text:
Q: Android Notification Channel sounds stop working when using sound URIs that reference resource ids We have created notification channels for devices running on Oreo and above, that use a custom notification sound that is located in our /res/raw folder. Recently, when users upgraded our app, the notification sound just stopped working and the notification only vibrates the device.
We have confirmed that uninstall/reinstall or clearing app data resolves the issue. However, in order to get notification sounds to work for everyone again without having to reinstall, we need to essentially delete and recreate these channels.
We create the notification channel as follows:
fun initNotificationChannel(channel: PSSNotificationChannel) {
        if (Build.VERSION.SDK_INT >= Build.VERSION_CODES.O) {
            val id = channel.id
            val name = context.getString(channel.nameResId)
            val importance = channel.importance
            val channel = NotificationChannel(id, name, importance)

            ...

            // Default sound
            val soundUri = Uri.parse(ContentResolver.SCHEME_ANDROID_RESOURCE + "://" +
                    context.applicationContext.packageName + "/" + R.raw.notification)
            val audioAttributes = AudioAttributes.Builder()
                    .setUsage(AudioAttributes.USAGE_NOTIFICATION)
                    .setContentType(AudioAttributes.CONTENT_TYPE_SONIFICATION)
                    .build()
            channel.setSound(soundUri, audioAttributes)

            val notificationManager = context.getSystemService(Context.NOTIFICATION_SERVICE) as NotificationManager?
            notificationManager?.createNotificationChannel(channel)
        }
    }

I have verified that the file still exists in /res/raw. And the commit that seemed to cause this was just some added/modified files to the /res folder.

A: It seems like this issue setting the soundUri as follows:
val soundUri = Uri.parse(ContentResolver.SCHEME_ANDROID_RESOURCE + "://" +
                    context.applicationContext.packageName + "/" + R.raw.notification)

It looks like the value of R.raw.notification changed from 2131689979 (version where sound works) to 2131755515 (version where sound doesn't work). And since you can't change your notification sound with Notification Channels, I am almost certain that the channel is trying to resolve the soundUri with the old resource id (android.resource://our.package.name/2131689979).
I think the better approach is to reference the file directly by name as follows:
val soundUri = Uri.parse(ContentResolver.SCHEME_ANDROID_RESOURCE + "://" +
                    context.applicationContext.packageName + "/raw/notification")

I also notice apps like Facebook Messenger and Slack use a public Notifications folder where they probably just copy the file over and reference that exact path. This also seems to allow the user to re-select the app-provided sound because it is visible in the filesystem.


IXOR's Circle VFX Breakdown (Part 01) for the Swedish feature Film "Cirkeln".
On-Set Supervision to final delivery of +320 vfx shots including set extensions, fire and smoke, digital doubles and matte paintings.
IXOR was established in 2005 and offers CG visuals / 3D Animation & Visual Effects Services.


text:
Section A General
Section B Player Registration
Section C Rep Teams
Section D Team Conduct
Section E Discipline and Suspensions
Section F Complaints, Protests and Appeals
Section G Coaching Requirements
Section H Injuries
Section I Ice
Section J Tournaments/Exhibition
Section K Equipment
Section L Financial
Section M Fundraising
Section N Team Apparel
Section O Team Duties
Section P Minor Officials
SECTION A - GENERAL
1. Interpretation:
(a) In these Rules and Regulations, unless the context otherwise requires:
"PCMHA" refers to the Port Coquitlam Minor Hockey Association;
"PCAHA" refers to the Pacific Coast Amateur Hockey Association;
"BC Hockey" refers to British Columbia Hockey;
"CHA" refers to the Canadian Hockey Association; and
"Executive Committee" refers to the current directors and officers of the PCMHA as elected pursuant to the By-Laws of the PCMHA.
(b) Words importing the singular include the plural and vice-versa; and words importing a male person include a female person.
2. All PCMHA players, team officials, parents and referees shall be governed by the Constitution, By-Laws, Rules and Regulations of the PCMHA, the PCAHA, BC Hockey and the CHA.
SECTION B - PLAYER REGISTRATION
1. No player shall be permitted on the ice unless he has been first registered with PCMHA and entered in the Hockey Canada Registration system by the Registrar.
2. Final registration of all players shall be at the discretion of the PCMHA Executive Committee.
3. Application must be made to the Executive Committee for additional registrations after the registration close-off date.
4. Each team shall email the Registrar of the PCMHA with a copy of the team roster and sweater numbers allocated to the players immediately after the teams have been chosen.
5. No player may be placed on a team roster, either "A1 or A2 or C", after the start of league play unless application is made in writing to the Division Manager who will make recommendations to the Executive Committee.
6. There shall be no refunding of registration monies after December 31st for any reason other than residential moves or medical. All applications for refunds shall be in writing and submitted to the Registrar. Refunds shall be pro-rated from the application date according to the number of weeks remaining in the current hockey season and shall be subject to an administration fee.
7. PCMHA believes all players should play hockey with their same age peers. Only under special circumstances may a player be moved into a higher or lower division. The player must first register in their own age division. An appropriate request must be submitted to their Division Manager. Players applying to move down a division will be assessed and after approval by PCAHA Fraser Valley North will be approved if there is room in the lower division. If there is room in the higher division, players applying to move up a division will be assessed by an independent evaluator who shall first be approved by the Executive Committee. If the player is assessed to be in the top 5 of the higher age group, the assessment will be brought forward and reviewed by the Executive Committee. If a "move up" is approved by the Executive Committee a motion will be made and voted on approving the move for the one season. The player may play in the higher division at the C level for that particular season only if there is room (ie no waitlist).
SECTION C - REP TEAMS
1. All players shall be encouraged to play at the level of hockey they are capable of, within their own age division.
2. All registered players applying for a rep tryout shall be given an equal opportunity to try out for the "A1" or "A2" teams in their respective division.
3. Every reasonable effort shall be made to ensure that all players requesting a rep tryout receive a minimum of 3 tryout sessions.
4. Players that are injured must be available for at least 1 tryout to be considering for a rep team. Exceptions to this policy may be considered by the President upon review of the players prior two seasons, the level played and length of injury.
5. No fundraising events or team functions shall be undertaken prior to the finalizing of team rosters.
5. No assistant coaches, managers or other team officials shall be appointed prior to the finalizing of team rosters.
6. All rep teams shall card a minimum of 15 skaters, not including goaltenders. However, at the recommendation of the respective Division Managers and at the discretion of the Executive Committee, team rosters may be decreased or increased due to special circumstances.
7. Each rep team shall carry a maximum of two goaltenders (availability permitting).
8. No releases may be made after the commencement of league play without Executive Committee approval.
9. No player may play for more than one team on a "casual" basis without prior approval of the Division Manager. For example, a Peewee C player affiliated to the Peewee A2 team cannot play up for Bantam C.
SECTION D - TEAM CONDUCT
1. The team Coach and/or Manager shall be responsible for the actions and conduct of the team players, team parents and team officials at all times that the team is under jurisdiction of the PCMHA.
2. Employees of any arena, opposing teams, and game officials shall be treated courteously and with respect at all times.
3. All players shall confine themselves to their assigned dressing rooms 20 minutes before game time and must be supervised by a team official during that time and until all players have left the dressing room after the game.
4. The team officials will implement appropriate dress code for their team.
5. POCO Minor Hockey sanctions the use of a video camera at games and practices only the purposes of team training. If your team wishes to video tape a game or practice, the team manager should obtain permission from the Division Manager and provide the date, time and location of the game/practice to be videotaped. Individuals videotaping for any other purpose (ie taping for the purpose of timing the minutes players are on the ice) will be subject to our disciplinary process. A record/log must be kept by the manager (and with them at all games and practices) documenting all video sessions for the season.
SECTION E - DISCIPLINE AND SUSPENSIONS
Port Coquitlam Minor Hockey Association Disciplinary Process
The PCMHA Executive has implemented a formal code of conduct and disciplinary process for players, team officials, parents and spectators. The code of conduct is based on the Fair Play Code of Conduct as developed by BC Hockey and Hockey Canada. The disciplinary process is designed to create a fair, unbiased and objective process for disciplining behavior that violates our code of conduct.
All players, team officials, parents and regular spectators must sign the appropriate Code of Conduct. All players and parents provide consent to Code of Conduct upon successful registration for the season through TeamSnap. It is team manager's responsibility to collect Team Officials Code of Conduct and hold onto them for the season. It is within our guidelines that no player or team officials will be involved in a team function on or off the ice if the signed code of conduct has not been returned to the respective team managers.
PCMHA reserves the right to discipline players, team officials or parents in addition to, and regardless of, any discipline that may have occurred through Pacific Coast or BC Hockey.
Disciplinary Guidelines
Parents and Spectators
Parents and spectators are responsible for their own conduct. They may cause themselves to be ejected if they act in a manner that an on-ice officials or team manager views as unacceptable.
Team officials are responsible for supervising and controlling the conduct of their players before, during and after the practice or game. Failure by team officials to control the conduct of their team may result in suspensions or other disciplinary action as deemed necessary. For disciplinary reasons , a team Coach and/or manager, without the approval of the President of the Association, may suspend a player for up to 3 games for disciplinary reasons. Any further suspension may be imposed subsequent to Discipline Committee investigation and recommendation to the Executive Committee.
The best way to avoid disciplinary action is through the application of positive reinforcement. PCMHA disciplinary committee has set up 3 different levels of offences:
First level offence
This should be dealt within the individual team level unless the Coach deems it necessary to elevate to Executive level.
This may include:
unexcused absences
lack of dressing room etiquette
horseplay
other similar actions
Second level offence
It requires a review of the incident by the Executive and disciplinary committee.
Insubordination to coaching staff
Harassment or abuse of anyone while at hockey activity
Third level offence
Any player found with drugs and or alcohol in their possession, or any suspected to be under influence of drugs or alcohol while participating in a PCMHA activity, will be suspended immediately from further practice and game until the investigation is completed.
The committee consists of 1st Vice President of PCMHA, and 2 life time members.
SECTION F - COMPLAINTS, PROTESTS AND APPEALS
1. All grievances must be submitted in writing within 48 hours to the President. The President will appoint three Executive members to a Grievance Committee. This Committee will interview the complainant and investigate the grievance, referring their decision to the Executive Committee at the next Executive meeting. The Executive Committee will rule on the grievance and make their decision known to the complainant within 24 hours of the Executive meeting.
2. Any decision of the Grievance Committee may be personally appealed to the Executive Committee within 72 hours of being notified of the decision. Notice of any such appeal shall be submitted in writing to any member of the Executive Committee. If a player appeals, he must be accompanied by his parent or guardian.
SECTION G - COACHING REQUIREMENTS
1. All PCMHA Coaches shall acquire coaching certification as required under PCAHA and BC Hockey Rules and Regulations.
2. Failure to meet these requirements shall result in suspension until the required certification is obtained.
3. PCMHA does not pay for repeat clinics, ie. If a coach fails to complete the post-task and is required to redo the clinic – we will not pay for it the second time.
4. Team officials must apply for reimbursement within 30 days of taking the clinic. No reimbursement will occur after the 30 days.
SECTION H
1.In the event of an injury, the team Manager/Coach shall be responsible to see that all necessary action is taken.If considered necessary, arrangements for transportation and emergency treatment of the player must be made.The team manager must log the nature of an injury on INJURY LOG SHEET and assist parents for filling out the injury forms.
2. All teams must carry an up-to-date first aid kit. Team manager is responsible for replenishing the stock and can do so by contacting our equipment manager at equipmentmanager@pocominorhockey.com.
3. A CHA injury report must be provided to the parents of the injured player and completed as soon as possible. The parent is responsible for submitting the form to BC Hockey within 90 days and providing a completed copy to the team manager to keep on file for the duration of the season.
4. All injuries must be reported to BC hockey within 90 days. Forms can be downloaded athttps://www.bchockey.net/AdminAppForms/Hockey%20Canada%20Injury%20Report%20Form%202010-07-26.pdf
Hockey Canada recommends that all players returning to play after injury must get the physician to fill out the form. In consideration to health and safety of a player, PCMHA, requires a physician's note when a player has missed hockey due to injury. It is the parents' responsibility to inform the physician if player is involved in full contact hockey, U15 A or U18 A. Due to nature of the injury, the physician will have the better understanding of the injury and the return time will vary.
SECTION I - ICE
1. All ice slots are allocated to meet league requirements. The Ice Scheduler assigns each team a time that meets league start time and duration requirements.
2. Teams do not own the assigned ice slot. When necessary, the Ice Scheduler may use any team's practice time to facilitate a make-up game. Whenever possible, the affected team will be assigned a replacement practice time. Team Managers must not use their practice time for exhibition games without first obtaining permission from the Ice Scheduler.
3. Teams in the Hockey 1/2, Hockey 3/4 and Atom divisions will share practice ice with
another team in the same division
4. Teams are expected to cooperate with other teams to resolve schedule conflicts. The Ice Scheduler will intervene if necessary to ensure that all teams are able to meet their obligations.
The Ice Scheduler may at their discretion use a team's ice time to meet Association obligations. Game slots will be rescheduled. Practice times are reassigned when possible.
It shall be the responsibility of the team Manager or Coach to notify the Ice Scheduler and/or the Division Manager a minimum of 72 hours prior to any scheduled game or practice cancellation. Failure to do so will result in the team paying for the cost of the ice to PCMHA. Failure to pay the ice cost will result in the team being suspended from any further practices.
The Referee-in-Chief and/or the Referee Allocator must also be notified a minimum of 72 hours prior to cancellation of any game. Payment of referees by the offending team is still necessary if proper cancellation notice is not given.
SECTION J - TOURNAMENTS/EXHIBITION
1. No team shall play outside the PCAHA jurisdiction until PCMHA and PCAHA approval has been given. Requests must be presented to the Division Manager who will then conduct a silent vote. Approval requires a 2/3 majority support of the team parents.
2. Any team wishing to play an exhibition game shall first obtain permission from its League Manager by way of an exhibition game number.
3. In addition, permission must be obtained from the BC Hockey District Director for any exhibition games versus USA Hockey teams, whether at home or away, and permission must be obtained from BC Hockey for any exhibition games versus Canadian teams from other provinces, whether at home or away.
4. A team wishing to participate in any tournament or jamboree must first obtain a tournament permission number from its League Manager. Also a Letter of Permission from the President must be obtained if requested by the Tournament Host.
5. Failure to acquire proper permission as set out within this section may result in suspension or other disciplinary action against the team official(s) responsible.
SECTION K – EQUIPMENT
1. All property of PCMHA issued to teams within the Association shall be issued to, and therefore become, the sole responsibility of the Coach of the team or his designate, as indicated in writing by the Coach, at the beginning of the year.
2. All property belonging to PCMHA shall be returned to the Equipment Manager in good shape, other than reasonable wear and tear, by no later than April 30th of the current hockey season.
3. Registration privileges for players or reappointment of team officials not returning registered issued equipment may be withheld for the succeeding season until the equipment or replacement cost is rendered to the Association.
4. On return of all jerseys at the end of the season, the uncashed jersey deposit cheques will be returned to the team official or destroyed as requested. If a jersey is missing, the jersey deposit cheque for that player will be cashed as compensation for the loss of the jersey.
SECTION L - FINANCIAL
1. All team accounts will be with Van City Savings – Ottawa Street Branch, near Costco
2. All team accounts must be co-signatory accounts (2 signatures). The rostered team manager must be the 1st signor on the team bank account. The 2nd team signor must be the Head Coach.
3. Confirmation of account numbers and signatories must be provided to the 2nd Vice-President of the PCMHA by October 31st of the current hockey year. Failure to submit financial information will result in the said team not receiving reimbursement of referee fees for the second half of the season.
4. Team managers (in conjunction with coaches) must conduct a budget meeting with parents and submit the budget to the Division Manager prior to November 1st each year.
5. Team manager (in conjunction with coaches) will estimate the total cost per PLAYER to coincide with the approved budget and conduct a parent meeting to determine how the funds will be collected and/or raised.
6. Teams may collect from parents, fundraising or donation/sponsorship a maximum of $600.00 per player without Executive approval. Any expenditures or travel plans outside of the $600.00 must first be approved by a team vote (silent vote via ballot) conducted by the Division Manager. The budget must then be set out in a detailed plan and submitted to the Division Manager for Executive approval.
7. A parent meeting must be held with the Division Manager for all tournaments planned outside of the province. A silent ballot vote will be conducted by the Division Manager to ensure 75% of families are in favor. As well, a revised budget must be submitted and approved by the Executive to include the details of all costs to parents prior to the team confirming a place in the tournament. This must be conducted by an Executive member who does not have a player on the team.
8. The Team Manager must provide the Association 2nd Vice President and team parents with an interim financial statement setting out the current team financial information by January 1st in each season and a year end financial statement to both the team parents and the Association 2nd Vice President by April 1st in each season. Email to 2nd Vice President, 2ndvp@pocominorhockey.com
9. All fundraising monies not spent by individual teams during the season and all unused referee monies must be returned to the Association at the end of the current hockey year.
10. The Association has a program in place to assist families during times of hardship. Team managers must advise the 2nd Vice President of any families that have not yet met their team financial obligations by December 1st. Hardship cases are reviewed on an individual basis and if provided are to be used only for registration fees. Hardship assistance is not provided for payment of team fees nor is it provided for registration or otherwise for rep level players.
SECTION M - FUNDRAISING
1. All fundraising must be cleared through the 2nd Vice-President in order to avoid overlapping of teams running events in the same neighborhood at the same time, etc. and to avoid conflicts with our gaming/casino licenses. Team Managers must complete the Team Fundraising and Financial page by the October 31st deadline.
2. No team may apply for a Provincial B license for any fundraising activity. By so doing, the Association's gaming license and proceeds are put at risk.
SECTION N - TEAM APPAREL
1. When purchasing team apparel, official Association colors are to be used. They are a combination of black, white, purple and silver/grey.
2. The only Association crests that can be used are the PCMHA hockey stick, the round Association crest or the Pirates logo.
3. Custom team logos may be used following Executive Committee approval but must include the approved Association crests as set out in paragraph 2 above.
4. PCMHA requires its teams to wear Association jerseys at all games including exhibition, league, playoff and tournament. Teams purchasing third jerseys must first obtain approval before ordering. Requests should be made in writing to the Division Manager for approval from the Executive Committee. Third jerseys may only be worn for practice.
SECTION O - TEAM DUTIES
Bookkeeper/Treasurer – Referee fees will be transferred to teams in two installments based on receipt of the team financial statements. Keeping your financial statements up to date and filing on time will result in prompt transfer of referee fees.
Keep proper set of books (no money paid out without a receipt)
Provide Association and team parents with an interim financial statement setting out the current team financial information by January 1st
Submit yearend financial statement to 2nd Vice President by email 2ndvp@pocominorhockey.com". to the Association of PCMHA and parents by April 1st
Exhibition Games
As required by team
Involves phone/e-mail work
Need to arrange referees and ice times for these games
Need game numbers
Need team picture taken and developed right away
Apply to tournaments and submit required information ASAP
Can require long distance phone work
Need to obtain PCAHA and PCMHA approval
Arrange for appropriate accommodation
If traveling to the USA, obtain insurance coverage if your primary insurance does not cover travel. For more information please visit: http://www.hockeycanada.com/index.php/ci_id/7134/la_id/1.htm
Scorekeepers
Ensure scorekeepers and timekeepers are scheduled for every home game
Responsibility for schedule can be assigned to a parent
This is important – each score sheet must be mailed to PCAHA within 24 hours of each game without fail. PCAHA will fine teams who do not adhere to this rule. Atom Division and higher to submit game sheets via Team Link website.
The referee assignor requires 72 hours' notice for exhibition games
Need to ensure there is a game number and referees for each exhibition game
Sign in and pay the referee and linesmen prior to the start of each game
Game numbers and referees are pre-assigned for regular season and playoff games
Sample "Officials Game Sign-In & Record of Payment" form at end of this manual
Refer to Section L for specific regulations that team managers must follow.
Money raised and collected from parents must be reported in your year end financial statement
Fundraising events are not automatically sanctioned and additional insurance is required and may be obtained through BC Hockey.
Submit newsletter report to PoCo Minor Hockey by November 15th and February 15th
Newspaper Reports
Whenever there is something newsworthy to report please take advantage of the on-line newspaper team sports reporting system @www.thenownews.com or www.tricitynews.com
Dry land Training
Ensure you have adequate liability insurance – these are not sanctioned events but you may obtain additional insurance coverage for dryland training through BC Hockey.
Team Dress Code
As decided by the Coach and/or Manager
Socials and Windup Parties
Remember, referee monies are held in trust by the team in order to provide payment to the referees and are not to be used for your wind-up party
REMEMBER……………………A GOOD MANAGER IS GOOD AT DELEGATING!
SECTION P - MINOR OFFICIALS
Duties and instructions of minor officials appear in the CHA Rule Book. This handbook is intended to compliment the information already available and provide additional information when necessary.
Minor officials should know their duties for each game, but should also become familiar with the actual playing rules and regulations.
This knowledge will prove very beneficial in the performance of his or her role.
Scorekeepers should be familiar with most rules and especially those sections which deal with:
Players in uniform
Captain of team
Minor penalties
Bench minor penalties
Major penalties and coincidental major penalties
Misconduct penalties
Game misconduct
Match penalties
Delayed penalties
The minor officials are made up of the following:
Official scorer
Timekeeper
Goal judges
Penalty timekeeper
The responsibilities and functions performed by the minor officials are not minor but rather very important. Each individual is an integral member of the team.
Remember, you are an official and you must act accordingly, remaining neutral just as the officials on the ice.
The following is a list of the responsibilities carried out by each of the minor officials.
Minor officials are under the supervision of the Referee, who is the final authority and can over-rule any minor official
Minor officials should refrain from criticizing the work of any other official at any time
Minor officials should report to the referees' room before the game and be at their respective positions promptly at the start of the game and between periods
Appearance is important as you are part of the team
Concentrate on your job and avoid any unnecessary conversation
If mistakes are made, report them to the Referee
Official Scorer –
Obtain line-up of each team and include name and number of the Captain and Alternative Captains of each team. This information must be supplied by the team officials in charge of the teams and the referees should be given this information prior to the start of each game. The line-up gamesheet.
At the completion of the game, have the official Game Report signed by each referee.
If the Official Scorer encounters any difficulty in obtaining line-ups of the teams he should report this to the Referee.
Shall enter on the "Official Game Report" a correct record of the goals scored, by whom, and to whom assists, if any, are to be credited.
Shall record all penalties assessed, stating the names and numbers of penalized players, the duration of each penalty, the infraction and the time the penalty was assessed.
Check the report for date of game, category, division, names of teams, and time of periods.
Official scorer should deliver the game sheet to the manager of the home team.
Shall record the time of the start and finish of each game, and all actual playing time during the game.
If a player leaves the penalty bench before his time has expired the Penalty Timekeeper shall note the time and notify the Referee, who will stop play as soon as possible.
In any dispute regarding time, the matter shall be referred to the Referee and his decision is final.
Stop the clock only on Referee's whistle and automatically at the end of the period. The clock (time) shall start when the puck is dropped by the official.
If the goalie is changed, record the time on the game sheet.
PRE-GAME CHECKLIST AND PROCEDURES (OFFICIALSCORER AND TIMEKEEPER)
Be at the arena ½ hour – 1 hour prior to game time.
PRE-GAME DUTIES
Give game sheet to the home team official and check to ensure that a responsible official has signed and that the coach and managers names appear on the sheet as well as HCSP person.
Deliver game sheet to Referee for his approval before the game
POST GAME
After the game, ensure that the gamesheet is completed – i.e. goals recorded
Deliver report to Referee(s) for signature
Distribute copies as instructed by the Association
GAMESHEET LANGUAGE
Clarity and brevity is important
Print clearly and firmly
Should develop a standard code so that all information can be recorded
Do not record player's name but use only his number
Common Code:
SHG – short handed goal
PPG – power play goal
ENG – empty net goal
record numbers only
abbreviations are necessary but should standardize these:
Agg Aggressor HP Handling puck
AM Automatic minor hkp hooking
BDG Boarding HS High stick
BR S Broken stick ill s Illegal shot
BM Bench minor INT Interference
CC Crosschecking KNEE Kneeing
CK BHD Checking from behind LPB Leaving penalty bench
CHG Charging MISC Misconduct
DG Delay of game MM Major misconduct
ELB Elbowing RO Roughing
Fgb Failure to go to bench SL Slashing
FI Fighting SP Spearing
FOP Falling on puck TMM Too many men
GLC Goalie leaving crease TR Tripping
GM Game misconduct TS Throwing stick
HO Holding USC Unsportsmanlike conduct
When a match penalty has been assessed, enter MATCH on one line and the specific infraction (i.e. kicking, molest official) on the next line.
If a player is ejected from a game as a result of a third stick infraction, enter GAME EJECTION or the abbreviation G EJECT.

redpajama_set_name: RedPajamaCommonCrawl


text:
Bollywood Papa
Home Actor Amitabh Bachchan offered role in Telugu film 'Rythu'
Amitabh Bachchan offered role in Telugu film 'Rythu'
Filmmaker Krishna Vamsis highly anticipated Telugu drama "Rythu", about farmers grievances, might bring together Nandamuri Balakrishna and megastar Amitabh Bachchan.
"Both Krishna Vamsi and Balakrishna had met Amitji on the sets of 'Sarkar 3' not very long ago. They pitched the story to him and even discussed the idea of collaborating as they're very keen on having him on board, even if it means waiting for another six onths," a source close to Vamsi told IANS.
[ecp code="4″]
The source added that Big B is yet to give his nod.
"Apparently, he's busy till June 2017, and it's only after he is relieved of his current commitments can he think of taking up this offer," he said, adding both Balakrishna and Krishna Vamsi are ready to wait.
"Balakrishna Sir has decided to postpone the film's shoot and commence the project from second half of next year. The project will roll with Balakrishna from July 2017, and if Amitji comes on board, he will join the team a month later," the source said.
In 2014, Amitabh Bachchan made his Telugu debut with "Manam", in a special appearance.
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List of the Post-Offices in the United States (Washington, 1803)
Jefferson's Second Library
Jefferson's inscribed flyleaves from Cicero's De Re Publica (Boston, 1823)
The Life and Morals of Jesus of Nazareth (Washington, 1904)
VOLUME 1 - The Household Account Books of Anne Cary Randolph and Martha Wayles Skelton Jefferson; Thomas Jefferson's Record of Cases Tried in Virginia Courts, 1768-1769.
Description of Contents
VOLUME 2 - Weather Record, 1776-1818
Thomas Jefferson's meteorological observations in Philadelphia and at Monticello and Poplar Forest; also notes on scientific experiments and on plants grown on his estate, and his description of the September 17, 1811, solar eclipse.
VOLUME 3 - Historical Notes on Virginia
Jefferson made these Historical Notes on Virginia in 1781 while gathering material for his responses to queries about Virginia from François Henri Barbé-Marbois, secretary of the French legation in Philadelphia, which he later (1785) published under the title Notes on the State of Virginia.
VOLUME 4 - A Manual of Parliamentary Practice
As vice president of the United States from 1797 to 1801, Thomas Jefferson had the duty of presiding over the United States Senate. With the assistance of John James Beckley, clerk of the House of Representatives, he compiled a notebook or pocketbook of rules and precedents of parliamentary practice. Jefferson originally planned to leave a manuscript copy with the Senate for the use of his successors and solicited comments on it from knowledgeable friends, such as George Wythe and Edmund Pendleton. However, before leaving office as vice president, Jefferson decided to have the manual printed by his friend Samuel H. Smith. Smith published the first of many editions of A Manual of Parliamentary Practice for the Use of the Senate of the United States in Washington City in 1801. In an 1809 letter to John W. Campbell, Jefferson wrote that he did not include the Manual of Parliamentary Practice in his writings "because it was a mere compilation, into which nothing entered of my own, but the arrangement, and a few observations necessary to explain that and some of the cases." William S. Howell has edited a scholarly edition of Jefferson's parliamentary writings, which was published in 1988 by Princeton University Press as part of the second series of The Papers of Thomas Jefferson. A revised edition of the Manual is still in use today, though in the House of Representatives rather than in the Senate.
VOLUME 5 - Notes on Salkeld's Reports and handwritten drafts of two bills
William Salkeld (1515-1671) was an English legal writer and serjeant-at-law, known for his diligent work as a reporter of legal cases. His Reports of Cases Adjudged in the Court of King's Bench, 1689-1712 (1717-18) became a standard authority for precedents at the King's Bench. Salkeld was also one of the author-translators of Creswell Levinz's Reports of Cases in the King's Bench, 1660-1697 (1722). Like most law students in eighteenth-century Britain and its colonies, Jefferson took notes from Salkeld's Reports on the King's Bench cases, looking for precedents and practices that he would find useful in his own case work. Also included in this volume are drafts of two bills in an unknown handwriting, "An act further to amend the judicial system of the United States" and "An act to punish certain offences against the United States."
VOLUME 6 - List of the Post-Offices in the United States (Washington, 1803)
A book of the locations of post offices existing in 1803, with distances from Washington and annotations by Jefferson.
VOLUME 7 - Jefferson's Second Library
A catalog of the personal library that Jefferson accumulated after the sale of his first library to Congress. This second library was offered for sale at public auction on February 27, 1829.
VOLUME 8 - Inscribed Cicero
Jefferson's inscribed flyleaves from an edition of Cicero's De Re Publica published in Boston in 1823. The inscriptions are to Thomas Jefferson Smith, son of Samuel Harrison Smith, an old friend and political ally. The inscriptions include a poem and "A Decalogue of Canons for observation in practical life."
VOLUME 9 - The Life and Morals of Jesus of Nazareth.
This facsimile reproduction of Jefferson's original compilation (now in the National Museum of American History, Smithsonian Institution) was published in Washington in 1904. Jefferson used excerpts from the New Testaments in four languages to create a compilation of what he considered to be Jesus' most authentic actions and teachings. He probably prepared the "Life and Morals of Jesus of Nazareth" in 1820.
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Date of Submission 18-Jun-2020
Date of Acceptance 10-Mar-2021
Keywords: Cytotoxicity, Grewia flavescens Juss, immunomodulation, oxidative burst, T-cell proliferation, triterpenoids
M. ELhassan GO, Yagi S, Mesaik M A, Mohan S, Alhazmi HA, Al-Bratty M, Al-Amri MM, Khalid A. Immunomodulatory and cytotoxic properties of natural triterpenoids isolated from Grewia flavescens Juss. Phcog Mag 2021;17, Suppl S1:9-14
M. ELhassan GO, Yagi S, Mesaik M A, Mohan S, Alhazmi HA, Al-Bratty M, Al-Amri MM, Khalid A. Immunomodulatory and cytotoxic properties of natural triterpenoids isolated from Grewia flavescens Juss. Phcog Mag [serial online] 2021 [cited 2022 Jan 17];17, Suppl S1:9-14. Available from: http://www.phcog.com/text.asp?2021/17/5/9/318020
Grewia flavescens Juss (Malvaceae) is a species that is used in various traditional herbal practices for the treatment of various disease conditions
We have isolated one new triterpenoid in addition to four known triterpenoids from the G. flavescens Juss, which were evaluated for immunomodulatory and cytotoxicity properties
The new compound; (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde significantly interfere with the adaptive immune response (T cell proliferation). It inhibited the phytohemagglutinin-activated T-cell.
Abbreviation used: AIDS: Acquired immune deficiency syndrome; ATCC: American type culture collection; CHCl3: Chloroform; COSY: Correlation spectroscopy; FT IR: Fourier-transform infrared spectroscopy; HMBC: Heteronuclear multiple bond coherence; HMQC: Heteronuclear multiple quantum coherence; MeOH: Methanol; P. E: Petroleum ether; PBMC: Peripheral blood mononuclear cells; PHA: Phytohemagglutinin; PMS: Polymorph nuclear cells; ROS: Reactive oxygen species; SOZ: Serum-opsonized zymosan; TLC: Thin-layer chromatography
The immune system plays a vital role in monitor tissue homeostasis by the maintenance of the host defense system against pathogens and in cancer prevention. Immunomodulating drugs are needed for treating many diseases/conditions such as infections, organ transplantation, cancer, rheumatoid arthritis, systemic lupus erythematosus, down syndrome, Crohn's autoimmune diseases, and the acquired immune deficiency syndrome.[1] The interest in medicinal plants in immunomodulation has been increasing due to its contents of structurally diverse phytochemicals, which were found to have been involved in the modulation of phagocytes such as neutrophils, monocytes, macrophages, and phagocytes.[2] Large volume of reactive oxygen species (ROS) is released by these phagocytes by pathogens stimulation through a process called a respiratory oxidative burst.[3] This mechanism positively impacts the immune response.[4] The release of excessive volumes of ROS has severe implications in the pathogenesis of several inflammatory disorders and related diseases.[4],[5] Hence, plant-derived compounds with immune-modulatory properties for the use of clinically useful drug development become a major goal of herbal research laboratories.
Grewia flavescens Juss belongs to the family Malvaceae. The species is distributed throughout semi-arid and sub-humid tropical areas of Africa, Saudi Arabia, Yemen, and India.[6] In Sudan, the root bark of this plant is been used in traditional medicine to treat diarrhea. It is also considered as an aphrodisiac.[7] In Indian folk medicine, G. flavescens is used as anthelmintic, CNS depressant,[8] anti-inflammatory, antimalarial, antidiabetic, and analgesic.[9] In South Africa, the plant is used traditionally as an antidiabetic medicine.[10] In some parts of Sudan, the fruit is used as a general tonic especially during the fasting month of Ramadan.[11] The previous phytochemical investigations of G. flavescens have resulted in the isolation of some triterpenoids, i.e., α-amyrin, β-amyrin, betulin, friedelin, triacontanol, and β-sitosterol.[8] Triterpenes are naturally occurring compounds with growing interest as phytosterols due to their wide spectrum of biological activities.[12],[13] Triterpenes, which contain a broad chemical group of active principles, are implicated in the pharmacological mechanism of action of many herbs used in folk medicine. In addition, to be known as immunomodulation agent, it also is known for other significant pharmacological activities such as antimicrobial, antiviral, and anticancer.[14]
The presence of triterpenoids and compounds which were found in G. flavescens has been also found in different plants from Grewia species. For instance, Grewia asiatica which is a traditional medicinal plant, with high presence of triterpenoids, is known to exhibit anticancer and immune-modulatory activities.[15],[16] In efforts to screen anticancer plants from the African region in our laboratory, we have observed significant cytotoxicity exerted by G. flavescens extract. Looking into these facts and the G. flavescens's traditional use we propose that the triterpenoids of G. flavescens could also exhibit similar activity, especially in modulating the immune system. Hence, in the present study, we have isolated triterpenoids from G. flavescens and investigated their immune-modulatory and cytotoxicity activities.
The stem bark of G. flavescens was collected in the month of January from Kordofan region of Western Sudan. The plant was botanically identified and a voucher specimen number (GF/709) was provided, then deposited in the Herbarium of Botany Department, University of Khartoum.
Extraction and isolation
The dried and ground stem bark of G. flavescens (500 g) was extracted by maceration in petroleum ether and ethanol for 5 days with occasional shaking. Both extracts were filtered and concentrated under reduced pressure using a rotary evaporator. Thin-layer chromatography (TLC) was performed on precoated silica gel plates (DC-Alufolien 60 F254 of E. Merck) and spots were located by ceric sulfate spraying reagent.
The ethanol extract (11 g) was subjected to flash column chromatography (CC) on silica gel (silica gel 60, 70–230 mesh; Merck; 600 g) using a stepwise gradient elution of n-hexane to EtOAc and to methanol [MeOH]. A total number of 80 fractions (50 mL each) were collected and finally, 8 fractions were obtained on combining the eluates according to their similarity behavior on TLC. Fractions 2 (113 mg), 3 (120 mg), and 5 (122 mg) were applied repeatedly to silica gel CC and eluted with petroleum ether (P. E): EtOAc gradients to afford pure lupeol (1) (15 mg) and ß-sitosterol (2) (30 mg) in P. E: EtOAc (8:2), Fractions 4 (56 mg) and 5 (175 mg) were subjected to repeated flash chromatography using chloroform (CHCl3): EtOAce mixture of increasing polarity as eluent to obtain Betulin (3) (15 mg) and 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) (20 mg). Fraction 8 (601 mg) was subjected to repeated flash chromatography using CHCl3: MeOH mixture to afford ß-sitosterol glucopyranoside (5) (15 mg). All isolated compounds were over 95% pure as estimated by 1HNMR.
Structure elucidation
The FT-IR spectra were recorded on a vector 22 instrument. ultraviolet was recorded on Unicam Helos BVI 14 model No. 053925. The 1H NMR and 2D NMR spectra (correlation spectroscopy [COSY], heteronuclear multiple quantum coherence [HMQC], and heteronuclear multiple bond coherence [HMBC]) were recorded on a Bruker AMX 500 MHz and 100 MHz NMR (Avance) instruments using the UNIX data solvent. EI-MS spectra were recorded on a Finnigan MAT 312. FAB mass measurements were performed on Jeol JMS HX 110 mass spectrometer using glycerol as the matrix. HREI MS was carried out on Jeol JMS 600 mass spectrometer.
Oxidative burst assay
Luminometer (RS Labsystems Luminoskan, Finland) was used in this assay. Two milliliters of pooled human serum was mixed with 30 mg of zymogens (Sigma Chemical Co, St. Louis, MO) to prepare the serum-opsonized zymosan (SOZ). The volume was then make up to 10 ml with the addition of Tris base NaCl. The obtained mixture was then vortexed and incubated at 37°C in a shaker water bath for 30 min, followed by centrifugation at 2000 g at room temperature for the final wash to obtain the pellet by removing the supernatant. The pellet was re-suspended in 10 ml of Tris base NaCl. 0.037% concentration of SOZ was achieved in each experimental wells.[17]
Luminol (Research Organics Cleveland, OH, USA) was added with borate buffer to prepare the luminol solution as described earlier.[18] To perform the assay, heparinized blood was collected from the healthy volunteers aged 25–45 years. The whole study was conducted as per the guidelines from the International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan (UoK, No: ICCBS/IEC-009-BC-2017/Protocol/1.0.). The volunteers were well informed and explained the purpose of the study, then informed consent was obtained from them before the withdrawal of blood. The collected blood was then diluted with a ratio of 1:50 using Hank's Balanced Salt Solution (Sigma, St. Louis, MO, USA), followed by the addition of SOZ as an activator. The polymorph nuclear cells (PMS) contained buffy coat layer and mononuclear cells were obtained using dextran sedimentation technique and cells were obtained after LSM (MP Biomedicals, Inc., Germany) density gradient centrifugation. The purified PMNS was collected from the tube as described earlier.[19]
Chemiluminescence assay
The luminol-based assay was performed as described by Helfand, Werkmeister.[20] The luminol was used to measure the level of the released reactive oxygen generated from the whole blood or the isolated PMNs after activation with the opsonized zymosan. Ibuprofen compound was used as a standard control drug for comparison. Luminescence was monitored for 50 min.
Phytohemagglutinin stimulated T-cell proliferation assay
Peripheral blood mononuclear cells were isolated from heparinized venous blood of healthy adult volunteers by the standard Ficoll-Hypaque gradient centrifugation.[21] The cells were activated, proliferated following the addition of the 1.5 μg/mL PHA (Sigma Chemical Co., USA) as described by Nielsen, Gerwien.[22] The tested compounds were tested at concentrations ranging from 1 to 50 μg/mL and the reaction was incubated for 3 days at 37°C in a CO2 environment then pulse with tritiated thymidine (0.5 μg/mL) and further incubated overnight to monitor the level of proliferation. Cells were extracted onto a glass fiber filter paper using a cell harvester (SKATRON AS Flow Lab, Norway). The proliferation level indicated by the amount of the incorporated radioactivity was measured using the beta scintillation counter (1211 LKB WALLAC Rack Beta, USA).
Cytotoxicity assay
The MTT assay was performed according to the method of Mosmann[23] and Dimas et al, 1998.[24] The Normal 3T3 NIH mouse fibroblast adherent cells and cervical cancer Hela cells were purchased from ATCC. The cells at a concentration of 2 × 105/mL were used for monitoring the cytotoxic properties of serial concentration (0.1–100 μg/mL) of the tested compounds after a 72 h incubation in a CO2 incubator. The cell suspension was centrifuged for 15 min at 1500 rpm (433 g) at 4°C using AllegraTM X-22R centrifuge (USA). The absorption was measured at 540 nm in a microtiter plate reader (spectrophotometer).
All values are expressed as the mean ± standard deviation. All experiments were performed at least three times, each time with three to five independent observations. Statistical analysis was performed by Student's t-test to compare the significant mean differences between the control and tested compounds. The differences were considered to be significant at levels of P ≤ 0.05.
Isolation and characterization of compounds
Five compounds were isolated and identified from the ethanolic extract of G. flavescens stem bark. The isolation flow chart is given in [Figure 1]. The chemical structures of compounds were determined by NMR and mass fragmentation techniques. Compounds 1–3 and 5 were confirmed by comparison with published literature and authentic specimens and were identified as lupeol (1) (15 mg, 0.14%),[25] ß-sitosterol (2) (30 mg, 0.27%),[26] betulin (3) (15 mg, 0.14%),[27] and ß-sitosterol glucopyranoside (5) (15 mg, 0.14%).[26] [Figure 2].
Figure 1: Extraction, fractionation, and isolation of Grewia flavescence components
Figure 2: Chemical structure of isolated compounds from Grewia flavescens stem bark
Compound 4 was obtained as colorless crystals (20 mg, 0.18%) from the CHCl3-MeOH mixture. Rf value 0.69 in solvent system (CHCl3: MeOH (8:2, v/v)), developed violet color with ceric sulfate. IR spectrum showed absorption at 3334 cm-1 (O-H), 2851.9 cm−1 (C-H),1735 cm−1 (C = O) 1679 cm−1 (C = C). EI-MS gave the molecular ion peak at m/z: 468 (M+). HREI-MS gave molecular formula C31H48O3. 1H-NMR spectrum (500 MHz, in CD3OD) showed signals at δ 0.73, 0.79, 0.8, 0.91, 94, 0.99, 1.01 (7 CH3, each s), 3.17 (1 H, d, 8 Hz), 5.88 (1 H, d, J = 1.4 Hz), 6.26 (1 H, d, J = 3.2 Hz). 2D-NMR: COSY, HMBC, and HMQC spectra are represented in [Table 1] and [Figure 3]. Accordingly, compound 4 was identified as 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde. The spectroscopic data of all isolated compounds have been supplied as Supplementary File 1.
Figure 3: HMBC, COSY 450 & NOESY correlations of compound 4
{Table 1}
Cytotoxic and immune-modulatory effects
All compounds exerted almost no inhibitory effect (>100 μg/mL) on ROS production on whole blood phagocytes and neutrophils by chemiluminescence assay. The suppressive effect of the isolated compounds on PHA-activated T-cell proliferation stimulated by the thymidine incorporation method showed that 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) significantly repressed cell proliferation (IC50 of 8.7 μg/Ml). ß-sitosterol glucopyranoside (5) (IC50 of 16.7 μg/mL) and ß-sitosterol (2) (IC50 of 23.6 μg/mL) showed moderate activity compared to the standard immunosuppressive drug prednisolone (0.2 μg/mL).
It is of interest to note that none of the tested compounds showed any signs of cytotoxicity in normal cells. On the contrary, a selective cytotoxicity against the cancer cells has been observed. Betulin (3) revealed the highest cytotoxicity activity toward Hela cancer cells, followed by 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) and ß-sitosterol (2) with IC50 11.10, 16.5 and 21.51 μg/ml, respectively [Table 2].{Table 2}
Phytochemical study on the ethanolic extract of G. flavescens stem bark resulted in the isolation and identification of one new triterpenoid; 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde together with the four known bioactive compounds; lupeol (1), ß-sitosterol (2), betulin (3) and ß-sitosterol glucopyranoside (4). Lupeol (1) is a dietary pentacyclic triterpene found in many vegetables and fruits. It was not toxic[28] and was reported to have potential therapeutic and chemopreventive applications for cancer and inflammation.[28] It was shown to exhibit higher anti-inflammatory activity than indomethacin, a commonly used non-steroidal anti-inflammatory drug in rat and mouse inflammation models. ß-sitosterol is also a well-known dietary phytosterols and has multiple biological properties such as antioxidant, anticancer, antidiabetic, antimicrobial, and immunomodulatory activities.[29] Betulin (3) is reported to retain an antiviral, analgesic, anti-inflammatory, and antineoplastic properties.[30]
Controlling oxidative metabolism by NADPH-oxidase inhibition and ROS scavenger drugs might be of therapeutic value in the treatment of inflammatory and autoimmune diseases.[31] In this study, the immunomodulatory properties of the isolated compounds from G. flavescens stem bark were evaluated. Poor chemiluminescence performance was observed for all the isolated compounds, and this could be attributed to the poor electron-donating nature of the aromatic ring substituent, which results in a lower yield of the chemiluminescence-triggering oxidation reaction.[32]
There are two types of immune system, innate and adaptive responses. The adaptive immune response is further classified into humoral and cellular immunity. They are mainly mediated by the T-Lymphocytes, which play a major role in many immune and autoimmune diseases.[32] During chronic inflammation, activated T-cells secrete cytokines, which negatively affect the situation by the activation and proliferation of various other immune cells. Graft rejection of transplanted organs and tissues is also mediated by the activated T cell through cell-mediated lysis or indirectly by antibody production enhancement or complement activation. Therefore, natural compounds that suppress the activated T cell could be considered as lead immunosuppressive drug.[33] In the present study, the new compound; 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) significantly repressed cell proliferation (IC50 of 8.7 μg/Ml). Although both ß-sitosterol glucopyranoside (5) (IC50 of 16.7 μg/mL) and ß-sitosterol (2) (IC50 of 23.6 μg/mL) exerted moderate effect, it was observed that the glycosylated ß-sitosterol exhibited significantly higher activity that the aglycone form. This observation may be explained, in part, by their physicochemical properties including appropriate lipophilicity.[32] ß-sitosterol has been found to be effective in modulating the secretion of pro/anti-inflammatory cytokines.[34] The immunomodulatory effects of glycoside ß-sitosterol have also been reported earlier.[35] Additionally, clinical trials have been conducted which established the immune-modulatory effects of ß-sitosterol with limited toxic profiles in low doses.[36] However, it has been linked with several toxicity symptoms at high concentrations.[37],[38] Together with this finding, our results are in well correlation with the literature showed that both beta-sitosterol and ß-sitosterol glucopyranoside exhibited immune modulation effect.
Many anticancer natural lead compounds fail to participate in the drug development process due to their side effects, which is more than their beneficial effect.[39] As such, any compound which has selective behavior in cancer cells, without harming normal cells will be of high significance. Triterpenoids exhibit remarkable and diverse physiological and therapeutic actions such as antiangiogenic and dedifferentiation effects that are related with anticancer actions.[40] They are even found to be a cancer reversal drug from multidrug resistant cancers.[41],[42],[43] It is interesting to note that the anticancer effects of triterpenoids have emerged as a selective apoptosis inducer in breast cancer cells while sparing normal cells.[40] In the present study, betulin followed by the new compound (29 [30]-lupene-3, 20-diol; 3 β-form, 29-Aldehyde) exhibited a significant anticancer effect against the Hela cell line and were proven to be not toxic to normal cell. A previous study had shown that betulin was capable of selective apoptosis induction on invasive breast cancer.[44] In addition, it was found to exhibit potent antitumor potential[45] and apoptosis induction in several other cancer cells, including glioblastoma, leukemia, and lung carcinoma.[46],[47] Our results in the current research are in well agreement with the literature indicating that the terpenoids as a phytochemical class with individual phytochemicals having significant anticancer potential.
We have isolated a new and four known triterpenoids from the stem bark of G. flavescens, which were evaluated for immunomodulatory and cytotoxicity properties. Among all isolated and tested compounds, the new compound; 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) significantly interferes with the adaptive immune response (T-cell proliferation). It inhibited the PHA-activated T-cell with an IC50 of 8.7 μg/mL. ß-sitosterol and its glycoside form exerted moderate activity. Moreover, betulin and the new compound, respectively, exerted significant anticancer activity against the Hela cell line while ß-sitosterol and lupeol also exhibited considerable anticancer property but with lower effect than the former two compounds.
Taking together all these results, we would like to conclude that G. flavescens has a good potential for future studies which might focus in other phytochemicals from the plant and animal model-based studies, which could bring more mechanistic facts about this plant activity.
The authors would like to acknowledge the assistance of Dr. Achyut Adhikari of Central Department of Chemistry, Tribhuvan, University, Kirtipur, Kathmandu, Nepal, in the elucidation of compound structures.
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Assmann G, Cullen P, Erbey J, Ramey DR, Kannenberg F, Schulte H. Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case-control analysis of the Prospective Cardiovascular ünster (PROCAM) study. Nutr Metab Cardiovasc Dis 2006;16:13-21.
Bin Sayeed MS, Karim SMR, Sharmin T, Morshed MM. Critical analysis on characterization, systemic effect, and therapeutic potential of beta-sitosterol: A plant-derived orphan phytosterol. Medicines (Basel) 2016;3:29.
Wang J, Jiang YF. Natural compounds as anticancer agents: Experimental evidence. World J Exp Med 2012;2:45.
Ghante MH, Jamkhande PG. Role of pentacyclic triterpenoids in chemoprevention and anticancer treatment: An overview on targets and underling mechanisms. J Pharmacopuncture 2019;22:55-67.
Yan XJ, Gong LH, Zheng FY, Cheng KJ, Chen ZH, Shi Z. Triterpenoids as reversal agents for anticancer drug resistance treatment. Drug Discov Today 2014;19:482-8. Available from: https://pubmed.ncbi.nlm.nih.gov/23954181/. [Last accessed on 2021 May 08].
Bishayee A, Ahmed S, Brankov N, Perloff M. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci (Landmark Ed) 2011;16:980-96.
Lima LM, Perazzo FF, Carvalho JCT, Bastos JK. Anti-inflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark. J Pharm Pharmacol 2007;59:1151-8. Available from: https://pubmed.ncbi.nlm.nih.gov/17725859/. [Last accessed on 2021 May 08].
Sudhahar V, Ashok Kumar S, Varalakshmi P, Sujatha V. Protective effect of lupeol and lupeol linoleate in hypercholesterolemia associated renal damage. Mol Cell Biochem 2008;317:11-20.
Apan AAMTR, Castorena ALP, Romo de Vivar A. Anti-inflammatory constituents of Mortonia greggii Gray. Z für Naturforsch C 2004;59:237-43. Available from: https://pubmed.ncbi.nlm.nih.gov/15241934/
Cháirez-Ramírez MH, Moreno-Jiménez MR, González-Laredo RF, Gallegos-Infante JA, Rocha-Guzmán NE. Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review. EXCLI J 2016;15:758-71.
Mullauer FB, Kessler JH, Medema JP. Betulin is a potent anti-tumor agent that is enhanced by cholesterol. PLoS One 2009;28;4:e1.
[Table 1]PhcogMag_2021_17_5_9_318020_t1.jpg, [Table 2]PhcogMag_2021_17_5_9_318020_t2.jpg


Enlarged isometric diagram of Lorica Segmentata "Corbridge" Armor Type-B. Note that the shoulder guard components are connected to the torso girdle section by bronze hooks and eyes, instead of by straps and buckles, as used on the Corbridge Type-A lorica armor. This was a later style of the Corbridge type lorica segmentata armor and retained most of the wearing comfort of the Corbridge Type-A. The "hook and eye" connections, along with one less girdle plate (7 versus 8 for the Corbridge-A) simplified its construction and assembly. Also, the shape of the main shoulder guard plates varied from those of the Corbridge-A. The "B" style had wider collar plates providing somewhat more coverage and protection for the chest and upper back. The shoulder hinges were of a slightly simpler and less decorative design.
The Corbridge-B is an example of the steps taken to simplify the manufacture and lower the costs of equipment when many thousands of the same item are required to be made and supplied. The even later "Newstead" type lorica segmentata, adopted toward the end of the First Century AD, carried this principle even further with a more durable, stronger and simpler design, but with a loss of some comfort for the wearer.


Need I remind you, that this is very good indeed?
You want your strategy to become to streamlined, that it's outright sheer damn boring.
That's exactly when the strategy will perform.
Thrill-seekers have a video-game experience of the markets and then burn out.
You will go on and on with your boring strategy.
What does this mean for your time?
You've got something streamlined, so you've got time on your hands.
Twiddle your thumbs, or do something new.
I'd go for another strategy.
Develop something in that market.
Make sure there's no overlap between your markets.
When you wind up the day's input for a market, you want to be exactly there, i.e. wound up with that market.
Entering the other market is something fresh for you.
You look forward to it.
Because of no overlap with something you're done with for the day.
Slowly, get a few strategies going, such that your working day is taken care of.
This is how you proceed with a market.
Once you're done with a market for the day, only look at it the next day.
This way you'll stay fresh, and your time and energy won't be exhausted by hourly nitty-gritties.
Once done with all your markets for the day, do other stuff in life.
Like cultivation of hobbies, spending family-time, sport, meditation, chanting, reading, what have you.
Do full justice to life.


text:
Q: Ball Trajectory end position calculation From the image, from bounce position, i want to predict position p1, p2 or p3 using some angle theta 1, 2 or 3.
How can i achieve this.
Any help please.

thanks
Edit:
I am trying to implement bowling control of Cricket.
To show the bowling trajectory, i need three points
start position, bounce position and end position
Start Position = the ball position where bowler releases ball from his hand.
Bounce Position = the pitching position of ball in front of batsman
End position = behind the stump (this will be calculated on the basis of swing i.e in swing or out swing or spin)
So my question is, i know the start position of ball, bounce position of the ball and i know the swing angle by which my ball is supposed to swing.
i need to calculated the end position of the ball by this.
i hope i make it clear now.

A: This is really just basic trig.  Using p1 for example, you know c_x, c_y, b_x, b_y. b_x and c_y make d.  subtraction gets you hard numbers.
So theta_1 is the inverse tangent of b -> d divided by d -> c (sohcahTOA!).  In a unit circle the tangent theta_1 becomes Y/X.
see diagram
I have no idea how to play cricket though.  I know it uses a flat(ish?) bat.  If you want to analyse the effect of a batters swing, that gets more complicated.

redpajama_set_name: RedPajamaStackExchange


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text:
NewsBLOGSIndiaBhopal's nightmare a warning sign for Gujarat
Bhopal's nightmare a warning sign for Gujarat
June 7, 2010, 8:23 PM IST Bharat Desai in ROVING i, India, TOI
Bharat Desai
Bharat Desai is resident editor of The Times Of India, Ahmedabad. A journalist with 27 years of experience, he has covered developments in Gujarat, Madhya Pradesh, Chhattisgarh, Bihar and Jharkhand. Hooked to journalism since he was 18, he is a postgraduate in English literature, has worked for India Today, Indian Express, Telegraph, Dainik Bhaskar, Free Press Journal and Associated Press, covering varied subjects like the Bhopal gas tragedy, Naxalite problem, dacoits of Chambal, caste killings in Bihar and the post-Babri riots in Surat. He lived through the Kutch earthquake of 2001 and the Gujarat riots of 2002 - the coverage of the latter in TOI-Ahmedabad going on to win the prestigious Prem Bhatia Award For Journalism. LESS ... MORE
Today is World Environment day and we are just a couple of days away from hearing a painfully delayed verdict in the world's worst industrial disaster which I survived in Bhopal more than 25 years back. Officially, you can call me a survivor of the Bhopal gas disaster on the night of December 2/3, 1984. I was paid Rs 50,000 as compensation. Wish it had been the same figure in dollars because this was tonnes of methyl iso cyanate (MIC) coming out of a pesticide plant run by the Indian subsidiary of American transnational, Union Carbide Corporation (UCC).
The latest death count is now put at 15,000 by my friend Raajkumar Keswani, a journalist who won the first B D Goenka Award for Journalism. At that time, a quarter of a century back, Rs 1 lakh cash award for a journalist was a huge windfall. While I would have prefered to get compensated as a Bhopal gas victim in dollars, I got the greenbacks instead working as a stringer for another American company, Associated Press, covering the Bhopal gas disaster and its aftermath for the next six years. At that time, you ran the risk in Bhopal of being called an 'American agent' if you were working for any foreign news agency, leave alone American.
The reason why the award was given to Keswani, an inspiration for cub reporters like me, was that he predicted this disaster a few months before it actually happened. I still remember that headline 'Bhopal jwalamukhi ki kagaar par' (Bhopal on the edge of a volcano). In a city where Carbide was the only multinational, one which used to keep officials, politicians and media happy, this was a bold piece of journalism, detailing the exact threat from a rather suspect Union Cabide pesticide plant existing in a thickly populated human habitat. Deservedly, the award went to Keswani first before it was confered to other media luminaries over the years like R.K.Laxman, Prem Bhatia, Prannoy Roy and N.Ram.
During my visit to Bhopal last week, I found the city quite excited about the upcoming verdict in the criminal case. For the victims, it has been a never-ending tragedy which had no hope once the Rajiv Gandhi government buckled under US pressure to sign an out-of-court settlement for a paltry $470 million. My Rs 50,000 compensation came from that amount. The day after the shocking deal, plunging Union Carbide shares soared on the NYSE and lives of lakhs of people, who came that night under that cloud of toxic gas, took a nose-dive as the after-effects of the gas started to deliver one blow after another to their failing health in the coming months and years.
My memory of that cold December night, as I was cuddled up into a quilt with my first dog Chicky, was to suddenly wake up because of his woofs, which soon turned to barks. Chicky was sniffing hard between his barks which were getting louder. I looked at my watch and it was 1.30am. Then I heard something unusual – sounds of traffic, unusual for that hour. I came out and saw the most unusual sight of my life – rows and rows of trucks, tractors, buses, cars, jeeps, scooters, motorcycles, cycles..all going in one direction in a city which had no one-ways then. I was just dazed for a moment — this was a city on the run. What has happened? Then my eyes started burning and I could smell something foul.
The phone rang and it was my bureau chief, Dr Suresh Mehrotra. Doctor saheb told me it was a gas leak from Union Carbide. Soon, reporters started coordinating. My parents woke up because of the commotion. It was around 5.30am, still dark on that cold December morning, that my colleague Sanjeev Majupuria and I rode on his Bajaj Chetak towards the source of the gas wearing our thickest winter jackets. I could see the concern on the faces of my mother and father as we drove away.
We headed into the most dreadful sight of our life. That year, in 1984, we had seen through enough violence during the anti-reservation agitation and anti-Sikh violence after Indira Gandhi's assassination. The campaign for Lok Sabha elections, which later swept Rajiv Gandhi to power, was reaching a peak and we were busy with political reporting. The roads had no vehicles but as we drove, the streetlights shone on people who had collapsed by the wayside on the footpaths, which were wet with morning dew. Some dead, others breathless, coughing vomit and rubbing their eyes in despair. There were shouts for help but our goal as journalists was clear. We reached the Union Carbide plant at 6am, supposedly the first two journalists to enter the plant which had scores of dead bodies of humans, buffaloes, goats strewn all over just outside its front gate. Inside, the plant looked like a ghost. We dared to go inside. There were no securitymen but we could see some activity inside. Met the top two Carbide officials, Mukund and Roychoudhary, who then didn't have a clue how it happened but then later went on to make a case that it was the work of a disgruntled employee.
It is a chief judicial magistrate who will give a verdict on the criminal case against American and Indian officials of UCC. This is the 12th CJM to hear the case in the last 25 years in what became a complete mockery of justice, adding to the sufferings of the survivors.
Mukund and Roychoudhary are among the accused and so is the then UCC chairman Warren Anderson, now 89. A week after the disaster, Anderson was arrested on a visit to Bhopal and then let off immediately, apparently under pressure from the White House by the Congress government, which also ensured his safe flight back to the home country. After 25 years, sitting in his Long Island mansion, don't think he is even remotely bothered about the verdict by a Bhopal court on Monday. Possibly, the case will knock on the doors of the sessions court and then kicked further up to the high court and the Supreme Court.
I moved from Bhopal to Gujarat, another toxic hotspot with its clusters of high-polluting units, especially along its famed Golden Corridor from Ahmedabad to Vapi. Hate to make specific predictions about disasters though, lest it comes true, as in the case of friend Keswani who still rues the fact that it took the most deadly toll of human life for him to be proved right. Not one thing moved when he gave the warning.
Blogs by Bharat Desai
The parivar's 'punishment' Modi baiters are waiting for
Chanakya to Chandragupta: Modi's mask is gone!
Modi rocks, even in the Himalayas!


text:
in: Countries, Locations, Artemis Fowl,
Alice in Wonderland locations
Peter Pan locations
The Great Mouse Detective locations
Phineas and Ferb locations
101 Dalmatians locations
Cars locations
Pocahontas locations
Disney Fairies locations
The Muppets locations
Saving Mr. Banks locations
Mary Poppins locations
Bedknobs and Broomsticks locations
Jake and the Never Land Pirates locations
House of Mouse locations
Mickey Mouse universe locations
Thor locations
Once Upon a Time locations
Schoolhouse Rock! locations
National Treasure locations
The Chronicles of Narnia locations
The Parent Trap locations
Winnie the Pooh locations
DuckTales locations
Chip 'n Dale Rescue Rangers locations
A Christmas Carol locations
Penn Zero: Part-Time Hero locations
Spider-Man locations
Brave locations
Gargoyles locations
The Avengers locations
Around the World in 80 Days locations
Robin Hood locations
Candleshoe
The Sword in the Stone
It's a Small World
The Story of Robin Hood and His Merrie Men
The Island at the Top of the World
Rob Roy, the Highland Rogue
Darby O'Gill and the Little People
X-Men Cinematic Universe
James and the Giant Peach locations
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK), U.K.B. United Kingdom of Britain, Great Britain, The U.K. of G.B. The Kingdom or simply Britain, is a sovereign state located off the northwestern coast of continental Europe. The country includes the island of Great Britain (a term sometimes also loosely applied to the whole state), the northeastern part of the island of Ireland, and many smaller islands.
1 Attractions
3 Territories
United Kingdom Pavilion
Hong Kong (August 29, 1842-July 1, 1997)
India (1612–1947)
Flag of the United Kingdom


text:
The move places state taxpayers, workers and schoolchildren in the middle of a political battle over budget cuts.
Republicans, who hold majorities in both chambers, blocked Gov. Kathleen Sebelius' proposal to borrow $225 million from healthy state funds to cover shortages in accounts used to meet the state's payroll and issue tax refunds.
GOP leaders said they won't approve the IOUs until Sebelius either cuts the current budget herself or signs the bill they passed last week slashing $326 million - including $32 million for education - to balance the budget.
Republican leaders said they had no choice, that by law the state can't borrow any more money from itself. Sebelius and Democrats disagree and accuse the GOP of playing politics with people's paychecks.
"Through their refusal to act today, the Republican legislative leadership is jeopardizing our citizens' pocketbooks for no other reason than to play political games - games in which the only ones set to lose are Kansas families , workers and schools," Sebelius said in a written statement.
Replied House Speaker Mike O'Neal: "While we all can agree that these are trying times for Kansas families, seniors and business owners, the Kansas House of Representatives respectfully disagrees with breaking the law in order to gain political capital."
The Senate approved the budget-cutting bill Thursday, but the governor has yet to receive it. It is being proofread and could reach Sebelius as early as today.
Her spokeswoman has said she will carefully consider it. She could sign it, veto it or veto portions of it.
Lower tax revenues
Kansas' cash-flow problem stems in part from the worsening recession and lower-than-expected tax revenue. As a result, the state had only $10 million in its checking account Monday morning.
Most immediately, that means the state does not have $24 million to cover payroll for the state's 42,000 employees and about $20 million for payments to Medicaid providers such as doctors, hospitals and nursing homes, Goossen said. Usually the state processes the payments on Wednesday and sends the checks out Friday.
"State employees simply have no more to give. Paychecks shouldn't be held hostage for political maneuvering," said Lisa Ochs, president of the Kansas Organization of State Employees.
Kansas taxpayers also are due about $12 million in income tax returns. The state stopped payments on the refunds Friday.
Washburn University political science professor Bob Beatty likened the impasse to the 1995 budget battle between President Clinton and U.S. House Speaker Newt Gingrich. That dispute prompted a shutdown of the federal government. He said Kansas legislative leaders are making a dangerous gamble.
"Gingrich went too far," Beatty said. "If you go too far, you lose."
Options for borrowing
The state will pay its bills -"in a lawful manner," said O'Neal, R-Hutchinson.
At issue is whether the state can borrow now from other state funds. Such loans - called certificates of indebtedness - have routinely been used in the past when the state runs short on cash.
The move is similar to a family shifting unused money from one banking account to another to temporarily cover an expense, then putting the money back into the original account later.
The state would borrow unused money from one state agency's fund to pay immediate expenses for another agency, then replenish the borrowed amount later. The money has to be paid back by June 30, when the budget year ends.
State leaders already have authorized $550 million in certificates this fiscal year - $300 million last summer and $250 million in December.
In December, Republican leaders worried the state wouldn't have the money to pay itself back. That's the concern now, they say.
They say that although the state has borrowed from itself before, it has never borrowed this much in one year.
The Kansas Finance Council - which includes Sebelius and six Republican leaders - must approve any certificates of indebtedness.
"We cannot issue more certificates if the funds will not materialize by the end of the year," O'Neal said in a statement. "Without the revised 2009 budget bill, there is no way that we can legally issue a certificate knowing full well that the money will not be available to retire the debt."
Legislative leaders contend that if Sebelius had made cuts to state programs in late 2008, then the state wouldn't be facing this problem. She could still make cuts to programs, guaranteeing the money would be available at the end of the year, O'Neal said.
Goossen said even if the governor ordered the cuts, called allotments, it wouldn't fix the current predicament.
"The problem today is we don't have cash to pay our bills in a timely fashion," he said. "Allotments only allow the governor to hold spending back."
State Treasurer Dennis McKinney, a Democrat, said the legislative leaders' move put the state's reputation as a reliable bill payer, and its credit rating, at risk.
"This is taking a budget fight one step too far," McKinney said.
Other ripples
In addition to payroll spending, the tax refunds and Medicaid payments, payments to schools and cities could be affected eventually if the impasse continues.
The state is scheduled March 2 to pay $185 million to public schools and $25 million to cities and counties to offset money lost when the state abolished the machinery and equipment tax, Goossen said.
Diane Gjerstad, lobbyist for Wichita schools, said she didn't expect the district to be harmed. She added that the situation pointed to why districts need to have their own contingency fund.
"If the state is short, we want to be able to make our payroll," she said.
Andover schools would be able to pay employees for the near future, said district spokeswoman Keturah Austin.
"If the state didn't make it on time in February, we have enough cash reserves for one month," she said.
"No place like home" for WSU's Garrett Stutz returning to Koch Arena
'Bizarre and illegal sentence': ACLU seeks to end man's court-ordered exile from Kansas
By Amy Renee Leiker
Bo Dana Rupert's plea agreement in the 2017 case orders him to "transfer his corrections to another State and not return to Kansas," or risk additional criminal charges.
Former Kansas Jayhawks forward Perry Ellis to play basketball in Japan this season
Early Marshall-era Shockers like Durley, Stutz excited to 'wear black and gold' again
Wichita council delays airport hotel deal again — this time to give competitor a chance
Here's how many drivers were stopped, arrested at weekend DUI check lane
Robber in duct-tape-covered rubber mask holds up gas station employee


Just one word to conjure up colourful images of festivity & conviviality.
When I was a little boy, my parents used to bring me and my sister to brave the crowds along Orchard Road to catch a glimpse of those magnificent floats and performances. How I vividly remember those times, especially as I remained perched on my dad's shoulders. Until I ballooned in size during my later years that is.
Being Chingay's 40th anniversary this year, Chingay 2012 celebrates love in all its guises, flowing with passion, romance, harmony and community spirit, with the theme of "Love, Care and Kindness Everywhere".
I was kindly invited to its media conference and full dress rehearsal about 2 weeks back, and it was really an eye-opener to see how everything is put together.
Since this year is the Year of the Water Dragon, it is fitting that the whole Chingay parade takes place ON water. Yup, a 360-metres waterway has been specially constructed behind the F1 Pit Building where performers will literally make a splash with their performances.
As everyone waited for nightfall, the whole area was gradually transformed into an illuminating and magical platform right before my eyes.
And that was the perfect cue for the parade to get underway!
The grand opening segment features a whole array of - what else - dragons; from a LED Hip Hop dragon dance, straw dragons, water dragons, a human dragon from Zhangjiang, a dazzling dragon float to two magnificent dragon and phoenix from Xi'an, Shaanxi of China with 36m-long bodies and 16m-wing!
Coupled with the enthusiastic participation of the performers, it was truly a spectacle of colours, lights and sounds.
International cultures were also displayed in their fullest vibrancy, with various performances and floats from China, Japan, Taiwan, Indonesia and even Egypt!
One particular segment was the showcase of Chinese Culture featuring "踏歌" (Ta Ge) - a Chinese Classical Dance of Han Dynasty accompanied by a towering float.
The grandeur of the floats were replicated in the other culture segments too, with each being a performance in its own right.
2 float representatives from the NUS Rag Day (an annual float competition) even took part in the parade, with one coming from the Kent Ridge Hall & Sheares Hall while the other was a joint effort from Eusoff & Temasek Halls.
To me, these floats are the highlights as I used to have a hand in constructing this kind of floats every year during my NUS days. The floats are entirely made up of recycled materials, like newspapers, tetra paks, drink cans, etc, so it is a really Herculean task to construct one of these.
The next half of the show shifts its focus to the Community, featuring a multitude of dance forms from line dancing, folk dancing, Samba dancing to a synchronized symphony of 600 'dikir barat' singers and dancers and a tai chi fan dance, and even spectacular bicycle stunts on water.
Oh, and a point to note - be prepared to get REALLY WET if you are seated among the first few rows. The performers really know how to make full use of the water!
Barring the inevitable hiccups (since it was only a rehearsal), Chingay 2012 looks set to be a truly splashing good time for all! And I think Andy (of sengkangbabies) will attest to that too.
There are 2 parade shows on 3 and 4 Feb, but tickets are already sold out for the 4 Feb show. Limited tickets are still available for the 3 Feb one, so do hurry if you want to catch the the parade! You can purchase the tickets via Sistic HERE.


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Pawlenty, Franken, and 2012
Nick Baumann
On Tuesday, Minnesota governor Tim Pawlenty said he will not run for reelection in 2010, fueling speculation that he is clearing his schedule in order to run for the Republican presidential nomination in 2012. Pawlenty also promised that if the Minnesota Supreme Court orders a certificate of election when it rules on Al Franken and Norm Coleman's battle for a Senate seat, he will "not hold it up" or "delay in any fashion." (Franken is almost certain to win the court fight.) There's still some speculation that Pawlenty might break his promise and delay Franken's certification so as to appeal to the GOP primary electorate, but it's pretty far-fetched—Pawlenty made a clear promise that would be hard to break, and holding up Franken probably wouldn't help him anyway. The Economist's anonymous Democracy in America blog explained last month:
The conservative argument is that Mr Pawlenty, if he wants to run for president in 2012, would boost his chances if he blocks Mr Franken. That's just not true. Becoming identified with a partisan election count is the political equivilent of biting down on a cyanide capsule. What was Katherine Harris's reward for verifying the Florida election count in 2000? Two terms in Congress, sure, but a total party abandonment in 2006 when she ran for Senate. What was Ken Blackwell's reward for protecting George Bush's Ohio campaign in 2004? More disrespect from his own party, which tried to deny him the 2006 nomination for governor and then abandoned him. If Mr Pawlenty wants a political second wind, it's good news for Mr Franken.
If The Economist is right, you can expect to see Senator Franken strolling around Capitol Hill by early July.
Photo courtesy of flickr user ohad*.
Senator Franken, Almost
Franken-Coleman
Doggone It, People Like Him: Al Franken Gets Serious About the Senate in Minnesota


22 year old rapper SlickMick was traveling threw Asia when he had hoped off a bus in Pattaya, Thailand coming from Siem Reap in Cambodia, as soon as he hoped off he told his mate to hold his bag he and tried crossing the road instantly getting hit by a car braking multiple bones and having hid head smash threw the windscreen causing him to have a bleed on his brain putting him in post traumatic amnesia for several months, so he lost the ability to make new MEMORIES!!! CHECK HIM OUT!!!


Geodesic pixel neighborhoods for 2D and 3D scene understanding.
International Journal of Computer Vision (IJCV), Springer Verlag. The final publication is available at www.springerlink.com.
OCT-measured plaque free wall angle is indicative for plaque burden: overcoming the main limitation of OCT?