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Tag: robert de niro
New York-born US actor and producer (1943-) (Wikipedia entry)
Published on 22 November 2019 2 December 2019 by Ewan MLeave a comment
Today sees the UK release of Harriet, but only two weeks ago we got a brand new biopic from Martin Scorsese. For that I did a themed week around very long films, but this week's theme means I can revisit that film and post a review. I liked it. I gather some didn't or felt it somehow less consequential in Scorsese's oeuvre, but a lot of people have been gunning for him for some throwaway but no less deeply felt comments about superhero movies. Still, there's a place for everything in modern cinema, and even if three-and-a-half hour gangster epics are mostly being made for streaming services now, it was still a solid box office draw given the very large packed cinema I saw this one in on a Saturday afternoon.
Look, I mean yes Scorsese has some good films (even some great ones) in all genres, but the stuff he's always been best at capturing is the world of gangsters — a shady world of men closed away behind dark glasses in subterranean lairs — but those worlds have changed as he's got older. Now the gangsters are old too, they're old men who have lost things in life, maybe lost everything, lost their friends, alienated their families and are just these old men, dying off and being forgotten. No matter how powerful you were, how much influence you had, eventually people forget your name, your legacy and everything that made you important when you were in your prime, and that's eventually what it feels like he's getting at by the end of this film. The de-aging technology has been much discussed, but even when these men are presumably playing 20 or 30-year-olds, back in the 1950s, they still look like old men, move in a hulking slow way — I don't think that's wrong for the characters, but in practice they always seem old no matter what the time period is. The timelines are all mixed up, though, as events from one era rush into those from another, because this is a story being told from the perspective of that old, forgotten gangster, as snippets of events seem to hit him and pull him along, and for all of its length, the film is never slow or boring, provided you like this slow-burning vibe that Scorsese is going for. Pacino does his usual big thing, though increasingly looking like Steve Van Zandt as he gets older in the film (and Little Steven is in the film too, in a small part, playing some old school crooner on stage I believe), but the rest of the cast are all about intensity, not least Joe Pesci, who feels like the real standout in this ensemble. It's a good film, is what I'm saying.
Director Martin Scorsese; Writer Steven Zaillian (based on the non-fiction book I Heard You Paint Houses by Charles Brandt); Cinematographer Rodrigo Prieto; Starring Robert De Niro, Al Pacino, Joe Pesci, Ray Romano, Anna Paquin, Stephen Graham; Length 209 minutes.
Seen at Curzon Mayfair, London, Saturday 9 November 2019.
Categories Classification: 15, Country: USA, Rating: EXCELLENT•Tags 1950s, 1960s, 1970s, 1980s, 2019, al pacino, anna paquin, based on real events, biopic, crime film, film reviews, films seen at the cinema, gangster film, historical drama, joe pesci, mafia, martin scorsese, murder, ray romano, robert de niro, rodrigo prieto, stephen graham, usa, very long film
Published on 7 January 2016 18 November 2019 by Ewan MLeave a comment
Another year (or two), another David O. Russell film starring Jennifer Lawrence, in what is becoming something of an end-of-year holiday tradition by this point. However, unlike 2013's American Hustle and Silver Linings Playbook before that, here Bradley Cooper is relegated to what's little more than a supporting role, leaving Robert De Niro (another recent Russell stalwart) to step in as the main support to Lawrence, which doesn't entirely pay off. Still, it does mean that romance very much takes a back seat to the 'based on real events' story of Joy, a frustrated American housewife who invents… a mop. You get the sense that this aspect of the story, the very ordinariness of her invention, was the draw for Russell, who uses it to craft an arc from Joy at home watching TV soap operas with her agoraphobic mother (Virginia Madsen), to a literal soap opera in which her sudsy invention conquers living rooms across the country via the Home Shopping Network (which is where Cooper comes in). Along the way there's plenty to enjoy, including a big performance from Isabella Rossellini as Joy's financier Trudy, but it all fades in the memory rather quickly once the film's finished.
Director/Writer David O. Russell; Cinematographer Linus Sandgren; Starring Jennifer Lawrence, Robert De Niro, Édgar Ramirez, Diane Ladd, Isabella Rossellini, Virginia Madsen; Length 124 minutes.
Seen at Cineworld Haymarket, London, Monday 28 December 2015.
Categories Classification: 12(A), Country: USA, Rating: GOOD•Tags 1990s, 2015, american dream, based on real events, biopic, david o. russell, diane ladd, drama, edgar ramirez, film reviews, films seen at the cinema, hollywood, isabella rossellini, jennifer lawrence, linus sandgren, period film, robert de niro, usa, virginia madsen
Criterion Sunday 51: Brazil (1985)
Published on 22 November 2015 20 August 2019 by Ewan MLeave a comment
Terry Gilliam's films feel like a lot of work sometimes. It's not that they're complicated or pretentious, just that they're filled with lots and lots of stuff. The set design is claustrophobic and packed with detail, there are gags happening in multiple parts of the frame, little visual jokes or passing fancies, the performances are hectic and filled with excess: he just constructs really very busy worlds. It was evident in Jabberwocky and Time Bandits and it's even more so here, the film which in many ways defines his visual and directorial style. Brazil is an anarchic experience that sprawls over two-and-a-half hours, as low-level bureaucrat Sam Lowry (Jonathan Pryce) starts to discover the state-imposed limits to his freedom. The film's interest seems not to be in that he falls in love (though he does, to the mysterious Jill, played by Kim Greist), but that his dream world unlocks a vision of a reality that has been systematically shut down by the government for whom he works. Its functionaries are buried in a mountain of papers and filing, from under which Lowry can only slowly and with great effort crawl. This Kafkaesque quality of struggle is what gives the film its style, as obstacles both technological (the cranky mechanical systems that spill across every set like human viscera) and bureaucratic (blue-collar workers like Bob Hoskins, or white-collar mandarins like Ian Holm and Michael Palin are particularly memorable) get in his way. This all should make the film-viewing experience heavygoing (and later films like The Zero Theorem return to the same milieu to lesser effect), yet there's an underlying lightness of touch. His world is a dystopia, certainly, but it isn't the brooding chiaroscuro of, say, 1982's Blade Runner. Instead, it's dystopia as comedy.
FILM REVIEW: Criterion Collection
Director Terry Gilliam; Writers Gilliam, Tom Stoppard and Charles McKeown; Cinematographer Roger Pratt; Starring Jonathan Pryce, Kim Greist, Ian Holm, Robert De Niro, Katherine Helmond; Length 143 minutes.
Seen at a friend's home (DVD), London, Sunday 23 August 2015.
Categories Classification: 15, Country: UK, Criterion Sunday, Rating: EXCELLENT•Tags 1001 films, 1985, criterion collection, dystopia, fantasy film, film reviews, films seen at home, ian holm, jonathan pryce, katherine helmond, kim greist, robert de niro, roger pratt, science fiction film, terry gilliam, uk
Having just written about Miss You Already, another recent directed-by-a-woman comedy/drama, and criticising its somewhat patchy use of musical cues, along comes this fluffily inoffensive new Nancy Meyers comedy and oh boy, what was I even talking about yesterday? To be fair, like Anne Hathaway's little indie romance Song One, if I'd seen this film on a plane or on TV when I was feeling ill, then I'd undoubtedly be giving it an easier ride. It's perfect for those occasions. But in a cinema with a crowd of other chattering (perhaps somewhat cynical) attendees, it has its difficult stretches, and most of those for me revolve around the treacly orchestral score that kicks in whenever something meaningful or emotional is happening, generally in the last third. However, if you can get past that, the precociously annoying kid and the rather overextended later stretch that deals with romantic infidelity, there's still enough to make it passably entertaining. There are some good jokes as the film is setting up its premise, that 70-year-old Ben (Robert De Niro) has applied for a 'senior intern' position within Jules (Hathaway)'s internet fashion company, and has to fit in with clued-up tech-savvy youngsters. A lot of that revolves around familiar age-vs-experience clashes, but Ben is also called on to show his sensitive side quite a lot, so your tolerance for De Niro's mugging for the camera will be tested — though luckily he's largely pretty good at it, and inoffensive, which is this movie's watchword. But I love Anne Hathaway, and am always happy to watch her; she has an easy on-screen charisma. So despite all that manipulative music, despite her "adorable" daughter and the fact that everyone seems to live in homes that look like boutique hotel fashion plates, despite the fact that the company (for all its financial success) never in the end actually seems to pay any of their interns a salary — perhaps a sly commentary on the modern workplace — I still didn't leave hating this movie. Your mileage may vary.
Director/Writer Nancy Meyers; Cinematographer Stephen Goldblatt; Starring Anne Hathaway, Robert De Niro; Length 121 minutes.
Seen at Cineworld Wood Green, London, Monday 28 September 2015.
Categories Classification: 12(A), Country: USA, Rating: MEDIOCRE•Tags 2015, anne hathaway, comedy, directed by a woman, film reviews, films seen at the cinema, hollywood, nancy meyers, new year's resolution 2015, new york, old age, relationship drama, robert de niro, stephen goldblatt, usa, workplace drama, written by a woman


Overall Wellness: Does Location Really Dictate Wellness?
A little bit of info on me, I am originally from Iowa and moved to Kentucky for grad school and then moved to Kansas for my job. I tell you this because when I lived in Kentucky, my roommates got be hooked on a certain news station pretty much just for the morning weather guy. No lie. Anyway, I liked their page on Facebook back then and I never un-liked them and continue to keep up with the new (er robberies and murders) of that area. This is actually pertinent because recently, Gallup published a study about the top 10 worst places to live (aka places that have the lowest scores on their well-being finder). Kentucky, was ranked the 2nd worst place to live in the US. The local news station posted this and asked viewers to weigh in on how they felt about this ranking. Honestly, I just scrolled through some of the 300+ comments and there are massive mixed reviews.
But also interestingly enough, I was discussing with a co-worker yesterday at an event about how people feel being labeled the best worst thing. Some people see being told this as an opportunity to change while others will fight against the label. Is there really a right way to change this? I mean, a lot of Kentuckians are proud to be Kentuckians and believe that it is the greatest place on earth. Others still feel that way but can see where the state is lacking in some areas. Others still think the state is complete crap and can only rag on it at every chance they get. And there are a million different shades of grey between just those three categories.
It's just interesting to think about if you state can have an effect on your well-being. Iowa is consistently in the top 10 of best places to live so I have lived in "the best" and "the worst". And the only thing that I can tell you is that while there are somethings you can't change, you still dictate how happy you are and how high your wellbeing is. There are different factors that are associated with wellbeing and if you can't control and do anything to improve one aspect…think about concentrating on some of the others.


A handful of East Cambridgeshire pupils were lucky enough to visit Simon Cowell's production company headquarters as part of a school initiative to "identify what makes each student tick" last week.
Students and staff from Witchford Village College headed to London on Friday, January 25, after one of their teachers organised the trip to Syco Entertainment, owned by Britain's Got Talent judge and TV star Simon Cowell.
Syco is based within the Sony Music UK offices in posh West London. The Sony subsidiary has famous musicians such as One Direction, George Ezra, James Arthur and Labrinth under their management wing.
The group of students were shown around the offices and met with different members of staff to learn about their experiences and what it takes to get a job in the media and entertainment industry.
The trip gave pupils with a keen interest in showbiz the chance to get a feel of what they would be doing day-to-day at work. Managers and interns took time out of their day to speak with the youngsters and answer any questions they may have.
As a surprise, Abi gave the students the 'best seats in the house' for filming of the Britain's Got Talent auditions in the auditorium where they got to see how the television show with a live studio audience was produced.
The trip was run as part of Witchford Village Colleges SPARK initiative which aims to identify "what makes each student tick, ignite their love of learning and raise their aspirations". It was launched last year by new college principal Daniel Baxby.


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By Steven Lloyd Wilson | Film | March 6, 2010 |
Neill Blomkamp is a South African director who got his start as a 3D animator for a variety of sci-fi films and television series (including "Stargate SG-1," "Dark Angel," and "Smallville"). In 2005, he directed a short six minute film entitled Alive in Joburg, a faux documentary that explored the idea of extraterrestrial refugees exploited in South Africa. The film impressed Peter Jackson of Lord of the Rings fame enough that he backed Blomkamp with $30 million to adapt the themes of Alive in Joburg into the feature length District 9.
The resulting film is simply fantastic.
The film uses documentary footage to establish that 20 years prior to the film's start, an alien spacecraft coasted down and halted above Johannesburg, South Africa. For months it hovered there, before teams were sent to cut into the hull. They find refugees, too sick and terrified to be of any threat or any help. They are shuttled down to Earth, a refugee camp is established called "District 9." First contact is nothing like anticipated. The leadership of the aliens is apparently dead or absent. The survivors are ignorant laborers with no education or knowledge of the ship's technology. What technology there is cannot be stripped and used by humans. It is partly biological in nature, only functioning in the hands of one of the aliens.
After 20 years, sentiment has turned against the million aliens, slurred as "prawns," living in District 9. Many contend that the money spent supporting the aliens is a waste, better spent on human problems. The stagnant situation is not viable in the long run. At last, control of the camp is turned over to a private conglomerate, MNU, which sets out to move the aliens far outside of Johannesburg into concentration camps. It's all wrapped in petty legalism. The aliens must be notified individually of eviction, keeping it all legal and within regulations. Teams are dispatched with armed escorts in order to get signatures from each alien resident in the district.
After the documentary introduction, we zoom in to the point of view of Wikus van der Merwe (Sharlto Copley), a low-level bureaucrat put in charge of the forced migration. Wikus is introduced dorkily struggling with a clip-on microphone and rambling to the camera about the nature of their work. He's meek and endearingly incompetent, but with an undercurrent of intelligence and strength gleaming through. He understands the alien language, can communicate with them. He's a quick study of alien behaviors and culture, explaining to the cameras how they make nests, how they eat the rubber tires off of unguarded cars, how to stop a fight before it starts by tossing them food. The cruelty with an honest face becomes rapidly apparent as Wikus supervises the destruction of an alien nest. Joking with a new guy about keeping a souvenir of his first "abortion," he points out that when the flamethrowers hit the eggs, they explode and sound just like popcorn popping. The brutality is casual, a shrug to the perpetrators because the victims aren't human. Then the critical moment: Wikus accidentally sprays himself with a black fluid that makes him sick. His team leaves the district, but Wikus' condition steadily worsens until the horrifying revelation that makes him a target.
Sharlto Copley superbly conveys the descent of a fundamentally decent and quiet man into the depths of hell, transforming from a meek office drone into someone taking up arms to save his own life. It's a beautiful performance, resembling Edward Norton's metamorphosis in Fight Club. There's a particular moment of desperation that ratchets the horror of Wikus' predicament even tighter: when he stands at a payphone collect calling everyone he knows, none of them accepting the call. "We've been friends for 19 years!" He shrieks.
Other characterization is done with a quick hand, letting broad brush strokes show us who these people are, not meandering too deeply as the story moves quickly along. The brutal father in law, the too-pretty wife, the meek bureaucrats, the vicious mercenaries, the superstitious human gangs preying on the prawns. Even the aliens: father, son, red-shirt.
At its heart, the film is about the lines we draw around "us" and "them," and how truly shaky those lines are. We can accept any sort of horror, any torture, as long as it isn't one of us. The film feeds on the horror implicit in how easy it is to carry a one and move someone back and forth across that line. A man in charge of an operation can in five minutes become nothing more than a pile of resources "worth billions of dollars," that must be harvested quickly. Anesthesia? That's for people not things, it might interfere with the procedure. Vivisection first, get the heart out as quickly as possible.
Bits and pieces of humor run throughout, laugh-out-loud gallows humor. The authorities release photoshopped footage of Wikus screwing one of the aliens to explain his condition, to turn the sentiment of any friends and family against helping him. It's mined here and there, a thug asking Wikus late in the film whether he'd used a condom. An alien asks Wikus why he killed a man after insisting that there should be no killing and Wikus erupts with the inarguable logic of "that was before he tried to kill me."
It is an intelligent and layered film, but as the old adage goes, ideas are boring, so if you must tell a story about ideas, be sure to wrap it with a bunch of explosions. MNU's primary concern is in figuring out a way to allow humans to use the prodigiously powerful alien weapons. And these aren't wee little ray guns, we're talking exotic rifles that auto-target and detonate people like spam in a microwave. And the jaw dropping kingmaker: gorgeous ten foot tall power armor that single-handedly eradicates entire squads of soldiers sent to take it down.
One complaint of other reviewers has been that the central questions of the film are never resolved. They're missing the point. We never find out why the aliens came, why most of them seem to have no understanding of their own technology, why they never rose up against those holding them. But that's because the story is told tightly focused on Wikus. He is preoccupied with survival during the 72 hours over which the film unfolds. He is not in any position to learn those tidbits, and the answers, while tempting, are completely irrelevant to the story being told here. If given, such answers would just be tacked on, gratuitous to the personal journey of Wikus.
The film ends in a curious mix of triumph, tragedy and ominous anticipation. One hopes that the implied and inevitable sequel can live up to the high bar set in District 9.
Steven Lloyd Wilson is the last scion of Norse warriors and the forbidden elder gods. He is a hopeless romantic who can be found wandering San Diego's strip malls and suburbs looking for his mislaid soul and waiting for the revolution to come. Burning Violin is still published weekly on Wednesdays at www.burningviolin.com, along with assorted fiction and other ramblings.
I Focus on the Pain, the Only Thing That's Real
Steven Lloyd Wilson is the sci-fi and history editor. You can email him here or follow him on Twitter.

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Consume an endpoint using optional parameters in angularjs I have a form with 2 sections. From each section, at least one value must be selected.
I know how to pass compulsory parameters but passing the appropriate parameters based on user selection is what I am not sure of.
Any ideas please?
Template plunker here
 <form>

   Section 1

   <input type="checkbox" name="chkBox1" value="chkBox1">chkBox1

   <input type="checkbox" name="chkBox2" value="chkBox2">chkBox2

   <input type="checkbox" name="chkBox3" value="chkBox3">chkBox3

   Section 2

    Optional 1:
    <input type="text" name="fname" value="fname" />

    Optional 2:
    <input type="text" name="lname" value="lname" />

  <button ng-click="getAll()">Get result</button>
 </form>

Controller function
 $scope.getAll = function() {
    return $http.get('/api/testing?chbox1='+ 1 +'&chbox3=' + 1
     +'&chbox2=' + 0 +'&optional1=' + fname +'&optional2=' + lname);
    },

A: You can concat your URL depending of fname & lname defined or not:
return $http.get('/api/testing?chbox=' + 1 + '&chbox3=' + 1 + '&chbox2=' + 0 + ((fname !== undefined) ? '&optional1=' + fname : '') + ((lname !== undefined) ? '&optional2=' + lname : ''));
},

I used ternary conditions for writing it faster, but you can use multiple conditions for this case too:
$scope.getAll = function(){
    var url;
    if (fname !== undefined && lname !== undefined)
        url = '/api/testing?chbox1='+ 1 +'&chbox3=' + 1 +'&chbox2=' + 0 +'&optional1=' + fname +'&optional2=' + lname;
    else
        if (fname !== undefined)
            url = '/api/testing?chbox1='+ 1 +'&chbox3=' + 1 +'&chbox2=' + 0 +'&optional1=' + fname;
        if (lname !== undefined)
            url = '/api/testing?chbox1='+ 1 +'&chbox3=' + 1 +'&chbox2=' + 0 +'&optional2=' + lname;
}

Second option is less elegant!

redpajama_set_name: RedPajamaStackExchange


NEW Now updateHandler of the getData() API call is triggered also when a number format is changed.
NEW SSAS Filtering added to the drill-through view.
NEW Now, when the showHeaders option parameter is set to false, the column resizer is placed on the second row.
FIX The issue with filtering and grand total percent in the formula was fixed.
FIX The issue with the "max" aggregation and negative values was fixed.
FIX The issue with showing empty cells instead of zeroes for "count" aggregation was fixed.
FIX The issue with resetting measure's format when formatting with the Toolbar was fixed.
FIX The issue with exporting to Excel when the starting layout is the chart's layout was fixed.
FIX The issue with opening filters in the flat table was fixed.
NEW A new option property dateTimezoneOffset was added. It allows setting the timezone for the following data types: "date", "year/month/day" and "year/quarter/month/day".
NEW A new property useCustomizeCellForData was added for Excel export.
FIX The issue with "year/quarter/month/day" data type was fixed.
FIX The issue with deselecting fields on the flat table when there are fields in the filters area was fixed.
FIX The issue with fullscreen mode in Chrome and Firefox on macOS was fixed.
FIX The issue with drag and drop fields on the flat table with a large number of columns was fixed.
FIX The issue with drag and drop fields order was fixed.
FIX An extra \n when copying selected cells data was removed.
FIX Accelerator SSAS The optimization for large data sets was made.
NEW The recordId parameter of Cell Data Object is available for all table forms: compact pivot table, classic pivot table and flat table.
NEW A new beautifyFloatingPoint formatting property was added. It allows showing numbers like 1.560000000000001 either as 1.56 or 1.560000000000001.
NEW Accelerator SSAS Added support for Azure Analysis Services for Flexmonster Accelerator.
NEW Accelerator SSAS Now drillThroughMaxRows property is supported for SSAS Accelerator.
FIX Accelerator The issue with empty data set when loading multiple instances was fixed.
FIX The issue with right-click on the filters area was fixed.
FIX Chart type names were replaced with more common ones. "bar_stack" was renamed to "stacked_column". "bar_line" was renamed to "column_line". Old names are working in terms of backward compatibility.
FIX The issue with formulas parser was fixed.
NEW Now it is possible to add a new field to the calculated formula by double-clicking it.
NEW Our sample Flexmonster + Angular integration project was updated to support Angular 7.
FIX The issue with exporting numeric data to Excel was fixed.
FIX The issue with merging default and custom number formatting was fixed.
FIX The issue with calculated values not added to Format cells drop-down in the Toolbar was fixed.
FIX The issue with displaying an unnecessary pop-up warning for calculated measures was fixed.
FIX The issue with the context menu for more than 20000 rows in the report was fixed.
FIX The issue with filtering date/time members in SSAS was fixed.
FIX The issue with undefined d3v3 when using Flexmonster in an Angular application was fixed.
FIX PHP data compressor The issue with PHP Data Compressor when connecting to Oracle databases was fixed.


Sadly we have to scrap this vehicle due to a badly rusted body, the engine, gearbox,wheels etc still in working, order.Want R9500 negotiable for complete vehicle.
OPEL A14 XER TIMING TOOL NEW R2500Brand new item on promotion BASED IN DURBAN, BUT CAN COURIER OR POST IN ANY PROVINCE @ THE BUYERS COST!COMPANY - RADHELLA BOLTS & TOOLS CCCONTACT RIVEN @ 072-6581627 FOR ALL YOUR AUTOMOTIVE TOOL ENQUIRIES.
Year : 2005Colour : Red Service History : Full ServiceMileage : 163 212km5 Speed – Manual Alarm ImmobilizerPower SteeringElectric WindowsCentral LockingAccident FreeRust FreeNo Re-sprays or dentsCloth Seats ImmaculateInterior very neat and cleanExterior in excellent conditionEngine is sound – nothing needs to be done.
Jurgens Magnificent caravan 1984 very good condition. 2xDouble beds, fridge, bathroom etc. licensed and Registration papers in order. Very clean, with extras.
Jurgens Magnificent caravan very good condition. 2 x double beds, bathroom, fridge, gas stove, sink etc. Very Clean. Tent, awning, groundsheet etc.


The Winter Lab is investigating molecular mechanisms related to the function of lysosomes. We are using state of the art proteomics, molecular biology and biochemistry approaches to characterize proteins located at the lysosome and to investigate how they change in response to different stimuli. Our aim is not only to identify changes on these proteins using mass spectrometry based proteomics approaches, but also to characterize the role these changes play for the function of the lysosome.
The lysosome is the degradative compartment of the cell. Present in almost any living cell, it is degrading macromolecules and organelles and organizing the recycling of cellular components. Furthermore, it is involved in host defense mechanisms, receptor mediated endocytosis and antigen presentation to name just a few of the plethora of mechanisms it is involved in. Currently, around 150 lysosomal proteins are confirmed and the list is constantly growing.
The inside of the lysosome, its lumen, is home to a variety of hydrolases which catalyze various degradation reactions. Almost every molecule which is important to keep a cell functional can be broken down here to its building blocks. Like a molecular shredder, it can take on everything ranging from single molecules to whole organelles (for example mitochondria). These large molecules are then degraded to their building blocks which are lipids, sugars, proteins and nucleotides.
The molecules located in the lysosomal membrane take on various functions being important for its structure, acidification, localization in the cell, import of molecules to be degraded, fusion with other organelles and transport of the degradation products to the cytosol. Various proteins also serve as docking station for others and there is an emerging picture of membrane proteins interacting with each other. Despite decades of research, for many lysosomal membrane proteins the function is still unclear and constantly novel functions are discovered making the field of lysosomal research an exciting and vibrant area.
Malfunctions of each of the lysosomal hydrolases result in severe inherited diseases termed lysosomal storage disorders (LSDs). The common hallmark of these diseases is the accumulation of not degraded material in the lysosome which impairs its function. Currently, about 50 LSDs are known with a cumulative incidence of ~ 1 in 5.000 new-borns. A prominent subgroup of LSDs originates from defects in sphingolipid degrading enzymes resulting in sphingolipid storage diseases such as Gaucher disease, Fabry disease or metachromatic leukodystrophy (MLD). Despite many years of research, the effects of these disorders on the cellular level are still poorly understood.
To gain more insight in the processes involved leading to malfunction of the lysosome, we are investigating changes in whole cell or lysosomal protein composition as a consequence of increasing lipid storage. For this purpose, we analyze animal and cell culture models using state of the art liquid chromatography tandem mass spectrometry methods. We also establish novel methods, if needed, and apply them to model systems performing mainly quantitative analysis of proteins and their posttranslational modifications.
Stable isotope based labeling strategies like SILAC (stable isotope labeling of amino acids in cell culture), TMT (tandem mass tags) or dimethyl labeling play a prominent role in our research. These methods allow us to simultaneously identify and quantify thousands of proteins and their posttranslational modifications in one mass spectrometry experiment. In order to deal with the high complexity of the samples, we perform enrichment and fractionation of peptides and proteins using a variety of methods. Once we identify interesting candidate proteins in these experiments, we conduct follow up studies using a variety of approaches. We confirm protein expression levels using western blots, qPCR or enzyme assays and once we are convinced that we found something interesting, we investigate cells using immunohistochemistry and perform knockdown, overexpression or mutation studies, just to name the most important.


Pontus Alv, Ollie, TBS, Malmo.
Kingpin #98 is now out and about, this one's a DIY spectacular. Included is an article I shot with Pontus (and friends) in Malmo a few of months back, we built some stuff, skated some stuff, shot some stuff... Check it out.
Jerome Campbell for Converse Skateboarding.


WRITING – I haven't finished it. It's about my nurse life.
LISTEN – Janet Jackson – Together Again. Yeah pang Now 4 Music lang ang galawan 😅.
THINKING – Why am I here?
WISHING – I want to have more energy!!!!!!
HOPING – I won't get sick. The weather has been unpredictable the past couple of weeks.
LOVING – My new desk!
WANTING – To sell more of my stuff. I donated and sold my unused make-up and other things that I don't need anymore. I always do this way before that Marie Kondo shizzles.
FEELING – I'm in pain. Damn you dysmenorrhea!!!!! And yup, I'm not pregnant.
CLICKING – Candy Crush Saga on Facebook.
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Register after your sign up at 12n.de free domains. You can choose from 12n.de domain endings, such as .12n.de up to 500 free domains. You can set up these domains on your free storage at 12n.de or forward to an already established website.


text:
European Union regulation
Concession (contract)
Typical Toll Concession P3 Structure
A concession or concession agreement is a grant of rights, land or property by a government, local authority, corporation, individual or other legal entity.[1]
Public services such as water supply may be operated as a concession. In the case of a public service concession, a private company enters into an agreement with the government to have the exclusive right to operate, maintain and carry out investment in a public utility (such as a water privatisation) for a given number of years. Other forms of contracts between public and private entities, namely lease contract and management contract (in the water sector often called by the French term affermage), are closely related but differ from a concession in the rights of the operator and its remuneration. A lease gives a company the right to operate and maintain a public utility, but investment remains the responsibility of the public. Under a management contract the operator will collect the revenue only on behalf of the government and will in turn be paid an agreed fee.
A grant of land or a property by the government may be in return for services or for a particular use, a right to undertake and profit by a specified activity, a lease for a particular purpose. A concession may include the right to use some existing infrastructure required to carry out a business (such as a water supply system in a city); in some cases, such as mining, it may involve merely the transfer of exclusive or non-exclusive easements.
In the private sector, the owner of a concession — the concessionaire — typically pays either a fixed sum or a percentage of revenue to the owner of the entity from which it operates.[2] Examples of concessions within another business are concession stands within sporting venues and movie theaters and concessions in department stores operated by other retailers. Short term concessions may be granted as promotional space for periods as short as one day.
Depending on what the law that is related to a sector states, concession can either allow the authority to retain or keep actual ownership of the assets, turning over to the concessionaire and reverting the control and ownership back to an authority once the duration of their concession ended, or both the authority and concessionaire control and own the facilities. Concession agreement may also state that the assets and facilities that were built, designated, and acquired prior to the turnover of operations and maintenance from the authority to the concessionaire and are included on a plan of a project that was planned by an authority are pre-identified as owned by the authority and to be operated and maintained by the concessionaire upon the turnover of operations and maintenance of the facilities and assets to the concessionaire.
Muhammad Ali of Egypt used contracts called concessions to build cheap infrastructure - dams and railroads - whereby foreign European companies would raise capital, build projects, and collect most of the operating revenue but would provide Ali's government with a portion of that revenue.[3] For other examples of concessions, see Gibbons v. Ogden and United States railroad policy.
Within the European Union, the granting of concessions by public bodies is subject to regulation. Works concessions have been subject to award rules for some time as Directive 2004/18/EC of the European Parliament and of the Council of the EU on public procurement applied to works concessions. The award of services concessions with a cross-border interest has been subject to the principles of the Treaty on the Functioning of the European Union. The European Commission had originally included public concession contracts in the Services Directive of 1992, but these were removed from its scope by the European Council.[4] However, the European Parliament and the Council issued a further Directive 2014/23/EU on the award of concession contracts on 26 February 2014,[5] which required EU member states to introduce national legislation covering the award of concession contracts in excess of EUR 5,186,000 awarded on or after 18 April 2016.
In the UK, the equivalent threshold for concession contracts is £4,104,394.
Production sharing agreement
^ What is a concession agreement?, wisegeek.com
^ Definition of concession agreement investorpedia.com
^ Karabell, Zachary (2003). Parting the desert: the creation of the Suez Canal. Alfred A. Knopf. p. 34,36. ISBN 0-375-40883-5.
^ England and Wales Court of Appeal (Civil Division), JBW Group Ltd v Ministry of Justice (2012) EWCA Civ 8 (16 January 2012), accessed 3 January 2021
^ Directive 2014/23/EU of the European Parliament of the Council on the award of concession contracts
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What is the second largest movie industry in the world? Nollywood! The Nigerian counterpart of America's blockbuster industry is an undisputable ambassador of Nigerian-ness. If literature truly mirrors life, then Nollywood dramas can be said to mirror the Nigerian life. For Nollywood, apologies to Kunle Afolayan and similar divergents, movies are dramas in multiple parts. This multi-section drama culture is playing out in Nigerian politics, the latest part being Buhari's school certificate saga.
In the run-up to the 2015 General Elections, Muhammadu Buhari faced a series of roadblocks designed to keep him from contesting for the country's top job. From negative adverts to questions about his health, including a bizarre advert that mimicked an obituary announcement, Buhari had more than enough on his plate. The most challenging roadblock was the question about the existence/inexistence of his secondary school certificate. In the midst of chants for a certificate, he informed Nigerians that being a former military officer, his credentials were with the Nigerian Army. When a spokesman for the army declared that Buhari's certificate could not be found, he tendered a statement of results signed by the principal of the school where he "sat" for the 1961 Cambridge West African School Certificate exam.
The tendered document, dated 21 January 2015, was accepted by Nigerians eager to witness a change of government. Although the released document featured a F9 in mathematics, which ought to have prevented Buhari from joining the officers' corps, it was explained that the army accepted him based on the recommendation of his school principal. This explanation was accepted by people so fed up with the Jonathan administration that they were willing to vote for Buhari "even if he presents a NEPA bill". Several suits were filed against Buhari as a final roadblock on his path to the presidency. However, nothing came out of the cases, Buhari was elected President, and everything went silent—until now.
Justice Adeniyi Ademola of the Federal High Court Abuja struck out a motion challenging the competency of a suit filed concerning Buhari's certificate. Out of the blues, the judge's decision to hear the subsisting suit awoke Nigerians to the fact that the forces against Buhari have not relented. President Buhari has now filed a motion at the Court of Appeal, seeking to truncate the certificate trial on the basis of a claim that the court papers were wrongly served at the APC national secretariat instead of his residence in Kaduna. The spectacular thing about this appeal is that it has the signature of THIRTEEN Senior Advocates of Nigeria, in addition to about ten other lawyers.
Thirteen SANs to represent Buhari? If this number is not extreme for a case that ordinarily should not exist, then "extreme" needs a redefinition. When the embattled Senate President, Bukola Saraki, showed up with about 90 SANs, Nigerians screamed that he was trying to intimidate the tribunal. His defence by that unbelievable number of senior lawyers was interpreted as implying guilt. Thirteen is far less than ninety, but a parallel can be drawn between both cases. Although it is clear that the plaintiff in Buhari's certificate case is being sponsored by hidden "principalities and powers", most likely in the PDP, the delay/evasion tactics being used by the Buhari camp makes one wonder if he actually has a certificate.
In case the potential consequences of this lawsuit are not understood, here is a pessimistic view of the outcome. The plaintiff, Nnamdi Nwokocha-Ahaaiwe, has asked the court to nullify Buhari's election, and compel INEC to withdraw the certificate of return, and issue same to the runner-up, Goodluck Jonathan. If it happens that the Buhari camp drags the case all the way to the Supreme Court, they may buy enough time to complete the official four-year tenure of his administration. While this strategy may work, it would perpetually cast doubts on the sincerity of Buhari's fight against corruption. Assuming, without conceding, that Buhari did not sit for the said exam, as claimed by the plaintiff, it would be hypocritical to be at the vanguard of the anti-corruption fight while living a life built on lies. Lying, just like stealing, is a form of corruption.
Conversely, should any of the approached courts rule that Buhari's election is invalid, and should that judgement be upheld, chaos lies at the horizon. The bulk of the north would not accept such a judgement, and would interpret it as a ploy to take power out of their hands. Jonathan's concession of defeat shows that he has no more interest in the presidency. Coupling his concession with the present state of the economy, Jonathan would likely hide from another shot at the presidency (except pushed by the usual suspects). Even if he were to accept, chaos may come from those Nigerians who do not care about paper qualifications. Whichever way this goes; Nigeria would enter uncharted territory that even the doctrine of necessity may be helpless for navigation.
This chaos, potential chaos, and confusion have a simple solution. As President Obama did with the birther doubters, President Buhari should publish his original certificate, or if missing, get Cambridge University (or WAEC) to write a covering letter for him. Immediately after the elections, the army announced that Buhari's school certificate had been found. This copy can also be published to end the uncertainty. I believe, and want to keep believing that he has a school certificate. He does not need to waste money on thirteen expensive SANs. The distraction is unhelpful at this time of economic turmoil (except it is intentional). If his handlers do not care about the feelings of Nigerians, they should at least consider Nigeria's image. We cannot have foreign media carrying headlines about our president being dragged through the courts over an ordinary school certificate. I believe that Buhari wrote his final exam in 1961, regardless of whatever grades he may have earned. If against all hope, it is true that Buhari has no certificate, then we can simply give up because corruption has won.
PS. I am not a lawyer, so I refuse to enter into the debate on whether the "School Certificate" in Section 131(d) of the 1999 Constitution (as amended) refers to the primary school leaving certificate or the senior school certificate.
Image Credit: ichilly.com
To Serve and Protect?
Male Heroines and Fathers' Day


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Harmony of the Spheres
Today, when we consider live music in gallery spaces we're perhaps more likely to think of feverishly boho Dalston or downtown New York mash-ups, if not The Velvet Underground jamming at Andy Warhol's silver Factory (or that city's minimalist composers getting their early exposure in loft galleries after being rebuffed by the conservatoire). But, of course, there are all kinds of art and all kinds of music; the wonder is how infrequently the potential synergy between the two creative spheres is truly explored in a gallery context. Which is one reason why the Courtauld Gallery's monthly series of musically enhanced evening Lates offers such a refreshingly rarefied yet uplifting marriage of the visual and the sonic, as Angèle David-Guillou discovers.
The Courtauld Gallery may well be London's most famous hidden gem; one of those under-explored places that everyone who has visited once will visit again and again. This small but perfectly formed museum, set within the impressive 18th century Somerset House building, is rightly publicised as "one of the nest small art museums in the world", having the delightful specificity of presenting outstanding works of art in an intimate, even personal, setting. It also hosts some of the best late openings in London– confidential yet bounteous, instructive and compelling at the same time and, perhaps even more distinctively, musical.
Founded in 1932 as part of the Courtauld Institute of Art (specialising in the study of the history of art and conservation), the Courtauld Gallery is the result of a series of gifts and bequests by 19th and 20th century collectors, not least English industrialist Samuel Courtauld. The latter is largely responsible for the collection's iconic Impressionist and Post-Impressionist paintings, which he collected in the 1920s. us, in the first- floor rooms Manet's Bar Aux Folies-Bergère holds salon with Renoir's La Loge and Van Gogh's Self-Portrait with Bandaged Ear, to cite but a remarkable few. Elsewhere, the museum houses treasures from the early Renaissance up until the second half of the 20th century (paintings, prints but also drawings, sculptures, decorative art, etc.) including an altar piece by Bernardo Daddi, Cranach's beautiful Adam and Eve.
This plurality is reflected in the temporary exhibitions organised three times a year, usually highlighting one particular masterwork from the collection and putting it in the context of other borrowed art. It is to celebrate these seasonal events, that the Courtauld Lates take place an average of one evening a month. For the modest entrance fee of £6, the viewer is invited to commune with the pictorial collection, an experience enhanced not by the usual alcoholic mediations, but through live music, interlaced with creative workshops and talks. Here, more than anything else, it is the harmony of the spheres that lifts the spirits and places the audience in closer contact with the oeuvres on display. Superb musicians provide the extraordinary soundtrack to the nights, and award visitors with a rare holistic experience of visual art – historical and cultural, but also sensory and sensual.
'I did not expect to go to a late opening in a museum and be touched by a sense of art history in such a way'
At the Young Dürer Late evening, staged back in January, The Bagatino Trio performed 15th and 16th century compositions by Ludwig Sen , Paul Ho aimer, Georg aw and Jacob Obrecht. The audience listened reverentially as the warm sound of baroque recorders (each cut from the same tree, we were told) filled the rooms and let the mind wander a few centuries back. The contrapuntal melodies, as beautiful as they were, were not being produced simply for entertainment's sake or to say 'And now some tunes from Dürer's time'; there was a palpable discourse behind the material chosen, in particular, the resonance of Italian style on Germanic music, which echoed the influence of artists such as Antonio Pollaiuolo and Andrea Mantegna on Dürer's early drawings. Later, during the intervals, a drawing workshop and fascinating talks gave insights into the artist's techniques and creative context. Finally, to conclude the evening, the Courtauld's own Community Choir, under the direction of Joseph Timmons, sang music by Heinrich Isaac and JS Bach and enticed the audience to join in for the epiphany songs We Three Kings from Orient Are and Wassail, leaving professionals and dilettantes alike with the satisfying feeling of completion.
By a turn of synchronicity, as I was leaving the building, I stopped by a series of new drawings by Richard Serra, commissioned by the Courtauld. I could not help but imagine if instead of the baroque trio we had heard that night, Philip Glass or Steve Reich had performed their early work in this very room, amidst Serra's work, just like they did some 40 years ago in the loft galleries and art museums of New York City.
Two months later, the gallery unveiled the next in their series of Late events, tying in with the exhibition Court and Craft, which considered the luxury craft tradition of Northern Iraq before and after the Mongol invasion, with a small, metal lady's bag delicately inlaid with gold and silver as a centrepiece. This time, Francesco Iannuzzelli at the oud, accompanied by Lucile Belliveau on the double bass, performed music from the classical and traditional Iraqi and Persian repertoire dating from the 13th century onward. The sophistication of the compositions, as well as their minimalism, perfectly illustrated the subtlety and complexity of the courtly art and Mosul metalwork on show. A very detailed programme explained the origin of the classical repertoire of Iraq and in particular the notable impact of Sa al-Din al-Urmawi's theory of music and compositions. In an adjacent room, an Iraqi artist introduced and then demonstrated the methods and materials of Persian calligraphy. I was particularly fascinated by the ritual of the slicing of the tools: a simple piece of reed was transformed in front of our eyes into the most advanced and multifaceted art implement.
To see artists perform and create among pieces of art conveys in the most directly perceptible way that there is a creator and a performer behind the art, not just a 'feeling individual' with a personal life story (which is what most museum catalogues too often concentrate on), but a working craftsman. The choir, with its communal singing, partakes, I think, in a similar experience – a highly unusual one. Interestingly, the fact that, unlike for Glass and Reich, the performances take place away from the exhibition it is supposed to complement, allows the visitors a totally unspoiled appreciation of each art form. The interdisciplinarity is never synonymous with cacophony; each artistic point of view can be enjoyed in its full form.
I did not expect to go to a late opening in a museum and be touched by a sense of art history in such a way. I was already won over by Persian craftsmanship but was much more reticent about Dürer's drawings. However, the musical element opened a hidden door and allowed me to access his work differently. After the performance I felt an urge to go back and look at his drawings once again, with a renewed outlook. I wonder why galleries so rarely organise this kind of event. Perhaps it is better this way, as not everyone would be able to pass on so much pleasure with the dedication and authority of the Courtauld Institute and its staff . I really do highly recommend these Lates. Not only will you be able to admire beautiful art, but you will have a wonderful evening, both enriching and entertaining.
Author: Gemma deCruz
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Navratan literally translates to the nine jewels but the product we have for you here is nothing less than a jewel in itself! A mixture unlike any other, Navratan takes your taste buds for a joyride in a burst of different flavors and textures, which the different ingredients give it! Even though Navratan mixtures are available throughout the country, this one is a little special because it is made by the famous Hira Sweets which is located in the Shahdara area. Hira sweets might be located in a busy Delhi locality but FoodFeasta.com brings it to your house, no matter where you live! Just buy it online from our website -and treat yourself to this fantastic snack!


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Q: Finding Number of ways to a location. I have come across this question recently and cant find an answer but instead have come up with a number of answers. Please tell me what answer you get.
A __ __ __ __
 |__|__|__|__|
 |__|     |__|
 |__|__ __|__|
 |__|__|__|__|
              B

In how many ways is it possible to travel from A to B (following the lines) if you can only travel right or downwards.
I'm not sure but I think 38 is the answer.
Thanks in advance, Monacraft.

A: Here's a systematic way to count the paths in a small problem like this one. The array below shows the intersections in your diagram as dots ($\bullet$), except that the corner intersections are shown with their labels instead; the non-existent intersection is shown as $\oplus$.
$$\begin{array}{ccc}
A&\bullet&\bullet&\bullet&\bullet\\
\bullet&\bullet&\bullet&\bullet&\bullet\\
\bullet&\bullet&\oplus&\bullet&\bullet\\
\bullet&\bullet&\bullet&\bullet&\bullet\\
\bullet&\bullet&\bullet&\bullet&B
\end{array}$$
The idea is to work from upper left to lower right, replacing each dot or letter by the number of paths from $A$ to that dot. The key insight is that you can reach a dot in one step only from the dot immediately above (if any) and the dot immediately to the left (if any). Thus, if the dot immediately above can be reached in $a$ ways from $A$, and the dot immediately to the left can be reached in $\ell$ ways, then the given dot can be reached in $a+\ell$ ways.
There is just one way to reach $A$: don't move. Thus, we can replace the $A$ with a $1$. The dot immediately to the right of $A$ can be reached only from $A$, so there's only one way to reach it. In fact, each dot in the top row can be reached from $A$ in only one way, and the same goes for the dots in the lefthand column. After filling in these values, we have the following array:
$$\begin{array}{ccc}
1&1&1&1&1\\
1&\color{red}\bullet&\bullet&\bullet&\bullet\\
1&\bullet&\oplus&\bullet&\bullet\\
1&\bullet&\bullet&\bullet&\bullet\\
1&\bullet&\bullet&\bullet&B
\end{array}$$
We now have enough information to replace the red dot with a number: it can be reached from the left and from above, so it can be reached from $A$ in $1+1=2$ ways. Once we have it, we see that the dot to its immediate right can be reached from $A$ in $2+1=3$ ways, and the dot immediately below it can be reached in $1+2=3$ ways. Continuing in this fashion, we fill in the remainder of the second row and second column:
$$\begin{array}{ccc}
1&1&1&1&1\\
1&2&3&4&5\\
1&3&\oplus&\color{red}\bullet&\bullet\\
1&4&\color{blue}\bullet&\bullet&\bullet\\
1&5&\bullet&\bullet&B
\end{array}$$
The red dot can be reached only from above, so it can be reached in $0+4=4$ ways. Similarly, the blue dot can be reached only from the left, so it can be reached in $4+0=4$ ways. Completing the rest of the array is straightforward, and we end with this:
$$\begin{array}{ccc}
1&1&1&1&1\\
1&2&3&4&5\\
1&3&\oplus&4&9\\
1&4&4&8&17\\
1&5&9&17&34
\end{array}$$
There are $34$ paths from $A$ to $B$.

A: I thinks matrix multiplication could be a general method for this kind of questions.

*

*Redefine your given road topology as a 24 node graph.

*Construct a $24\times24$ adjacent matrix $M$, A is node 1, and B is node 24.

*The city block distance (Loops are not allowed) from A to B is 8. Then the number of ways from A to B is equals to $a_{(1,24)}$ of $M^8$ [Reference].
The answer is 34 (verified by Matlab).


Coming next – we're heatedly planning an evening of Kurt Weill. Soprano Marcy Richardson and baritone Ian Greenlaw will join me and a wonderful handful of additional artists to bring New York audiences a cabaret chronology for two toasty Friday evenings in the Gershwin Hotel next month.
Two Fridays, February 11 and 18, 2011, both at 8pm, please join us. Check back here for more details on the repertoire as we flesh out the program. The postcard is here, and the press release, if you'd like to share them.
Still in the planning stages is the third in the series 'HANDEL at the Gershwin,' as well as an evening which will take a slice of an exciting opera-in-progress which operamission has commissioned and is developing, Antinous and Hadrian by Clint Borzoni, libretto by Edward Ficklin. If you're curious about exactly what it takes to create a new opera, this is your chance. We will split open the process for you and show you each stage of this most complex of collaborations, while presenting a sneak preview of the music and libretto in its current state.
Happy New Year, and thank you for supporting operamission!
This entry was posted in Jennifer and tagged american, antinous, antinous and hadrian, art song, baritone, borzoni, cabaret, chanson, chronology, clint borzoni, edward ficklin, ficklin, gershwin hotel, handel, handel at the gershwin, history, ian greenlaw, kurt weill, lied, lieder, marcy richardson, music, opera, operamission, some assembly required, song, soprano, voice, weill. Bookmark the permalink.


This past Thursday, momentum magazine threw a little party for us all bike lovers in the city in celebration of their San Francisco issue. It took place in a nice studio-art space on 7th st. Raffles, beer, bikes, bikers etc. I'm very happy I got to meet the super nice woman that is the editor here in SF! and more peeps that are also Bay Area staff. Cheers!
That's what I named these shoes after one of my favorite female singers. I got them over a year ago, but only felt like trying them out a couple of months ago. Sometimes you just gotta do things when the timing feels right.
Yes, they are clipless and they go on some gadget-y looking pedal, but I'll be the first one to explore all ways of cycling and yet, remain to prefer high-heels and my frenchie above it all. Having so many beautiful mountains to climb and endless miles to explore around the Bay Area, I'm game. So, here we are. These shoes are still worn with dresses. Indeed. In these pictures I have knee-high socks and tights so, not much of a change. However, I do miss having my basket.
wo Thursdays ago the Ride of Silence took place here in San Francisco. t was a nice quiet ride to honor those who have been injured or killed while cycling on public roadways. The ride brought together a small sized-but good group of riders to pay the respect. We all know, that next year the group will continue to grow. It was nice to meet the group, including people from all over the country for such a small group, it was very nice. I also got to meet nicole, who is a reader of this blog and was visiting from the midwest for a few days. That was very cool.


text:
How Trump's Immigration Crackdown Threatens The Dairy Boom In Idaho
By Tom Michael & Susan Ferriss • Sep 20, 2017
An immigrant woman cleans cows' teats and attaches pumps in a state-of-the art milking parlor. Hundreds of cows file in and instinctively turn around to be milked, three times a day. Sometimes the animals kick and defecate, milkers say.
Joy Pruitt / The Center for Public Integrity
A dairy farm in the Magic Valley in Idaho, where immigrant workers have helped turn the state into one of America's biggest milk producers – and fractured conservative opinion in the process.
Hildegardo Torres, who maintains a dairy's machinery, says undocumented workers are nervous about ICE's plan to rent beds at the Jerome County Detention Center. The beds would be reserved for immigrant detainees bound for deportation.
Farms like this, largely operated by conservatives restive at the thought of increased immigration, risk running dry of workers if ICE widens its regional footprint.
Immigrant workers hold an older calf to administer medicine. Farmers say immigrant workers are needed to do the close-to-the-ground tasks from which Americans shy away.
There's a cultural and economic collision occurring in southern Idaho. On one side, the anti-immigrant sentiment has expanded, fueled by conservative talk radio and the rhetoric of the Trump administration. On the other side, the dairy industry – long quiet – is speaking out about their reliance on a foreign-born labor force. And the prospect of a new contract for the county jail has both sides agitated.
How Trump's Immigration Crackdown Threatens The Dairy Boom in Idaho
This gleaming warehouse is clean for a dairy farm. We're in Jerome County, at the center of the booming Idaho dairy industry. A worker – female, Hispanic, in a baggy uniform – is popping rubber nipples off a plastic rack. They've just been washed and are about to be used on bottles to feed hundreds of young calves.
The owner of the dairy marvels at the woman's speed and skill and says, "Look at that; it's amazing. The babies got to be fed twice a day."
The dairy owner won't give his name, because of the stories he's been telling, about the dairy workers who are undocumented immigrants. Foreign-born labor is the engine of this industry that provides Idaho with $10 billion in annual sales. And it's hard to find workers – with or without papers - when unemployment is at 3 percent, the lowest in a decade.
A dairy worker sorts rubber nipples for bottles to feed hundreds of baby calves. According to industry estimates, between 85 to 90 percent of on-site dairy workers in Idaho are foreign-born.
Credit Joy Pruitt
"Clearly without a doubt," says the farmer, "the number-one issue facing agriculture today, especially dairies, is labor. And it's reached a critical stage. And it's all the way from Maine to California to Idaho."
It's tough to hire in a competitive market. There are "pull factors." For example, higher wages elsewhere that pull workers away. But there are "push factors," too. In early July, a group of protestors overwhelmed the Jerome County Courthouse. Residents were protesting a proposed contract with Immigration and Customs Enforcement, or ICE, to lease space at the county jail to detain and deport immigrants.
Shannon Perez, an American who was married to a Mexican dairy worker who was deported, said Americans don't understand that immigrant workers can't just "get legal" with the current immigration system.
Credit Tom Michael / Boise State Public Radio
At this public hearing, the crowd spilled out of the courtroom, down the stairwell, and out the doors. Jerome resident Shannon Perez, who is not Hispanic, says "we actually pushed our way up into the courthouse, into the courtroom upstairs. It was hot. But it was such a touchy subject. I have never seen that big of a turnout of Hispanics, going against . . . wanting to be heard."
County commissioner Charlie Howell has been chairman for the past a decade. He was "flabbergasted" by the turnout, and explains why it touched a nerve, "The opposition is: the presence of ICE in the community. It's the presence of ICE in the community, an extended presence, that intimidates the local workers."
But he also hears from those who favor the ICE contract. "There's kind of two main thrusts," explains Charlie. "'Why are we concerned about illegals, because are they supposed to be here anyway?' That's one of the concerns, but the main plus of the project is 50 beds at $75 a day, guaranteed. That's about $1.3 or $1.4 million dollars a year. It's kind of tough to turn down those numbers when you first initially look at it."
Charles Howell, an electrician and chairman of the Jerome County Commission, said local farmers and Hispanic families have made him think long and hard about whether to support the proposed agreement with ICE.
Credit Joy Pruitt / The Center for Public Integrity
Howell has to weigh that potential income gain against the potential income loss from the dairy farmers who claim that just the specter of deportation has scared away their workers.
"Jerome's economic driver is the dairies," says Howell, "and the agriculture. That's what drives the county. And the Magic Valley basically. So we gain the $1.3. or $1.4 million. What's your return on investment of losing workers, losing employees, slowing your businesses down?"
Others aren't persuaded by the plight of the dairy industry, like conservative talk radio host Bill Colley, from his program on Fox affiliate KLIX in Twin Falls.
On a program this summer, he asked, "Did you happen to see the story in the Times-News this week that if Idaho had a drop in its illegal alien population, we would lose a good chunk of the farm workers in this state? As if somehow that's all the more reason to keep people here and keep them lined up at social services and dropping anchor babies."
Bob Naerebout leads the Idaho Dairyman's Association and knows rhetoric like this has taken hold. "Talk radio's purpose is for ratings," he says. "Their purpose isn't to try to bring the facts. It's all about ratings for them."
He says they're missing the point. Unlike other agriculture, dairy is year-round. There are no temporary work visas like those allowed for seasonal crop workers.
According to Naerebout, "there's not a program we can go to and apply for workers. The fact that our country for the last decade-plus been trying to do something on immigration reform and hasn't been able to get anything accomplished."
It's not just milk producers, but milk processors, too, like Chobani, which built one of the world's largest yogurt factories in the valley. Statewide, Idaho dairies employ 8,100 people and create another 3,700 jobs for milk processors. Chobani signed onto the Dairyman's Association's letter opposing the jail contract, reminding the commissioners the industry's economic impact goes far beyond cheese, milk and yogurt.
The number-one issue facing agriculture today, especially dairies, is labor. And it's reached a critical stage. And is all the way from Maine to California to Idaho.
As goes the dairies, so goes southern Idaho, according to this dairy farmer: "I mean, put yourself in our shoes. The perfect storm is brewing. They're building a wall, tougher immigration policies. Low unemployment rate. A booming economy. And we're still milking cows and trying to get them milked every day."
In the milking room, a woman is working through a 12-hour day, moving along a row of cows, attaching suction pumps to their udders. It's dirty work. "The cows poop all the time," she says in Spanish. An occupational hazard is getting kicked in the head.
More than one-third of Jerome County is Hispanic, at least, those who are counted. Above this dairy fly three flags: Idaho, the U.S. and Mexico. But on the main street in Jerome, outside a motorcycle accessories shop, there's another flag flying: the confederate battle flag. It signals the latest front in the culture wars. Inside the shop, there's strong support for leasing the county jail to immigration officers.
"I think it's good for the town. I think it's good for the community," states Marty Fuqua, from behind the counter. He says his business has grown, but he doesn't tie his success directly to the dairy industry in Jerome, even though this city of 23,000 is dominated by 55 dairies.
A dairy farm in the Magic Valley, Idaho, where immigrant workers have helped turn the state into one of America's biggest milk producers.
He supports the Trump administration's hard line on immigration, saying "the problem is that they're coming across illegally, doing their drugs, doing their crimes, doing, you know, rape, rob and murder. And then they expect a free ride. Well, you're going to get a free ride. Straight to our jail and straight back to your country."
Ryan Bennett sits nearby and nods his head in agreement. He grew up here and knows the tensions first-hand. One day at work, at the Jerome Cheese factory, a friend of his suddenly disappeared.
"He got deported," says Bennett. "And he was one of the greatest guys I know. I had no idea. He was paying taxes and stuff. But he had false documents. And that really hit me in the heart."
He feels the debate is tearing up his town, with "this side is fighting that side and that side fighting this side; it's kind of a big mess. He looks beyond Jerome for political solutions, saying, "I wish the state and federal agencies could help out more."
Bob Naerebout, director of the Idaho Dairymen's Association, says protecting immigrant workers is the "moral position."
Idaho's representatives in Washington are well aware of Jerome's problems. U.S. Senator Jim Risch tells Boise State Public Radio, "Their industry is clear evidence why we need a good, workable guest worker program." It's a sentiment U.S. Congressman Mike Simpson echoes, but critics say neither politician is doing much about it.
Meanwhile, other lawmakers are making it even harder. Earlier this year, Idaho's other U.S. Congressman, Raul Labrador, sponsored legislation that would allow local officials to prohibit refugees from settling in their communities.
Back on the dairy farm, Bob Naerebout and the dairy owner bounce along in a truck between the vast cattle pens and towering storage silos. They reminisce about legislative attempts in years past that came close to a solution. But now that political gridlock is entrenched, their business future seems to be in limbo.
In quiet frustration, the dairy owner asks Naerebout a question to which he well knows the answer: "Bob, why can't they – why we get an immigration bill?" Naerabout responds, "Because we have too many politicians and we do not have enough statesmen."
Indecision is a problem in Washington D.C and here in Jerome County. At the moment, leasing the jail to immigration enforcement is on hold, as the commissioners weigh their options.
In the Magic Valley, there's a saying: "The milk never stops going, the cheese never stops going." But political solutions, on the other hand, take a long time.
EDITOR'S NOTE: This reporting is a collaboration between Boise State Public Radio and The Center for Public Integrity, a non-profit that produces investigative journalism. There is another version of this investigative story in the online magazine, POLITICO.
Find Tom Michael on Twitter @tom2michael
Idaho Dairymen's Association
Magic Valley
In Idaho's Dairy Country, Undocumented Workers Fear Trump's Policies
By Matt Guilhem • Apr 18, 2017
Matt Guilhem / Boise State Public Radio
Idaho may be synonymous with potatoes, but the state is also one of the largest dairy producers in the country. Like much of the agriculture sector, a majority of the labor at dairies comes from foreign-born workers.
In southern Idaho, cows' hooves clack gently as they stand in the milking parlor of a small dairy. Taking the noise of the automated milkers in stride, the cows are calm as they're milked in 10 minute sessions. Monitoring the animals, overseeing the machinery and wrangling the cows in and out of the milking parlor is Pedro.
Idaho Dairy Industry Creates Training Program To Protect Workers After Grisly Deaths
By Frankie Barnhill • Aug 18, 2017
Frankie Barnhill / Boise State Public Radio
Thirty-seven-year-old Ruperto Vazquez-Carrera drowned in a manure pond in February 2016. The horrific death at Sunrise Organic Dairy in Jerome – followed by another seven months later near Idaho Falls – prompted federal investigations.
Idaho Dairymen's Association Expects Flat Market In 2017
By Matt Guilhem • Jan 3, 2017
CompassioninWorldFarming / Flickr
Idaho's dairy industry will be watching the new Trump administration's trade policy, as one of the state's biggest sectors is bracing for a flat year.
The president of the Idaho Dairymen's Association told an agriculture conference last month that any increase in Idaho's milk production would be exported abroad.
The U.S. Department of Agriculture forecasts that by November of this year, dairy exports will be 8.9 billion pounds – that's slightly higher than last November's 8.7 billion pounds.
Idaho Dairy Sued By Former Workers From Mexico
By Frankie Barnhill • Jan 13, 2017
Kay Ledbetter / AgriLife
A lawsuit filed in district court in Boise earlier this month pits an Idaho dairy against former employees from Mexico.
Six veterinarians are suing Funk Dairy southeast of Twin Falls for human trafficking and breach of contract, among other charges. The vets are from Mexico, and say they were hired to work at the dairy in 2014 under false pretenses.


text:
Q: Optimizing unions I'm having trouble trying to optimize the following query for sql server 2005. Does anyone know how could I improve it. Each one of the tables used there have about 40 million rows each. I've tried my best trying to optimize it but I manage to do the exact opposite.
Thanks
SELECT
        cos
      , SIN
    FROM
        ConSisHis2005
    union all
    SELECT
        cos
      , SIN
    FROM
        ConSisHis2006
    union all
    SELECT
        cos
      , SIN
    FROM
        ConSisHis2007
    UNION ALL
    SELECT
        cos
      , SIN
    FROM
        ConSisHis2008

Maybe I should have said something else about the schema, all the tables used here are historical tables, they are not referenced to any other table. And theres already an index for cos and SIN. I was just wondering if there was any other way to optimize the query... as you can imagine 160millon records are hard to get :s

A: It seems that the query is just combining the separated history tables into a single result set containing all the data. In that case the query is already optimal.

A: Another approach would be to tackle the problem of why do you need to have all the 160 million rows? If you are doing some kind of reporting can you create separate reporting tables that already have some of the data aggregated. Or do you actually need a data warehouse to support your reporting needs.

A: Put a composite index on cos and sin on each of the tables.  That's as good as you're going to get without restructuring the table design (in this example, it looks like you should have just 1 table to begin with)

A: Since there is no WHERE clause, I don't believe there's anything you can do to improve the performance from this PoV.
You've correctly used UNION ALL so there's no help there.
The only other thing I can think of is whether there are more columns on the tables?  If so, you might be fetching more data from disk than you need, thus slowing the query down.

A: It might be worth experimenting with indexed views. You could put the above statement into a view with the indexes Dave suggested. This would take a little time to build initially but would return your results a little quicker (this is on the assumption that the data set does not change much and therefore you can live with the extra transactional overhead).

A: You might consider using a single partitioned table with a year indicator.
I'm still curious - is this code in a view or SP which operates on 160m rows or is it actually going to return 160m rows down the wire.  If so, that's an awful lot of data to return that's effectively an extract and it's going to take a while just to come down the wire.

A: There's no optimization to be done. Since you're selecting all the records from all the tables, by definition you get all the records from all the tables in one result set.
What's the reason for doing this?


text:
The International House of Mojo
Return to Monkey Island "continues" or "concludes" series?
By Captain Mystery,
September 2, 2022 in General Discussion
Captain Mystery
Anyone notice that the official website for Return to Monkey Island and the Steam pre-order page no longer say that the game "concludes" or is the "conclusion" to the entire series?
Just before July, the website still touted the upcoming game as wrapping up the saga. And now both the website and Steam simply say it "continues" the series. Is this because Ron and Dave want to downplay the significance of this being their planned finale for Monkey Island? Are more chapters already in the works based off the positive development of this one? ¬ ¬
Apologies if this has been asked and debated already, I am very lazy and could only manage typing this up before a nap.
I hope it "confuses"
LowLevel
12 minutes ago, Captain Mystery said:
Yes, I've noticed it, the changes (in all their websites) happened around the same time they revealed the release date at Gamescom.
My guess is that they used the term "concludes" from a narrative point of view, meaning that the game might show the last phase of the saga, with Guybrush recalling past events.
I think they changed that word either because it could easily be mistaken for information about the production of possible future games or because it was too spoilerish.
Vainamoinen
We've debated that it uses the word "conclude", but we didn't debate that they've changed it.
Back then I said that a successful series will never be concluded, but marketing is of course hell bent on telling people that the narrative will give you closure.
It's interesting that they changed it, because it raised exactly the right, diffuse idea in the customers' heads: That this would be the final last crowning finishing ultimate Monkey Island game and if they're not on board, they will have eaten fries and slaw yet not the fried chicken. 🍖
It doesn't mean that part seven is in the works, it doesn't mean that they got a gazillion pre-orders and will definitely continue. But it's nice to think that was the case.
BillyCheers
Let's just hope this is still a Monkey Island game, when it releases... 👀
Joke aside, I would like to see it "answer" some questions (especially regarding the MI2 ending) and ask a lot of new questions - no matter if there are more games or not.
I for one am now pretty relaxed with sequels to the point that a sequel can't ruin anything for me anymore. If it's good and an enrichment for the series, great! If not, the other games (or whatever) still remain to enjoy and discuss. 🙂
Whatever the ending in ReMI is... there's always a way to continue a story if you want to.
JacquesSparkyTail
1 hour ago, Marius said:
I vote for conquistadores
Mojo Updater
"Captain Mystery." Glad to see the legacy lives on. ;-*
3 minutes ago, Remi said:
Older, far less wiser, and irritable about *everything* now! ¬ _¬
KestrelPi
What I'd like is a game that would work really well as the last one ever released, even if it isn't.
MI1: yes
MI2: yes if like me you're fond (largely due to MI2 existing for most of my teens without a sequel of mysterious, freakout endings) no if you like things explained/resolved
CMI: Yeah, it works
EMI: Sure
Tales: I think... no? The Voodoo Lady stuff is too intriguing to leave hanging, but if they decided to ignore it for ReMI I guess it doesn't matter any more (if they pull one thread from Tales, I hope it's this)
None of these games were called the conclusion, but most of them work as one.
BaronGrackle
27 minutes ago, KestrelPi said:
Funny enough, I disagree on your last two. After Escape, I was disappointed that the series ended with my least favorite game, the last puzzle being a Monkey Kombat response that worked for reasons I didn't fully understand, and the final moment being Guybrush calling for Jar Jar.
With Tales, yes the conversation between Voodoo Lady and Morgan come as a sequel hook, but it was easy for me to interpret it as normal stuff that was going to keep happening in the universe. Like the tvtropes article "And the Adventure Continues". As far as pre-credits is concerned, the Tales ending reflected the conversation between Guybrush and Elaine at the end of Secret... so it felt full circle in my mind.
2 minutes ago, BaronGrackle said:
Oh sure, you can be happy or unhappy with the ending - I think EMI is not a good conclusion to the series narratively, but it IS fairly conclusive. LeChuck is defeated, Elaine's thread is resolved, status quo is restored and all is well. There's not any sort of compelling sequel hook there that I recall, even CMI had a little bit of one with the post-credits and Murray. So I would say EMI was the most conclusive game since MI1.
Tales I say is inconclusive because of that sequel hook, I feel like they wanted to line up some ideas for a potential Season 2 that never materialised. It feels to me much less like that trope you mentioned, and more like very specific story things being set up to be picked up on later.
With that perspective, I daresay that RMI had better not ignore the Voodoo Lady as a manipulator, or else that thread will hang forever and never be resolved.
While I don't know what they'll do with it, that is something they introduced in MI2. Odds that it might be touched on seem decent.
With Grossman also being familiar with Tales, maybe we can hope for it.
I also share the opinion that they wanted to make it clear that this isn't necessarily, definitely the final one. As soon as the site was updated, certain websites wrote articles with headlines like "Return is the Final Monkey Island" despite the fact that Ron said pretty early on in interviews that he wouldn't say no to making another if they had the right story. If anything, he just made it clear that, at the very least, he needs to take a break from the material and let his brain rest before considering diving back into the same series.
I'm expecting this game will be a conclusion to the story arc established in the first game, but will still leave things where another one could easily come after it. I think almost everyone here got that same impression. I think there will also be a lot of surprises in terms of what is referenced from the other games. I think those type of plot points would be strictly off the table with marketing; they don't even want to hint at it. I'm actually a little surprised that nothing of the Voodoo Lady has been shown outside of one clip of her in the first trailer. If she isn't featured in the final Monkey Island Monday, it would make me think something big will be going on with her in this game.
Edited September 5, 2022 by demone
Not that my take matters on someone else's read of the text of the game - your own read is your own read, which is part of the fun and the point of fiction imo - but the end of Tales was not lining up any specific plan. It was, in my eyes at least, far closer to "the adventure continues," where the basic cycle of the status quo was allowed to roll on and on, even as the arcs of the characters reached something close to a resolution. I find it a little too much of a cliffhanger at this point, because of how much is hung on the Voodoo Lady in particular, but at the time didn't see it as much more than Chuckie's eyes flashing, or LeChuck being buried beneath the ice of the monkey coaster.
(To clarify a tiny bit: the voodoo lady being a third party with separate ends, who is willing to push guybrush and lechuck around for whatever those ends are, is something I was very proud of surfacing in Tales, and liked how well it ties into the sudden turn to LeChuck's fortress at the end of 2. I think the cliffhanger is a little too specific, and that probably came from us being so inside the world of our own game at the time we were ending it. I don't mind it, and I love the idea of that voodoo lady storyline, but I think it could have been rolled a tiny bit farther back into ambiguity than it is!)
Honestly, I always viewed the Voodoo Lady's actions and words in Tales as more of a conclusion for her character than any of the previous games. Simply not knowing anything about her after an entire series would've made her character feel a bit empty, which I felt about the character in Curse and Escape. Finally learning a bit more of her past with De Cava and knowing that she's not simply giving Guybrush advice, but does have a goal of her own, adds a lot of layers to her character and made past actions actually make more sense.
Yes, one could make the argument that not knowing the specifics of that agenda could be seen as a sequel hook, but I always thought the game's writing did a good enough job to leave you with just enough clues to come up with your own conclusion. As Jake said, it's nice to have a plot point like that where everyone has a unique perspective on it. She's neither good nor evil, but is working to keep things a certain way. It's a nice culmination of her character and, again, I saw it as a nice conclusion for her character is many ways.
Just now, Jake said:
I believe you! I am just going with how I personally felt about it. I always thought LeChuck's eye flash was more than anything a gag. Just a little 'or... IS IT?' just to mess with the player a little more than they've already been messed with. The stuff in tales felt so specific to me - first of all with the voodoo lady talking about the larger plan she was a part of, but then especially the transaction between her and Morgan.
You know how the scene at the end of Back to the Future was never really supposed to be set up for a sequel, but just a fun way to end the film? But so many people who watch the series now assume that it was always planned as a trilogy because of that ending directly leading into it, and people are surprised to find out that the ending was really just nothing, a joke...? That's kind of how this situation feels to me, if there had been a Tales Season 2 I think it absolutely would have had to address those plot points or people would have said 'what the hell?' But I always read Chuckie's eyes as a little 'gotcha' gag, and would have accepted a sequel interpretation that totally ignores it, or goes with it (as CMI seems to). The fun thing is, because ReMI picks up there, we may soon very well get to see how literal that moment is.
I guess the danger of leaving little teasing, dangling threads in your ending always carries the risk that later you'll be expected to resolve them no matter how tongue in cheek they were meant
This is almost definitely true!
(And, to be fair and clear, I'm sure that if a Tales season two was made it would have used or referenced that epilogue moment in some way. But I doubt it would have been a direct continuation from that scene.)
How I felt about Chuckie's flashing eyes, the first time I finished MI2, is exactly how Ron Gilbert has described the ending: "a huge cliffhanger". (Source)
I'm aware that many players didn't perceive it as such, but I've always considered it not just "a" cliffhanger, but a very big one.
While a cliffhanger, the thing that makes MI2's ending a bit different to other kinds of cliffhangers is that it refuses to explain itself. It just does something confusing, then messes with that setup in ways which are, in themselves, confusing. It -could- be a set up for a sequel, but it's not like you're given ANY idea how. They could, and did, take things in pretty much ANY direction from there.
As soon as they decided to make a sequel to BTTF they had to address the fact that Marty, Jennifer and Doc had gone into the future to do something about their kids, which is more of how I think about cliffhangers - a specific situation is set up, that we understand needs a resolution. We're not in any way confused about where the next film is going. (Yes, I know this was supposed to be a 'the adventure continues' moment but the existence of the sequel turns it into a straight up cliffhanger)
With MI2, we can't even agree on what happened. Was it all just Guybrush's imagination? Is this some kind of dream? A Voodoo spell? At what point did that take over, if so? Are they really brothers?
To me, that fits with another category of cliffhanger, which is - an ending that leaves you with lots of questions, but invites a lot of interpretations which could in themselves be conclusive. So, I think they CAN be satisfying as conclusions. And if MI2 had been the last MI game I think I would have been okay with it. I'd have had my interpretation, I would have liked to speculate about other ones, but I think I could make peace with MI2's ending, as it is. It's 2001: A Space Odyssey territory, in a way: you aren't exactly sure what just happened, but it sure does stick in the head.
CMI's ending credits thing is so vague it can be dismissed. It's just a vague 'lechuck is defeated... OR IS HE?' thing which is well worn.
EMI wraps stuff up even if I don't care for how it does it.
Tales... I dunno, for me tales is still the one that to me most overtly throws a sequel bone. But I see why people feel more that way about 2.
MI2 does have the mid-credits scene of Elaine wondering what had happened to Guybrush, hoping that LeChuck hadn't put a terrible curse on him.
I remember in the late 90s, people who didn't want to interpret that ending as a curse chose to believe that LeChuck's glowing eyes and Elaine's comments were added against Ron Gilbert's will.
23 minutes ago, BaronGrackle said:
Curious about where you saw/heard that. Can't recall seeing that at TSB/Mojo forums back then.
1 hour ago, Remi said:
It was probably early 2000s. I wasn't on Monkey Island forums, but I did read articles from the webrings. And I probably got the idea from an article like this: https://scummbar.com/resources/articles/index.php?newssniffer=readarticle&article=2
...with the eyes dismissed in a Bill Tiller quote:
Well this is all I know, and I learned it from Larry Ahern and Dave Grossman. [..] The explanation I heard is that Guybrush was lost in the Pirates Ride at Big Whoop Amusement Park the whole time, imagining the whole adventure. Then Chucky, his mean older brother goes and pulls him back to reality. The end.
And that magical lightning coming out of Chucky's eyes and Elaine waiting by the hole on Dinky Island (which sounds a lot like Disney Land) was put there just in case there was to be a Monkey Island 3. The secret is that the MI world is not real.
So let me backtrack... maybe I didn't read that those things were put in against Ron's will. I read that they were thrown in as a just-in-case room for a sequel, but they were unrelated to the ending's true meaning. Put that on Bill Tiller!
Ah yeah, that old article might look very outdated two weeks from now, but I think it held its own at the time. We'll see soon enough!


text:
Home Books Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e
Chapter 50: Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections
Margaret A. Phillips; Samuel L. Stanley, Jr
Phillips MA, Stanley SL, Jr. Phillips M.A., & Stanley S.L., Jr Phillips, Margaret A., and Samuel L. Stanley, Jr.Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections. In: Brunton LL, Chabner BA, Knollmann BC. Brunton L.L., & Chabner B.A., & Knollmann B.C.(Eds.),Eds. Laurence L. Brunton, et al.eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. McGraw Hill; 2015. Accessed January 21, 2022. https://accesspharmacy.mhmedical.com/content.aspx?bookid=1613&sectionid=102162958
Phillips MA, Stanley SL, Jr. Phillips M.A., & Stanley S.L., Jr Phillips, Margaret A., and Samuel L. Stanley, Jr. (2015). Chemotherapy of protozoal infections: amebiasis, giardiasis, trichomoniasis, trypanosomiasis, leishmaniasis, and other protozoal infections. Brunton LL, Chabner BA, Knollmann BC. Brunton L.L., & Chabner B.A., & Knollmann B.C.(Eds.),Eds. Laurence L. Brunton, et al. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. McGraw Hill. https://accesspharmacy.mhmedical.com/content.aspx?bookid=1613&sectionid=102162958
Phillips MA, Stanley SL, Jr. Phillips M.A., & Stanley S.L., Jr Phillips, Margaret A., and Samuel L. Stanley, Jr. "Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections." Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e Brunton LL, Chabner BA, Knollmann BC. Brunton L.L., & Chabner B.A., & Knollmann B.C.(Eds.),Eds. Laurence L. Brunton, et al. McGraw Hill, 2015, https://accesspharmacy.mhmedical.com/content.aspx?bookid=1613&sectionid=102162958.
INTRODUCTION TO PROTOZOAL INFECTIONS OF HUMANS
ANTI-PROTOZOAL DRUGS
Humans host a wide variety of protozoal parasites that can be transmitted by insect vectors, directly from other mammalian reservoirs or from one person to another. Because protozoa multiply rapidly in their hosts and effective vaccines are unavailable, chemotherapy has been the only practical way to both treat infected individuals and reduce transmission. The immune system plays a crucial role in protecting against the pathological consequences of protozoal infections. Thus, opportunistic infections with protozoa are prominent in infants, individuals with cancer, transplant recipients, those receiving immunosuppressive drugs or extensive antibiotic therapy, and persons with advanced human immunodeficiency virus (HIV) infection. Treatment of protozoal infections in immunocompromised individuals is especially difficult, and the outcome is often unsatisfactory.
Most antiprotozoal drugs have been in use for years despite major advances in bioscience relevant to parasite biology, host defenses, and mechanisms of disease. Satisfactory agents for treating important protozoal infections such as African trypanosomiasis (sleeping sickness) and chronic Chagas' disease still are lacking. Many effective antiprotozoal drugs are toxic at therapeutic doses, a problem exacerbated by increasing drug resistance. Development of drug resistance also poses a serious threat to better tolerated antiprotozoal agents in current use. Unfortunately, many of these diseases afflict the poor in developing countries, and there is little economic incentive for pharmaceutical companies to develop new antiparasitic drugs. Scientists and physicians working in this field must be creative and have turned to drugs developed originally for other indications (e.g., amphotericin and miltefosine for leishmaniasis), to investigational drugs made available directly from the Centers for Disease Control and Prevention (CDC), or to agents developed for veterinary use to discover new antiparasitic therapies.
This chapter describes important human protozoal infections other than malaria and the drugs used to treat them.
Amebiasis. Amebiasis affects ~10% of the world's population, causing invasive disease in ~50 million people and death in ~100,000 of these annually (Stanley, 2003). In the U.S., amebiasis is seen most commonly in the states that border Mexico and among individuals living in poverty, crowded conditions, and areas with poor sanitation. Three morphologically identical but genetically distinct species of Entamoeba (i.e., E. histolytica, E. dispar, and E. moshkovskii) have been isolated from infected persons. Although the proportions vary worldwide, E. dispar and E. moshkovskii account for ~90% of human infections, with E. histolytica responsible for only 10%. However, only E. histolytica is capable of causing disease and thus requires treatment.
The organisms can be differentiated by antigen-detection enzyme-linked immunosorbent assays or by polymerase chain reaction (PCR)–based diagnostics. Humans are the only known hosts for these protozoa, which are transmitted almost exclusively by the fecal-oral route. Ingested E. histolytica cysts from contaminated food or water survive acid gastric contents and transform into trophozoites that reside in the large intestine. The outcome of E. histolytica infection is variable. Many ...