (MAC)-MAC pairing that doesn't often change or changes within a certain bound (e.g., Dynamic Host Configuration Protocol (DHCP) addressing)). The MAC address of a computer is a unique identifier assigned to network interfaces for communications at the data link layer of a network segment. MAC addresses are used as a network address for most IEEE 802 network technologies, including Ethernet and Wi-Fi. DHCP is a network protocol that enables a server to automatically assign an IP address to a computer from a defined range of numbers (i.e., a scope) configured for a given network. As virtualized network functions (VNFs) on universal hardware are instantiated, used and destroyed over an optimizable software defined network, an equivalent to the well-known Domain Name System (DNS) must be established to track and map these VNFs so they can be effective used in the software defined network (SDN) environment. VNFs, are responsible for handling specific network functions that run in one or more virtual machines on top of the hardware networking infrastructure, which can include routers, switches, servers, cloud computing systems and more. (i.e., may use a constrained set of DHCP addresses in combination with a MAC address). These physical devices are typically specific use (i.e., a router, a particular computer, a switch). In an infrastructure in which there is universal hardware which can simultaneously perform multiple virtual functions instantiated at any time (effectively becoming any machine-function type) and in which functionality can be moved from one piece of universal hardware to another with no anticipated service interruption, there is a need to track, map, and optimize data associated with the virtual functions and their activity. |
/**
* Copyright Soramitsu Co., Ltd. All Rights Reserved.
* SPDX-License-Identifier: Apache-2.0
*/
#ifndef IROHA_GET_ASSET_INFO_HPP
#define IROHA_GET_ASSET_INFO_HPP
#include <string>
#include "model/query.hpp"
namespace iroha {
namespace model {
/**
* Get meta data of asset
*/
struct GetAssetInfo : Query {
GetAssetInfo() {}
GetAssetInfo(std::string asset_id) : asset_id(asset_id) {}
/**
* Asset Id
*/
std::string asset_id{};
};
} // namespace model
} // namespace iroha
#endif // IROHA_GET_ASSET_INFO_HPP
|
Electronic structure and chemical bonding in the lowest electronic states of TcN.
Multiconfiguration second-order perturbation theory, with the inclusion of relativistic effects and spin-orbit coupling, was employed to investigate the nature of the ground and low-lying Lambda-S and Omega states of the TcN molecule. Spectroscopic constants, effective bond order, and potential energy curves for 13 low-lying Lambda-S states and 5 Omega states are given. The computed ground state of TcN is of Omega = 3 symmetry (R(e) = 1.605 A and omega(e) = 1085 cm(-1)), originating mainly from the (3)Delta Lambda-S ground state. This result is contrasted with the nature of the ground state for other VIIB transtion-metal mononitrides, including X(3)Sigma(-) symmetry for MnN and Omega = 0(+) symmetry for ReN, derived also from a X(3)Sigma(-) state. |
The roles of activins, inhibins and estrogen in early committed follicles.
The hypothesis that activin and inhibin are autocrine/paracrine mediators of ovarian folliculogenesis has a solid basis. In mouse and rat models, granulosa cells (GC) of committed follicles express mRNA and protein for the activin/inhibin subunits and mRNA for the activin receptors (type I and II). Dimeric inhibin-A and -B are produced by postnatal ovarian cell dispersates and (GC) in culture. Similar levels of inhibin-A and -B are produced by postnatal ovarian cells, but thereafter as the ovary develops, inhibin-A becomes the predominant form. Activin was more effective than transforming growth factor-beta (TGF-beta) in enhancing follicle stimulating hormone (FSH)-stimulated inhibin production by ovarian cells. Evidence for a local regulatory role of estrogen in the ovary is also accumulating. Murine models of estrogen receptor (ERalpha or ERbeta) disruption produce mice with abnormal ovarian phenotypes. Female mice, which lack the capacity to produce estrogen (ArKO mice), have arrested folliculogenesis, no corpora lutea, elevated levels of luteinising hormone (LH), FSH and testosterone and are infertile. These data are consistent with autocrine/paracrine actions of activin in the early growth of committed follicles and estrogen in follicular maturation. |
Mitochondrial DNA‑induced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin.
Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged‑associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro‑inflammatory mediator. Epigallocatechin‑3‑gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG‑regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG‑mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)‑6 and ‑8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL‑6 and ‑8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG‑treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide‑3‑kinase (PI3K) inhibitor. These results suggested that EGCG‑mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC‑α serine/threonine‑protein kinase associated signaling pathway. |
Zjrms.ir
Zahedan Journal of Research in Medical Sciences Antibacterial Effect of Myrtus Communis Hydro-Alcoholic Extract on Pathogenic Bacteria Ali Taheri,*1 Amir Seyfan,2 Samira Jalalinezhad,3 Fatemeh Nasery4
1. Department of Fisheries (Seafood Sciences), Faculty of Marine Sciences, Chabahar Maritime and Marine Sciences University, Chabahar, Iran 2. Department of Fisheries, Faculty of Marine Sciences, Chabahar Maritime and Marine Sciences University, Chabahar, Iran 3. Medical Student, Zahedan Medicine University, Chabahar International Branch (Sina), Sistan and Balouchestan, Iran 4. Department of Agricultural Biotechnology, Iranian Veterinary Organization, Chabahar Office, Sistan and Balouchestan, Iran
Article informationAbstract Background: Today, due to the changes in the form of the resistance of pathogenic
bacteria, discovering new antimicrobial drugs is under study. So, the aim of this study is to
evaluate the antimicrobial properties of the extract of the myrtle herb on some of
Materials and Methods: Hydroalcoholic extract of the leaves of myrtle herb was
evaluated at 4 concentrations including 10-80 mg/ml on four strains of pathogenic bacteria
using penetrative dissemination method together with the measuring diameter of the
growth inhibition zone; then the results were compared to four conventional antibiotics.
The minimum inhibitory and bactericidal concentrations were studied using macro dilution method.
Results: Treatment by the concentration of 80 mg/ml extract of this herb showed the
Department of Fisheries (Seafood Sciences), Faculty of
greatest effect on the bacterium Staphylococcus aureus and Vibrio cholera serotype
Ogawa which had a significant difference with all other treatments and standard antibiotics
(p< 0.05). The extract showed no effect on the bacterium Pseudomonas aeruginosa and
just concentration of 80 mg/ml showed a little effect on E. coli and other antibiotics had no
significant effect except tetracycline which has little effect on this strain. Minimum
inhibitory concentration was 0.2 mg/ml for bacterium Staphylococcus aureus (S. aureus) and the maximum for E.coli by 8 mg/ml. Conclusion: This study showed that under study bacteria were more resistant to the antibiotics and the extract of Myrtus communis leaves showed greatest antibacterial effect against S. aureus and V. cholerae cerotype Ogawa.
Copyright 2013 Zahedan University of Medical Sciences. All rights reserved.
Introduction
oday, environmental problems and high prices of
Khorasan River Valley, Sarab, Guilan-e-gharb, Kerman,
some antibiotics have reinforced a tendency to
Maharlu in Shiraz, Neyriz, Fasa, Mamasani and Bandar
replace them with less harmful substances. Among
Abbas [5]. The dried leaves of this herb contain
the various materials to replace antibiotics, products of
terpineolene, cineol, linalool, terpineole, linalyl acetate,
plant origin have recently gotten a special place [1, 2].
tannins and flavonoids compounds and there are
Herbal medicines have been the only source of pain
numerous reports about the anti-parasitic and anti-
treatment during the centuries and now with the
infective properties of the extract of this herb [6- 10].
advancement of sciences and development in the
Also its anti-virus effect has led to the production of anti-
application of synthetic drugs, medicinal plants are still
used in large-scale [3]. This issue is very important for the
Today, the anti-parasitic and antimicrobial drug
application in drug therapy or side applications such as
resistance is a major problem in the world which is due to
the uncontrolled use of antimicrobial drugs. This
However, due to the climatic variation and the vast area
resistance is so important that the theme of 2011 World
of Iran, wide spectrum of medicinal plants are found there
Health Organization was "Resistance to antimicrobial
which are the basis of Iran's traditional medicine [4-6].
drugs is a global threat". This resistance can be
Thus, in recent years, extensive researches have been
transmitted by microbes from one generation to another
conducted to evaluate the antimicrobial effect of the
generation and even from a microbial species to another
essential oils and extracts which shows the strength and
species through the creation of an antibiotic-resistant gene
ability of these compounds to inhibit the growth of a wide
by them and ultimately the high levels of infection
range of pathogenic microorganisms [7]. Myrtle (Myrtus
remained stable despite the administration of antibiotics.
communis) of the Mytaseae family is a shrub, evergreen
Until recently, several studies have been conducted on the
and aromatic herb with numerous stems and branches.
antimicrobial properties of the leaf and stem extracts of
This herb is found in the white Lab of Bakhtiari valley,
myrtle against pathogenic bacteria and good results have
Zahedan J Res Med Sci 2013 June; 15(6): 19-24.
been obtained about its effects on staphylococcus aureus
Concentration of bacteria became equal to the
[12-4], E. coli [15-16], Lactobacillus plantarum [16],
McFarland standard tube No. 0.5 (108×1.5) after 24 h
Bacillus cereus [12], Listeria monocytogenes and
incubation in the logarithmic phase of growth, using a
Pseudomonas aeruginosa, [17-18], Klebsiella and
spectrophotometer. This suspension was considered as a
Shigella [17], though its antimicrobial effect against some
reserve and diluted in a similar medium based on 1:100
strains of bacteria such as E. coli has been rejected in
ratio while taking on the same day (6 10×5/1) [23].
Susceptibility to the nosocomial microorganisms to the
Some gram-negative bacteria such as E. coli and
myrtle extract was conducted using penetrative
Pseudomonas aeruginosa and some gram-positive
dissemination method. Bacterial suspension was seeped
bacteria such as Staphylococcus aureus have specific
on the medium using 20 ml sampler and was spread on
characteristics as far as bacterial infections are concerned
the medium with a sterile cotton swap; then it was dried
and they are removed or isolated from the most of the
for 5 minutes and incubated for 15 minutes in order to
clinical samples referred to the diagnostic laboratories
equilibrate the moisture inside the plates.
[19, 20]. On the other hand, some reports on the cases of
Sterile crude discs with 6 mm diameter were placed on
being infected with cholera by Vibrio cholerae which is a
the surface of medium and 15 microliters of the myrtle
gram-negative bacterium are annually published and
solution was seeped in a specified concentration on the
being infected with this bacterium has been observed in
discs. Standard discs of streptomycin 10, gentamicin 10
the southern districts of the country due to the
and erythromycin 15 and tetracycline 30, produced by
consumption of contaminated raw or semi raw fishes and
vegetables irrigated with sewage. Accordingly, given the
Plates were incubated for 24 hours at 37°C and bacterial
importance of medicinal plants in the traditional medicine
inhibition zone was measured and recorded using Vernier
and very few side effects of these medicines on human
calipers. Experiments were conducted with three
and also due to the changes in the form of the resistance
replications. The minimum growth inhibitory
of pathogenic bacteria which requires monitoring of
concentration and Minimum Lethal Concentration (MLC)
antibacterial effects substances in periodic intervals, the
of antimicrobials were determined using the tube dilution
antimicrobial effects of hydroalcoholic extract of Myrtus
method [24, 25]. A series of nine test tubes were used for
communis leaves against the above-mentioned pathogenic
each concentration and each bacterium. There were 7
bacteria have been evaluated in this study.
tubes for different dilutions, a positive control tube and a
negative control tube. 9 ml nutrient broth was added to
Materials and Methods
the test tubes and then was sterilized. 1000 microliters of
the diluted extract was added to the first tube and after
This study was conducted in 2011 at the Laboratory of
being homogenized, 1000 microliters of the homogenized
Microbiology of Chabahar University of Maritime and
fluid was added to the second tube and this operation was
Marine Sciences. Extraction was carried out with slight
continued and 1000 microliters of homogenized solution
variations based on the study conducted by Sadeghi [21].
(from 7th tube) was discarded. 10 microliters of the
Accordingly, the leaves of myrtle were collected in spring
bacterial suspension was added to all tubes except the
from Zaranjan located in the district of Fasa and they
negative control tube based on McFarland tube 1.
were dried in the shade after washing. 600 grams of the
All tubes were incubated for 24 h at 37 C and then the
ground leaf powder was mixed with 500 ml of distilled
tubes were evaluated in terms of turbidity due to the
water and ethyl alcohol 96 at 1:1 ratio and was kept in a
bacterial growth. The last tube in which no turbidity was
dark place for 48 hours. The contents of the Erlenmeyer
seen was considered as the minimum growth inhibitory
flasks were stirred for 25 minutes once every 16 hours.
concentration. The solutions inside all tubes with no
After 48 hours, the contents of the Erlenmeyer flask were
growth turbidity were cultured using pour plate method
smoothed by the filter paper and smoothed fluid was
for determining minimum bactericidal concentrations of
extracted in the rotary evaporation apparatus under
the myrtle extract and the final concentration of the
vacuum and 50̊C temperature. The concentrated extract
extract which was able to kill 99.9% of the live bacteria,
was poured in sterile Petri dish and dried in the oven with
40̊C. Dried powders were collected and were prepared at
concentration of the microorganisms [26, 27].
concentrations of 10, 20, 40 and 80 mg using sterile
Statistical analysis: Experiments were performed in
distilled water. Staphylococcus aureus, Pseudomonas
three replications and Graphpad-Prism 7.00 software was
aeruginosa, Vibrio cholerae serotype Ogawa and E. coli
used for the data analysis under analysis of variance test;
Bacteria were prepared from the samples of patients
and Duncan test was used to compare treatments at 95%
referred to Imam Ali hospital of Chabahar city after doing
specialized microbiologic tests for confirming the
presence of microorganisms. Cultures were purred and
stored at refrigeration temperature until the start of the
study [22]. One day before experiments, a small portion
Table 1 shows the results of penetrating emissions test
of the mother culture was added to the Hinton broth
of the myrtle extract with different concentrations on
under-study microorganisms. Accordingly, the
concentration of 80 mg/ml of myrtle extract showed the
Antibacterial effect of myrtus communis Taheri A et al.
greatest effect on the Staphylococcus aureus bacterium
Table 2. Comparison of the minimum growth inhibitory concentration
and no significant difference was seen with all other
and minimum bactericidal concentrations of the myrtle leaf extract on microorganisms
treatments and control antibiotics and showed a higher
efficacy (p<0.05). Lower concentrations also showed a
significant difference with each other and all of them had
significant differences with antibiotics except the
concentration of 10 mg/ml that had no significant
difference with gentamicin (p<0.05). Erythromycin and
streptomycin did not show any effect on bacteria. Myrtle
extract, at any concentration, did not show any effect on
the bacterium Pseudomonas aeruginosa and the highest
Discussion
effect of control group of antibiotics was observed in
gentamicin which had a significant difference with
In the present study, hydroalcoholic extract of the myrtle
leaves showed the greatest effect on Staphylococcus
The study conducted on the effects of myrtle extract on
aureus which had significant difference with the standard
E. coli bacteria also showed that only the concentration of
antibiotics. The positive effect of the myrtle extract on
80 mg/ml has the effect on this strain of bacteria and
Vibrio cholerae serotype Ogawa was well. In this study
except for the very light effect of tetracycline on this
on these two strains of bacteria, concentration of the used
strain, other control antibiotics did not have any effect.
extract also caused a significant difference in the results.
Concentration of 80 mg/ml showed the highest effect on
Myrtle extract showed a very little effect on E. coli only
the Vibrio chlorea Bacterium which had a significant
at the highest concentration but Pseudomonas aeruginosa,
difference with all other treatments (p<0.05).
was completely resistant to the extract.
Lower concentrations also showed a positive effect, all
For centuries in Iran, several herbs have been used to
of them had a significant difference with each other
treat diseases. Different generations' trust in the treatment
(p<0.05). Tetracycline was the only antibiotic effective on
with the traditional medicine demonstrates the positive
this bacteria which had a significant difference with other
impact of this type of treatment. On the other hand, the
concentrations except that concentrations of 10 and 20
increasing resistance of pathogenic bacteria and
mg/ml (p<0.05). Results of minimum inhibitory
continuous change of the resistance form of these
concentration of growth and minimum bactericidal
microorganisms have led to the major challenges in the
concentrations after 24 h culture were shown in table 2.
use of common antibiotic drugs which requires the search
According to the results of this table, myrtle extract had
for the new compounds with anti-bacterial properties.
no effect on the bacterium Pseudomonas aeruginosa.
Myrtle is an aromatic and medicinal herb for which
Minimum inhibitory concentration belonged to the
antibacterial, antifungal, antiviral, antioxidant and anti-
bacterium Staphylococcus aureus and the highest rate
mutagenicity properties have been reported [28-32].
belonged to the E. coli. Similar results were obtained
Positive properties of the myrtle extract on hospital
about the minimum bactericidal concentration.
bacteria have been reported. In a study, effects of several
plants, including myrtle against Streptococcus Table 1. Comparison of the inhibition zone diameter (mm) of myrtle pneumoniae, Haemophilus influenzae and Moraxella
extracts and standard antibiotics on under study microorganisms
catarrhalis isolated from the patients in hospitals were
evaluated and the results showed that the myrtle extract
creates 30, 50 and 22 mm growth inhibition zone in the
diffusion penetration test; therefore the use of myrtle
extract for the treatment of sinusitis and bronchitis was
The positive effect of the myrtle extract on S. aureus in
this study was consistent with the results obtained by
Salvagnini. These researchers were studied the effect of
the oil and ethanolic extract of myrtle on several strains of
bacteria and reported that the ethanolic extract of myrtle
has a positive effect on S. aureus with 12 mm inhibition
zone. But the oil has shown a greater effect [29]. Alem
also reported the antibacterial effects of the myrtle extract
on S.aureus isolated from human samples with 0.5 mg/ml
of the minimum inhibitory concentration [14].
Ghlamhsynyan Najjar et al. who had observed a very
positive effect of the chloroform, ethyl acetate and
* There was no inhibition zone; treatment of any columns indicated
methanol extracts of the myrtle leaves on S. aureus
significant difference with dissimilar letters
acknowledged that antimicrobial effects of myrtle extract
on this bacterial strain is partly related to the stimulation
of free radicals and the concentration of the extract has an
Zahedan J Res Med Sci 2013 June; 15(6): 19-24.
effect on antibacterial activity [34]. In the study of control
the bacteria [36- 38]. Due to this reason, a gram-positive
bacterium is more susceptible to the extract than gram-
concentrations of the myrtle extract on Pseudomonas
No report on the effects of myrtle extract against the
Fewer efficacies of these antibiotics can confirm the
bacteria causing cholera (i.e. Vibrio cholera) has been
resistance of the mentioned strains of bacteria and on the
reported yet. The results of this study show the positive
other hand, various studies have shown the effects of
effect of the hydroalcoholic extract of the myrtle on this
myrtle extract on P. aeruginosa [6, 35].
strain of bacteria; serotype Ogawa which is much better
For example Alem reported the effect of myrtle extract
than that of tetracycline which is the only antibiotic
on Pseudomonas aeruginosa isolated from human cases
effective on this bacterium. In a study conducted by
with a minimum inhibitory concentration of 120 mg/l
Rahbar et al. Vibrio cholerae serotype Inaba and Ogawa
[14]. But the myrtle extract used in this study had no
were sensitive to Tetra Doxycycline, erythromycin and
effect on bacteria which could be due to the mutations in
ampicillin [39]. It can be said that the less efficacy of
the bacterial strains which are still sensitive to antibiotics
antibiotics in this study can be due to the resistance of this
but are resistant to the myrtle extract, although differences
strain of pathogenic bacteria. Several studies have
in the extracted essential oil and even used concentrations
reported the antibacterial activity of essential oil extracted
could be another reason for the lack of conformity with
from the herb. In recent years, many of these researchers
the present findings. In a study conducted by Amensour,
came to this understanding that the presence of phenolic
leaf and stem extract of myrtle was examined on 15
compounds in the leaves of myrtle herb is due to the
strains of bacteria which cause food borne diseases. They
presence of Flavenols (Quercetin glycosides and
reported that the methanol and ethanol extracts of the
myricetin) and derivatives of Galoyl including Galoyl
myrtle leaves and branches have respectively
glycosides, Alajytanyn, the Galvyl–quinic acid [40] and
antimicrobial properties on Listeria monocytogenes,
they attributes the antibacterial activity of these
Pseudomonas aeruginosa and Staphylococcus aureus and
compounds to the presence of polyphenols [41].
the diameters of the inhibition zone of ethanol extract in
Many studies have shown that the mechanism of this
these bacteria are respectively 30, 23 and 37 mm and
effect is due to the influence on the cell wall and reported
minimum bactericidal concentration for Staphylococcus
that the cell wall and cell membrane are affected and their
aureus was reported less than 0.075 mg/ml. Also the
permeability is changed and lead to the release of
highest antibacterial activity was against gram-positive
intracellular contents which can be accompanied with the
bacteria [18]. Comparison of the results of this study
disrupt in the membrane function such as electron
shows that the extract has no effect on Pseudomonas
transfer, enzyme activity or nutrient absorption [18].
aeruginosa and the inhibition zone of Staphylococcus
In sum, it can be said that the results of this study
aureus was about 20 mm in the best condition and the
indicate the antibacterial effect of hydroalcoholic extract
minimum bactericidal concentration for Staphylococcus
of the leaves of myrtle herb on some pathogenic bacteria,
especially Staphylococcus aureus and Vibrio chloreae
The comparison shows the difference between
which can be an alternative for the treatment of diseases
pathogenic bacteria and food born disease agents and may
resulted from these bacterial strains that the resistance
be another proof for the resistance of bacteria studied in
form of which has been changed as an herbal antibiotic
this study. In the studies conducted on the effects of
with side effects fewer than conventional antibiotics. Also
extracts on E. coli, most of the reports show that the
working on other extraction materials and methods such
myrtle extract has no effect on these bacterial strains [18,
as extracting by methanol and ethyl acetate may indicate
29]. In a study conducted in Iran in the past, the positive
different functions. Also clinical confirmation and
effect of alcoholic extract of the myrtle herb on E. coli
pharmacological standardization is required before their
had been reported. Also according to the report of
Ghasemi Pirbalouti et al. although the methanol extract
showed no effect on the diffusion penetrating activity, but
Acknowledgements
the minimum lethal concentration for E. coli was 10
mg/ml [6, 35]. Comparison of the results of this study
We sincerely appreciate the staff of Imam Ali Hospital
revealed that myrtle extract, even in the highest
and Chabahar Veterinary Office for their cooperation with
concentration, has little effect on the diffusion penetration
us. This study has been conducted in the framework of
of E. coli and minimum lethal concentration was
Mr. A. Seyfan's research project of Fisheries Engineering
determined as 40 mg/ml. The resistance of this strain of
at the University of Maritime and Marine Sciences of
pathogenic bacteria could be a reason for this finding. It
Chabahar. Therefore, we appreciate the authorities of this
has been generally reported that the gram-negative
university for the provision of the laboratory facilities for
bacteria are more resistant to the extracts and essential
oils of this herbs, because hydrophilic structure of the cell
walls of the gram-positive bacteria is mainly composed of
Authors’ Contributions
penetration of hydrophobic oil and also prevents
All authors had equal role in design, work, statistical
accumulation of its compounds in the cell membrane of
Antibacterial effect of myrtus communis Taheri A et al.
Conflict of Interest
The authors declare no conflict of interest.
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Composition and antimicrobial activity of Achillea
Hypericum hyssopifolium and Hypericum heterophyllum. Flavour Fragrance J 2004; 19(1): 62-68.
Please cite this article as: Taheri A, Seyfan A, Jalalinezhad S, Nasery F. Antibacterial effect of Myrtus communis hydro-alcoholic extract on
pathogenic bacteria. Zahedan J Res Med Sci (ZJRMS) 2013; 15(6): 19-24.
Time of Abraham begins Mesopotamian and Egyptian civilization in flower Time of Isaac begins Time of Jacob begins Joseph sold into slavery Joseph welcomes his family to Egypt Israelites enslaved in Egypt Egyptian cities of Pithom and Ramses are built Time of Moses begins Torah given at Mt. Sinai Conquest of Promised Land Time of the Judges begins Phillistines occupy c |
The present invention relates to an improved heat-melting glue gun which has simple and compact structure and is more convenient for use.
FIG. 1 illustrates a conventional heat-melting glue gun 10 which includes a heating member 11 receiving a heat-melting glue stick 20 therein. The heating member 11 is heated by high temperature caused by an electric resistance, so that the heat-melting glue stick 20 in the heating member is melted to bond things together.
In brief, the conventional heat-melting glue gun 10 utilizes electric resistance to produce thermal energy needed to melt the glue stick 20. To achieve this purpose, a wire 12 must be provided as an interface between the glue gun and an electric power source to produce necessary electric resistance. The wire 12 usually has limited length and therefore, an extension cord is frequently needed when a long distance exists between a socket--the electric power source--and a place at where a gluing work proceeds. Such prolonged wire will often bring inconvenience to a user of the heat-melting glue gun. Moreover, the high-temperature heating member 11 will possibly unexpectedly contact with and destroy the electric wire skin and causes exposed conductors of the wire 12. A dangerous electric shock will occur when the heated heating member 11 unexpectedly contacts with an exposed conductor.
In a worse condition, when the skin of the wire 12 is melted by the heating member 11 to expose conductors for the positive and negative electrodes and the two conductors are electrically connected through the heating member 11, a serious short circuit will occur to injure the user and even cause a fire.
Another disadvantage existing in such conventional heat-melting glue gun is that a very high power consumption is needed to produce thermal energy through electric resistance. This is, of course, unacceptable from an energy-saving point of view.
It is therefore tried by the inventor to develop an improved heat-melting glue gun with simple components and structure to eliminate the drawbacks existing in the conventional heat-melting glue gun. |
Image caption Mr Lieberman 'abused the public trust' the Israeli police say
Israeli police have recommended that Foreign Minister Avigdor Lieberman face fresh charges in a corruption scandal.
Mr Lieberman and another official are accused of trying to manipulate a police investigation into alleged money laundering.
Police have previously recommended that the foreign minister, a right-wing member of the governing coalition, should be indicted on other charges.
They have added "breaching the public trust" to the list of charges.
Israel's attorney general must now decide whether to take up the charges. This is a process that can take months.
The police say that the country's former ambassador to Belarus, Zeev Ben Aryeh, is alleged to have given Mr Lieberman -a political ally - a document detailing a the police investigation.
Mr Lieberman had reportedly plucked Mr Ben Aryeh from obscurity at the foreign ministry and made him an ambassador, the Haaretz newspaper reported.
The minister worked as a nightclub bouncer in his youth in the USSR, and is known for his abrasive style.
He famously once said that Egyptian President Hosni Mubarak could "go to hell".
Last August police recommended indicting Mr Lieberman on charges of bribery, money laundering and obstruction of justice. |
Q:
Permutation Question with two independent conditions
In how many ways can $8$ boys $(B_1,B_2,...,B_8)$ and $5$ girls we arranged linearly such that $B_1$ and $B_2$ are NOT together and exactly four girls are together?
I can solve when either of the conditions is imposed, the former would give $13!-2!\cdot12!$ and the latter would be ${5 \choose 4} \cdot 4! \cdot 10! - 5! \cdot 9!$
However I'm not getting how both these conditions together are meant to be evaluated. I thought it won't follow from principle of inclusion, as these are two independent cases.
Answer given is $5! \cdot 8! \cdot 58$
A:
Without inclusion exclusion:
Select the group of four girls and permute them in $\binom{5}{4}4!=5!$ ways.
There are two option for the guys, either $B_1$ and $B_2$ are together or not. If the former is true, then you have to put one of the group of girls exactly in the middle. So there are $2$ ways to choose which of the two groups of girls goes in the middle and $8$ ways to put them in any slot of the boys. You have to multiply this by the number of ways boys are together: $7!\cdot 2!.$ So this gives $2\cdot 8 \cdot 7!\cdot 2=4\cdot 8!$
Now the bows have to be non together in $8!-7!\cdot 2!$ and we can put the girls in any possition we like, there are $9$ slots so in $\binom{9}{2}\cdot 2$ ways by choosing the slots and permuting the group of girls. Putting this process together:
$$5!\cdot (4\cdot 8!+\binom{9}{2}\cdot 2\cdot (8!-7!2!))=5!\cdot 8!\cdot (4+\binom{9}{2}\cdot 2-9\cdot 2)=5!\cdot 8!\cdot (76-18)$$
|
External Affairs Minister Sushma Swaraj makes a statement in Rajya Sabha on 39 Indians missing in Iraq
The government says there is no evidence to support a media report that claimed 39 Indians who went missing in Iraq in June have been killed by Islamic State militants.
Foreign Minister Sushma Swaraj said the same allegation - that the Indians have been killed - has been reported in different newspapers over the last few months. "We are not trusting these reports, we continue to make every effort to locate the Indians and bring them back safely," she said in Parliament.ABP news last night claimed that in Erbil in Iraq, its reporter met with two Bangladeshi construction workers who said one of 40 Indians taken hostage by IS earlier this year had managed to escape and told them that the rest of his group had been killed.The Indians worked with a construction company in Baghdad. They were kidnapped in Iraq's second largest city of Mosul after it fell to IS. No ransom demand has been received, the government has said. |
The present invention relates to an X-ray apparatus and more particularly relates to techniques which can effectively be applied to exposure control for controlling properly or pertinently the conditions for generating X-rays in a fluoroscopy as well as in a radiography for X-ray diagnosis.
In the conventional X-ray fluoroscopy/radiography system, the automatic X-ray exposure apparatus is so designed as to pick up a portion of output light of an X-ray image intensifier or X-ray I.I. for detection by means of a photomultiplier or the like to thereby effect X-ray fluoroscopy and radiography controls on the basis of the detection signal. By way of example, for the X-ray fluoroscopy control, a feedback control is performed for a tube current and a tube voltage of an X-ray tube or aperture of an optical stop or iris so that an integral value of the detection signal outputted from the photomultiplier per unit time can assume a constant value, whereby brightness of the X-ray fluoroscopic image is constantly held at a pertinent level or value. Further, in the X-ray radiography control, X-rays are interrupted at a time point when the integral value of the detection signal outputted from the photomultiplier has attained a predetermined value, to thereby render available the X-ray radiographic image of proper brightness (phototimer).
As another example of the automatic X-ray exposure control method, there can be mentioned an automatic X-ray exposure apparatus described in Japanese Patent laid-open Publication JP-A-57-88698. In this automatic X-ray exposure apparatus, a plurality of photodiodes are employed for detecting output light of the X-ray I.I. in place of the photomultiplier mentioned above, wherein the X-ray fluoroscopy and radiography control is carried out on the basis of outputs of several photodiodes selected from the plural photodiodes.
In the automatic X-ray exposure control apparatus in which the photomultiplier is employed, as described above, a portion of the output light of the X-ray I.I. is picked up by the photomultiplier by way of a half mirror. Consequently, the amount of light inputted to a television camera will decrease, giving rise to a problem that light utilization efficiency is degraded. Besides, because the light pick-up field is disposed at only one location in the vicinity of the X-ray I.I., difficulty is encountered in effecting the control so that the image having proper or desirable brightness as a whole can be ensured for the X-ray images exhibiting various X-ray absorption dose distributions.
On the other hand, in the automatic X-ray exposure control apparatus described in Japanese Patent laid-open Publication JP-A-57-88698, the light pick-up field can be enlarged by disposing a plurality of photodiodes in place of the photomultiplier. However, the number of photodiodes is ordinarily in a range of eight to twelve or so. Consequently, in the case where one or more photodiodes are positioned near to a boundary between the X-rays transmitted through an object under inspection and the directly incident X-rays, a slight movement of the object under inspection will bring about significant variation in the amount of X-rays impinging onto these photodiodes, incurring a problem that the tone of the displayed image undergo remarkable variation.
As a method of coping with the problems described above, there has been proposed a method of performing the X-ray fluoroscopy/radiography control for an object under inspection by using directly a video signal outputted from a television camera.
However, this method suffers problems described below and thus encounters difficulty in realization for practical applications.
By way of example, because the dynamic range of the television camera is very narrow when compared with that of the photomultiplier and the photodiode array, halation will take place as the amount of light increases, making it impossible to detect accurately the X-ray output, to a disadvantage. Furthermore, in the X-ray radiography control, the time taken for controlling the generation of X-rays is short when compared with a time taken for frame reading of the television camera, involving thus another problem. Additionally, control algorithm for ensuring proper brightness for the fluoroscopic image as well as the radiographic image of a concerned part as required for diagnosis is not definite, bringing about a further problem.
An object of the present invention is to provide an X-ray control method and an X-ray apparatus which make it possible to perform the X-ray fluoroscopy/radiography control more pertinently or properly when compared with the conventional techniques in the X-ray fluoroscopy/radiography control in which a video signal is employed.
Another object of the present invention is to provide an X-ray control method and an X-ray apparatus which can ensure enhanced diagnosis performance for inspectors.
For achieving the objects mentioned above, in the X-ray apparatus according to the present invention, a fluoroscopic image in an X-ray fluoroscopy or an X-ray image picked up in a preliminary radiography is used as a reference image for determining a histogram representing a distribution of numbers of data corresponding to image intensities (pixel values) of the reference image. On the other hand, a weighting function having a variable dependent on the image intensities is determined in order to extract properly the image data. In succession, the weighting function and the histogram are multiplied to thereby determine a weighted histogram, and then output power of an X-ray tube is so controlled that a mean value of the weighted histogram assumes a predetermined value.
Describing briefly the effects achieved by typical embodiments of the invention disclosed in the present application, they are as follows:
(1) In the X-ray fluoroscopy/radiography control for which the video signal is made use of, the X-ray fluoroscopy/radiography control can be carried out more properly when compared with the conventional technique.
(2) With the X-ray fluoroscopy/radiography control in which the video signal is made use of, diagnostic performance can be enhanced.
(3) Because the X-ray apparatus can be implemented in a simplified structure, there can be provided an X-ray diagnosis system of low cost.
(4) The X-ray fluoroscopy can be realized in a stabilized manner.
(5) Sensitive reaction of the sensor in response to movement of an object under inspection can be suppressed. |
0.12938
What is 1 minus -642275330196?
642275330197
What is 0.3 + 367085379901?
367085379901.3
Sum 0.1725327508343 and 11.
11.1725327508343
What is the difference between 245175 and 238407372?
238162197
-0.0355141857921+-5
-5.0355141857921
Add 458451358 and -286.
458451072
What is -0.0755 less than 201.664911?
201.740411
Add together -49 and -361137291755.
-361137291804
What is the difference between 105.8 and 3235166663?
3235166557.2
What is -242706158297 minus -0.013?
-242706158296.987
Subtract 1.69 from -186134930563.
-186134930564.69
Work out -0.08 - 66280347247.
-66280347247.08
-11271+-1404.2842181
-12675.2842181
What is 466629876 less than 0.040231?
-466629875.959769
Calculate 4.7551 + 109.44544.
114.20054
What is -434.24831623 minus 0?
-434.24831623
Add together 23269090644 and -0.5.
23269090643.5
What is 13.7 less than 520452295441?
520452295427.3
Work out 945396 - 311.777476.
945084.222524
Total of -3.5 and -9590216599.
-9590216602.5
Total of -4774258858 and -113.85.
-4774258971.85
Put together 4314444.78919 and 0.544.
4314445.33319
What is -76.6 take away -904754499.43?
904754422.83
What is 147 minus -2020525776726?
2020525776873
What is 233 plus -5416823.77395?
-5416590.77395
Add 357.179 and 281975.
282332.179
Subtract -8721.622610314 from 35.
8756.622610314
Add together -3504 and -20510729.
-20514233
What is -4313098 minus 858.6259?
-4313956.6259
What is -14890559450.95 minus -13?
-14890559437.95
What is -1403763 less than -0.17298869?
1403762.82701131
Subtract -866.85 from -202474.
-201607.15
What is 8791 + -1285164.8507?
-1276373.8507
Sum -3138853991312 and 0.2.
-3138853991311.8
Total of -11.41538299 and -87005.
-87016.41538299
Put together -1.8469 and -41108664.
-41108665.8469
Sum -73.726 and -28713.64.
-28787.366
What is 3931 - 76241288205?
-76241284274
What is -1.7 + 143451.182598?
143449.482598
What is -10.2 take away -3724467463.4?
3724467453.2
Calculate -205 - 1.0038557122.
-206.0038557122
What is 8508 plus -53441465?
-53432957
What is 784549 - 16327.11?
768221.89
What is the difference between 0.46 and 18.023015568?
17.563015568
What is -733094 minus -5298.461?
-727795.539
What is -44156 plus 86406475?
86362319
Put together -8673822760418 and 5.
-8673822760413
What is 1534236 take away -509.8561?
1534745.8561
What is 213.467391 plus -3660?
-3446.532609
What is the difference between 1.12 and 66216277438?
66216277436.88
2.2+1.27564110354
3.47564110354
What is the distance between -5 and 489693725.315?
489693730.315
Add together -0.831 and -434244584.
-434244584.831
What is -38900 minus -8552.17639?
-30347.82361
What is -0.026 minus -8920307509?
8920307508.974
What is 0.25554 plus -5.865858426?
-5.610318426
Put together -9008.7 and -242818716.
-242827724.7
Add -67957291 and 0.399757.
-67957290.600243
Add -11984043 and 26.041846.
-11984016.958154
Add together 19368806453392 and -9.
19368806453383
What is 575990 minus 132990329?
-132414339
-2840754 + -7770974
-10611728
34794578 + -12419
34782159
Calculate -5.4442561 - -1.01974.
-4.4245161
Calculate 178477 + 57216.63.
235693.63
What is -57190 + 8140.6?
-49049.4
Put together -4037.3584028 and 0.3.
-4037.0584028
Calculate 60219 + 1586547271.
1586607490
What is -20756681282 plus 0.03?
-20756681281.97
Calculate -15752236.015 + 1.11.
-15752234.905
1.052427622893 - -7
8.052427622893
What is the distance between 0.09 and -305596576075?
305596576075.09
What is 69.432 + -422235.7?
-422166.268
What is the difference between -1818 and -6225464323?
6225462505
Add together -563473.2 and -9690.
-573163.2
-1668894158176+-0.1
-1668894158176.1
Total of 5 and -3997233.39870622.
-3997228.39870622
Add together -27 and -20490910210316.
-20490910210343
What is -7.39 plus -411893456?
-411893463.39
Subtract 28664717266 from 0.3.
-28664717265.7
-5 + 0.13238982176589
-4.86761017823411
Sum 3.8121 and 0.26880678369.
4.08090678369
-437896182405+0.3
-437896182404.7
What is the distance between -376135 and -124200.3?
251934.7
What is the difference between 0.6676874866663 and 101?
100.3323125133337
-378533+-101780
-480313
What is -22113554 plus -671640?
-22785194
What is 45757 + 101053.74?
146810.74
Sum 0.95566073307 and -751.
-750.04433926693
4.92 - 14840.7416335
-14835.8216335
-4.427752355847 + 220
215.572247644153
-444378847 + 179.4
-444378667.6
What is 1440.1 - -44257623?
44259063.1
Total of 108802199188 and -4.
108802199184
Calculate -1862.7177 + -0.030388.
-1862.748088
-538.90656686 - 5957
-6495.90656686
Work out -489377 - -0.28701115.
-489376.71298885
Add -0.5 and 1788684.2146441.
1788683.7146441
What is 73646248876959 minus 4?
73646248876955
Calculate -371 - -787353132.
787352761
Calculate 0.082267950749607 + -5.
-4.917732049250393
What is -0.01687 less than -18.6415304?
-18.6246604
Calculate 943261172393 + -0.1.
943261172392.9
Calculate -854421452406 + -0.439.
-854421452406.439
What is 695319824615 less than -0.3?
-695319824615.3
Add together 947.17564992 and -0.291.
946.88464992
Add -0.4948 and 52763067576.
52763067575.5052
What is 29071013261 plus 0.04?
29071013261.04
What is 0.62243 less than -2031602.44?
-2031603.06243
Total of 0.06 and -14127.288029.
-14127.228029
What is 962504 plus 62.9046?
962566.9046
What is -14.6 take away -0.8425972796?
-13.7574027204
Add 1115.8492 and 3261.182.
4377.0312
Calculate 152.71 - -14903.75.
15056.46
Work out 95018.949 - 0.01569442.
95018.93330558
5 + 6273630954931
6273630954936
-325221 - 1776768
-2101989
Calculate 1.2152111153 - -16.
17.2152111153
Add -0.1 and -21183074015061.
-21183074015061.1
What is -1072 + 29188.4991?
28116.4991
What is 6593 + 5723.3142?
12316.3142
Calculate 24 + 5.503611183834.
29.503611183834
176+-473235675449
-473235675273
What is the distance between -2.20922 and -96475.8?
96473.59078
Subtract 247121 from 309846.
62725
What is 47.5111650478 take away 0?
47.5111650478
Put together 5807826942.4 and -101.
5807826841.4
-0.032522721917 + 1.12
1.087477278083
What is the distance between 0.4 and -534.76997033?
535.16997033
What is 0.05 - 1585238945940?
-1585238945939.95
What is -8 less than -4166511381.26?
-4166511373.26
Calculate -1968093374 + 9966.
-1968083408
Subtract 4989053 from 35794.
-4953259
Work out -0.1 + -413375020993.
-413375020993.1
Calculate 423165124108 + 0.1.
423165124108.1
2361139263391 - 0.3
2361139263390.7
What is -3902241766 - 39?
-3902241805
Calculate 0.767310069 - 79030.
-79029.232689931
What is 29075.15 + -1850223?
-1821147.85
Work out -0.3 - 120030.16538.
-120030.46538
What is 55 minus -52.032798319?
107.032798319
Calculate -0.043 - 638159491948.
-638159491948.043
Calculate -802.86165 - -0.04707.
-802.81458
What is -108042951989362 plus 2?
-108042951989360
Add -3 and -238801601147.
-238801601150
What is -0.009 take away 1294503899?
-1294503899.009
Put together -1691342.75743 and 2.
-1691340.75743
Work out -1960585437473.8 - 2.
-1960585437475.8
Work out -357138055190 - -419.
-357138054771
Calculate 2732138385426 + 0.08.
2732138385426.08
Put together -0.7 and 249417.1543.
249416.4543
What is -6142178 minus -12509?
-6129669
What is the distance between -163110 and 10686319?
10849429
What is -0.4 less than -40320075294?
-40320075293.6
Subtract 86 from 73499016089.
73499016003
Add together -0.763 and 1813.8405.
1813.0775
-139.23 + -434456017
-434456156.23
-6597303+-235791
-6833094
What is 108457892 minus 20967.79?
108436924.21
Work out 0.4 + 27773531693153.
27773531693153.4
What is the distance between -2.53168928 and 197.677?
200.20868928
27464795+329.6
27465124.6
Calculate -0.0469777533 - 0.0568.
-0.1037777533
-46204930389.4+18
-46204930371.4
Calculate 98718857616 - 0.
98718857616
What is 0.0407 + -1827477539.085?
-1827477539.0443
What is the distance between 2.6 and -5079620256324?
5079620256326.6
Add -168.8 and -27693720.
-27693888.8
What is 172.4973 plus 3074.6?
3247.0973
Add -2.6761721 and -12.64.
-15.3161721
0.3+4516.2134661
4516.5134661
What is 14752 less than -16132.9287?
-30884.9287
Put together -12166 and -1851189471.
-1851201637
What is the difference between -76877 and -55.33711?
76821.66289
What is the difference between -0.273190424 and 2408?
2408.273190424
Calculate -27775787.747 - -2.3.
-27775785.447
Add 1962186.23 and 918519.
2880705.23
Total of 4 and 1209157411299.
1209157411303
-153756 - 52.87021858
|
Everything we know, our strongly held beliefs, and in some cases, even what we consider to be “factual,” creates the lens through which we see and experience the world, and can contribute to a critical, reactive orientation. This can serve us well. For example: Fire is hot; it can burn me if I touch it. These strongly held beliefs can also compromise our ability to observe and to think in an expansive, generative way.
Every year, John Brockman, asks a community of academics and thought leaders, a question, and posts the responses on Edge.org. This year’s question was:
Barbara McClintock was ignored and ridiculed, by the scientific community, for thirty-two years before winning a Nobel Prize in 1984, for discovering “jumping genes.” During the years of hostile treatment by her peers, McClintock didn’t publish, preferring to avoid the rejection of the scientific community. Stanley Prusiner faced significant criticism from his colleagues until his prion theory was confirmed. He, too, went on to win a Nobel Prize in 1982.
Barry Marshall challenged the medical “fact” that stomach ulcers were caused by acid and stress; and presented evidence that H. Pylori bacteria is the cause. Marshall is quoted as saying, “Everyone was against me.”
Progress in medicine was delayed while these “projective thinkers” persisted, albeit on a slower and lonelier course.
Projective thinking is a term coined by Edward de Bono to describe generative rather than reactive thinking. McClintock, Prusiner, and Marshall offered projective thinking; suspending their disbelief regarding accepted scientific views at the time.
Articulate, intelligent individuals can skillfully construct a convincing case to argue almost any point of view. This critical, reactive use of intelligence narrows our vision. In contrast, projective thinking is expansive, “open-ended” and speculative, requiring the thinker to create the context, concepts, and the objectives.
Twenty years of studying maize created a context within which McClintock could speculate. With her extensive knowledge and keen powers of observation, she deduced the significance of the changing color patterns of maize seed. This led her to propose the concept of gene regulation, which challenged the theory of the genome as a static set of instructions passed from one generation to the next.
The work McClintock first reported in 1950, the result of projective thinking, extensive research, persistence, and a willingness to suspend disbelief, wasn’t understood or accepted until many years later.
Everything we know, our strongly held beliefs, and, in some cases, even what we consider to be “factual,” creates the lens through which we see and experience the world, and can contribute to a critical, reactive orientation. This can serve us well: Fire is hot; it can burn if touched. It can also compromise our ability to observe and to think in an expansive, generative way.
When we cling rigidly to our constructs, as McClintock’s peers did, we can be blinded to what’s right in front of us. Can we support a scientific rigor that embraces generative thinking and suspension of disbelief? Sometimes science fiction does become scientific discovery.
Related
5 responses to “Suspending Disbelief”
I will be thinking about this post for days… Thank-you. And I could not agree more.
I would argue that “suspending disbelief” might be THE key skill for innovation in virtually any area. In my tiny examples, the longest-running computing/tech bestsellers today would not have happened if Tim O’Reilly had not been willing to suspend disbelief. Perhaps the next key skill, then, is to help others learn to suspend disbelief, though good filmmakers/novelists have that one nailed already :).
Which is precisely why I used screenplay guides when writing computer programming books…
Yes! You are so right!
When we brainstorm we allow ourselves to push limits aside just to imagine for a minute how things could be different, this allows us to create other solutions in our minds. Perhaps the scientific method has gone beyond its place, we should always imagine possible solutions beyond it, the method should only be used to prove facts, not to limit posibilities in our minds. But we are so afraid of not being rational. We ignore the fact that imagination and intuition maybe the reasons why we are still here!
Scientists are so accustomed to their secular monothetic environment, they have no patience for eccentricities that invade the consensual objective reality and threaten their irresponsible fact-mongering. Send them to church, or better still, India, where people and ethics – arguably what really matters – takes precedence over the blind idealist ratiocination that has thrown this world into turmoil.
There they will seek out, through humility born from the recognition of the immeasurable, unprovable reality that is their own mind, the forerunner of all experience, a guru, who will guide them in bridging that fearful gap of irrational and subjective nature, the space between thoughts, so long repressed by endless clouds of cognition.
Knowledge being infinite, they will instead capture the fortress of that one phenomena they could never grasp, the mind, and through the one they will know all, and then act in some bizarre ways that will make everyone laugh and cry with untold benefit before their last admonition to keep the faith sees their unestablished aggregates finally dissolve into the timeless bliss of emptiness.
This is an awesome post Linda. I heard Eben Pagan mention you talking about continuous partial attention. I think it’s a phenomenon and am experimenting diligently with creating solutions to untrain that kind of.. partial attention conditioning.
Anyway, I think you have a great point. It’s refreshing to see other people talking about this. I’ve been noticing more and more that the rigidity of people’s perspectives, and convictions blocks the reception of new information.
I believe firmly in a constant and never ending expansion as an extremely imperative, but not often enough used ingredient in the recipe of both happiness and fulfillment as a human being. (on an individual level and collectively)
The Attention Project
Attention is the most powerful tool of the human spirit. We can enhance or augment our attention with practices like meditation and exercise, diffuse it with technologies like email and Blackberries, or alter it with pharmaceuticals. In the end, though, we are fully responsible for how we choose to use this extraordinary tool. |
Q:
MySQL query optimization for max value
I'm trying to see if a particular hashcode is within the newest 1000 inserts for a table, what is the most efficient technique to achieve this query:
SELECT a.idsearch
FROM searches a
WHERE a.hashcode = 549716444
AND a.idsearch > (SELECT MAX(b.idsearch) - 1000
FROM searches b);
idsearch is an auto_increment column and is the PK.
A:
Use your existing query but add two indexes if they don't already exist:
A single column index on (idsearch)
A multi-column index on (haschode, idsearch)
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Q:
This selector should be .thisclass using Jquery
$("#maindiv").focusout(".thisclass", function(){
$(this).addClass("warning");
})
I can't use this as an equivalent of .thisclass. In the above code, this refers to #maindiv. Please help me to make the selector this refer to .thisclass.
A:
focusout() doesn't take a selector as it's first argument.
It sounds like you may be confusing it with the delegated on() handler instead, which would require this logic:
$('#maindiv').on('focusout', '.thisclass', function() {
$(this).addClass('warning');
});
Note that this requires the .thisclass elements to be descendants of #maindiv
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A dramatic change is currently on the horizon in the sector of visual display unit and illumination technology. It will be possible to manufacture flat displays or illuminated surfaces with a thickness of less than 0.5 mm. These are notable for many fascinating properties. For example, it will be possible to achieve illuminated surfaces in the form of wallpaper with very low energy consumption. In addition, color visual display units with hitherto unachievable trueness of color, brightness and viewing angle independence will be producible with low weight and very low power consumption. The visual display units will be configurable as microdisplays or large visual display units of several m2 in area, in rigid or flexible form, or else as transmission or reflection displays. In addition, it will be possible to use simple and inexpensive production processes such as screen printing or inkjet printing or vacuum sublimation. This will enable very inexpensive manufacture compared to conventional flat visual display units. This new technology is based on the principle of OLEDs, Organic Light Emitting Diodes, which is shown schematically and in simplified form in FIG. 36.
Such components consist predominantly of organic layers, as shown schematically and in simplified form in FIG. 36. At a voltage of, for example, 5 V to 10 V, negative electrons pass from a conductive metal layer, for example from an aluminum cathode, into a thin electron conduction layer and migrate in the direction of the positive anode. This consists, for example, of a transparent but electrically conductive thin indium tin oxide layer, from which positive charge carriers, called holes, migrate into an organic hole conduction layer. These holes move in the opposite direction compared to the electrons, specifically toward the negative cathode. In a middle layer, the emitter layer, which likewise consists of an organic material, there are additionally special emitter molecules where, or close to which, the two charge carriers recombine and lead to uncharged but energetically excited states of the emitter molecules. The excited states then release their energy as bright emission of light, for example in a blue, green or red color. White light emission is also achievable. In some cases, it is also possible to dispense with the emitter layer when the emitter molecules are present in the hole or electron conduction layer.
The novel OLED components can be configured with a large area as illumination bodies, or else in exceptionally small form as pixels for displays. A crucial factor for the construction of highly effective OLEDs is the luminous materials used (emitter molecules). These can be implemented in various ways, using purely organic or organometallic molecules, and complexes. It can be shown that the light yield of the OLEDs can be much greater with organometallic substances, called triplet emitters, than for purely organic materials. Due to this property, the further development of the organometallic materials is of high significance. The function of OLEDs has been described very frequently.[i-vi] Using organometallic complexes with high emission quantum yield (transitions including the lowermost triplet states to the singlet ground states), it is possible to achieve a particularly high efficiency of the device. These materials are frequently referred to as triplet emitters or phosphorescent emitters. This has been known for some time.[i-v] For triplet emitters, many property rights have already been applied for and granted.[vii-xix]
Copper complexes of the Cu2X2L4, Cu2X2L′2 and Cu2X2L2L′ form (L=phosphane, amine, imine ligand; L′=bidentate phosphane, imine, amine ligand, see below) are already known in the prior art. They exhibit intense luminescence on excitation with UV light. The luminescence can originate either from an MLCT, CC (cluster centered) or XLCT (halogen-to-ligand charge transfer) state, or a combination thereof. Further details of similar Cu(I) systems can be found in the literature.[xx] In the case of the related [Cu2X2(PPh3)2nap] complex (nap=1,8-naphthyridine, X=Br, I), a transition between the molecular orbital of the {Cu2X2} unit (Cu d and halogen p orbitals) and the π* orbitals of the nap group is discussed.[xxi]
Triplet emitters have great potential for the generation of light in displays (as pixels) and in illuminated surfaces (for example, as luminous wallpaper). Very many triplet emitter materials have already been patented and are now also being used technologically in first devices. The solutions to date have disadvantages and problems, specifically in the following areas: long-term stability of the emitters in the OLED devices, thermal stability, chemical stability to water and oxygen, availability of important emission colors, manufacturing reproducibility, achievability of high efficiency at high current densities, achievability of very high luminances, high cost of the emitter materials, emitter materials are toxic and syntheses are complex.
Accordingly, it was an object of the present invention to overcome at least some of the abovementioned disadvantages. |
Ma (goddess)
Ma was a local goddess at Comana in Cappadocia. Her name Ma means "Mother", and she also had the epithets "Invincible" and "Bringer of Victory".
History
Ma has been interpreted as a mother goddess, but at the same time as a warrior goddess, as her name and epithets indicate both.
She was associated with the transition of adulthood of both genders, and sacred prostitution was practiced during her biennial festivals.
Ma has been identified with a number of other deities, indicating her function. She has been compared to Cybele and Bellona. The ancient Greeks compared Ma to the goddess Enyo and Athena Nicephorus. Plutarch likened her with Semele and Athena. Ma was introduced and worshiped in Macedonia together with other foreign deities.
Cult
Ma is described as a local Anatolian goddess, with her cult centered around her temple at Komana in Cappadocia. Her temple in Comana is described at length by Strabo (XI, 521; XII, 535, 537).
See also
Mah
Men (deity)
References
Yulia Ustinova, The Supreme Gods of the Bosporan Kingdom: Celestial Aphrodite and the Most High God (1999), p. 138.
Robin Lane Fox, Pagans and Christians (1988), p. 536.
George Perrot, 'History of Art in Phrygia, Lydia, Caria and Lycia'' (2007), p. 30.
Category:Ancient Cappadocia
Category:Ancient Anatolia
Category:Phrygian goddesses
Category:Cybele
Category:War goddesses
Category:Mother goddesses |
387 N.W.2d 194 (1986)
In re the WELFARE OF M.S.M.
No. C2-85-2206.
Court of Appeals of Minnesota.
May 13, 1986.
*195 Michael S. MacDonald, St. Paul, for M.S.M.
John S. Connolly, St. Paul, for M.S.M.'s father.
Hubert H. Humphrey, III, Atty. Gen., Robert A. Stanich, Sp. Asst. Atty. Gen., St. Paul, Robert W. Kelly, Washington Co. Atty., Stillwater, for Washington County.
Heard, considered and decided by FOLEY, P.J., and SEDGWICK and NIERENGARTEN, JJ.
OPINION
NIERENGARTEN, Judge.
Appellant M.S.M. was charged by delinquency petition with two counts of first degree criminal sexual conduct with four-year-old T.K. and five-year-old M.K. The court adjudicated M.S.M. delinquent and *196 placed M.S.M. under the care and custody of the Washington County Department of Court Services for residential placement at a treatment facility. The trial court further ordered M.S.M. and/or his parents to reimburse the county for the services of court appointed counsel and to pay certain costs. The trial court also denied M.S.M.'s motion for a new trial. M.S.M. appeals.
FACTS
In the fall of 1983 M.S.M. and his parents moved into a house across the street from M.K. and T.K. The two families became fairly well acquainted, and in the spring of 1984 M.S.M. occasionally babysat M.K. and T.K. In June 1984 five-year-old M.K. began to complain of a burning sensation while urinating, and her mother observed a redness on her crotch and slightly enlarged vaginal opening. M.K.'s mother questioned her about sexual contact, but M.K. denied that anyone had touched her.
On the evening of September 4, 1984, M.S.M. babysat M.K. and T.K. for approximately one hour at his house. Later that evening, M.K.'s mother gave her a bath, and M.K. complained again about a burning sensation and complained of pain, pointing to her vagina. M.K.'s mother noted that M.K.'s vagina was red and open, and that there was a scratch in that area.
M.K.'s mother suggested to M.K. that diapers were the cause of the pain, and that perhaps they should be replaced with towels. M.K. spontaneously replied that "it's not the Pampers. [M.S.M.] put his finger in there," and pointed to her vagina. M.S.M. characterizes M.K.'s reply as an attempt to divert her mother's attention away from the threatened loss of diapers (M.K. was a bedwetter) by changing the focus of her mother's attention through the use of a statement implicating M.S.M. After M.K.'s father arrived on the scene, M.K. repeated what M.S.M. had done. M.K. added that M.S.M. had her touch and lick his penis and had showed her magazines with pictures of nude women that he kept in his bedroom.
On September 7, 1984, a child protection worker visited with M.K. at M.K.'s home. Employing a coloring book designed to aid children in describing good and bad touches, the child protection worker talked with M.K. M.K. reported that M.S.M. had given her a "red flag" touch; she colored in the genital area of a figure to indicate where M.S.M. touched her. M.K. stated that the touching occurred at M.S.M.'s house while T.K. and M.S.M.'s brother played in another room. M.K. repeated what happened, adding that M.S.M. had sharp fingernails and had scratched her.
On September 10, 1984, M.K. was examined by a medical doctor specializing in child abuse. M.K. reiterated her story, and also described M.S.M. as having put his penis in her mouth and touching her vagina and anus with his penis. The doctor testified that M.K.'s vaginal opening was wider than normal for a five-year-old, and that in her opinion M.K. had been vaginally penetrated. The doctor concluded that M.K.'s physical examination was consistent with what M.K. told her occurred.
On the way home from the doctor's office, M.K. reported to her mother that M.S.M. had told T.K. a secret. M.K. refused, however, to reveal the secret. Later that evening, T.K. denied knowing any secret, but then told his parents that M.S.M. had threatened to kill his parents if T.K. told them what M.S.M. had done. Both M.K. and T.K. stated that M.S.M. showed them a gun with bullets, which M.S.M. kept in his bedroom closet. On further questioning, T.K. told his parents that M.S.M. had put his penis on T.K.'s butt, "peed" in it, and penetrated him with his finger.
The same doctor who examined M.K. examined T.K. on September 21, 1984. In the doctor's opinion, T.K. was sexually abused in the manner described.
M.S.M. denied any sexual contact with M.K. in an interview with the deputy. Upon learning of the allegations against him, M.S.M. responded that M.K. was lying, although M.S.M. admitted having two Playboy magazines in his bedroom. M.S.M. explained that M.K. had found the *197 magazines in his bedroom. In late September authorities searched M.S.M.'s bedroom pursuant to a warrant, and seized four toy guns from his bedroom closet.
In late October and early November 1984, M.K. and T.K. were interviewed on videotape by the child protection worker and the deputy. After a pre-trial hearing, the trial court determined that the videotaped interviews and the children's statements were admissible at trial.
Trial was held in the latter part of June 1985. M.K. and T.K. were found to be competent witnesses, and both testified at trial as to what M.S.M. allegedly did to them. M.S.M. also testified, confirming that he babysat T.K. and M.K. on September 4, 1984 but that he never had sexual contact with the children or threatened them. In addition, the videotaped interviews were received into evidence.
Several events occurred at trial that are relevant on appeal. First, the sheriff's deputy referred to a lie detector in response to four questions by the defense and one question by the prosecutor. Second, because defense counsel failed to disclose to the prosecution the results of psychological testing on M.S.M., the court sustained the prosecution's objection to the introduction of the psychological assessment as a sanction for a violation of discovery. The defense's offer of proof showed that, according to the test results, M.S.M. was not capable of sexually abusing children.
A third event occurred toward the end of respondents' cross-examination of the appellant's expert when M.S.M.'s counsel requested a recess at 5:30 p.m. so she could pick up her child from daycare. The trial court denied her request. When a second request was denied, defense counsel and M.S.M. left the courtroom. The trial court permitted the cross-examination to be completed in their absence. Before proceeding with trial on a subsequent date, however, defense counsel was given the opportunity to review a tape of the cross-examination and make objections. In a subsequent written order, the trial court concluded that the evidence elicited during the absence of M.S.M. and defense counsel was cumulative and not determinative of any of the issues before the court.
On July 1, 1985, the trial court issued its order finding M.S.M. guilty of two counts of first degree criminal sexual conduct. See Minn.Stat. § 609.342, subd. 1(a) (1984). In the dispositional order of October 29, 1985, the trial court: denied M.S.M.'s motion for a new trial, which was not based on any affidavits or legal documents; placed M.S.M. under the care and custody of the Washington County Department of Court Services for residential placement at Boys Totem Town, a treatment facility; and ordered M.S.M. and/or his parents to reimburse the county for attorney's fees, expert witness fees, transcript costs, and investigation expenses totaling $3,191.00. M.S.M. appeals.
ISSUES
1. Was M.S.M. deprived of his right to counsel when the trial court permitted the continuation of cross-examination of M.S. M.'s expert witness after M.S.M. and his attorney voluntarily left the courtroom?
2. Was M.S.M. deprived of a fair trial because of the cumulative effect of alleged errors occurring during trial?
3. Did the trial court abuse its discretion in requiring M.S.M. and/or his parents to reimburse the county for services rendered by court appointed defense counsel and other expenses?
ANALYSIS
I
The right to assistance of counsel is guaranteed by the Sixth and Fourteenth Amendments to the United States Constitution. See Herring v. New York, 422 U.S. 853, 856, 95 S.Ct. 2550, 2552, 45 L.Ed.2d 593 (1975). See also Minn. Const. art. I, § 6. Furthermore, the rules of the juvenile court provide that children have a right to be represented by counsel. See Minn.Stat. § 260.155, subd. 2 (1984); Minn.R.Juv.Ct. *198 4.01, subd. 1. M.S.M. argues he was denied his constitutional and statutory right to counsel when the trial court continued the cross-examination of his expert witness after he and his court-appointed counsel left the courtroom.
The trial court concluded that because M.S.M.'s attorney reviewed a tape recording of the part of the proceeding she missed and was given the opportunity to recall the witness, M.S.M.'s case was not damaged by the continuation of the proceeding in her absence. While the court found that M.S.M.'s attorney's conduct in this instance was unwise and unprofessional, it did not prejudice the case.
The state argues that the conduct of M.S.M.'s counsel in leaving the court proceedings did not constitute a per se deprivation of the right to counsel that "so undermined the proper functioning of the adversarial process that the trial cannot be relied on as having produced a just result." Strickland v. Washington, 466 U.S. 668, 686, 104 S.Ct. 2052, 2064, 80 L.Ed.2d 674 (1984). The state emphasizes that M.S.M.'s counsel was in no way excluded from the hearing, but instead voluntarily chose to leave proceedings that were in progress. The state adds that any potential prejudice to M.S.M.'s case was avoided by permitting counsel the opportunity to listen to the tape recording of the proceedings continued in her absence and by giving her the opportunity to recall the expert.
Under the circumstances, we think the trial court should have adjourned for the day when M.S.M.'s counsel made such a request, especially in light of the conflicting allegations that she had notified the court of her time conflict prior to the hearing. Generally, however, it is the duty of counsel to be present at all stages of the trial of a case. See VonEnde v. Marxen, 280 Minn. 24, 27, 157 N.W.2d 525, 527 (1968). See also Hudson v. Minneapolis, L. & M. Railway Co., 44 Minn. 52, 54, 46 N.W. 314, 315 (1890) ("it is the duty of the counsel to remain in, or be represented at, the court during its sessions until the trial is ended"). The trial court stated at the time it denied the request for adjournment that it wanted to continue on and complete the cross-examination of M.S.M.'s expert because of the court's limited time to hear the case and for reasons of convenience to the witness. The Minnesota Supreme Court has stated that:
[b]earing in mind the heavy schedule of trials, the court, in proper exercise of its discretion, could deny an adjournment which if granted would unreasonably extend the length of trial and disrupt the orderly disposition of pending cases.
Ford v. Kline Oldsmobile, Inc., 274 Minn. 284, 287, 143 N.W.2d 209, 211 (1966). Thus, we conclude that the trial court was within its discretion in denying the request of M.S.M.'s counsel to adjourn for the day.
In addition, we note that the trial court found the cross-examination conducted in the absence of M.S.M. and his counsel to be cumulative. This, coupled with the fact that the cross-examination was not prejudicial to M.S.M.'s case, lends support to our conclusion that the trial court did not deprive M.S.M. of his right to counsel.
II
M.S.M. asserts that the cumulative effect of three alleged errors occurring at trial deprived him of his right to a fair trial.
1. Reference to the Lie Detector M.S.M. contends that the prosecution witness improperly made reference to a lie detector. M.S.M. admits, however, that his counsel at trial failed to object or request a mistrial.
The state contends that M.S.M., not the state, elicited testimony concerning a lie detector. In any event, the state contends this issue is not properly before this court because it was not raised in the trial court or in the motion for a new trial. The state adds that the references to the lie detector did not prejudice M.S.M. because it was not clear he ever took a polygraph, and no polygraph results were ever alluded to at trial.
2. Admissibility of M.S.M.'s Psychological Assessment Because M.S.M. failed to *199 disclose the results of psychological testing on M.S.M., see Minn.R.Juv.Ct. § 24.02, subd. 1(B), the trial court refused to admit them into evidence as a sanction for violation of discovery rules. M.S.M. asserts that the court should have used a sanction that did not prejudice M.S.M.'s case.
The state notes that the prosecutor made a formal request for disclosure more than six months prior to trial, which disclosure M.S.M. failed to provide. The state contends sanctions for the violation of discovery rules are within the discretion of the court, and here the trial court did not abuse its discretion.
3. Extrajudicial Statements of M.K. and T.K. M.S.M. contends that he was denied the right of confrontation under the six and eighth amendments through misapplication of Minn.Stat. § 595.02, subd. 3 (1984) because the trial court admitted into evidence ten statements made by M.K. and T.K. out-of-court. According to M.S.M., the trial court improperly admitted the statements of the children to four witnesses and the statements of the children on videotape for a total of ten misapplications of section 595.02, subd. 3. In addition, M.S.M. argues that the trial court placed undue weight on the videotaped statements by reviewing them after the conclusion of the hearing. M.S.M. also argues that after nine months, since the time from the alleged offense, the memories of M.K. and T.K. faded.
The state asserts that the trial court conducted a hearing and found that all the section 595.02, subd. 3 criteria were satisfied. Allowing the children's extrajudicial statements into evidence was thus correct. Because the children testified at trial and were subject to cross-examination, the state concludes that M.S.M. was not denied the right to confrontation.
Based on the cumulative effect of these alleged errors, M.S.M. contends he was denied a fair trial. See State v. Jahnke, 353 N.W.2d 606, 611 (Minn.Ct.App.1984).
We find these are not errors at all. The record contains no evidence that M.S.M. ever took a polygraph test. Furthermore, no objection was made at trial, and M.S.M. did not raise this allegation in his motion for a new trial. A party is not allowed to raise an issue for the first time on appeal. See Morton v. Board of Commissioners, 301 Minn. 415, 427, 223 N.W.2d 764, 771 (1974).
Sanctions for discovery violations are within the discretion of the trial court. State v. Lindsey, 284 N.W.2d 368, 373 (Minn.1979). Here the trial court's refusal to admit into evidence the results of a psychological assessment was permissible under the circumstances and does not constitute an abuse of discretion.
As to the extrajudicial statements of M.K. and T.K. contained in the videotape, the trial court was satisfied that the criteria of section 595.02, subd. 3 were met. Thus, the trial court did not err in admitting the children's extrajudicial statements into evidence. The record does not disclose that he was denied the right of confrontation.
M.S.M. was not denied a fair trial.
III
In juvenile proceedings in which the court has appointed counsel for the juvenile, "the court may inquire into the ability of the parents to pay for such counsel's services and, after giving the parents a reasonable opportunity to be heard, may order the parents to pay attorneys fees." Minn.Stat. § 260.251, subd. 4 (1984) (emphasis added). When parents can afford to retain counsel but have not retained counsel for the child and the child cannot afford an attorney, the child is entitled to representation at public expense. Minn.R. Juv.Ct. § 4.01, subd. 3(B). A court may order, after giving the parents an opportunity to be heard, "that service of counsel shall be at the parent(s)' expense in whole or in part depending on their ability to pay." Id.
The trial court determined that both of M.S.M.'s parents are gainfully employed and possess the resources to contribute to *200 the payment of expenses and attorney's fees expended in the defense of M.S.M. and ordered M.S.M. and/or his parents to reimburse the county for $3,191.00.
M.S.M. argues the trial court did not provide a hearing and opportunity to be heard for his non-custodial parent, and that this omission constitutes a statutory violation and a deprivation of the constitutional right to due process. In addition, M.S.M. contends the court failed to provide notice of the pendency of the case pursuant to Minn.Stat. § 260.135, subd. 2 (1985) to his non-custodial father prior to the appointment of counsel, thereby denying his noncustodial father the opportunity to employ the counsel of his choice.
The State counters with several arguments. First, M.S.M. did not raise this issue before the trial court at anytime prior to appeal; therefore, M.S.M. waived the issue. Second, the reimbursement issue arose after the adjudicatory order of July 1, 1986, and was raised in neither the August 23rd nor October 9th hearings. It was after the October 9th hearing that the trial court ordered reimbursement. Because M.S.M. has not provided transcripts of the two post-trial hearings, the state contends the record is inadequate for purposes of review. On the record that exists, the state asserts that both of M.S.M.'s parents were present at the two hearings.
Based on the record, we must affirm the trial court.
DECISION
M.S.M. was not deprived of his right to counsel when the trial court permitted the continuation of cross-examination of his expert witness after M.S.M. and his lawyer voluntarily left the courtroom. M.S.M. was not denied a fair trial by the cumulative effect of three alleged errors. The trial court did not abuse its discretion in requiring M.S.M. and/or his parents to reimburse the county for services rendered by court-appointed defense counsel and other expenses.
Affirmed.
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