text:
Review of 2018: television
by Gillean Craig
A glorious year for high-quality drama
BBC/Sid Gentle Films/Jason Bell
Villanelle (Jodie Comer) and Eve (Sandra Oh), in Killing Eve, one of the highlights of a glorious year for TV drama
IT WOULD be quite unfair to say that there was no religion on TV throughout 2018. Looking back over my year's notes, I find at least four programmes devoted to our faith, including the fly-on-the-wall series about Herefordshire clergy, A Vicar's Life (BBC2); Pilgrimage: The road to Santiago (BBC2); and Jesus' Female Disciples: The new evidence (Channel 4) — which wasn't new at all, but needs to be told.
What our religion does formally was on show in The Royal Wedding: Harry and Meghan, and many programmes that commemorated the Centenary of the Armistice. Religion in a more general sense received thought-provoking attention in Bettany Hughes's Bacchus Uncovered: Ancient god of ecstasy (BBC4); Grayson Perry's Rites of Passage (Channel 4); and that extraordinary meditation on the high places of this earth, Mountain (BBC4).
Religion was, as always, a constant theme in many arts and cultural programmes, especially The Art That Made Mexico, on BBC4, and in Civilisations, presented by Simon Schama, Mary Beard, and David Olusoga, the curiously underwhelming remake of Kenneth Clarke's 1960s masterpiece in the singular (BBC2).
BBC/PLAYGROUND/PATRICK REDMONDBBC 1's Little Women
Science, too, played with religious themes: for example in Alice Robert's redesign of the human body (her own, actually) in Can Science Make Me Perfect? (BBC4). Politics brought a slew of major BBC2 documentaries in which religion was a key factor: House of Saud; Syria: The world's war; and Dangerous Dynasty: House of Assad.
Weinstein: The inside story (BBC1) paid proper attention to a current issue, while several programmes inspired by the 70th anniversary of the NHS raised many questions about today as they saluted the past. Nothing brought the reality of the slaughter of the First World War closer to home than Peter Jackson's remarkable reworking of contemporary footage in They Shall Not Grow Old (BBC1).
But 2018 was, above all, and gloriously, the year of TV drama. All channels have decided that their laurels depend more than anything else on commissioning high-quality productions: intelligent, well-written, sharply directed, magnificently designed, and brilliantly acted by top stars. We have never had such a feast.
As usual, we saw adaptations of classic novels: BBC1's Little Women, The Woman in White, and ITV's Vanity Fair. But far more unusual was the bumper harvest of new dramas: McMafia, Hard Sun, Kiri, Collateral, The Split, Keeping Faith, Bodyguard, Wanderlust, Strangers, Trust, Black Earth Rising, Killing Eve, The Cry: it is an astonishing tally.
BBC/CTV/Brigid McFallPilgrimage: The road to Santiago (BBC2)
Too many of them rely on sensational criminal material; too many glory in violence and bloodshed; and, very often, the final episode, with a far-fetched denouement exposing the flaws in the plot while keeping open the possibility of a further series, is less satisfactory than what has gone before; but all of them pay serious attention to serious themes.
If it's all too much, the year's best new comedy was Stath Lets Flats (Channel 4).
Michaelmas 2018 represented a significant moment for me as I retired after four decades of full-time parochial ministry; so expect this column to read very differently, focusing henceforth on daytime TV and shopping channels.
Pawn in the game
In front of the box
Insects on display
Honest intentions
Unexpected scoop
Human experiences
TV review: Alexander Armstrong's Best Christmas Ever, Death and Nightingales, and People Just Do Nothing
Week aheadFaithRegulars
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Mission and Evangelism Development Officer
We are looking for a new lay or ordained colleague to enhance our capacity for mission at every level of Diocesan life by: Overseeing and coordinating diocesan engagement with parishes and leading mission planning support.
Rector (Full Time)
Our Benefice is just west of Stafford and the four churches cover several rural villages. Farming is the main local activity but there are also significant numbers of commuters who work in the surrounding towns and cities. All our churches are within a 3 mile radius from the rectory, which is in Haughton, the largest village.


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Atrix 2 finally gets Ice Cream Sandwich
Ex Contributor
Motorola's successor to the Atrix phone is now getting its just desserts.
The device is joining many other Motorola devices since the Google acquisition to get the update to Ice Cream Sandwich, known officially as Android version 4.0.
The update will be heading to the device soon via an over-the-air software push. However, those who can't wait can just go into their phone menu to download the update manually, according to AT&T.
Many Motorola devices have been seeing upgrades lately, thanks most likely to the fact that Motorola's smartphone operations now belong under the Google umbrella.
Ice Cream Sandwich is one of the biggest updates to Android yet, and includes such features as scanning your face to unlock the phone, a much more robust speech-to-text software program, and an entire platform of data sharing that focuses on Near Field Communication (NFC).
Several other manufacturers have pledged support for the new update, and a bunch of phones currently running an older version of Android.
Ice Cream Sandwich is now powering more than 20% of active Android devices, according Google's most recently released official statistics.
Video: Forza Horizon demo hits the Xbox Live track
Game of Thrones loves Dubrovnik
Picking a New CEO for Twitter: Why Most CEO Selections End Badly
8 Ways for Your Ecommerce Business to Take Advantage of the Holiday Season

redpajama_set_name: RedPajamaCommonCrawl


The past week saw the staging of a ladies' triples match at home to Honiton, writes Carol Smith.
The match, our first of 2019, was meant to be one of three in the opening week, but, sadly, the other two scheduled matches were cancelled.
The meeting with Honiton proved a successful one for Sidmouth with home wins on all three rinks.
It left the final score as 52 shots to 25 in Sidmouth's favour. The top home rink was the one of Sue Turner, Pat Harvie and skip Susie Bonnell, who won 20-6.
That represents a good start to the year, ladies.


text:
/*
 * Licensed under the Apache License, Version 2.0 (the "License"); you
 * may not use this file except in compliance with the License.
 * You may obtain a copy of the License at
 *
 * http://www.apache.org/licenses/LICENSE-2.0
 *
 * Unless required by applicable law or agreed to in writing, software
 * distributed under the License is distributed on an "AS IS" BASIS,
 * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
 * See the License for the specific language governing permissions and
 * limitations under the License.
 */
package org.esipfed.eskg.nlp;

import java.io.File;
import java.io.IOException;
import java.io.InputStream;
import java.nio.charset.Charset;
import java.nio.charset.StandardCharsets;
import java.nio.file.Files;
import java.nio.file.Paths;
import java.util.List;

import org.apache.commons.io.FileUtils;
import org.slf4j.Logger;
import org.slf4j.LoggerFactory;

import edu.knowitall.openie.Argument;
import edu.knowitall.openie.Instance;
import edu.knowitall.tool.parse.ClearParser;
import edu.knowitall.tool.postag.ClearPostagger;
import edu.knowitall.tool.srl.ClearSrl;
import edu.knowitall.tool.tokenize.ClearTokenizer;
import opennlp.tools.sentdetect.SentenceDetector;
import opennlp.tools.sentdetect.SentenceDetectorME;
import opennlp.tools.sentdetect.SentenceModel;
import scala.collection.JavaConversions;
import scala.collection.Seq;

public class OpenIE {

  private static final Logger LOG = LoggerFactory.getLogger(OpenIE.class);

  private OpenIE() {
    // default constructor
  }

  static String readFile(String path, Charset encoding) throws IOException {
    byte[] encoded = Files.readAllBytes(Paths.get(path));
    return new String(encoded, encoding);
  }

  public static void main(String[] args) throws IOException {

    SentenceDetector sentenceDetector = null;
    try {
      // need to change this to the resource folder
      InputStream modelIn = OpenIE.class.getClassLoader().getResourceAsStream("en-sent.bin");
      final SentenceModel sentenceModel = new SentenceModel(modelIn);
      modelIn.close();
      sentenceDetector = new SentenceDetectorME(sentenceModel);
    } catch (IOException ioe) {
      LOG.error("Error either reading 'en-sent.bin' file or creating SentanceModel: ", ioe);
      throw new IOException(ioe);
    }
    edu.knowitall.openie.OpenIE openIE = new edu.knowitall.openie.OpenIE(new ClearParser(new ClearPostagger(new ClearTokenizer())), new ClearSrl(), false, false);

    // any text file that contains English sentences would work
    File file = FileUtils.toFile(OpenIE.class.getClassLoader().getResource("test.txt"));
    String text = readFile(file.getAbsolutePath(), StandardCharsets.UTF_8);

    if (sentenceDetector != null) {
      String[] sentences = sentenceDetector.sentDetect(text);
      for (int i = 0; i < sentences.length; i++) {

        Seq<Instance> extractions = openIE.extract(sentences[i]);

        List<Instance> listExtractions = JavaConversions.seqAsJavaList(extractions);

        for (Instance instance : listExtractions) {
          StringBuilder sb = new StringBuilder();

          sb.append(instance.confidence()).append('\t').append(instance.extr().context()).append('\t').append(instance.extr().arg1().text()).append('\t').append(instance.extr().rel().text())
                  .append('\t');

          List<Argument> listArg2s = JavaConversions.seqAsJavaList(instance.extr().arg2s());
          for (Argument argument : listArg2s) {
            sb.append(argument.text()).append("; ");
          }

          LOG.info(sb.toString());
        }
      }
    }

  }

}

redpajama_set_name: RedPajamaGithub


This Wednesday, August 10th, The Cool Kids will be in New York City at Harlem's http://uristocrat.com/side-effects-viagra-drug/ for an in-store meet & greet. This is part of their promotional run for their latest album, When Fish Ride Bicylcles. When Fish Ride Bicycles out now, exclusively on pre filing bankruptcy counseling! The Cool Kids will also be playing at the Brooklyn Bowl on Wednesday event. Tickets are on sale now and this event is 21 & up.


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Rivian Reports R1T/R1S Production And Delivery Numbers
Rivian reports that as of December 15, it produced and delivered respectively 652 and 386 Rivian R1T/Rivian R1S electric vehicles.
Production and deliveries
The numbers include exactly two R1S, which means that the cumulative production and deliveries of the R1T stand at respectively 650 and 384.
Comparing the numbers with the previous report (as of the end of October) – it turns out that within one and a half months, the company produced and delivered respectively 470 and 228 R1T. The average production rate of the R1T over the past 45 days improved to 10.4/day (from 3.8/ day in the initial 48 days).
"Our first consumer vehicles, the R1T and R1S, are our handshake with the world and the first step in building a relationship with our customers. In September, we delivered our first R1T. This was an emotional moment for our team who have poured its energy and soul into bringing this vehicle to life. As of December 15, 2021, we have produced 652 R1 vehicles and delivered 386 of those, including the production and sale of our first two R1S vehicles earlier this week."
R1T/R1S production plan
The ramp-up progresses, however, the company notes that it will not be able to fulfill its target of about 1,200 R1T/R1S, which will be missed by a few hundred units.
"Our team is incredibly focused on ramping our production output to get vehicles to our excited customers. We expect to be a few hundred vehicles short of our 2021 production target of 1,200, however, we are encouraged by the progress and learnings our team continues to incorporate into our operations. We are continuously improving as we refine our manufacturing operations and remain focused on ensuring the highest possible level of product safety and quality as well as the health and safety of our employees."
The company reassures us that the major goal for 2021 is certifying the R1T, R1S, and EDV 700 for sale and starting deliveries through our direct-to-customer operations. The volume production and sales will follow in 2022.
The 3.3 million square foot manufacturing plant in Normal, Illinois is equipped for the annual production of up to 150,000 vehicles on the R1 and RCV platforms, which after an upcoming investment, related to the R1 line, is expected to produce up to 200,000 vehicles annually.
There are two separate body shop and general assembly lines for each vehicle platform (R1 and RCV), but the battery, drive unit, and stamping portions of the plant are shared across platforms.
Rivian EDV coming soon
As promised, before the end of this year, Rivian intends to deliver the first units of Rivian EDV electric vans for Amazon, which placed an order for 100,000 units by 2025, including 10,000 in 2022.
"We plan to deliver our first saleable EDVs to Amazon this month. Every commercial vehicle sold to Amazon is complemented by FleetOS, our proprietary, end-to-end, centralized fleet management platform with a recurring monthly subscription fee."
The Rivian EDV 700 (the first version) has been certified and is ready to sell. According to Rivian internal testing using official EPA test procedures, the EDV 700 will have a range of 201 miles (323 km).
In early 2022, also the narrower and shorter EDV 500 version is expected to complete certification.
Gallery: Rivian-Amazon Delivery Van
71,000 Rivian R1T/R1S pre-orders
The number of pre-orders (in the U.S. and Canada) improved significantly during the recent period and now stands at about 71,000.
Let's take a look at how it increased:
September 30: 48,390 R1T/R1S pre-orders
October 31: about 55,400 – 7,010 or 14.5% more
December 15: about 71,000 – 15,600 or 28% more
As we can see, within only 45 days or so, 15,600 new pre-orders have been placed, which is almost 350 per day on average (35x the production rate by the way).
"As of the end of our third quarter (September 30, 2021), we had approximately 48K R1 preorders from customers across the United States and Canada. Since then, we have seen accelerated growth in the daily number of preorders due to media attention and the positive experience consumers and the media have had with our R1 vehicles. As of December 15, 2021, we had approximately 71K R1 preorders."
With such feedback, Rivian appears to be in a really great position with one main task – focus on execution and ramp-up.
FIRST DRIVE: 2021 Isuzu D-Max 3.0L 4×4 AT X-Terrain, RM142k
BMW Design Boss Says 'Good Design Is Not About Pretty Or Ugly'
Lotus Evija Pumps Out Slowed Down Cosworth V8 F1 Engine Noise
2022 GMC Hummer Preproduction Ends, Customer Deliveries Begin Soon
Ford Ranger gets optional grille, off-road pack in Brazil – paultan.org
« buy depo provera
Volkswagen Golf receives infotainment upgrade for 2022 »


text:
Onthophagus taprobanus é uma espécie de inseto do género Onthophagus, família Scarabaeidae, ordem Coleoptera.

Foi descrita cientificamente por Arrow em 1931.

Referências

Ligações externas

taprobanus
Coleópteros descritos em 1931

redpajama_set_name: RedPajamaWikipedia


Ferretti 175 Fly: Luxury yacht to rent.
What would a Mediterranean holiday be without a yacht trip and the possibility to explore the secluded coasts and hidden bays from the waterside.
Would you like to discover with a luxury yacht the most beautiful bays of Balearic Islands and swim in crystal-clear water?
Are you searching for a luxurious engine yacht to hire?
Is exclusivity, all-inclusive options with luxurious equipment and many more extras important to you?
Then book with us the Ferretti 175 Fly Motor yacht, ... exclusive, luxurious and comfortable.
Other amenities include fine linens, fluffy terry towels, selected cosmetics, sun protection and snorkel sets.
Set the course for your yacht excursion with extra class! On board the ALL IN MOTION you can either enjoy relaxation and maritime glamor on thesundeck, or ride swiftly through the waves of the Mediterranean Sea.
Discover with our yacht, accompanied by our experienced skipper, the crystal-clear waters around the Balearic Islands and let yourself be carried away to the most beautiful bays of Majorca, Ibiza & Co. Our comfortable motor yacht, 'Ferretti' is 18 meters long, runs under the Spanish flag and is fully licensed and insured.
Feel as comfortable with us on board as in a luxury hotel. Our motor yacht ALL IN MOTION is equipped with high-quality materials and accessories.
Be perfectly relaxed within the comfortable furnishings both indoors and outdoors. Let yourself be indulged on your own personal cruise, whilst we at Dreammotion take care of your wishes around the clock, making your holiday an unforgettable experience. Our charming, multilingual stewardess accompanies the charter trip, ensuring you are well attended.
Life is short. Make time for the sea!
Whether only for a few hours or several days: you decide your time at sea. If you would like to enjoy the seaside for longer, why not stay overnight on our yacht, we have enough space for 4 persons with two double cabins (including private bathrooms). During the day we can welcome up to 8 passengers on board.
Orbit the most beautiful island in the world?
Realise your dream and circle Majorca with us! In 3 to 4 days we show you picturesque bays, impressive mountain ranges and places that even connoisseurs of Majorca have never seen. Guaranteed!
The sound of the waves accompanies the sunset ...Enjoy your refreshing drink while a sea breeze blows through your hair ... Are you ready for the journey of your life?
We are happy to organise and offer you a journey on the open sea. Please use the request form and we will contact you as soon as possible.
Your 8-hour day trip starts at 10:00 am in Cala D'Or and at 6:00 pm we bring you safely back to the port.
The programme includes 2 bay stops, all-inclusive meals with a bottle of Moët & Chandon, 2 bottles of wine and high-quality finger food.
In one of the most beautiful bays of Majorca, we take an anchorage of two hours depending on the weather in Porto Colom, Porto Petro, Cala Mondragó, Cala Virgili or Cala Barca. You can enjoy the lunch buffet on board.
Later we continue to the port of Cala Virgili, where you can swim in a dream like bay and the coffee break is served.
Afterwards we will return to Cala D'Or, where you can relax and enjoy dreaming about an unforgettable day.


Self description: Hello, I will be glad to tell you about myself! I am a woman with my own desires, wishes, and ambitions. I love life so much and I try to live it fully filling every day with something interesting, unusual, amazing. It's wonderful to make every day a little brighter. I have chosen to be a business coach because I like to make other people happy and show that life is not about problems only, that everybody can change his life for better. People around me say that I am a positive woman with warm and soft character, an open and honest person. I believe in power of smile, theory of soul mates and eternal love.
Hobbies and interests: As you have probably understood, I am an active person therefore I have a lot of hobbies, like reading, theatre, painting and traveling.
Developing as a personality plays a very important role in my life, in my career, so I never stop learning something new - I visit different exhibitions, concerts, presentations. I am very curious and I always try to find something interesting in my daily life and make my day brighter and more dynamic. As every woman I love to take care of myself as well! I like yoga, jogging and swimming.
What you are looking in your partner: I am looking for a noble, smart, strong and confident man with big passion for life. I see my future partner as a person, with whom I will be able to share everything that life has prepared for us, who can understand and support me. It would be great if my man is gentle and caring, does not have bad habits and leads a healthy lifestyle. I want him to be a real man and gentleman, a person who is ready to develop himself, to learn something new and who is not afraid of showing his emotions. I see my future husband as a bright person, whom I can't stop admiring and adoring, giving him all my love and devotion. And the main thing, the man of my dreams has a huge desire to start a family and he is ready to have two or even three children.


text:
Membrane pores: from structure and assembly, to medicine and technology
Scientific discussion meeting organised by Professor Robert Gilbert, Professor Hagan Bayley FRS and Professor Gregor Anderluh
Carbon nanotube porin
Biological membranes define and protect living cells. Proteins can open aqueous pores through these barriers. Such pores play critical roles in infection, parasitism, immunity and neurodegeneration. This meeting will showcase our current understanding of the structure and function of membrane pores, the medical significance of pores, and how pore-forming proteins can be used in nanotechnological applications.
Speaker biographies, abstracts, and recorded audio of the presentations is available below. Papers from the meeting are available in an issue of Philosophical Transactions B.
Professor Robert Gilbert, University of Oxford, UK
Professor Hagan Bayley FRS, University of Oxford, UK
Professor Gregor Anderluh, National Institute of Chemistry, Slovenia
Robert Gilbert did his BSc in Molecular Biology and Biochemistry at Durham University and completed a PhD at the University of Leicester on pneumolysin, a pore-forming toxin from Streptococcus pneumoniae. He has continued to work with pneumolysin and related proteins, alongside developing interests in RNA biology and protein biophysics with particular relevance to virology, cancer and immunology. He is now Professor of Biophysics and Director of Graduate Studies in the Nuffield Department of Clinical Medicine at Oxford University, and Managing Editor of the European Biophysics Journal.
Hagan Bayley is the Professor of Chemical Biology at the University of Oxford. Major interests of his laboratory are the development of engineered pores for stochastic sensing, the study of covalent chemistry at the single molecule level, ultrarapid DNA sequencing and the fabrication of synthetic tissues. In 2005, Professor Bayley founded Oxford Nanopore to exploit the potential of stochastic sensing technology. The company has developed the MinION portable DNA sequencer. His research and entrepreneurial skills have been recognised several times. Professor Bayley was the 2009 Chemistry World Entrepreneur of the Year. In 2011, he was elected a Fellow of the Royal Society. In 2012 he was awarded the Royal Society of Chemistry's Interdisciplinary Prize, in 2017 the Menelaus Medal of the Learned Society of Wales and in 2019 the Mullard Award of the Royal Society. In 2018, Professor Bayley held the Kavli Chair at the Delft University of Technology.
http://bayley.chem.ox.ac.uk/
Gregor Anderluh is director of the National Institute of Chemistry, Ljubljana, Slovenia. He received his PhD in Biology from the University of Ljubljana and did postdoctoral studies at the University of Newcastle, UK. He established an Infrastructural Centre for Molecular Interaction Analysis at the University of Ljubljana, Slovenia. He is studying protein-membrane interactions and how cellular membranes are damaged by proteins in bacterial pathogenesis and the immune system. His current interests are establishing novel biophysical approaches for studying protein binding to membranes and developing protein nanopores for applications.
Session 1 09:00-12:15
Structural basis of pore formation
09:00-09:30 Membrane pore-forming proteins in the molecular arms race between host and pathogen
Professor Helen Saibil FMedSci FRS, Birkbeck College, UK
Pathogens have evolved weapons to invade and damage our cells, and our immune system has evolved defences against these attacks. Among the weaponry used by both sides in this continual war are proteins that punch holes in cell membranes. Membrane perforation enables pathogens to take over host cells and resources for their own replication, and also enables host immune systems to kill invading pathogens. The membrane attack complex-perforin (MACPF)/ cholesterol dependent cytolysin (CDC) superfamily of membrane pore-forming proteins is used by a wide range of pathogens as well as by host immune systems. This talk focuses on the mechanisms by which MACPF and CDC proteins convert from their soluble, monomeric forms into large arcs and rings that insert into membranes and perforate them. Studies of pore assembly on liposomes in vitro and examples of their action in vivo will be presented.
Listen to the audio recording
Helen Saibil was educated in biophysics at McGill University, Montreal and then at Kings College London, where she did her PhD on the structure of retinal photoreceptor membranes. In her present position at Birkbeck College, her main interests are in analyzing conformational changes in macromolecular machines and the actions of intracellular pathogens on their hosts, using cryo-electron microscopy and image processing. These studies include work on protein folding, unfolding and disaggregation by molecular chaperones, and refolding during membrane pore formation by bacterial toxins and by pore forming proteins of the immune system. She is involved in setting up the national facility for cryo EM at the Diamond synchrotron, and is a member of EMBO, a Fellow of the Royal Society and a Fellow of the Academy of Medical Sciences.
Web page: people.cryst.bbk.ac.uk/~ubcg16z/
09:30-10:00 Assembly mechanism of the pore-forming toxin Cytolysin A from Escherichia coli
Professor Rudolph Glockshuber, ETH Zurich, Switzerland
The a-pore-forming toxin Cytolysin A (ClyA) is responsible for the hemolytic phenotype of several Escherichia coli and Salmonella enterica strains and is cytotoxic towards cultured mammalian cells. ClyA is a soluble, monomeric 34 kDa protein that spontaneously forms ring-shaped, homododecameric pore complexes upon contact with target membranes or detergent. The pore complex forms a hollow cylinder with an inner diameter of 70 Å that is reduced to 30 Å in the membrane-inserted part of the complex. The structural comparison between the soluble momoner and the protomer in the pore complex revealed one of the largest conformational transitions observed in a protein so far, in which more than half of the ClyA residues are reorganized and 16% of the residues are located in different secondary structure elements after protomer formation. Analysis of detergent-induced ClyA assembly in vitro showed that the rate-limiting step in pore formation at ClyA concentrations above 100 nM is the unimolecular transition of the soluble monomer to the assembly-competent protomer, which is followed by rapid protomer assembly. Single-molecule Förster resonance energy (FRET) experiments at picomolar ClyA concentrations preventing pore assembly showed that a molten globule-like off-pathway intermediate is formed during the monomer-to-protomer transition. The global kinetic analysis of detergent-induced pore formation from picomolar to micromolar ClyA concentrations supports a model in which all sterically compatible, linear oligomeric ClyA intermediates participate in pore assembly.
The research of the Rudi Glockshuber focuses on mechanisms of protein folding and assembly. Besides general topics in protein folding such as catalysis of disulfide bond formation and slow folding reactions determined by proline cis-trans isomerization, the Glockshuber group investigates the assembly of supramolecular protein complexes, including the formation of amyloid beta fibrils and the assembly of virulence factors of bacterial pathogens such as adhesive type 1 pili and the pore poring toxin ClyA from Escherichia coli.
10:00-10:25 Discussion
10:25-10:50 Coffee
10:50-11:20 Designing water-soluble and membrane-spanning peptide barrels
Professor Dek Woolfson, University of Bristol, UK
This talk will describe how we have developed an understanding of natural coiled-coil sequence motifs found in proteins, which lead to specific protein oligomerization; and then how we can apply this knowledge in rational peptide and protein design. For the latter, it is now clear that nature has almost certainly only shown us a glimpse of what is possible structurally and functionally with polypeptide chains. To help explore past the confines of natural coiled-coil structures, and into what has been termed the dark matter of protein space, a toolkit of de novo peptides has been developed. These can be used as building blocks for the rapid construction of new protein structures and assemblies. The talk will demonstrate the utility of this approach to make water-soluble protein-like barrels and pores, which can be engineered to bind biological molecules and catalyse simple reactions. More recently membrane-spanning variants of these α-helical barrels have been engineered, and in collaboration with the Bayley lab, it has shown that these insert into lipid bilayers and conduct ions in voltage-dependent manners. The two systems have been explored. In both cases, the insertion and orientation of peptides into the membranes can be directed, and the channel activities can be controlled through mutagenesis and blocking experiments.
Professor Dek Woolfson took his first degree in Chemistry at the University of Oxford, UK. He then did a PhD at the University of Cambridge followed by post-doctoral research at University College London and the University of California, Berkeley. After 10 years as Lecturer through to Professor of Biochemistry at the University of Sussex, he moved to the University of Bristol in 2005 to take up a joint chair in Chemistry and Biochemistry. Dek's research is at the interface between chemistry and biology, applying chemical methods and principles to understand biological phenomena. His group is interested in the challenge of rational protein design, and how this can be developed for synthetic biology. He places particular emphasis on making completely new protein structures and biomaterials for applications in cell biology and medicine. In 2011, Dek became the first recipient of the Medimmune Protein and Peptide Science Award of the Royal Society of Chemistry; and in 2014 he received a Royal Society Wolfson Research Merit Award. Dek is Director of BrisSynBio, a £13.6M BBSRC/EPSRC-funded Synthetic Biology Research Centre.
11:20-11:50 Analysis of designed and natural proton transporters
Professor William DeGrado, University of California, San Francisco, USA
The mechanism of proton transport through membrane proteins is of general interest to multiple areas of biology. Using a variety of spectroscopic, crystallographic, and computational methods, the mechanism by which protons are conducted through the M2 proton channel from influenza A virus was investigated, and this information was used to design new anti-influenza drugs that target highly drug-resistant forms of the virus. A second topic of the talk will focus on the use of de novo protein design to test the mechanism by which a class of transporters uses proton gradients to drive the conduction of molecules into or out of cells. Transporters have been hypothesized to arise by physical association or gene duplication of primordial units, leading to an assembly with "frustrated symmetry" that rocks between two states with the substrate-binding site alternately accessing each side of the membrane. Rocker, a minimalist Zn2+/proton antiporter was designed to test these principles, although it bears no sequence similarity to any known natural protein. Structural, dynamic and functional studies indicate that Rocker is a primordial transporter, which recapitulates many of the properties of this class of proteins. These studies also demonstrate the feasibility of using de novo design to design membrane proteins with complex dynamic and functional properties.
William (Bill) DeGrado's work focuses on the design of small molecule drugs, peptides, proteins, and peptide mimetics. Bill is currently a professor in the Department of Pharmaceutical Chemistry at the University of California San Francisco, where he is also a member of the Cardiovascular Research Institute. Before joining UCSF in 2011, he was a member of DuPont Central Research and DuPont Merck Pharmaceutical Company from 1981 to 1996 and the Raiziss Professor in the Department of Biochemistry and Biophysics at the University of Pennsylvania (1996 – 2011). Some of Bill's research interests include: de novo design of proteins and peptides; peptide mimetics; structure/function of membrane proteins, including integrins and viral ion channels; small molecule drug design; bioinorganic chemistry. Bill is a member of the U.S. National Academy of Science, the U.S. National Academy of Inventors, the American Academy of Arts and Sciences, and a fellow of the American Association for the Advancement of Science. Bill graduated from Kalamazoo College in 1978, received his Ph.D. in organic chemistry from the University of Chicago (1981), and joined DuPont Central Research without an intervening postdoctoral position.
Pore formation and membrane lipids
Professor Mauro Dalla Serra, National Research Council of Italy, Italy
Mauro Dalla Serra is a Senior Research Scientist of the National Research Council of Italy and Head of the Unit at Trento of the Institute of Biophysics. His scientific research interest is to investigate the structural and functional aspects of the interaction of membrane-active molecules with natural and model lipid membranes. A large portion of his work has been dedicated to protein-protein and protein-lipid interaction, to understand the mechanism of action of pore-forming proteins, that are relevant for human health. He has published more than 90 peer reviewed articles and contributed 17 chapters to multi-authored books.
13:10-13:40 Structural basis for complement membrane attack complex formation
Dr Doryen Bubeck, Imperial College London, UK
The membrane attack complex (MAC) is a fundamental component of immune defence that drills holes in bacterial membranes and kills pathogens. MAC lesions were first identified in 1964, yet half a century later details of its structure and assembly mechanism remain undiscovered. Here electron cryo-microscopy is used to visualize the human pore complex at subnanometer resolution. The protein composition of the MAC is determined and interaction interfaces that hold the assembly together are identified. Unlike closely related pore-forming proteins, the MAC's asymmetric pore and "split-washer" shape suggest a killing mechanism that involves not only membrane rupture, but also distortion.
Doryen Bubeck received her PhD in Biophysics from Harvard University in 2005 where she used cryo-electron micrsocopy to investigate the cell entry mechanism of poliovirus. As an EMBO postdoctoral fellow and Cancer Research Institute Fellow at the University of Oxford, she continued to explore the structures of membrane proteins, focusing on the complement immune pathway. A recent highlight (Hadders & Bubeck et al., Cell Rep. 2012) is the discovery that complement components associate through a sideways alignment of their central MAC-perforin domains (MACPF). These results provide a structural framework for understanding the complex protein associations underlying activation of this innate immune effector. Doryen Bubeck is a lecturer in Structural Biology within the Department of Life Sciences and recipient of a Cancer Research UK Career Establishment Award. Her current research adopts an integrated structural approach merging cryo-electron microscopy and Xray crystallography to investigate the role of membrane proteins in host-pathogen interactions. She aims to investigate how membrane attack complex (MAC) pore formation is controlled, a process important for fighting infections and preventing complement-mediated tissue damage.
13:40-14:10 Pore formation assisted by lipids
Dr Jose Caaveiro, University of Tokyo, Japan
Pore-forming toxins (PFT) constitute a fascinating group of proteins belonging to the molecular offensive and defensive machinery of virtually all kingdoms of life. This class of water-soluble proteins shares the remarkable ability to metamorphose in the presence of cell membranes, generating lytic pores and causing cell-damage. Actinoporins are a family of potent hemolytic toxins from sea anemone forming alpha-helical pores on cellular and model membranes.
In general, two requirements are sufficient to trigger pore-formation by actinoporins:
(i) the presence of the lipid sphingomyelin, and (ii) the segregation of the membrane on domains or lipid-rafts. Until recently, the molecular basis of pore-formation by actinoporins, and specially the specific requirement for sphingomyelin were unclear.
However, a number of recent studies have shed light into critical steps of their mechanism of action, such as binding of the toxins to the membrane, self-assembly via protein-protein interactions, and assembly of the transmembrane pore.
Collectively, the data suggests that sphingomyelin facilitates pore-formation at the binding and assembly stages, and reveal the first example of a hybrid lipid/protein pore by a PFT. The structural and thermodynamic basis of this novel architecture will be explained in detail during this presentation. Surprisingly, the entire process can be made reversible under mild experimental conditions by the careful selection of detergents, challenging current perceptions in the field of membrane-protein interactions.
Dr Caaveiro graduated in the University of the Basque Country (Spain), where he studied the modulation of peptides and proteins by lipids. After a postdoctoral period in USA (MIT and Brandeis University) he then joined the University of Tokyo (since 2008). Dr. Caaveiro's research program combines structural and thermodynamic data to address a broad range of biologically inspired phenomena. His ultimate goal is to understand the physicochemical basis underpinning biomolecular recognition at the atomic scale. Recently, Dr. Caaveiro and co-workers has revealed an unprecedented role for lipids in the pore-forming mechanism of the potent hemolytic class of actinoporins.
14:35-14:55 Tea
14:55-15:25 New insights into Bax pore formation from advanced microscopy methods
Dr Ana-Jesus Garcia-Saez, University of Tübingen, Germany
Bax is a key player in apoptosis that mediates of the permeabilization of the outer mitochondrial membrane. Despite intense research, the underlying process remains poorly understood. By combining biophysical approaches at different scales, new insight into the molecular mechanism of Bax is provided. Electron paramagnetic resonance data shows a key conformational change in the central hairpin of Bax that is involved in pore formation. In this configuration, Bax is present as a mixture of oligomers based on dimer units, as revealed by single molecule imaging. Moreover, the nanoscale organization of Bax at mitochondria of apoptotic cells is provided by superresolution microscopy. Based on this, a new model for the molecular mechanism of Bax is proposed.
Ana-Jesus Garcia-Saez is academic background includes Professor (W3) at the Interfaculty Institute for Biochemistry (IFIB), Universität Tübingen, Germany (October 2013), Max Planck Research Group Leader and Deutsches Krebsforschungzentrum (DKFZ) Junior Group Leader. Bioquant, Germany (2010 - current), Post-doc at the BioTec, TU Dresden, Germany (2005-2009) and PhD at the Department of Biochemistry and Molecular Biology, University of Valencia, Spain (2000-2005)
Fellowships and awards include:
• European Research Council (ERC) Starting Grant (project acronym: APOQUANT), 2012-2017.
• Max-Planck Gesellschaft Postdoctoral scholarship, Jan 2009- Dec 2009.
• Marie Curie Intra European fellowship. 6th Framework Programm, Marie Curie Actions. BIOTEC, TU Dresden (Germany). Jan 2007-Dec 2008.
• Short-term Fellowship. Federation of European Biochemical Societies. Biotechnologisches Zentrum, Technische Universität, Dresden (Germany). May-July 2005.
• Predoctoral Fellowship. Formación de Profesorado Universitario, Ministerio Español de Educación y Cultura. Faculty of Biology, University of Valencia. 1st April 2001- 31st March 2005
• Predoctoral Fellowship. Formació de Personal Investigador, Conselleria de Cultura i Educació de la Generalitat Valenciana. 1st March – 1st April 2001.
• Predoctoral Fellowship. Formación de Personal Investigador, Ministerio Español de Ciencia y Tecnología. 13th July 2001- 13th July 2001.
• Undergraduate Student Fellowship. Beca de Colaboración, Ministerio Español de Educacion y Cultura. Faculty of Biology, University of Valencia. Sept. 1999-June 2000
15:25-15:55 Regulating Bak and Bax pore formation in the mitochondrial outer membrane
Dr Ruth Kluck, The Walter and Eliza Hall Institute of Medical Research, Australia
Two members of the Bcl-2 family, Bak and Bax, drive apoptotic cell death by changing conformation and forming oligomers that permeabilise the mitochondrial outer membrane. The two proteins are activated by BH3-only family members binding to the α2-α5 hydrophobic surface groove. Newly exposed hydrophobic regions then either "collapse" onto the membrane surface to lie in-plane, or interact to generate BH3:groove symmetric dimers. We found that in each Bak dimer the N-termini are fully solvent-exposed and mobile, allowing disulphide bonding between certain residues (e.g. V61C:V61C') to specifically interrogate how dimers associate into high order complexes. These data informed mathematical simulations that support a model in which Bak dimers interact in a random manner to form compact clusters that generate lipidic pores.
It was also found that antibodies can trigger activation of Bak and mitochondrial Bax, and do so by binding to a new activation site, the α1-α2 loop. The mechanism of antibody-mediated Bak activation involves α1 dissociation, revealed by biochemical studies and a structural model of Fab bound to Bak. Intriguingly, antibodies to the α1-α2 loop in cytosolic Bax could block its translocation to mitochondria. These data thus identify the α1-α2 loop as a new target for regulating Bak and Bax apoptotic function.
Dr Kluck is a cell biologist who has studied apoptotic cell death since her PhD at the Queensland Institute for Medical Research, in collaboration with John Kerr who discovered apoptosis. As a postdoc at the La Jolla Institute for Allergy and Immunology (1995-2002), she made the seminal discovery that Bcl-2 proteins inhibit apoptosis by blocking mitochondrial release of cytochrome c. In 2002, she moved to the Walter and Eliza Hall Institute for Medical Research in Australia where she has focused on the regulation and function of the Bak and Bax pore-forming proteins.
16:20-16:50 Peptide-stabilized membrane pores: insights from simulations
Professor Themis Lazaridis, City College of New York, USA
The mechanism by which amphipathic peptides permeabilize biological membranes is not well understood. Do the peptides form well-defined pores or simply dissolve the membranes in a detergent-like fashion? What is the lifetime of these pores? How do the sequence and structure of these peptides determine their permeabilizing function? Both experiment and theory face formidable challenges in obtaining detailed information on such labile structures. We have used two theoretical approaches to study peptide-induced pore formation in lipid bilayers. The first treats water and lipids implicitly and the peptide in atomistic detail. This simplified representation allows one to obtain useful insights into protein-membrane interactions. Using this approach we showed that antimicrobial peptides bind more strongly to membrane pores than to the flat membrane, consistent with the idea that they stabilize them. The second approach is fully atomistic molecular dynamics simulations, some on the 10-microsecond timescale, starting from inserted peptide aggregates. Such simulations of melittin, magainin, PGLa, alamethicin, and protegrin have revealed interesting differences between these peptides and possible explanations of the observed synergy between some of them.
Themis Lazaridis received a Diploma in Chemical Engineering from Aristotle University in Thessaloniki, Greece in 1987. He went on to earn a Ph.D. in Chemical Engineering from the University of Delaware, USA. His Ph.D. research involved, among other topics, the development of a practical approach to calculate the entropy of hydration in water, elucidating the molecular origin of the unfavorable entropy of hydrophobic hydration. He was a postdoctoral fellow at Harvard University from 1992 to 1998, continuing to work on the statistical thermodynamics of solvation. He also worked on the energetics of protein folding and developed an implicit solvation model for proteins in solution. Since 1998 he has been a faculty member at the City College of New York. His current research interests focus on modeling protein-membrane interactions and especially the process of pore formation in membranes by antimicrobial peptides or protein toxins using implicit solvent models and all-atom simulations.
Pores, infection and immunity
09:00-10:30 Punching giant holes in cells: The MACPF/CDC family of pore forming toxins
Dr Michelle Dunstone, Monash University, Australia
Membrane attack complex/perforin-like (MACPF) proteins are an excellent example of self-assembling, integral membrane proteins and comprise the largest superfamily of pore forming proteins. These pore forming proteins are an ancient family found in all kingdoms of life with diverse roles in immunity, venom toxicity, predator defense, pathogenesis and uncharacterized roles in development biology. Moreover the MACPF family share a common evolutionary ancestor with the CDC family of pore forming toxins from Gram positive bacteria.
The over-arching mechanism of this MACPF/CDC superfamily starts with soluble monomeric proteins that recognise and assemble on the target membrane into a large ring-shaped oligomer. The oligomer can then undergo a massive conformational change to become an integral membrane protein complex. These membrane complexes range from 1 – 3 Mega Daltons in size and are capable of the passive transport of folded globular proteins. Recently, the field has started to tackle the outstanding questions of the MACPF field by combining single particle cryo-electron microscopy (SP cryo-EM), combined with cutting edge computational and biophysics techniques.
The combined structural data of key distinct clades of the MACPF/CDC family now shed light on how the MACPF/CDC family evolved and help us understand the common mechanism of MACPF/CDC proteins. More importantly, by studying a diverse range of MACPF/CDC proteins, it is now possible to see how the common MACPF/CDC fold has evolved for specific activities within the organism and how the ancillary domains modulate the activity of the common MACPF/CDC fold.
Dr Dunstone is currently an ARC Future Fellow and group leader in Monash University's Department of Biochemistry & Molecular Biology. Dr Dunstone passion lies in discovering the conformational change that occurs in the Membrane Attack Complex / Perforin-like superfamily of pore forming proteins.
Dr Dunstone was initially trained in crystallography in the laboratory of Prof Michael Parker at St. Vincent's Institute, Australia. Her original PhD project focused on the structure of C9 from the Membrane Attack Complex. Michelle continued researching the wider MAC/perforin family of pore forming proteins as a postdoctoral researcher at Monash University.
In 2007 this her bioinformatic and crystallography research culminated in the first representative structure of a MAC/perforin-like protein. Her recent research on pleurotolysin explores the structure MACPF toxins by combining single particle cryo-electron microscopy, biophysics and bioinformatics.
09:30-10:00 Mechanisms of cell-to-cell spread by Listeria monocytogenes
Professor John Brumell, The Hospital for Sick Children, Canada
Listeria monocytogenes has a remarkable ability to disseminate within its host during infection. My laboratory is examining how these bacteria can spread from cell-to-cell using the actin-based motility mechanism powered by ActA. In a recent study we showed that ActA-mediated Arp2/3 recruitment promotes actin polymerization in the cytosol (comet tail formation) but is primarily not responsible for the formation of cell surface protrusions. Instead, we find that protrusion formation requires recruitment and activation of mDia formins. Thus, Listeria exploits two types of actin polymerization to enable cell-to-cell spread. We also showed that efferocytosis, the process by which dying/dead cells are removed by phagocytosis, promotes cell-to-cell spread by Listeria during infection. We showed that protrusion formation is associated with plasma membrane damage due to LLO's pore-forming activity. LLO also promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial PS. The PS-binding receptor TIM-4 contributes to efficient cell-to-cell spread by Listeria in macrophages in vitro and growth of these bacteria is impaired in TIM-4-/- mice. Thus, Listeria promotes its dissemination in a host by exploiting efferocytosis.
Dr Brumell completed undergraduate studies at the University of Western Ontario with a major in Biochemistry. He completed his PhD at the University of Toronto in 1997. His doctoral research focused on phosphoryation-dependent signaling mechanisms in human leukocytes that encounter bacteria. He extended these studies from 1997-1998 at Mt. Sinai Hospital in Toronto. His postdoctoral studies at the University of British Columbia from 1998-2002 examined how Salmonella subverts host cells to cause infection. In 2002 Brumell returned to Toronto where he established a laboratory at the Hospital for Sick Children. He is now a Senior Scientist in the Cell Biology program and a Co-Director of the SickKids Inflammatory Bowel Disease Centre. In 2014 Dr. Brumell was awarded the Pitblado Chair in Cell Biology.
10:50-11:20 Pilus biogenesis at the outer membrane of bacterial pathogens
Professor Gabriel Waksman FMedSci FRS, UCL and Birkbank College, UK
Gram-negative pathogens commonly exhibit adhesive pili on their surface that mediate specific attachment to the host. A major class of pili is assembled via the chaperone/usher (CU) pathway. Type 1 and P pili have served as model systems for the elucidation of the CU biosynthetic pathway. Pilus assembly requires a periplasmic chaperone (FimC and PapD for type 1 and P pili, respectively) and an outer-membrane assembly platform termed "usher" (FiimD and PapC for type 1 and P pili, respectively). CU pilus subunits are produced in the cytoplasm, translocated to the periplasm by the Sec translocation machinery, and then taken up by a chaperone to cross the periplasmic space to reach the outer-membrane. At the outer-membrane, chaperone-subunit complexes are recruited to an outer-membrane assembly platform, the usher, which orchestrates recruitment and polymerization of subunits. Previous work has elucidated the molecular basis of chaperone function. Recent progress has shed light into the mechanism of pilus subunit assembly at the usher, leading to the elucidation of the entire cycle of pilus subunit incorporation.
Gabriel Waksman obtained his PhD in 1982 from the University of Paris. After a short spell in industry and a postdoctoral training at the Rockefeller University in New York, he joined the faculty of Washington University School of Medicine (St Louis, USA) in 1993. In 2000, he became the Alumni Endowed Professor of Biochemistry and Molecular Biophysics, and in 2002 was appointed the first Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics. In 2003, he moved to London (UK) to take up the Joint Chair of Structural and Molecular Biology at University College London and Birkbeck College London. The same year, he was awarded a Wolfson-Royal Society Merit Award and was appointed the Head of the Institute of Structural and Molecular Biology at UCL/Birkbeck. In 2006, he was appointed to the Courtauld Chair in Biochemistry at UCL, became Head of the Department of Biochemistry and Molecular Biology (now Research Department of Structural and Molecular Biology) at UCL and was appointed Head of the School of Crystallography (now Department of Biological Sciences) at Birkbeck. He was elected to EMBO in 2007, a Fellow of the Academy of Medical Sciences in 2008, a Fellow of the Royal Society in 2012, and a member of the German Academy of Sciences in 2013, He maintains an active research programme in the Structural and Molecular Biology of Bacterial Secretion Systems funded by a senior investigator award from the Wellcome Trust, an Advanced ERC grant, and a programme grant from MRC.
11:20-11:50 Structural insight into the biogenesis of beta barrel membrane proteins
Dr Susan Buchanan, National Institute of Health, USA
β-barrel membrane proteins are essential for nutrient import, signaling, motility, and survival. In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex is responsible for the biogenesis of β -barrel membrane proteins, with homologous complexes found in mitochondria and chloroplasts. Structures of BamA, the central and essential component of the BAM complex, were determined from two species of bacteria: Neisseria gonorrhoeae and Haemophilus ducreyi. BamA consists of a large periplasmic domain attached to a 16-strand transmembrane β-barrel domain. Three structural features speak to the mechanism by which BamA catalyzes β-barrel assembly. The first is that the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the β-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. And third, the β-barrel can undergo lateral opening, evocatively suggesting a route from the interior cavity in BamA into the outer membrane. A new structure of the BamACDE complex illustrates how the BamC, BamD, and BamE lipoproteins assemble on the BamA periplasmic domain and provides further evidence for lateral opening of the β -barrel.
Dr Buchanan is Chief of the Section on Structural Biology of Membrane Proteins in the National Institute for Diabetes & Digestive & Kidney Diseases, at the National Institutes of Health. She received her Ph.D. from the Johann-Wolfgang-Goethe Universität in Frankfurt, Germany in 1990. She completed postdoctoral fellowships at the MRC Laboratory of Molecular Biology, Cambridge, UK, and at UT Southwestern Medical Center, Dallas, before returning to the UK to establish a research group at Birkbeck College, London in 1998. She joined the NIDDK as a tenure track investigator in 2001 and is currently a Senior Investigator and Chief of the Laboratory of Molecular Biology, NIDDK. Research in Dr Buchanan's laboratory focuses on the structure determination of integral membrane proteins by X-ray crystallography and functional analysis of these proteins using biophysical, biochemical, and cell biological techniques. Current topics include small molecule and protein import across the bacterial outer membrane, protein secretion by pathogenic bacteria, and protein import across mitochondrial outer membranes.
Pore nanotechnology
13:10-14:40 From DNA-based pores toward membrane motors
Professor Hendrik Dietz, Technische Universität München, Germany
It is notoriously difficult to observe, let alone control, the position and orientation of molecules because of their small size and the constant thermal fluctuations that they experience in solution. Molecular self-assembly with DNA provides a route for placing molecules and constraining their fluctuations in user-defined ways and with up to Angstroem-scale precision. These positioning options open attractive and unprecedented avenues for scientific and technological exploration, in particular with respect to the creation of artificial membrane pores membrane-embedded mechanisms. This talk will introduce some of the key concepts and methods, and highlight a number of recent developments.
Since 2009 Hendrik Dietz has been a Professor for Biophysics and Principal Investigator of the Laboratory for Biomolecular Nanotechnology at Technische Universität München. Previously he was a Postdoctoral research Fellow at the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School. Prizes include Gottfried Wilhelm Leibniz-Preis, Deutsche Forschungsgemeinschaft (2015), Engelhorn Forschungspreis, Peter-und-Traudl-Engelhorn Stiftung (2012), Hoechst Dozentenstipendium, Aventis Foundation and Fonds der Chemischen Industrie (2012), Arnold Sommerfeld Award, Bayerische Akademie der Wissenschaften (2010) and European Research Council Starting Grant (2010).
13:40-14:00 Carbon Nanotube Porins: A biomimetic membrane pore for nanofluidics studies
Dr Alex Noy, Lawrence Livermore National Laboratory, USA
Living systems control transport of ions or small molecules across biological membranes using ion channels that form pores in lipid bilayers. Although bottom-up synthesis and top-down fabrication could produce pores of comparable size, an unresolved challenge remains to build a simplified membrane nanopore scaffold. Carbon nanotube porins (CNTPs) formed by ultra-short carbon nanotubes (CNTs) modified with lipid surfactants show a set of behaviors that come remarkably close to imitating biological nanopores.
The defining features of these nanostructures are their inner pores that have atomically smooth hydrophobic walls, which confine water on a molecular level, and, in some cases, down to a single-file configuration. We present experimental results that use bulk-scale and individual nanopore measurements to explore the physical origins of efficient transport in CNT porins, and focus on the role that molecular confinement plays in determining the transport characteristics and selectivity of the pore for water, protons, and ions. Overall, CNT porins represent a simplified biomimetic system that is ideal for studying fundamentals of nanofluidic transport and transport in biological channels, and for building complex engineered mesoscale structures.
Alex Noy is a Senior Research Scientist at LLNL. He joined LLNL in 1998 as the Lab's first E.O. Lawrence Fellow after getting his Ph.D. from Harvard University. His current research interests center on biophysics, biomaterials, and nanoscience with a common theme of using one-dimensional nanomaterials to build biomimetic and bioengineered structures. His research group is currently active in the areas of (1) bioelectronics, where they develop devices that combine nanomaterials with biological and biomimetic components to with a goal to create a seamless bidirectional neural interface, (2) nanofluidics and biomimetic molecular transport, where they develop carbon nanotube porins: artificial membrane channels based on carbon nanotubes, and (3) high speed atomic force microscopy, where they aim to image biological processes in-situ in real time. Noy has also been an Adjunct Associate Professor at the School of Natural Sciences at the University of California Merced since 2005.
14:55-15:25 Toroidal pore formation in lipid membranes
Professor Mark Wallace, King's College London, UK
A wide range of important biological processes involve the formation of toroidal pores in lipid membranes. Here we employ a combination of single-molecule fluorescence imaging and optical Single Channel Recording in Droplet Interface Bilayers to help understand the biophysics of this process. We image the formation of individual punctate mobile defects both in pure lipid bilayers, and in bilayers where this process if mediated by the presence of a range of peptides and proteins.
Mark studied Chemical Physics as an undergraduate at the University of Bristol, followed by a PhD in Chemistry at the University of Cambridge under the supervision of Professor David Klenerman. He was awarded the 2002 Gregorio Weber International Prize in Biological Fluorescence for this work. Mark then spent 2 years as a postdoctoral fellow at Stanford University, working with Professor Richard Zare. He returned to the UK in 2002 to undertake a second postdoctoral position at the National Institute for Medical Research with Dr Justin Molloy, before moving to Oxford in 2005 as a Royal Society University Research Fellow. He was subsequently appointed as a University lecturer and fellow of Wadham College in 2006. He joined King's in 2016 as part of its expansion of Chemistry. In 2009 Mark was appointed to the steering committee of the British Biophysical Society. Patents arising from his work have also been licensed in the UK Mark has also been active in raising awareness of his group's research beyond the lab, including video podcasting and participation in the 2014 "I'm a scientist get me out of here" competition. He was awarded the RSC Norman Heatley Award in 2015 in recognition of his work. He was made a Fellow of the RSC in the same year.
15:25-15:55 Single-protein analysis with a nanopore test-tube
Dr Giovanni Maglia, University of Groningen, Netherlands
The specific modulation of the ionic current through biological nanopores reconstituted in artificial membranes has been used to identify and analyze individual molecules. Here we show that ClyA, a biological nanopores with a 6.5 nm diameter and a 13 nm length, can be used as a nanoscale test-tube to study proteins. We found that the electrophoretic forces inside the nanopore can be used to trap and orient individual proteins for tens of minutes. The binding of analytes to the internalized protein is then reported by specific ionic current blockades. Remarkably, despite the diffusion of charged analytes inside the nanopore is strongly affected by the electric field, the binding constants for proteins inside the nanopore are identical to the values measured in bulk, indicating that the confinement and the electrophoretic forces inside the nanopore do not alter the folding and the binding properties of proteins. This technique will allow the label-free investigation of enzymatic reaction at the single molecule level, while nanopores with internal protein sensors might be incorporated into low-cost and portable analytical devices.
Giovanni Maglia was born in Bologna (Italy). He attended the University of Bologna for his undergraduate studies in Pharmaceutical Chemistry, and went to the University of Pennsylvania (USA) for his Masters thesis. He obtained his PhD from the University of Birmingham (UK) investigating the physical bases of the hydride transfer reaction catalyzed by dihydrofolate reductase. After a short spell at the university of Leuven (BE), he moved to the University of Oxford for his post-doctoral research on DNA nanopore sequencing. In 2010 Giovanni Maglia received an ERC starting grant to initiate his independent research at the University of Leuven (BE). From November 2011, he is associate professor of Chemical Biology at the University of Groningen (NL). His research interests include single-molecule enzymology, single-molecule proteomics and sensing, and designing and engineering artificial transmembrane machines.
16:20-16:50 Mass spectrometry of membrane pores - the lipid connection
Dame Carol Robinson FMedSci FRS, University of Oxford, UK
The realization that the lipid environment is crucial for maintaining the structure and function of membrane proteins prompts new methods to understand lipid interactions. One such method, mass spectrometry, is emerging with the potential to monitor different modes of lipid binding to membrane protein complexes. Initial studies monitored the addition of lipids and deduced the kinetic and thermodynamic effects of lipid binding to proteins. Recent studies have focused on identifying lipids already present, explicitly in plugs, annular rings or cavities. Lipids that bind within these orifices to membrane proteins will have higher residence times than those in the bulk lipid bilayer and consequently can be quantified and characterized by mass spectrometry. In special cases, lipids identified within cavities have been proposed as substrates following activity assays. Alternatively, a gas phase unfolding protocol can be used to distinguish lipids that are important for stability. This lecture will provide an overview of recent advances in mass spectrometry, with a particular focus on the distinction of the various modes of lipid binding and their implications for structure and function of membrane pores.
Carol Robinson has pioneered the use of mass spectrometry for structural biology and biophysics, with applications to a broad spectrum of biologically important macromolecular assemblies. Recent highlights from her work include the discovery that membrane protein complexes can be liberated from micelles in the gas phase while retaining their subunits interactions, lipid binding properties and overall topology. Carol currently holds the Chair of Doctor Lee's Professor of Chemistry at the University of Oxford. Her research has attracted international awards and prizes including the Anfinsen Award from the Protein Society, the Biemann Medal from the American Society of Mass Spectrometry, the Davy Medal and the Rosalind Franklin Award from the Royal Society, the HUPO Award for Distinguished Achievement in Proteomic Science, and the Anatrace Award for Membrane Proteins from the American Biophysical Society. Carol also holds three honorary doctorates and received a DBE in 2013 for her contribution to science.
Membrane pores: from structure and assembly, to medicine and technology https://royalsociety.org/science-events-and-lectures/2016/06/membrane-pores/


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The above formulae are on the assumption of a three-coat job. If four coats are intended, the third should be like the second.
It may be mentioned here that there is some difference of opinion as to the respective merits of raw and boiled linseed oil. Boiled oil has superior drying qualities but it is darker in colour and therefore not so suitable for mixing pale colours. For dark colours, boiled oil may be safely substituted for the raw oil specified above, and for colours of a medium depth of shade, either pale boiled or a mixture of raw and boiled is quite suitable. However, in mixing white, raw oil should always be used.
Making 33 lb. or 1- gals, and covering about 1,150 square feet one coat. Mixing varnish is a recognized material obtainable from any oil or colour merchant; to obtain the correct quality it is as well to state that it is for mixing with white lead.
The above formulae will serve equally well for plaster and other surfaces, except that the priming or first coating of previously untreated plaster requires a little variation.
In all the above formulae paste driers are specified. If the far more powerful liquid driers are used the quantities must be divided by four; thus, where 1 lb. of paste driers is mentioned, only 4 oz. of liquid would be required.


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text:
John Howard Francis Shattuck (born 1943) is an international legal scholar and human rights leader. He served as the fourth President and Rector of Central European University (CEU) from August 2009 until July 31, 2016. He is a senior fellow at the Harvard Kennedy School, and he joined the faculty of Fletcher School of Law and Diplomacy in January 2017.

Biography

Shattuck received a  BA from Yale College in 1965, an MA in 1967 from Clare College, Cambridge University, with First Class Honors in International Law, and a JD degree in 1970  from Yale Law School.  While at Yale and subsequently, Shattuck was an active member of the Yale Russian Chorus.

Career
His first position was National Staff Counsel at the  American Civil Liberties Union 1971-76; he then served from 1967 to 1984  as Executive Director of the Washington office and national staff counsel,   handling a number of prominent civil rights and liberties cases, including Halperin v. Kissinger.

From 1984 to 1993 he was appointed vice president, government, community and public affairs, at Harvard University, and beginning in 1986 was also a Lecturer at Harvard Law School, and Senior Associate, Program on Science, Technology and Public Policy, Harvard Kennedy School.

From 1993 to 1998, he was  United States Assistant Secretary of State for Democracy, Human Rights and Labor under President Bill Clinton, where he played a key role in the establishment by the United Nations of the International Criminal Tribunals for Rwanda and former Yugoslavia, working closely with Secretary of State Madeleine Albright. In 1995, he   was the first international diplomat to reach survivors of the Srebrenica genocide in Bosnia, assembling evidence for the UN Security Council vote authorizing NATO intervention in Bosnia. During this tenure, he visited Chinese dissident Wei Jingsheng and the Chinese government used the meeting as a pretext to arrest Wei and re-imprison him.

Shattuck served as U.S. Ambassador to the Czech Republic from 1998 to 2000. Shattuck participated with  US special envoy Richard Holbrooke in negotiating the Dayton Peace Agreement and other efforts to end the war in Bosnia.

In 2001 he became as Chief Executive Officer of the John F. Kennedy Library Foundation, and in 2007 also Senior Fellow at Tufts University, where he taught international relations. In 2001 and 2002, the Library and Foundation delivered a widely broadcast series of public events, "Responding to Terrorism," that examined issues of international security and human rights following the September 11 attacks.

He was elected to the Common Cause National Governing Board in 2003.

In August 2009 he became the fourth President and Rector of Central European University (CEU). He was also Professor of Legal Studies and International Relations, and taught an interdisciplinary course entitled "U.S. Foreign Policy, Human Rights and The Rule of Law."

Under Shattuck's leadership, CEU continued to pursue to its mission to promote open societies that respect human rights and the rule of law, introducing new initiatives in that direction. Protecting academic freedom and the autonomy of the university were among Shattuck's main priorities. At his initiative, CEU launched the Frontiers of Democracy Initiative in 2014, which brings together academics and practitioners from across the globe to explore what democracy means in today's complex world.

Shattuck also oversaw the introduction of cutting-edge interdisciplinary programs and initiatives into CEU's academic program, such as cognitive science, network science, a religious studies specialization and the Humanities Initiative. CEU also embarked on a major redevelopment project of its downtown Budapest campus, with the first phase to be completed in 2016.
CEU's academic excellence was recognized in recent university rankings, as CEU is constantly improving on its Quacquarelli Symonds (QS) rankings, with politics and international studies ranked as 29th in the world in 2015, and also featured in Times Higher Education's Top 100. CEU also secured the most European Research Council Grants among the Central-Eastern European member states' universities in the 2007-2013 period.

Following a seven-year tenure as CEU's President and Rector, Shattuck stepped down on July 31, 2016. He became President Emeritus of CEU on August 1, and moved to Boston to take up his new responsibilities as professor of practice at the Fletcher School of Law and Diplomacy and senior fellow at the John F. Kennedy School of Government.

Publications

Shattuck is the author of two books: Freedom on Fire: Human Rights Wars and America's Response, published by Harvard University Press in 2003, about the international response to genocide and other crimes against humanity in the 1990s, that, according to WorldCat, is held in 1636 libraries and the textbook Rights of Privacy, published by National Textbook Co. in 1977, and held in 515 libraries. He has also written many book chapters, and more than 50 articles.

Recognition
He has received honorary degrees from Kenyon College, the University of Rhode Island, the John Jay College of Criminal Justice at the City University of New York, and the University of West Bohemia. He received the Ambassador's Award from the American Bar Association Central and East European Law Initiative, the Human Rights Award from the United Nations Association of Boston, and the Yale Law School Public Service Award. In 2007, he was elected to the American Academy of Arts and Sciences.

References

External links
 "John Shattuck Commences Term as New CEU President and Rector", 06/08/2009. Appointment as President of Central European University
 , JFK Library and Museum

Ambassadors of the United States to the Czech Republic
Living people
Central European University
Yale Law School alumni
Alumni of Clare College, Cambridge
United States Assistant Secretaries of State
Tufts University faculty
1943 births
American Civil Liberties Union people
Institute for New Economic Thinking
Yale College alumni
Carnegie Council for Ethics in International Affairs
20th-century American diplomats


"E-waste" is a term applied to consumer electronic equipment that is no longer wanted. This E-waste includes computers, printers, televisions, old VCRs, cell phones, fax machines, stereos, and electronic games. Electronics may contain lead and other heavy metals or potentially toxic substances and needs to be treaded careful and not be disposed of in a land fill for example.
It is important to the environment to reduce e-waste by the reuse of electronic items that still work, and to recycle electronics at the end of their useful life.
There are various forms of electric waste but they generally form the electronic equipment waste that have ceased to be of value to their users. Electronic waste (e-waste) products have exhausted their working life and need replacement, or have suffered breakage and this includes both "white goods" such as refrigerators, washing machines, and microwaves and "brown goods" such as televisions, radios, computers, and cell phones.
Given that the information and technology revolution has exponentially increased in recent years, it has also produced growing volumes of obsolete products; e-waste is one of the fastest-growing waste streams that countries are struggling to cope with. Although e-waste contains complex combinations of highly toxic substances that pose a danger to health and the environment, many of the products also contain recoverable and sometimes precious materials, making it a different kind of waste compared with traditional sewerage or green waste.
Globally, e-waste constitutes more than 5 percent of all municipal solid waste. It is increasing with the rise of sales of electronic products in all developing countries. The majority of the world's e-waste is recycled in developing countries, where informal and hazardous setups for the extraction and sale of metals are common.
Recycling companies in developed countries face strict environmental regulatory regimes and an increasing cost of waste disposal and have found the exporting of e-waste to developing countries more profitable than recycling in their own countries. Unfortunately, e-waste profiteers can harvest substantial profits owing to lax environmental laws, corrupt officials, and poorly paid workers in those countries.
The complex composition and improper handling of e-waste adversely can seriously affect human health. A growing body of epidemiological and clinical evidence has led to increased concern about the potential threat of e-waste to human health, especially in developing countries such as India and China. The primitive methods used by unregulated backyard operators (e.g., the informal sector) to reclaim, reprocess, and recycle e-waste materials expose the workers to a number of toxic substances. Processes such as dismantling components, wet chemical processing, and incineration are used and result in direct exposure and inhalation of harmful chemicals. Safety equipment such as gloves, face masks, and ventilation fans are virtually unknown, and workers often have little idea of what they are handling.
Operators in some countries for instance, in terms of health hazards, cause great harm by doing open burning of printed wiring boards increases the concentration of dioxins in the surrounding areas. These toxins cause an increased risk of cancer if inhaled by workers and local residents. Toxic metals and poison can also enter the bloodstream during the manual extraction and collection of tiny quantities of precious metals, and workers are continuously exposed to poisonous chemicals and fumes of highly concentrated acids. Recovering resalable copper by burning insulated wires causes neurological disorders, and acute exposure to cadmium, found in semiconductors and chip resistors, can damage the kidneys and liver and cause bone loss. Long-term exposure to lead on printed circuit boards and computer and television screens can damage the central and peripheral nervous system and kidneys, and children are more susceptible to these harmful effects.
There are a number of specific ways in which e-waste recycling can be damaging to the environment. Burning to recover metal from wires and cables leads to emissions of brominated and chlorinated dioxins, causing air pollution. During the recycling process in the informal sector, toxic chemicals that have no economic value are simply dumped. The toxic industrial effluent is poured into underground aquifers and seriously affects the local groundwater quality, thereby making the water unfit for human consumption or for agricultural purposes. Atmospheric pollution is caused by dismantling activities as dust particles loaded with heavy metals and flame retardants enter the atmosphere. These particles either redeposit (wet or dry deposition) near the emission source or, depending on their size, can be transported over long distances. The dust can also enter the soil or water systems and, with compounds found in wet and dry depositions, can leach into the ground and cause both soil and water pollution. Soils become toxic when substances such as lead, mercury, cadmium, arsenic, and polychlorinated biphenyls (PCBs) are deposited in landfills.
E-waste can be classified on the basis of its composition and components. Ferrous and nonferrous metals, glass, plastics, pollutants, and other are the six categories of materials reported for e-waste composition. Iron and steel constitute the major fraction in waste electrical and electronic equipment (WEEE) materials, with plastics being the second largest. Nonferrous materials, including metals such as copper and aluminum, and precious metals such as silver, gold, and platinum are third in abundance and have significant commercial value. Toxic materials include lead and cadmium in circuit boards, lead oxide and cadmium in cathode ray tubes, mercury in switches and flat-screen monitors, brominated flame retardants on printed circuit boards, and plastic and insulated cables; when these exceed the threshold quantities, they are regarded as pollutants and can damage the environment if disposed of improperly.
Large household appliances: refrigerators, freezers, washing machines, clothes dryers, dishwashers, electric cooking stoves and hot plates, microwaves, electric fans, and air conditioners.
Small household appliances: vacuum cleaners, toasters, grinders, coffee machines, appliances for haircutting and drying, toothbrushing, and shaving.
Information technology (IT) and telecommunications equipment: mainframes, minicomputers, personal computers, laptops, notebooks, printers, telephones, and cell phones.
Consumer equipment: radios, televisions, video cameras, video recorders, stereo recorders, audio amplifiers, and musical instruments.
Lighting equipment: straight and compact fluorescent lamps and high-intensity discharge lamps.
Electrical and electronic tools: drills, saws, sewing machines, soldering irons, equipment for turning, milling, grinding, drilling, making holes, folding, bending, or similar processing of wood and metal.
Toys, leisure equipment, and sporting goods: electric trains or racing car sets, video games, and sports equipment with electric elements.
Medical devices: radiotherapy equipment, cardiology, dialysis, pulmonary ventilators, nuclear medicines, and analyzers.
Monitoring and control instruments: smoke detectors, heating regulators, and thermostats.
Automatic dispensers: for hot drinks, hot or cold bottles, solid products, money, and all appliances that automatically deliver various products.
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text:
Sisu K-44 is a three-axle 4×4+2 driven lorry made by the Finnish heavy vehicle manufacturer Suomen Autoteollisuus (SAT) from 1959 to 1965. The most usual applications were for log transportation and earth moving vehicles. The  K-44 was noted for its excellent gradient capabilities. The legally permissible maximum vehicle payload was between 7 800 and 11 750 kg: with a trailer this increased to 20 000 kg. The K-44s were powered by Leyland diesel engines with power outputs of between 85.8 and 156.7 kW.

The K-44 was replaced in 1965 by the K-145.

Development
Single axle semi-trailers were commonly used for log transportation in Finland in the 1960s. The maximum axle load of the existing 4×4 Sisu K-40 was often exceeded in logging work. The solution was a truck incorporating the addition of a non-driven third axle at the back, paired in a tandem axle with the rear driven axle. The new model, the Sisu K-44, was introduced in 1959, with a choice of engine sizes for both the middle-weight ("Kontio") and the heavy ("Jyry") classes. The K-44's driven front axle and transfer case were borrowed from the existing K-40, while the bogie, of which only the first axle was driven, came from the K-34. This drivetrain layout, called 4×4+2, is seldom seen outside Finland. However, Vanajan Autotehdas, SAT's main domestic competitor, had already introduced a similarly configured vehicle a year earlier.

Characteristics

The Sisu K-44 was expressly designed for good rough-terrain capability. The vehicle's ability to grip on many types of terrain and retain traction on steep slopes is further enhanced by a mechanism whereby the non-driven rear axle could be raised, thus maximising the proportion of vehicle weight available to push down on the driven axle at the front of the tandem axle. On a surface with friction coefficient of μ=0.65 its maximum gradeability is 86%. A corresponding 6×4-model has a 55% and a 6×2-model just a 29% gradeability.

The K-44 was 27% more expensive than the corresponding Sisu K-34 6×2 with a non-driven front axle and same capacity.

The Leyland O.375 engine, used in early Kontio-Sisu K-44SU models, was a further development of the O.350, that had gained a good reputation since becoming available in Sisus early in the 1950s. The O.375 unit's performance enhanced the reputation of Leyland as an engine producer. Unfortunately users' experience with the slightly larger O.400, introduced in 1962, was less positive. The unit's thin cylinder liners cracked and became detached. Although this defect was soon fixed, problems with the O.400 damaged the reputations of both Leyland and Sisu.

The powerful and reliable Leyland O.680 used in the stronger Jyry K-44 models had helped to make Sisu a market leader in Finnish heavy-duty road transportation. Problems began in 1963 when the Jyry's received the new O.680 "Power Plus" engine. Sisu was the first vehicle powered by the Power Plus unit, and suffered badly from the teething problems experienced by this engine.

Usage
Although the K-44 was originally designed for hauling a logging semi-trailer, the trucks were soon being used to tow conventional twin axle trailers, which permitted a significantly greater overall load capacity.

At least some Jyry versions with demountable platforms were delivered to the Finnish Defence Forces in 1965.

Technical data

Engine
The K-44 was offered with one of five different engine types, the power units being supplied by Leyland Motors. The middle-weight "Kontio-class" K-44SU is powered by the  Leyland O.375 engine. This was replaced in 1962, after which the Kontio K-44 was delivered with a more powerful  Leyland 0.400 unit which on paper promised 18% more power and 15% more torque in return for an increase in engine displacement of just over 6%.

In the heavy-duty "Jyry-class" the K-44ST is fitted with Leyland's  O.600 unit while the K-44SP came with the  Leyland O.680. Later, for the more powerful "Jyry-class" K-44, the manufacturer also offered the option of the  Leyland O.680 "Power Plus" unit.

All the engines are six-cylinder inline direct injection diesels incorporating dry cylinder liners: the light alloy pistons are fitted with three pressure rings and two oil rings. The crankshaft is supported by seven main bearings. The injection pump and the 24-volt electrical system were supplied by CAV. A gear driven compressor is fitted as standard.

Transmission

Clutch and gearboxes
The dry single-plate clutch has a diameter of 412 mm and features torsional rubber damping. Early Kontio models were fitted with a five-speed main gearbox while the heavy-duty Jyry's came with a six speed gearbox on which the sixth gear was an overdrive. There is no synchromesh, but the gear-cog tooth ends were bevelled in order to ease shifting. An additional power output shaft, used to power additional functions such as a dumping mechanism, was available as an option.

The gearbox of the middle-weight Kontio model was changed when the  Leyland O.375 engine was replaced by the  O.400 power unit in 1962. Despite being more powerful, the new engine reached maximum output only at a much higher engine speed, with maximum torque now achieved at 1600 rpm rather than 1100 rpm. The very different torque curve of the new engine required a new set of gear ratios, and the Kontio now received a six-speed gearbox in which the lower gears applied higher ratios than in the previously used five-speed box. The ratio of the top (now sixth) gear was approximately the same in both the old five speed and the new six speed transmissions.

The other key component in the transmission is a transfer case incorporating the torque-splitter, located between the main gear box and the tandem axle. This apportiones the torque from the gearbox between the front axle and the driven rear axle. The torque-splitter incorporates a two-step reduction gear and a longitudinal differential. The splitter was available in two versions, featuring slightly different low speed ratios. The "AVV" model provides the vehicle with slow ratio of 2.48:1 whereas the "AVD" provides a ratio of 2.47:1. Using the slow ratio also engages the front axle drive. The "AVD" uses a planetary gear that splits the torque in the ratio 23:77 between the front axle and the driven rear axle.

Tandem axle

The foremost axle on the tandem axle is powered. When fully loaded, the K-44 carries approximately 62% of the weight lying on the tandem axle. The rear, non-driven axle, is linked to the driven axle through a simple sub-assembly consisting of  wide and  long leaf springs and rocker arms. When the torque delivered to the rear axle is increased, the mechanism automatically shifts vehicle weight away from the non-driven axle to the driven axle, improving traction when most needed. Additionally, more of the weight can be moved to the driven axle manually using an electro hydraulic system. In order to reduce fuel consumption and tyre wear the non-driven rear axle can also be raised completely off the road/surface, if a third load-bearing axle is not needed because the vehicle is running empty: running on just two axles also reduces the K-44's turning circle.

The wheel size is 7.5–20" and each wheel is held in place with ten nuts. Both axles on the bogie are fitted with double wheels as standard other than on the K-44ST, which made do with single wheels on the non-driven rearmost axle.

The normal wheelbase of the tandem is : alternative bogie wheelbases of  and  also appear on the manufacturer's data sheets.

On the early K-44s the tandem's driven axles are identical on the middle-weight "Kontio" and the heavy-weight "Jyry" versions. The axle, designated "Type ATK" was designed by SAT and was based on the manufacturer's "Type ATD" axle originally introduced for earlier models n the early 1950s. The "Type ATK" proved durable in the Kontios, but was unable to cope with the greater power and load of the Jyry trucks, and in the early 1960s SAT developed a more robust driven axle, known as the axle "Type BTK", for the heavier variants.

The axle housing is a welded construction made from formed steel. The transaxle used hypoid gears.

Front axle
The K-44 features a driven double reduction front axle incorporating an interlockable differential. The steering knuckles are attached via bevel roller bearings, while the front drive shaft uses homokinetic joints. The wheel hubs incorporates planetary gears, which permits a higher ground clearance through the inclusion of a small differential unit. The front suspension uses  wide by  long leaf springs and telescopic shock absorbers. The wheel size is 8.0–20", and each wheel is held in place with ten nuts.

Brakes
Earlier models use hydraulically operated and pneumatically assisted drum brakes. Later K-44's are equipped with S-cam brakes of SAT's own design. SAT advertised that the brakes are especially robust and stable due to their cast-steel shoes and thick anchor pins. The handbrake is operated mechanically against a brake drum mounted directly on the transmission.

A manually operated pneumatic trailer brake system and exhaust brake were optional accessories.

Cabin and other equipment

The standard cabin contains seating for driver and two passengers. An extended cabin with a bed was available as an option. The cabin includes upholstery and insulation. The heating system incorporates air nozzles to provide, in particular, windscreen demisting. Dashboard instruments include a speedometer and odometer along with an ammeter and gauges showing water temperature, oil pressure, fuel levels and, separately for each of the two braking circuits, air pressure. The braking system also has a separate alarm light triggered by low air pressure in the circuits or a too long stroke of the air brake actuators.

The air brakes are driven by an engine powered compressor which also feeds the servo for the hydraulic brake circuit. The compressor system also includes a filter, a 40-litre vessel with a drainage valve, its own anti-freeze system as well as a valve and a hose to be used for inflating the tyres.

A tachometer and tachograph were optional. A hydraulic power steering system was available as an option for the worm type steering gear.

The 12-volt electrical system was fed by two 135-Ah batteries. Power can be switched off using a manually operated circuit breaker controlled from the cabin.

The  fuel tank is located beneath the cabin on the left side of the vehicle. A  tank was available as an option.

Also available as an option was a front winch with 8–10 tonnes capacity, powered from the reduction gear using through a multi-joint shaft and worm gear. The direction of the winch can be reversed using the reduction gear.

Dimensions and weights
The fully laden maximum weights in the table below follow the contemporary Finnish legislation, and are not necessarily the same as the manufacturer's own structural values.

The total permitted laden weights were raised by slightly more than 3% in 1967, after production of K-44 had already ended. For certain designated uses, for example on road construction sites, a special permit could be obtained authorizing an even higher maximum total weight of  for a fully loaded heavy-duty Jyry K-44.

The total weight of Sisu K-44SP with a four wheel Sisu "FA-22"" or "FA-32" trailer was given in 1962 as , and the maximum payload was up to .

Sources

References

External links

K44
Vehicles introduced in 1959


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