In a speech at the National Press Club today, U.S. Energy Secretary Spencer Abraham outlined the Department of Energy's Office of Science 20-year science facility plan, a roadmap for future scientific facilities to support the department's basic science and research missions. The plan prioritizes new, major scientific facilities and upgrades to current facilities.
The 28 facilities cover the range of science supported by the DOE's Office of Science, including fusion energy, materials science, biological and environmental science, high energy physics, nuclear physics and advanced scientific computation.
"This plan will be the cornerstone for the future of critical fields of science in America. These facilities will revolutionize science and society," said Abraham. "With this plan our goal is to keep the United States at the scientific forefront.
"These facilities are needed to extend the frontiers of science, to pursue opportunities of enormous importance, and to maintain U.S. science primacy in the world. Investment in these facilities will yield extraordinary scientific breakthroughs and vital societal and economic benefits."
The Office of Science priority list for new facilities will help the department plan its potential future scientific investments. The list identifies 12 facilities as near-term priorities. Priority one is ITER, an international collaboration to build the first fusion science experiment capable of producing a self-sustaining fusion reaction, called a "burning plasma." Priority two is an UltraScale Scientific Computing Capability, to be located at multiple sites, that would increase by a factor of 100 the computing capability available to support open scientific research.


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Layout ist ein US-amerikanischer Pornofilm des Regisseurs Paul Thomas aus dem Jahr 2007. Der Film wurde bei den AVN Awards 2008 in acht Kategorien ausgezeichnet, unter anderem als "Best Film" und zählt damit zu den erfolgreichsten Filmen der Branche.

Handlung
Der Film spielt in Hollywood. Ein junger Journalist nimmt eine Position bei dem Adult Trade Magazine "AVG" und taucht in eine Welt ein, in der sich Pornografie und Journalismus treffen. Er entwickelt sich schrittweisen von einem Volontär zu einem erfahrenen Schreiber und es gelingt ihm, die Ablenkungen und Fallen dieser Welt zu meistern.

Kritiken
Mark Kernes vom AVN Magazin schreibt: "Truly a great movie..shows the dark side of adult in bondage and headlines.."

Auszeichnungen
 2008 – AVN Award – Best Actor – Film (Tom Byron)
 2008 – AVN Award – Best Actress – Film (Penny Flame)
 2008 – AVN Award – Best Couples Sex Scene – Film (Penny Flame und Tom Byron)
 2008 – AVN Award – Best Director – Film (Paul Thomas)
 2008 – AVN Award – Best Film
 2008 – AVN Award – Best Oral Sex Scene – Film (Kylie Ireland)
 2008 – AVN Award – Best Screenplay – Film
 2008 – AVN Award – Best Supporting Actress – Film (Kylie Ireland)
 Der Film war in 11 weiteren Kategorien nominiert, konnte diese aber nicht gewinnen.

Weblinks

 Layout Parodies AVN, April 19, 2007, auf ainews.com

Filmtitel 2006
Pornofilm
US-amerikanischer Film

redpajama_set_name: RedPajamaWikipedia


International Shipping is now an option though our web store.
As previously mentioned, international shipping is in many cases prohibitively expensive (see here). We understand that, and wish there were better solutions available. We do not have an international distributer at this time, meaning that all orders must ship from the United States.
In truth, we are only offering international shipping as an option to those willing to pay the premium.
So why not team with an international distributer? It boils down to simple economics. We have a very slim profit margin on our products (especially Tact-Tiles). So once you factor in the cost of overseas freight, and the distributer's cut, we'd be lucky to make any money at all. And it's very difficult to justify the effort required to set all that up, and maintain it, virtually for free.
This would be a far more viable option if we manufactured our products in China, but we simply aren't willing to do that. In addition to a general dislike of outsourcing labor, previous experience with Chinese (and other foreign) manufacturers has taught me that you get what you pay for.
You can't expect a quality product for cheap.


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Justia › US Law › Case Law › Federal Courts › District Courts › Missouri › Eastern District of Missouri › 2020 › Robison v. Sanderson et al › Filing 10
Robison v. Sanderson et al, No. 4:2019cv01871 - Document 10 (E.D. Mo. 2020)
Court Description: OPINION, MEMORANDUM AND ORDER (See Full Order) IT IS HEREBY ORDERED that this action is DISMISSED without prejudice for failure to comply with the Court's order of November 12, 2019. See Fed. R. Civ. P. 41(b). A separate order of dismissal wil l be entered herewith. IT IS FURTHER ORDERED that this dismissal will not constitute a "strike" under 28 U.S.C. § 1915(g). IT IS FURTHER ORDERED that an appeal from this dismissal would not be taken in good faith. Signed by District Judge Henry Edward Autrey on 1/22/20. (EAB)
UNITED STATES DISTRICT COURT EASTERN DISTRICT OF MISSOURI EASTERN DIVISION DWAYNE ROBISON, Plaintiff, v. LISA SANDERSON, et al. Defendants. ) ) ) ) ) ) ) ) ) No. 4:19-cv-01871-JMB OPINION, MEMORANDUM AND ORDER This matter comes before the Court on its own motion. On November 12, 2019, the Court ordered plaintiff to file an amended complaint within thirty days. (Docket No. 9). Plaintiff has failed to respond. Therefore, for the reasons discussed below, plaintiff's complaint will be dismissed without prejudice for failure to comply with the Court's order. See Fed. R. Civ. P. 41(b). Discussion Plaintiff is an inmate at the Eastern Reception, Diagnostic and Correctional Center in Bonne Terre, Missouri. On July 1, 2019, he filed a pro se civil action pursuant to 42 U.S.C. § 1983. (Docket No. 1). He also filed a motion for leave to proceed in forma pauperis. (Docket No. 3). The case caption of the complaint named Lisa Sanderson, Teri Lawson, and Elizabeth Atterberry as defendants. The Statement of Claim contained further allegations against defendants Kay McIntyre and Karen Salesmen. Plaintiff's complaint contained various claims, but his chief contention appeared to be defendants' allegedly wrongful decision to place him in a single-man cell, and to deny him transfer to a two-man cell. The Court reviewed plaintiff's complaint pursuant to 28 U.S.C. § 1915 and determined that it was subject to dismissal. With regard to defendants Lawson and Sanderson, the Court noted that plaintiff's allegations contained only conclusory statements, with no factual support. The Court explained that it was not required to accept such conclusions as true. See Torti v. Hoag, 868 F.3d 666, 671 (8th Cir. 2017) ("Courts are not bound to accept as true a legal conclusion couched as a factual allegation, and factual allegations must be enough to raise a right to relief above the speculative level"). As to defendant Atterberry, the Court stated that Atterberry was only mentioned once, and that plaintiff did not accuse her of a constitutional violation. See Wong v. Minnesota Dep't of Human Servs., 820 F.3d 922, 934 (8th Cir. 2016) ("To state a claim under section 1983, a plaintiff must allege the violation of a right secured by the Constitution and the laws of the United States"). The Court further explained that for all three defendants, plaintiff had failed to state an official capacity claim because he neglected to allege facts showing the liability of defendants' respective employers. See Johnson v. Outboard Marine Corp., 172 F.3d 531, 535 (8th Cir. 1999) (stating that a "suit against a public employee in his or her official capacity is merely a suit against the public employer"). As to defendants McIntyre and Salesmen, the Court noted that plaintiff had failed to indicate the capacity in which they were sued. If a plaintiff's complaint is silent as to capacity, the complaint is interpreted as including only official capacity claims. Baker v. Chisom, 501 F.3d 920, 923 (8th Cir. 2007) (stating that a "suit against a public employee in his or her official capacity is merely a suit against the public employer"). However, as with the official capacity claims against defendants Lawson, Sanderson, and Atterberry, plaintiff had not presented facts alleging the liability of these defendants' respective employers. On November 12, 2019, the Court granted plaintiff's motion for leave to proceed in forma pauperis and assessed an initial partial filing fee of $3.33. Plaintiff was ordered to pay the initial partial filing fee within thirty days. The Court also directed plaintiff to file an amended complaint, 2 according to the instructions set forth in the order. To aid plaintiff in filing an amended complaint, the Court directed the Clerk of Court to send him a copy of the Court's prisoner civil rights form. Plaintiff was given thirty days in which to file an amended complaint. He was advised that failure to submit an amended complaint would result in the dismissal of his case without prejudice and without further notice. The amended complaint was due by December 12, 2019. Plaintiff's thirty-day period in which to file an amended complaint and pay the initial partial filing fee has expired. Indeed, the Court has given plaintiff significantly more than thirty days in which to respond. However, plaintiff has not submitted an amended complaint or filed a motion with the Court seeking an extension of time. Under Rule 41(b), an action may be dismissed for failure to comply with a court order. See Fed. R. Civ. P. 41(b). See also Brown v. Frey, 806 F.2d 801, 803 (8th Cir. 1986) (stating that district court may dismiss a pro se litigant's action for failure to comply with a court order on its own initiative). Because plaintiff has not complied with the Court's November 12, 2019 order, his action will be dismissed without prejudice. Accordingly, IT IS HEREBY ORDERED that this action is DISMISSED without prejudice for failure to comply with the Court's order of November 12, 2019. See Fed. R. Civ. P. 41(b). A separate order of dismissal will be entered herewith. IT IS FURTHER ORDERED that this dismissal will not constitute a "strike" under 28 U.S.C. § 1915(g). 3 IT IS FURTHER ORDERED that an appeal from this dismissal would not be taken in good faith. Dated this 22nd day of January, 2020. HENRY EDWARD AUTREY UNITED STATES DISTRICT JUDGE 4

redpajama_set_name: RedPajamaCommonCrawl


St. Michael's Hospital infection preventionist Shara Junaid is at her desk when the phone rings. It's the hospital lab; a patient in the Emergency Department has tested positive for Influenza A.
In the past, Junaid's next step would have been to create a case profile by opening the patient's electronic medical record and cutting and pasting details into a new Excel spreadsheet.
Today, thanks to RL6:Infection software, provided by the Canadian company RL Solutions, the lab results have already popped up on her computer in an alert, and the patient's details are already on her desktop when the lab calls.
Junaid is part of a dedicated group of infection control professionals who provide 24/7 coverage for infection prevention emergencies at St. Michael's, as well as education, surveillance and policy development. While the patient's care team is responsible for isolating and treating the patient, the Infection Prevention and Control Team helps track and prevent an infection's spread.
Everyone involved must move quickly. First, Junaid needs to know the patient's basic clinical details.
The patient's history shows that he was discharged from St. Michael's Orthopedics Ward the previous day. This means that Junaid must quickly trace the patient's contact history, to identify other patients in the ward who may have been exposed to the virus.
About 15 minutes later, Junaid is ready to notify units about the patients who may have been exposed to the influenza virus. At minimum, they'll be isolated and closely observed for the next few days.
Each potentially exposed patient now has his or her own profile in RL6:Infection.This means that if a patient is discharged and then readmitted a few days later, the software will notify the Infection Prevention and Control Team with an alert. They can then follow up to find out if the new admission is related to the in-hospital influenza exposure – an early warning sign of a hospital outbreak.
These profiles not only help the team keep track of current cases and potential exposures, but also draw attention to patients who may need special precautions due to a positive test at another facility, or a recent stay in a facility that's experiencing an outbreak.


STOP PRESS: 14 NUT Executive members have requisitioned an emergency meeting of the National Executive in late April to discuss the strategy and action calendar for the pensions campaign.
The final session of NUT Conference completed a number of important debates including those on workload, sixth form colleges, "a woman's place is in the union" and against the forced academisation of primary schools (excellently seconded by Karen Parkinson from Lewisham NUT).
However, it was the debate on the motion on the 'economy' that most clearly revealed the overwhelming opposition of delegates from across the Union to cuts to pay, jobs, pensions and services – whether being carried out by Tory, Liberal Democrat or Labour politicians.
Jane Nellist from Coventry (who also topped the poll in the delegates' ballot for the Conference Business Committee) seconded an amendment that "condemns the statements by Ed Milliband and Ed Balls that in office they would maintain the bulk of the Coalition Government's spending cuts and austerity measures". It also affirmed its solidarity with workers elsewhere, particularly in Greece, and instructed the executive to press the TUC to call another national demonstration against cuts and austerity as well.
Jane described the queues for food hand-outs in the centre of Coventry and contrasted that with the £730 billion in cash hoarded by big business, instead of being invested to meet the needs of society. She pointed out how cuts in her city had been started by a Tory Council under a Labour Government – and were now being made by a Labour Council under a Tory Government – a seamless transition. That's why, Jane explained, she would be supporting anti-cuts candidates from the Trade Unionist and Socialist Coalition in the local elections on May 3.
But perhaps the most telling illustration of teachers' opposition to cuts – from whatever party - was that not a single delegate chose to speak against the amendment - which was then overwhelmingly carried. The final amended motion, also reaffirming the Union's policy of "no cuts", was then agreed – unanimously!


A: We cannot hold a property without an approved application and paid security deposit.
A: The security deposit is paid separately from the rent. First month's rent (or prorated first month's rent) is required to be paid prior to occupancy.
A: All occupants 18 years and older must submit a separate application.
A: As stated in our Rental Qualifying Criteria the Application Fee is non-refundable.
A: A co-signer may be required in cases where our minimum qualifying criteria is not met. Please see our Rental Qualifying Criteria for further information.
A: Go to our Available Properties tab at www.DeGuireProperties.com. Scroll to the property you are interested in and click Apply Now.
A: Tenants conveniently pay rent electronically through their tenant portal.
Q: I have a pet. What do I do?
A: Most of our properties allow up to 2 small pets (less than 20 lbs). DPM utilizes a 3rd party pet screening service called Petscreening.com. Please see our Pet Policy by clicking on the Pets link in the Tenant drop down menu.
A: The lease agreement is a legally binding contract between the landlord and each tenant 18 years and older.
A: The lease agreement automatically renews on a month to month basis unless the tenant provides 60 days notice prior to the expiration date.
Q: What do I do if I have a maintenance request?
A: Tenants are able to submit maintenance requests, communicate with management and maintenance, choose repair times, provide feedback, and more through our maintenance system called PropertyMeld. PropertyMeld can be accessed from your phone (no app required), computer, or any internet-connected device.


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Theatrhythm Final Bar Line New Songs Revealed
Posted By: Rafael Hernandezon: November 29, 2022 In: Gaming, News, PS4, SwitchNo Comments
Theatrhythm Final Bar Line has revealed new songs that will be in the game, focusing on music from Final Fantasy XV. This reveal comes just in time, as today is also the 6th anniversary of FFXV. The list shows 18 songs that will be included and even includes some music from the DLC Episodes.
Six years since we first adventured with Noctis in Final Fantasy XV, and the beautiful melodies still live strong in our hearts.
To celebrate this anniversary, we'd like to show you the FFXV songs you'll be able to enjoy when Theatrhythm Final Bar line launches on February 16th! pic.twitter.com/hGatbh5VSr
— FINAL FANTASY (@FinalFantasy) November 29, 2022
Theatrhythm Final Bar Line New Songs
To help celebrate the 6th anniversary of Final Fantasy XV's release, Theatrhythm Final Bar Line revealed which songs it would be pulling from that game. There will be 18 songs from FFXV, including music from the various DLCs, such as Episode Gladiolus and Episode Prompto.
Veiled in Black
Valse di Fantastica
The Fight Is On!
Apocalypsis Noctis (Uncovered Trailer)
Flying R
Omnis Lacrima
Up for the Challenge
Magna Insomnia
Main Theme from Final Fantasy
Shield of the King – Theme of Episode Gladiolus
Home Sweet Home – Theme of Episode Prompto
Episode Ignis – The Main Theme
The Dance of Silver and Crimson
Along with the music from Final Fantasy XV, the confirmed characters from this game so far include Noctis, Gladiolus, Ignis, Prompto, and Aranea. So that will basically give players the entire party at their disposal, plus the mercenary Dragoon who helped them on their journey.
Final Fantasy 14 Will Release a New Deep Dungeon
Theatrhythm Final Bar Line is a rhythm game that features characters and music from all across the Final Fantasy series. It is also a sequel to Theatrhythm Final Fantasy for the 3DS. The gameplay involves pressing buttons to the rhythm of songs from the series to take out enemies. It will have a total of 385 songs and 104 characters and can be played in solo or co-op.
The game is set to release on February 16 for both the Playstation 4 and Nintendo Switch. As we get closer to the release day, we will hopefully get more reveals on what songs we can look forward to.
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YOSEMITE – With the enactment of the continuing resolution by lawmakers in Washington, D.C., Yosemite is in the process of returning to normal operations.
The Yosemite Valley Visitor Center, Yosemite Museum, and Hetch Hetchy area will all reopen with normal hours today.
Hodgdon Meadow and Wawona Campgrounds and the Mist Trail/John Muir Trail winter route also reopened today.
The Mariposa Grove and Crane Flat Snow Play Area will reopen later in the week after restroom maintenance can be completed.
Ranger-guided hikes and programs will resume today, and rangers will be staffing entrance stations to provide information and collect fees as usual.
"Throughout Yosemite's history, the stewardship of those who love it has carried it forward to the next chapter," said park officials in a statement released this morning. "Thanks to all our visitors and staff for their commitment to the park over the past month.


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Esta entrada foi postada em 2012/02/09 por poolfeden. Foi arquivada sob Uncategorized .


Turns out, the small screen adaptation of 'Lord of the Rings' is all set to be the most expensive TV series ever, according to The Hollywood Reporter.
The battle for rights of the popular series was going on for quite some time betweenNetflix and Amazon. The negotiations have resulted in Amazon acquiring the rights of the series, adapted from J.R.R. Tolkien's books for USD 250 million, according to The Hollywood Reporter.
The five-season series deal ensures that the show must be in production within two years. The series is expected to cost upward of USD 1 million, with all castings, producers, and visual effects factored in.


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Home » antibacterial » MEROPENEM
MEROPENEM
CAS number96036-03-2
IUPAC Name(4R,5S,6S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
WeightAverage: 383.463
Monoisotopic: 383.151491615
Chemical FormulaC17H25N3O5S
Antibiotic SM 7338
ICI 194660
CAS Name: (4R,5S,6S)-3-[[(3S,5S)-5-[(Dimethylamino)carbonyl]-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Additional Names: (1R,5S,6S)-2-[(3S,5S)-5-(dimethylaminocarbonyl)pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid
Percent Composition: C 53.25%, H 6.57%, N 10.96%, O 20.86%, S 8.36%
Literature References: Carbapenem antibiotic. Prepn: M. Sunagawa et al.,EP126587; M. Sunagawa, US4943569 (1984, 1990 both to Sumitomo).
Structure-activity study: M. Sunagawa et al.,J. Antibiot.43, 519 (1990).Crystal structure: K. Yanagi et al.,Acta Crystallogr.C48, 1737 (1992).HPLC determn in serum and bronchial secretions: M. Ehrlich et al., J. Chromatogr. B751, 357 (2001). Pharmacokinetics: R. Wise et al.,Antimicrob. Agents Chemother.34, 1515 (1990).Series of articles on antimicrobial activity, metabolism: J. Antimicrob. Chemother.24, Suppl. A, 1-320 (1989); and clinical performance: ibid.36, Suppl. A, 1-223 (1995).Review of clinical experience in intensive care: M. Hurst, H. M. Lamb, Drugs59, 653-680 (2000).
Derivative Type: Trihydrate
CAS Registry Number: 119478-56-7
Manufacturers' Codes: ICI-194660; SM-7338
Trademarks: Meronem (AstraZeneca); Meropen (Sumitomo); Merrem (AstraZeneca)
Properties: White to pale yellow crystalline powder. Sparingly sol in water; very slightly sol in hydrated ethanol. Practically insol in acetone, ether.
Therap-Cat: Antibacterial.
Keywords: Antibacterial (Antibiotics); ?Lactams; Carbapenems.
Meropenem sodium Not Available 211238-34-5 UBQRNADYCUXRBD-NACOAMSHSA-N
Meropenem trihydrate FV9J3JU8B1 119478-56-7 CTUAQTBUVLKNDJ-OBZXMJSBSA-N
International/Other BrandsAronem (ACI) / Aropen (Aristopharma) / Carbanem (Sanofi-Aventis) / Erope (Lincoln) / Fulspec (Acme) / I-penam (Incepta) / Merenz (Admac) / Merofit (FHC) / Meronem (AstraZeneca) / Meronis (Neiss) / Meropen (Swiss Parenterals) / Merotec (Zuventus) / Merrem I.V. (AstraZeneca) / Monan (AstraZeneca) / Ropenem (Drug International) / Zeropenem (Sanofi-Aventis)
Synthesis Reference
Yoon Seok Song, Sung Woo Park, Yeon Jung Yoon, Hee Kyoon Yoon, Seong Cheol Moon, Byung Goo Lee, Soo Jin Choi, Sun Ah Jun, "METHOD FOR PREPARING MEROPENEM USING ZINC POWDER." U.S. Patent US20120065392, issued March 15, 2012.
Carbapenem antibiotic. Prepn: M. Sunagawa et al., EP 126587; M. Sunagawa, US 4943569 (1984, 1990 both to Sumitomo). Structure-activity study: M. Sunagawa et al., J. Antibiot. 43, 519 (1990).
https://patents.google.com/patent/WO2012062035A1/enCarbapenem, a type of β-lactam antibiotic, is known for its broad spectrum of antibacterial activity and strong antibacterial activity, such as meropenem (Me r0 p e nem), imine South (Imipenem) and Biabenem, etc., play an important role in the cure of severe infections.
Meropenem Imipenem For the synthetic methods of the Peinan type, the previous studies have mainly synthesized the corresponding Peinan side chain compound and the parent nucleus MAP, respectively, and then condensed and removed the protecting group to obtain the Peinan product. Such as US patentsUSP4933333, starting from 4-acetoxyazetidinone (4AA), obtained a matrix MAP after several steps of reaction. The mother nucleus is then condensed and deprotected from the side chain to obtain meropenem. However, this method is cumbersome, the synthesis step is long, and the total yield is low, and the noble metal catalyst is inevitably used in the synthesis of the compound (9).
MAP (10) Meropenem The Chinese invention patent document CN200810142137.5 has introduced a method for synthesizing meropenem.
(XII) (I)(TBD S = Si (CH 3 ) 2 C (CH 3) 3; PNB = p-N0 2 -C 6 H 4 CH 2; PNZ = 2 -C 6 H 4 CH 2 OCO N0 p-) This method of Scheme Short, easy to operate, easy to get raw materials, but there are some areas for improvement.
Example 11) (3R, 4S)-3-[(R)-l-(tert-butyldimethylsilyloxy)ethyl]-4-[(2,S, 4'R)- 1- (allyl Synthesis of oxycarbonylxiaodimethylaminocarbonylpyrrolidinothio]-2-azetidinone (II) In a 500 ml reaction flask, add 22.6 g (0.075 mol) of (3S,4S)-3-[( R) l-(tert-Butyldimethylsilyloxy)ethyl]-4-[(R)-1-carbonylethyl]-2-azetidinone (IV), 17.1 g (0.083 mol) Dicyclohexylcarbodiimide (DCC) in 100 ml of acetone and 0.76 g of 4-dimethylaminopyridine (DMAP), 20.3 g (0.078 mol) of (2S, 4R)-2-dimethylamine was added dropwise with stirring. A solution of carbonyl-4-mercapto (i-propoxycarbonyl)pyrrolidine (V) in 125 ml of acetone was reacted at room temperature for 14 hours. Filtration, collecting the filtrate, concentrating, adding 200 ml of toluene thereto, using 200 ml of a 5 % acetic acid solution, 200 ml of a saturated sodium hydrogencarbonate solution and 150 ml of saturation Washed with brine, dried over anhydrous magnesium sulfate and evaporated to dryness <mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj 4-[(2,8, 4, ) small (propoxycarbonyl dimethyl dimethylaminocarbonyl)pyrrolidinyl]-2-azetidinone (II), directly without further treatment Invest in the next step.1H-NMR (400 MHz, CDC 13): </ RTI> <RTIgt; m), 2.816-2.849 (lH, s), 2.935-2.953 (3H, m), 3.027-079 (3H, d), 3.378-3.401 (lH, m), 3.792-3.796 (1H, d), 3.807- 3.953 (lH, m), 4.042-4.160 (3H, m), 4.492-4.570 (2H, m), 4.670-4.739 (lH, m), 5.164-5.295 (1H, m), 5.807-5.921 (lH, m ), 6.214(1H, s). Example 22) (31,48)-3-[(1 )-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(2,8,4,1 )- 1- (allyl Synthesis of oxycarbonyl-1-dimethylaminocarbonylpyrrolidinothio]-1-(zincpropoxyl)-2-azetidinone (III) In a 1000 ml reaction flask, add 34.8 g (0.064) Mol) (3R, 4S)-3-[(R)-l-(tert-butyldimethylsilyloxy)ethyl]-4-[(2,S, 4,R)-1-(allyl Oxycarbonyl-1-pyrimidinylcarbonyl)pyrrolidinylthio]-2-azetidinone (11), 15.0 ml of triethylamine and 350 ml of toluene, control temperature below -10 °C, add 18.9 g (0.128 mol) p-nitrobenzyl chloroacetate (VI), heated to 0 ° C (-20 ° 5 ° C can be) reaction l ~ 3h. Then slowly add 250 ml of ice water and stir for 10 min. The layers were static and the organic phase was washed three times with saturated sodium bicarbonate solution, 200 ml each time. Dry over anhydrous magnesium sulfate, filtered, and evaporated to dryness to give white crystals, 4,7g (0.0622mol, yield 97.3%) (3R, 4S)-3-[(R) small (tert-butyldimethylsilyloxy)ethyl ]-4-[(2,S, 4,R)-1-(allyloxycarbonyldimethyldimethylaminocarbonyl)pyrrolidinylsulfur]sodium (sweetoxypropanoyl)-2-azetidinone (III), the product was directly put into the next step without further purification.Mp: 33-34 °C1H-NMR (300 MHz, CDC 13):0.819(9H, s), 1.167(3H, d), 1.188(4H, d), 1.693(5H, s), 1.850-1.926(1H, m), 2.631-2.700(1H, m), 2.941-2.960( 3H,d), 3.029-3.080(3H,d), 3.357-3.433(lH, m), 3.506-3.545(2H, m), 3.918-3.968(1H, m), 4.054-4.123 (2H, m), 4.270-4.291(lH, m), 4.391(lH,s), 4.518-4.568(2H, m), 4.588-4.779(3H, m), 5.178-5.416(3H, m), 5.861-5.982(2H,m ). Example 33) (5R,6S,8R,2'S, 4,S)-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-3-[4-(1-allyloxycarbonyl) -1- dimethylaminocarbonylpyrrolidinothio]-6-(1-allyloxycarbonylethoxy)-1-azabicyclo[3.2.0]-hept-2-en-7-one- Synthesis of 2-carboxylate In a 500 ml reaction flask, 40; 7 g (0.0622 mol) of (3R, 4S)-3-[(R)-l-(tert-butyldimethylsilyloxy) was added. Ethyl]-4-[(2,S,4,R)-1-(indolyloxycarbonyl-1-dimethylaminocarbonyl)pyrrolidinylsulfate]small (sweetoxypropanoyl)-2-nitrogen Heterocyclic butanone (III) and 150 ml of toluene, 22 ml of trimethyl phosphite (furrowing lg of hydroquinone) were added under nitrogen. After reacting at 60 ° C for 16 hours, the solvent was evaporated under reduced pressure. It was recrystallized by adding 300 ml of ethyl acetate, and the solid was collected, and vacuum-dried at 40 ° C to obtain 32.8 g (0.0528 mol, yield: 85.0%) (5R, 6S, 8R, 2'S, 4,S)-[(R)- 1-(tert-Butyldimethylsilyloxy)ethyl]-3-[4-(1-allyloxycarbonyl-1-dimethylaminocarbonyl)pyrrolidinyl] -6-(1-ene Propoxycarbonyl ethoxy) small azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylate (oxime).1H-NMR (300 MHz, CDC 13):0.82(9H, s), 1.24(6H, d), 1.26(3H, s), 1.36(3H, s), 1.94(1H, m), 2.69(1 H, m), 2.97-3.11(6H, m ), 3.15-3.74(4H, m), 4.35(2H,m), 4.37-4.67(5H, m), 5.24-5.28(4H, m), 5.84(1H, m). Example 44) (5R, 6S, 8R, 2, S, 4'S)-[(R)小(hydroxy)ethyl]-3-[4-(1-allyloxycarbonylsuccinylcarbonyl)pyrrolidinyl Synthesis of thio]-6-(1-allyloxycarbonylethoxy)-1-azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylate (Vffl) at room temperature , in a 2000ml reaction flask, add 32.8g (0.0528mol) (5R,6S,8R,2'S,4,S)-[(R)-1-(tert-butyldimethylsilyloxy)ethyl] 3-[4-(1-allyloxycarbonyl-1-dimethylaminocarbonyl)pyrrolidinyl]-6-(1-indolyloxycarbonylethoxy)-1-azabicyclo[3.2.0 -Hept-2-ene-7-one-2-carboxylate (W), 27.4 ml of acetic acid, 41.3 g of fluorohydrogenamine and 1000 ml of dichloromethane, stirred at room temperature for 48 h. After completion of the reaction, 500 ml of a saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, and the mixture was stirred for 10 minutes, and the methylene chloride layer was separated and dried over anhydrous magnesium sulfate to give a white solid (26.2 g (0.0517 mol, yield 98.0). %) (5R, 6S, 8R, 2'S, 4'S)-[(R)小(hydroxy)ethyl]-3-[4-(1-allyloxycarbonylsuccinylcarbonyl)pyr Rhodium thio] -6-(l-allyloxycarbonylethoxy)-1-azabicyclo[3. 2. 0]-hept-2-en-7-one-2-carboxylate (ring The product was directly charged to the next step without further purification.1H-NMR (300 MHz, CDC 13):1.26(3H, s), 1.36(3H, s), 1.94(1H, m), 2.67(1H, m), 2.97-3.11(6H, m), 3.2-3.7(4H, m) ; 4.25(2H, m), 4.47-4.87 (5H, m), 5.15-5.50 (4H, m), 5.94 (2H, m). Example 55) (5R,6S,8R,2,S,4,S)-3-[4-dimethylaminocarbonyl)pyrrolidinyl]-6-(l-hydroxyethyl)-1-aza Synthesis of bicyclo[3.2.0]-hept-2-en-7-one-2-carboxylate (I) To the reaction flask, 26.2 g (0.0517 mol) (5R, 6S, 8R, 2'S, 4'S) was added. – [(R)-l-(hydroxy)ethyl]-3-[4-(1-allyloxycarbonyl-1-dimethylaminocarbonyl)pyrrolidinyl] -6-(1-allyloxy Carbonyl ethoxy)-1-azabicyclo[3. 2. 0]-hept-2-en-7-one-2-carboxylate (VDI), 21.3 g (0.152 mol) dimethylcyclohexane The ketone and 550 ml of ethyl acetate were heated to 30 ° C, and a solution of 1.0 g (0.865 mmol) of tetratriphenylphosphine palladium in 150 ml of dichloromethane was added dropwise thereto, and the mixture was reacted at room temperature for 3 h under nitrogen atmosphere. After adding 300 ml of water to the reaction mixture, the aqueous layer was separated, the aqueous layer was washed with ethyl acetate, and then, 500 ml of tetrahydrofuran was added dropwise with stirring in an ice bath, and the crystals were stirred, and the crystals were collected and dried in vacuo to give pale yellow crystals of 13.4 g (0.0352 md, Yield 68.1%) (5R,6S,8R,2,S,4,S)-3-[4-(2-dimethylaminocarbonyl)pyrrolidinylthio]-6-(1-hydroxyethyl) 1-Azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylic acid trihydrate (I)-Meropectin.IR max KBr cm- 1 : 1755, 1627, 1393, 1252, 1130NMR (D20, 300Hz): 1.25 (3H, d), 1.81-1.96 (1H, m), 2.96 (3H, s), 3.03 (3H, s), 3.14-3.20 (3H, m), 3.31-3.41 (2H, m), 3.62- 3.72 (1H, m), 3.90-4.00 (1H, m), 4.14-4.26 (2H, m), 4.63 (1H, t). Example 6 6) (5R,6S,8R,2'S,4'S)-3-[4-(2-Dimethylaminocarbonyl)pyrrolidinylthio]-6-(l-hydroxyethyl)-1-azabicyclo[ Synthesis of 3.2.0]-hept-2-en-7-one-2-carboxylate (I)21.3 g (0.152 mol) of dimethylcyclohexanedione in Example 5 was replaced with 45.1 g (0.155 mol) of tributyltin hydride, and 0.125 g (0.108 mmol) of tetrakistriphenylphosphine palladium was added dropwise, and the other amount was added. And the same method, the obtained 16.2g (0.0426mol, 82.5%) (5R,6S,8R,2'S,4'S)-3-[4-(2-dimethylaminocarbonyl)pyrrolidinyl Sulfur]-6-(l-hydroxyethyl)-1-azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylic acid trihydrate (1) ~ meropenem. Example 7 7) (5R,6S,8R,2,S,4,S)-3-[4-(2-dimethylaminocarbonyl)pyrrolidinyl]-6-(1-hydroxyethyl)-1- Synthesis of azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylate (I) To the reaction flask, 26.2 g (0.0517 mol) of (5R, 6S, 8R, 2, S, 4'S)-[(R)-l-(hydroxy)ethyl]-3-[4-(1-allyl was added) Oxycarbonyl-1-ylaminocarbonylcarbonylpyrrolidinothio]-6-(1-allyloxycarbonylethoxy)azaabicyclo[3. 2.]-hept-2-ene-7- Ketone-2-carboxylate 01), 6.0 g (0.0387 mol) of N, N-dimethylbarbituric acid and 500 ml of dichloromethane, and 6.0 g (5.2 mmol) of tetratriphenylphosphine was added dropwise thereto. A solution of palladium in 100 ml of dichloromethane was reacted at room temperature for 5 h under nitrogen. After adding 300 ml of water to the reaction mixture, the aqueous layer was separated, and the aqueous layer was washed with ethyl acetate. THF was evaporated and evaporated, and the crystals were evaporated, and crystals were collected, and the crystals were dried in vacuo to give 15.7 g (0.0413 mol, yield: 80.1%). 5R, 6S, 8R, 2,S,4,S) – 3-[4-(2-Dimethylaminocarbonyl)pyrrolidinylthio]-6-(1-hydroxyethyl)-1-azabicyclo [3. 2. 0] -Hept-2-ene-7-keto-2-carboxylic acid trihydrate (I)-Meropectin.
ClaimsHide Dependent
Rights requesta synthetic method of meropenem, characterized in that the specific reaction route of the synthetic method
The reaction steps are as follows:1) The compound of the formula (IV) and the compound of the formula (V) are dissolved in an organic solvent and then subjected to a condensation reaction to obtain a compound of the formula (Π), the reaction time is 2 to 24 hours, and the reaction temperature is 0 to 40 ° C. ;2) The compound of the formula (Π) and the compound of the formula (VI) are dissolved in toluene, ethyl acetate or tetrahydrofuran and reacted with a base to form a compound of the formula (III), and the reaction time is ! ~ 3 hours, the reaction temperature is -20~5 °C;3) The compound of the formula (III) is dissolved in cyclohexanyl, n-glyoxime, n-octyl, toluene or xylene, and a Wittig ring-closing reaction is carried out under the action of an organophosphorus reagent to obtain a compound of the formula (VD), the organophosphorus reagent Is triphenylphosphine, tri-n-butylphosphine, triethyl phosphite or trimethyl phosphite;4) The compound of the formula (VII) is dissolved in methanol, tetrahydrofuran, acetone, n-pentane, n-hexane, diethyl ether, acetonitrile, dichloromethane, chloroform or ethyl acetate to hydrolyze the silyl ether bond under the action of an acid to obtain a formula (W). a compound; the acid is dilute hydrochloric acid, hydrofluoric acid, tetrabutylammonium fluoride, benzyltributylammonium fluoride, hydrofluoric hinge or vinegar The acid, the molar ratio of the acid to the compound of the formula is 5 to 15: 1; the temperature of the hydrolysis reaction is 0 to 40 ° C, and the reaction time is 8 to 24 hours;5) a compound of the formula dissolved in one or more of methanol, ethanol, tert-butanol, isobutanol, isopropanol, tetrahydrofuran, dioxanthene, acetone, dichloromethane, chloroform and water After the solvent is formed, the allylic group is hydrogenated by a palladium catalyst to obtain the target product (1). The molar ratio of the palladium catalyst to the compound of the formula 1) is 0.0001 to 0.5:1; the reaction temperature is 0 to 40 ° C. , the reaction time is 2~24h.2. A method for synthesizing meropenem according to claim 1, wherein the molar ratio of the compound of the formula (IV) to the compound of the formula (V) is 1.05 to 1.0: 1, the condensing agent and The molar ratio of the compound of the formula (IV) is 1.50 to 1.05:1.The method for synthesizing meropenem according to claim 1 or 2, wherein the condensing agent is a carbodiimide reagent or hydrazine, Ν'-carbonyldiimidazole; and the organic solvent is acetone. , acetonitrile, toluene, tetrahydrofuran, chloroform or dimethylformamide.The method for synthesizing meropenem according to claim 1, wherein the molar ratio of the compound of the formula (VI) to the compound of the formula (VI) is from 1.5 to 2.5:1, the base and the The molar ratio of the compound of the formula (VI) is from 1.2 to 2:1.The method for synthesizing meropenem according to claim 1, wherein the molar ratio of the organophosphorus reagent to the compound of formula (III) in step 3) is 2-8: 1; The reaction temperature is 25 to 100 £ ^, and the reaction time is 10 to 24 hours.The method for synthesizing meropenem according to claim 3, wherein the carbodiimide reagent is dicyclohexylcarbodiimide, diisopropylcarbodiimide or 1-( 3-dimethylaminopropyl)-3-ethylcarbodiimide.7. A method for synthesizing meropenem according to claim 1, wherein the base in step 2) is an inorganic base or an organic base; when it is an inorganic base, it is sodium hydroxide, sodium carbonate or Sodium bicarbonate; when it is an organic base, it is pyridine, triethylamine, diisopropylethylamine or 2,6-lutidine.The method for synthesizing meropenem according to claim 1, wherein the palladium catalyst is palladium acetate, palladium chloride, palladium nitrate, bistriphenylphosphine palladium chloride or tetrakistriphenylphosphine. palladium.9. A method for synthesizing meropenem according to claim 1, wherein the protecting group acceptor in step 5) is morpholine, dimethylcyclohexanedione, tributyltin hydride, N, N-dimethylbarbituric acid, -ethylhexanoic acid or hexanoic acid.
Reference: Nadenik, Peter; Storm, Ole; Kremminger, Peter. Meropenem intermediate in crystalline form. WO 2005118586. (Assignee Sandoz AG, Switz)
SYN 2
Reference: Nishino, Keita; Koga, Teruyoshi. Improved process for producing carbapenem compound. WO 2007111328. (Assignee Kaneka Corporation, Japan)
Reference: Manca, Antonio; Monguzzi, Riccardo Ambrogio. Process for synthesizing carbapenem using Raney nickel. EP 2141167. (Assignee ACS Dobfar S.p.A., Italy)
Reference: Tseng, Wei-Hong; Chang, Wen-Hsin; Chang, Chia-Mao; Yeh, Chia-Wei; Kuo, Yuan-Liang. Improved process for the preparation of carbapenem using carbapenem intermediates and recovery of carbapenem. EP 2388261. (Assignee Savior Lifetec Corp., Taiwan)
Reference: Gnanaprakasam, Andrew; Ganapathy, Veeramani; Syed Ibrahim, Shahul Hameed; Karthikeyan, Murugesan; Sivasamy, Thangavel; Michael, Sekar Jeyaraj; Arulmoli, Thangavel; Das, Gautam Kumar. Preparation of meropenem trihydrate. WO 2012160576. (Assignee Sequent Anti Biotics Private Limited, India)
Reference: Gnanprakasam, Andrew; Ganapathy, Veeramani; Syed Ibrahim, Shahul Hameed; Karthikeyan, Murugesan; Sivasamy, Thangavel; Sekar, Jeyaraj; Arulmoli, Thangavel. Preparation of meropenem trihydrate. IN 2011CH01780. (Assignee Sequent Scientific Limited, India)
SYN7
Reference: Senthikumar, Udayampalayam Palanisamy; Sureshkumar, Kanagaraj; Babu, Kommoju Nagesh; Sudhan, Henry Syril; Kamaraj, Ponraj Pravin; Suresh, Thangaiyan. An improved process for the preparation of carbapenem antibiotic. WO 2013150550. (Assignee Orchid Chemicals & Pharmaceuticals Limited, India)
Reference: Ong, Winston Zapanta; Nowak, Pawel Wojciech; Kim, Jinsoo; Enlow, Elizabeth M.; Bourassa, James; Cu, Yen; Popov, Alexey; Chen, Hongming. Meropenem derivatives and uses thereof. WO 2014144285. (Assignee Kala Pharmaceuticals, Inc., USA)
Reference: Cookson, James; McNair, Robert John; Satoskar, Deepak Vasant. Preparation of a carbapenem antibiotic by hydrogenation in the presence of a heterogeneous catalyst. WO 2015145161. (Assignee Johnson Matthey Public Limited Company, UK)
SYN 10
Reference: Gruenewald, Elena; Weidlich, Stephan; Jantke, Ralf. Process for the deprotection of a carbapenem by heterogeneous catalytic hydrogenation with hydrogen in the presence of an organic amine. WO 2018010974. (Assignee Evonik Degussa GmbH, Germany)
Some improvements in total synthesis of meropenem; Hu, Lai-Xing; Liu, Jun; Jin, Jie; Zhongguo Yiyao Gongye Zazhi; Volume 31; Issue 7; Pages 290-292; Journal; 2000
synhttps://www.researchgate.net/figure/Synthesis-of-MRPD-starting-from-meropenem_fig9_283306781
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Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Sumitomo Pharmaceuticals. It is marketed outside Japan by AstraZeneca with the brand names Merrem and Meronem. Other brand names include Zwipen (India, Marketed by Nucleus) Mepem (Taiwan) Meropen (Japan, Korea) and Neopenem (NEOMED India) . It gained FDA approval in July 1996. It penetrates well into many tissues and body fluids including the cerebrospinal fluid, bile, heart valves, lung, and peritoneal fluid.
Meropenem, sold under the brandname Merrem among others, is an intravenous β-lactam antibiotic used to treat a variety of bacterial infections.[1] Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.[1]
Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection.[1] Serious side effects include Clostridium difficile infection, seizures, and allergic reactions including anaphylaxis.[1] Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem as well.[1] Use in pregnancy appears to be safe.[1] It is in the carbapenem family of medications.[1] Meropenem usually results in bacterial death through blocking their ability to make a cell wall.[1] It is more resistant to breakdown by β-lactamase producing bacteria.[1]
Meropenem was patented in 1983.[2] It was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines.[3] The World Health Organization classifies meropenem as critically important for human medicine.[4]
The spectrum of action includes many Gram-positive and Gram-negative bacteria (including Pseudomonas) and anaerobic bacteria. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. It works against extended-spectrum β-lactamases, but may be more susceptible to metallo-β-lactamases.[5] Meropenem is frequently given in the treatment of febrile neutropenia. This condition frequently occurs in patients with hematological malignancies and cancer patients receiving anticancer drugs that suppress bone marrow formation. It is approved for complicated skin and skin structure infections, complicated intra-abdominal infections and bacterial meningitis.
In 2017 the FDA granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections.[6]
Meropenem is administered intravenously as a white crystalline powder to be dissolved in 5% monobasic potassium phosphate solution. Dosing must be adjusted for altered kidney function and for haemofiltration.[7]
As with other ß-lactams antibiotics, the effectiveness of treatment depends on the amount of time during the dosing interval that the meropenem concentration is above the minimum inhibitory concentration for the bacteria causing the infection.[8] For ß-lactams, including meropenem, prolonged intravenous administration is associated with lower mortality than bolus intravenous infusion in persons with whose infections are severe, or caused by bacteria that are less sensitive to meropenem, such as Pseudomonas aeruginosa.[8][9]
The most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%) and thrombophlebitis (0.9%).[10] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin.[11][12] Meropenem has a reduced potential for seizures in comparison with imipenem. Several cases of severe hypokalemia have been reported.[13][14] Meropenem, like other carbapenems, is a potent inducer of multidrug resistance in bacteria.
Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. In contrast to other beta-lactams, it is highly resistant to degradation by β-lactamases or cephalosporinases. In general, resistance arises due to mutations in penicillin-binding proteins, production of metallo-β-lactamases, or resistance to diffusion across the bacterial outer membrane.[10] Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin.
In 2016, a synthetic peptide-conjugated PMO (PPMO) was found to inhibit the expression of New Delhi metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems.[15][16]
Meropenem vial
India Inzapenum Dream India
Penmer Biocon
Meronir Nirlife
Merowin Strides Acrolab
Aktimer Aktimas Biopharmaceuticals
Neopenem Neomed
Mexopen Samarth life sciences
Meropenia SYZA Health Sciences LLP
Ivpenem Medicorp Pharmaceuticals
Merofit
Lykapiper Lyka Labs
Winmero Parabolic Drugs
Meroject Eskayef Pharmaceuticals Ltd.
Merocon Beacon Pharmaceuticals
Indonesia Merofen Kalbe
Brazil Zylpen Aspen Pharma
Japan, Korea Meropen
Australia Merem
Taiwan Mepem
Germany Meronem
Nigeria Zironem Lyn-Edge Pharmaceuticals
US Meronem AstraZeneca
… Merosan Sanbe Farma
Merobat Interbat
Zwipen
Carbonem
Ronem Opsonin Pharma, BD
Neopenem
Merocon Continental
Carnem Laderly Biotech
Penro Bosch
Meroza German Remedies
Merotrol Lupin)
Meromer Orchid Chemicals
Mepenox BioChimico
Meromax Eurofarma
Ropen Macter
mirage adwic
Meropex Apex Pharma Ltd.
Merostarkyl Hefny Pharma Group[17]
^ Jump up to:a b c d e f g h i j "Meropenem". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 497. ISBN 9783527607495.
^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^ World Health Organization (2019). Critically important antimicrobials for human medicine (6th revision ed.). Geneva: World Health Organization. hdl:10665/312266. ISBN 9789241515528.
^ AHFS Drug Information (2006 ed.). American Society of Health-System Pharmacists. 2006.
^ Commissioner, Office of the (24 March 2020). "Press Announcements – FDA approves new antibacterial drug". http://www.fda.gov.
^ Bilgrami, I; Roberts, JA; Wallis, SC; Thomas, J; Davis, J; Fowler, S; Goldrick, PB; Lipman, J (July 2010). "Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration" (PDF). Antimicrobial Agents and Chemotherapy. 54 (7): 2974–8. doi:10.1128/AAC.01582-09. PMC 2897321. PMID 20479205.
^ Jump up to:a b Yu Z, Pang X, Wu X, Shan C, Jiang S (2018). "Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis". PLOS ONE. 13 (7): e0201667. Bibcode:2018PLoSO..1301667Y. doi:10.1371/journal.pone.0201667. PMC 6066326. PMID 30059536.
^ Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME (January 2018). "Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials". Lancet Infect Dis. 18 (1): 108–120. doi:10.1016/S1473-3099(17)30615-1. PMID 29102324.
^ Jump up to:a b Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc. 2006.
^ Erden, M; Gulcan, E; Bilen, A; Bilen, Y; Uyanik, A; Keles, M (7 March 2013). "Pancytopenýa and Sepsýs due to Meropenem: A Case Report" (PDF). Tropical Journal of Pharmaceutical Research. 12 (1). doi:10.4314/tjpr.v12i1.21.
^ "Meropenem side effects – from FDA reports". eHealthMe.
^ Margolin, L (2004). "Impaired rehabilitation secondary to muscle weakness induced by meropenem". Clinical Drug Investigation. 24(1): 61–2. doi:10.2165/00044011-200424010-00008. PMID 17516692. S2CID 44484294.
^ Bharti, R; Gombar, S; Khanna, AK (2010). "Meropenem in critical care – uncovering the truths behind weaning failure". Journal of Anaesthesiology Clinical Pharmacology. 26 (1): 99–101.
^ "New molecule knocks out superbugs' immunity to antibiotics". newatlas.com. 20 January 2017. Retrieved 2017-01-25.
^ K., Sully, Erin; L., Geller, Bruce; Lixin, Li; M., Moody, Christina; M., Bailey, Stacey; L., Moore, Amy; Michael, Wong; Patrice, Nordmann; M., Daly, Seth (2016). "Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo". Journal of Antimicrobial Chemotherapy. 72 (3): 782–790. doi:10.1093/jac/dkw476. PMC 5890718. PMID 27999041.
^ "Hefny Pharma Group". hefnypharmagroup.info. Retrieved 2018-05-22.
"Meropenem". Drug Information Portal. U.S. National Library of Medicine.
Merrem, others
AU: B2
Intravenous
J01DH02 (WHO)
AU: S4 (Prescription only)UK: POM (Prescription only)US: ℞-only
Approximately 2%
Elimination half-life
showIUPAC name
PubChem CID
FV9J3JU8B1
CHEBI:43968
ChEMBL127
PDB ligand
MEM (PDBe, RCSB PDB)
CompTox Dashboard (EPA)
DTXSID7045526
C17H25N3O5S
383.46 g·mol−1
3D model (JSmol)
showSMILES
showInChI
(verify)
Publication numberPriority datePublication dateAssigneeTitleUS4888344A *1986-07-301989-12-19Sumitomo Pharmaceuticals Company, LimitedCarbapenem compound in crystalline form, and its production and useCN101348486A *2008-08-292009-01-21深圳市海滨制药有限公司Preparation of meropenemCN101962383A *2010-11-122011-02-02上海巴迪生物医药科技有限公司Synthesis method of meropenemFamily To Family CitationsJPS6475488A *1987-09-171989-03-22Sumitomo PharmaProduction of beta-lactam compound* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitleFamily To Family CitationsCN101962383A *2010-11-122011-02-02上海巴迪生物医药科技有限公司Synthesis method of meropenemCN102250096B *2011-09-052016-04-06江西华邦药业有限公司A kind of preparation method of meropenemCN104072523B *2014-07-142017-10-24上海上药新亚药业有限公司The preparation method of BiapenemCN108191869A *2018-01-222018-06-22重庆天地药业有限责任公司The purification process of Meropenem
PublicationPublication DateTitleEP0007973B11984-02-01Process for the preparation of thienamycin and intermediatesUS4631150A1986-12-23Process for the preparation of penemsWO2012062035A12012-05-18Synthesis method for meropenemWO2010022590A12010-03-04Method for preparation of meropenemUS4443373A1984-04-17Process for the production of antibiotic penemsWO2008035153A22008-03-27Process for the preparation of beta-lactam antibioticEP0167154B11990-01-03Process for preparing 4-acetoxy-3-hydroxyethylazetizin-2-one derivativesKR101059339B12011-08-24Method for preparing carbapenem compound for oral administrationKR100886347B12009-03-03Process for stereoselective preparation of 4-BMA using a chiral auxiliaryUS4841043A1989-06-20Stereoselective synthesis of 1-β-alkyl carbapenem antibiotic intermediatesUS4772683A1988-09-20High percentage beta-yield synthesis of carbapenem intermediatesJP2000344774A2000-12-12Production of carbapenem compoundAU745980B22002-04-11Titanium catalyzed preparation of carbapenem intermediatesUS5700930A1997-12-234-substituted azetidinones as precursors to 2-substituted-3-carboxy carbapenem antibiotics and a method of producing themJP2002338572A2002-11-27Method for producing carbapenemsJP3684339B22005-08-17Method for producing carbapenem compoundsEP0066301B11986-01-22Intermediates for the preparation of thienamycin and process for preparing the sameWO2001053305A12001-07-26Processes for the preparation of carbapenem derivativesAU737502B22001-08-23Preparation of beta-methyl carbapenem intermediatesJP3213734B22001-10-02New β-lactam compoundsJP2004107289A2004-04-08Method for producing vinyl sulfide compoundJPH085853B21996-01-24Lactam compound and its manufacturing methodJPH0827168A1996-01-30Carbapenem intermediate fieldEP0204440A11986-12-10Azetidine derivatives productionWO1994021638A11994-09-29Process for the preparation of condensed carbapeneme derivatives
ApplicationPriority dateFiling dateTitleCN 2010105416652010-11-122010-11-12Synthesis method of meropenemCN201010541665.52010-11-12
Nmrhttps://www.researchgate.net/figure/1HNMR-spectra-of-meropenem-hydrolysis-catalyzed-by-NDM-1-Ecoli-cells-Only-1H-signals-of_fig3_272515470
NMRNMR spectra monitoring meropenem hydrolysis catalyzed by NDM-1. a¹H NMR spectrum of hydrolyzed meropenem recorded before and 6 or 20 min after NDM-1 addition to the reaction system. b Part of a ROESY spectrum of the hydrolysis product. Diagonal and cross peaks are shown in blue and red, respectively. Proton signal assignments are labeled beside the peaks. The chemical shifts of H2, H1, H5, and H10 are highlighted by dashed linesSEEhttps://www.mdpi.com/1420-3049/23/11/2738/htm
Figure 1. FT-IR spectra of unirradiated and irradiated (25 kGy) meropenem.
Figure 2. Raman spectra of unirradiated and irradiated (A-25 kGy) meropenem.
Figure 6. XRPD diffractograms of unirradiated and irradiated (25 kGy) meropenem.
Figure 7. Differential scanning calorimetry (DSC) curves of non-irradiated and irradiated (A-25 kGy, B-400 kGy) meropenem. The arrows indicate the changes in the DSC spectrum after irradiation.
Figure 9. FT-IR spectra of unirradiated and irradiated (400 kGy) meropenem. The arrows indicate the changes in the FT-IR spectrum after irradiation.
Figure 10. Raman spectra of unirradiated and irradiated (400 kGy) meropenem. The arrow indicates the change in the Raman spectrum after irradiation.
//////////////Meropenem, Merrem, intravenous β-lactam antibiotic, bacterial infections, meningitis, intra-abdominal infection, pneumonia, sepsis, anthrax, Antibiotic SM 7338, ICI 194660, SM 7338, ANTIBACTERIALS
[H][C@]1([C@@H](C)O)C(=O)N2C(C(O)=O)=C(S[C@@H]3CN[C@@H](C3)C(=O)N(C)C)[C@H](C)[C@]12[H]
Tags: /Meropenem, anthrax, ANTIBACTERIALS, Antibiotic SM 7338, bacterial infections, ICI 194660, intra-abdominal infection, intravenous β-lactam antibiotic, meningitis, MEROPENEM, Merrem, pneumonia, sepsis, SM 7338
By DR ANTHONY MELVIN CRASTO Ph.D in antibacterial, Antibiotics on October 12, 2021 .
← RTS,S/AS01, RTS,S Mosquirix	PIRACETAM →


text:
/*
This project uses Automatic Package Restore feature of NuGet to resolve Aspose.Imaging for .NET API reference
when the project is build. Please check https://Docs.nuget.org/consume/nuget-faq for more information.
If you do not wish to use NuGet, you can manually download Aspose.Imaging for .NET API from http://www.aspose.com/downloads,
install it and then add its reference to this project. For any issues, questions or suggestions
please feel free to contact us using http://www.aspose.com/community/forums/default.aspx
*/

using System;

namespace Aspose.Imaging.Examples.CSharp.ModifyingAndConvertingImages
{
    class BinarizationWithOtsuThreshold
    {
        public static void Run()
        {
            Console.WriteLine("Running example BinarizationWithOtsuThreshold");
            // The path to the documents directory.
            string dataDir = RunExamples.GetDataDir_ModifyingAndConvertingImages();

            // Load an image in an instance of Image
            using (Image image = Image.Load(dataDir + "aspose-logo.jpg"))
            {
                // Cast the image to RasterCachedImage and Check if image is cached
                RasterCachedImage rasterCachedImage = (RasterCachedImage)image;
                if (!rasterCachedImage.IsCached)
                {
                    // Cache image if not already cached
                    rasterCachedImage.CacheData();
                }

                // Binarize image with Otsu Thresholding and Save the resultant image
                rasterCachedImage.BinarizeOtsu();
                rasterCachedImage.Save(dataDir + "BinarizationWithOtsuThreshold_out.jpg");
            }

            Console.WriteLine("Finished example BinarizationWithOtsuThreshold");
        }
    }
}

redpajama_set_name: RedPajamaGithub


text:
Preparing the Nation for Space Weather: New Executive Order
October 13, 2016 at 10:00 AM ET by Dr. Tamara Dickinson
The Administration takes significant step towards preparing critical infrastructure and technology for the risk of space weather.
Solar flare and Coronal Mass Ejection from the NASA Solar Dynamics Observatory. (Photo Credit: NASA).
Today, President Obama signed an Executive Order that seeks to coordinate efforts to prepare the Nation for space weather events. The Executive Order will help reduce economic loss, save lives, and enhance national security by ordering the creation of nationwide response and recovery plans and procedures that incorporate technologies that mitigate the effects of space-weather events. By this action, the Federal Government will lead by example and help motivate state and local governments, and other nations, to create communities that are more resilient to the hazards of space weather.
The term "space weather" refers to effects on the space environment that arise from emissions from the sun, including solar flares, solar energetic particles, and coronal mass ejections. Space weather is a natural hazard that can significantly affect critical infrastructure essential to the economy, social wellbeing, and national security, such as electrical power, water supply, health care, and transportation.
These emissions can interact with Earth, potentially degrading, disrupting, or damaging the technology that forms the Nation's backbone of critical infrastructure. Because it poses a significant risk to the Nation's security, space weather is included in the Department of Homeland Security's Strategic National Risk Assessment, which outlines threats that pose the greatest risk to the security of the Nation and that, therefore, the Nation must prepare for.
Reducing vulnerability to space weather requires an all-of-nation approach, including collaboration across governments, the emergency-management community, academia, the media, the insurance industry, non-profits, and the private sector. Over the past 6 years, the Office of Science and Technology Policy (OSTP) and the National Security Council (NSC) have worked together to coordinate interagency efforts to improve understanding, prediction, and preparedness for potentially devastating space-weather events. These efforts combined the national- and homeland-security enterprise with the science and technology enterprise to create the 2015 National Space Weather Strategy and accompanying Action Plan. Those documents describe how the Federal Government will coordinate the efforts of Federal agencies towards space-weather preparedness, and how the Federal Government will engage academia, the private sector, and State, local, tribal, and foreign governments.
The Executive Order builds on the significant progress of the National Space Weather Strategy and Action Plan by:
Establishing a national policy for space weather;
Establishing an enduring interagency coordination body within the National Science and Technology Council to implement the national space-weather policy;
Articulating department and agency roles and responsibilities with respect to space- weather research, operations, and planning;
Ordering the implementation of necessary, high-level activities that were not included in the Action Plan; and
Reinforcing the need to work with non-Federal entities, including international partners, to achieve national preparedness for space weather.
We cannot ignore the potential impact space weather may have on key infrastructures and technologies. This new Executive Order will strengthen America's resilience to space weather and help to build a more secure and resilient Nation.
Dr. Tamara Dickinson
Principal Assistant Director for Environment and Energy
Follow @Tamara44


text:
As Oil Prices Drop And Money Dries Up, Is The U.S. Shale Boom Going Bust?
Oil prices are down amid weak demand, and investors no longer seem willing to write the industry a blank check.
https://www.npr.org/2019/11/20/780879474/as-oil-prices-drop-and-money-dries-up-is-the-u-s-shale-boom-going-bust
The shale oil boom that catapulted the U.S. into being the world's largest oil producer may be going bust. Oil prices are dropping amid weakening demand, bankruptcies and layoffs are up, and drilling is down — signs of a crisis that's quietly roiling the industry.
Some of the most successful companies in the oil business are household names — think Exxon Mobil or Chevron. But the boom in shale drilling has been driven by smaller, independent operators. These companies have pushed the limits of drilling technology and taken big risks on unproven oil fields.
Today, shale accounts for about two-thirds of U.S. oil production and nearly all of the industry's growth, but many of the companies that made that growth possible are now struggling to stay afloat.
That has a lot to do with the business model of U.S. shale, says David Deckelbaum, an analyst at investment bank Cowen. "This is an industry that for every dollar that they brought in, they would spend two," he says.
For years operators focused on drilling lots of new wells very fast, prioritizing explosive growth over profitability. Until now they've been able to rely on deep-pocketed investors who were willing to pour fresh capital into the industry, despite years of lackluster returns.
It's a story that may be familiar to anyone who's been following the tech industry in recent years. Deckelbaum compares it to a kind of a prospector mentality.
"There's always this idea of this brand new play that's going to have billions of barrels of upside and if you can just get in early, then it'll pay off in the long run," he says.
Oil has always been a boom-and-bust industry. In 2014, for instance, a catastrophic price crash left the industry reeling. But even then, billions in new investment flowed into U.S. shale.
Today, shrinking global demand for oil is driving the price down once again. What's different this time around? Investors no longer seem willing to write the industry a blank check.
"I think now you've seen a lot of pressure of, 'We want you to be a real business. Your cost structure's too high, you have too much debt, I'm not funding your drilling anymore with external capital. You have to live within your own means,' " Deckelbaum says.
Without access to new cash, many producers are pulling back on exploration. The number of rigs drilling for new oil is at its lowest point in two years.
That's bad news for people like Ron Fountain, who works on a drilling rig in the Bakken shale of North Dakota. He thinks back to a few years ago, when the price of oil was more than $100 a barrel and companies were drilling with abandon.
"That's when we were still booming," Fountain says. "There was rigs coming out every month. We couldn't keep up, there was so much work going on."
Today though, with more and more rigs sitting idle, life has become uncertain for Fountain and his fellow drillers.
"We went from having three-year contracts to well-to-well contracts, which means you drill one hole and if you did a good job, then they'll give you another. Or they drop you and you gotta figure it out from there," Fountain says.
He's not the only one feeling the pinch. Halliburton, one of the biggest players in U.S. shale drilling, has laid off nearly 3,000 workers. In the Permian Basin, the country's most prolific oil field, employment has almost completely stalled out — after growing more than 11% last year.
Meanwhile, many of the smaller producers who piled up debt are struggling to pay it back. That has led to a wave of bankruptcies — nearly three dozen so far this year.
All of this is adding up to slower oil output. Production was flat in the first half of 2019, after growing more than 20% last year, according to Department of Energy data. In theory, as production slows and supply shrinks, the price of oil should go back up, which could provide a much-needed boost. The question, Fountain says, is how many companies will be able to survive until then.
"I think as an industry we're going to be OK," he says. "But I think there's a lot of people that are kinda holding their breath."
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text:
You are here: Home / 101 Village adoption / Amrita University illuminating rural India via renewable resources
Amrita University illuminating rural India via renewable resources
Last September, in her birthday address, Amma pointed out that India is suffering from a split personality–success when it comes to technological advancement and failure in terms of poverty, illiteracy, health sanitation and crimes against women. "A split personality is never a sign of sound health," Amma said. "If we want to see India become powerful and healthy again, we need to merge these two faces into one beautiful face… If we can bring our collective knowledge, compassion and talent together, it will not be so long before we see India rising and thriving with peace, harmony and prosperity." {news}
For Amma, actions are at least as important as words. As Chancellor of Amrita University, she has fostered the institution's robust, highly acclaimed research and development with a laser-like focus on humanitarian goals and deployment in the field. Under Amma's guidance, the university is a trailblazer in the humanitarian application of emerging technologies.
In just one of many examples, staff and students of Amrita University, along with members of Amrita Self Reliant Villages (AmritaSeRVe) worked with residents of Komalikudi, one of the 101 villages adopted by the Mata Amritanandamayi Math (MAM), to identify key challenges that needed to be addressed. Approximately one third of India's 600,000 villages do not have access to electricity. Komalikudi, a tribal settlement in Kerala well-known for its abundant natural resources, is one such village. After assessing the requirements of the village, a plan was implemented to provide electricity to the village from available hydro resources.
The team designed, developed, and installed a distribution and transmission network which included: a check dam, a network of pipes, a 5KW micro hydro generator, an underground transmission line, and a power house. This initiative of the University helped students to apply theoretical knowledge to address and solve real world challenges faced by rural communities in India. In the process, they greatly improved the lives of the people of Komalikudi and themselves underwent a life-changing experience of service-oriented innovation. The experience awakened love and compassion in their hearts as they worked together to find creative solutions to the problems of the villagers, harnessing the power of the available resources to make targeted improvements in the infrastructure of the village.
In Komalikudi, the new micro hydro generator, constructed near the perennial water stream, currently provides 24/7 electricity. Each home has four connection points with 3 lighting points and a plug point. Villagers currently use energy efficient 7 watt LED bulbs for energy conservation.
A vocational skills trainer in Komalikudi, Mrs. Shobana, said, "Earlier we had to stop our work by 5 p.m. as there was no light in the room. Now we have electricity so we can work at night. We are so grateful to Amma and her children for the help." Echoing her sentiments, Mrs. Vellamma, a volunteer at the village's Anganwadi said, "Now we have lights in the room so students can study at night – many thanks to Amma. We are so grateful to Amma for the support."
In addition to access to electricity, the Amrita team designed and installed a water distribution system in the village which includes a bore well with a pump and two overhead water tanks connected to each cluster of homes through pipes. The entire water distribution framework is currently powered by the micro hydro generator. The villagers now have access to potable water throughout the year which has helped their lives to improve greatly {news}, particularly seen in the areas of sanitation and education. Access to sanitation facilities also increases the overall health of the village and encourages children and adults to adhere to better hygiene practices, greatly improving public health outcomes.
The details of the mini Hydro project in Komalikudi village
Population Houses Pipe L&H Transmission Length Network Members Labour hours
350 90 82×30 M 1000 M 320 M 49 8.500 +
Tags: AmritaSeRve, renewable energy, sanitation, village education
Celebration continues: Amma in Amdavad
Empowerment through sanitation in Odisha
Scientific and Industrial Research will bring better economic returns to AmritaServe farmers
Motherhood is not about being a lady, but to envelope the world with your love
12 Amrita SeRVe adopted villages are verified ODF
President launches MAM's 100 Cr clean drinking water project for 5,000 villages
Solar-charger for cell phones Amma to visit Kenya, Mauritius and Singapore


text:
N = int(input())
mark = list(input())
point = [mark.count(str(i+1)) for i in range(4)]
print('{} {}'.format(max(point), min(point)))


The above snippets might sound familiar to you. Maybe you can relate because those are the same phrases you are hearing from someone you care about, that you are over-caring for, or that you are fearful will have a severe accident if help in the home does not happen soon.
The following list contains five mistakes that families might be making when it comes to the care of their family member and some interventions or changes that you might want to consider to be successful in bringing in home care that in the end will increase the quality of life and allow your family member to live at home longer.
1) Families tend to assess the need and fear for the safety of their family member.
They use phrases such as: "You should…," "You need help," or "You are not safe." This approach typically leads to resistance because older adults don't generally like being told to do something. It could be construed as a threat to their independence, autonomy, and/or privacy.
It is better to say that you are concerned about their safety first or that you worry that if they break a hip, they could end up in a nursing center. Then you can say: "Let's look at options to keep you in your home and independent." Do your homework and know the community resources and the agencies that have a good reputation in your area.
2) Families hire care and expect the parent to pay for it.
Remember, your family member lived in a time where anything over $10 an hour was too much to pay for anything. So, telling them care is $28-40 an hour could bring resistance. Better to start slow and say, "I think we can get you the support or assistance (not saying the word "care") that you need for $250 a week." Followed by – "This is so much less expensive than assisted living and you get to stay in your home." Ask the family physician to prescribe help in the home on an Rx pad so they are more amenable to the idea as a health matter.
3) Some families want full-time care and often that is what is needed. However, you are not going to get buy-in that way.
If you start slowly, with maybe 4 hours a day three times a week, you have a chance of being successful. As the relationship develops, you can add days or hours. It is all about the relationship. Use the guidance of a Professional Care Manager who can be the conduit to the older adult receiving care and provide a little counseling along the journey. The Care Manager builds a relationship of trust. Often the older adult will take direction from the Care Manager, but not his or her child who might be 62 but is still seen as a ten-year-old.
4) Adult children want their parent to decide to bring in help and pay for it even when the parent has a dementia.
Those with dementias have difficulty with decisions and organization. I would say that this approach does not work in about 90% of clients with dementia because they are fearful of spending any money and they deny any deficits in their functioning. Adult children of aging parents who have legal powers need to make decisions without parental approval. You might need to use "therapeutic fiblets" to make it work. A "fiblet" is a necessary white lie, to redirect your family member that is struggling with dementias and discourage them from any behavior that might be detrimental. A fiblet might be, "Your doctor says you must have 4 hours of a personal assistant a day or else you need to move to assisted living. I am going to help you stay in your home. That is why we are trying this plan." A fiblet could be calling the caregiver a different term, such as a personal trainer, a cook, a handyman, or a driver. When in fact, the person is a generalist caregiver and can do all you need to be done, you just need to change the name of the job to something that sounds adult and not like a babysitter or nurse. We can help you design a personal strategy at Eldercare Services.
5) Families tell the parent that they can choose a caregiver thinking that agencies will send several care providers so they can be interviewed for the choice.
In reality, a family would have to pay each caregiver for his/her time and then again it would not be easy to choose, especially for someone with a dementia. It is best to leave the matching up to the home care agency you want.
In my experience, when you have resistance, dementia, denial of need, or on-going hospitalizations, you need to hire a Professional Care Manager to help you with the approach, the introductions, the creative instructions, and the coaching to both the new caregiver and to you, the caring family member.
When you need to use "therapeutic fiblets", remember you are doing it only to protect self-esteem and reduce anxiety for your family member and yourself. If this causes you to feel any guilt, join a support group. We have a free group on the 2nd Thursday of every month from 6-7:30 pm in our office.
Caring can be a joy, an opportunity, and a challenge at times. Allow your family member the opportunity to stay home for as long as possible and put together a team to assist you for all the transitions that this journey brings.


Ruby Tuesday I find this lovely tree full of red color fruits in the park, are there edible?
Looks very lovely but I don't want to poison you and asking you to try it.
They look delicious but I have no idea. Great shots, though.
Yes, they are edible sour fruits of the tree. In Kerala we call it ' Lololikkai. The tree is ' Lololi'.
The fruits are v. firm and sour.
They can be eaten ripe with salt. We even preserve them in salt and vineger with boiled and cooled water. Try them after 7 days. Yum...... You can make good mouth watering pickles too.
They are never toooo sweet. But taste so good.


Facebook Woos Mobile Developers, but Is It Too Late?
Not so long ago, the key to building a successful app business required piggybacking on an existing big network like Facebook.
But relying on Facebook for your paycheck also meant being subject to the whims of Facebook CEO Mark Zuckerberg. The "things" in Facebook's mantra, "Move fast and break things," frequently meant your app, your business.
So it is no surprise that as Zuckerberg took the stage at the f8 conference this week to woo developers back to the platform, his intended audience wondered if they really needed Facebook. After all, just a few weeks before the gathering, Facebook paid $19 billion for WhatsApp, a messaging company built without any help from the world's largest social network.
In fact, an entire generation of messaging apps have established strong followings without relying on Facebook's social graph or its powerful database of users. Aside from WhatsApp, there is Snapchat, Line, WeChat, KakaoTalk, Viber, Kik, Telegram — all with audiences in the tens of millions without assistance from a larger network.
Developing for mobile devices, where the new action is taking place, has empowered developers with one key tool — your smartphone's phone book. These new apps are bypassing gatekeepers like Facebook and building new networks right from your own smartphone by going directly to your contacts list.
While phone books have been around for ages, one prominent app developer reminded me that it was the advent of the smartphone app, kicked off by the iPhone, that started making the phone book such a vital tool to creating new social graphs for developers to tap into.
Another person intimately familiar with Facebook's platform noted that this method of tapping into cellphone contacts works particularly well for communication-based apps, though not for all types of apps.
Those who choose to work with Facebook say it comes with strings attached. Some call it the Facebook tax. As a developer, you're handing Facebook valuable data on the performance of your apps, the audiences that use it and how well your app is doing. And if developers choose to implement the new anonymous login tool the company introduced this week, they could be helping Facebook more than Facebook is helping them.
Trust is at an all time low after years of neglect to their concerns, developers say. In the past, Facebook would frequently make snap changes to its platform, often breaking other developers' integrated apps in the process with little or no immediate explanation.
Or say your app's popularity is seen as a threat to Facebook. It has been known to suddenly shut off access.
"There has been a flurry of mobile apps that have been trying to use Facebook as an anchor to build their own 'network' in a sense, and Facebook then deems them competitive and blocks them or shuts them off," said another prominent developer who has had a troubled relationship with Facebook. "That's something everyone has been fearful of," this person said.
To soothe developers, Facebook announced a series of improvements, including offering up to $30,000 worth of development services to promising a "stability guarantee" that it would continue to support apps for two years even if it made changes to its platform. So significant was the latter that it inspired Facebook to modify its motto to a less catchy "Move fast with stable infra" (short for infrastructure).
Facebook will also make better use of Parse, a startup it acquired last year that is beloved by developers. Parse sells tools and back-end support to smaller mobile apps developers.
The most powerful tool in Facebook's arsenal could turn out to be the creation of a new open-source code standard called App Links. With App Links, clicking a link in one app will send you directly to another a page or section on another app and bypass the clunky mobile browser altogether.
Though it is open source, this process, called mobile deep linking, could give Facebook more control over how the future of smartphone usage will play out.
Think of it in terms of how one Facebook ad competitor put it to us: "That whole deep-linking product that Facebook just announced? If that works? God, that's Google search," this person said. Facebook could become the thread that connects all mobile apps together.
To be fair to Facebook, some industry insiders think the social network can still make a strong case for many other kinds of apps to work with it.
But convincing developers to hand over more control will be a challenge for Facebook as it mends its relationship with the community.
"I'd say we should all be taking this news with a grain of salt, but it's more like buckets of salt," one prominent Facebook development partner, who did not want to be named, told Re/code.
It will take more than dropping the L-word.
"My goal over the next 10 years is to build a culture of loving the people we serve," Zuckerberg told a packed room full of developers at the f8 event on Wednesday, far gushier than the 29-year-old CEO has ever come off in public.