Old Worlds, New Travels: Jack London’s People of the Abyss, Ernest Hemingway’s The Sun Also Rises, and the Cultural Politics of Travel

Ye

Design of an acid labile traceless-cleavable click linker for use in a novel protein transduction shuttle

Intracellular protein delivery is offering numerous possibilities in research and in therapy. Aside gene therapy, protein delivery into living cells is one of the most promising tools for the treatment of various so far immedicable diseases including cancer. To develop a practicable protein delivery platform, a test system which allows easy control of successful intracellular delivery is needed. Therefore a test system based on two model proteins was established. A nuclear localization signal tagged EGFP molecule is enabling fast control of cellular uptake and endosomal release. The second model protein ß-galactosidase is evidencing that protein conformation is not irreversible disturbed by modification with the carrier molecules. Protein transduction technology is opening the door for a promising alternative to gene therapy, as it is lacking of the potential malignant side effects of gene therapy. The most limiting step in the development of a therapeutic drug remains the delivery process. In the last decade, many techniques to deliver proteins into living cells were developed. Although great efforts were made, so far no all-purpose technique is available that addresses all critical steps, like efficient uptake, endo-lysosomal escape, low toxicity, while maintaining enzymatic activity. Each method has got its limitation, for example cell type dependence. Among the so far used carriers, the most effective ones are cationic polymers like polyethylenimine. These carriers are lacking of precise structure and often show high toxicity, dependent on the molecular weight of the used polymer. In this thesis the properties of the three arm cationic oligomer 386, which was previously designed for siRNA delivery was investigated in regard of being applicable as a transduction carrier for protein delivery. This carrier molecule, in contrast to other cationic polymers used for protein delivery, is of precise structure, of low molecular weight and potentially degradable by proteases. The transduction oligomer was covalently bound to the protein by a bioreversible bond. Our results reveal that covalent coupling of the structure defined cationic oligomer 386 to a protein leads to a high efficient, serum insensitive and low toxic alternative to established protein transduction technologies. For a general all-purpose delivery system covalent coupling of the carrier to the cargo protein is indispensable. Protein delivery requires special properties to the linker molecule. Therefore in this work a new pH sensitive linker was developed which combines the advantages of click reactions with the implementation of a traceless cleavable bond between two conjugated molecules. Three different click chemistries were performed which all are compatible with the acid labile properties. A traceless cleavage may be a particularly important feature in protein transduction strategies, to maintain full bioactivity of enzymes and other proteins. The current example of 386 carrier-mediated cytosolic delivery and subsequent nuclear import of released nls-EGFP demonstrates the advantage of the traceless linker. To demonstrate that the modification does not irreversibly affect structure and biological activity of proteins, 386-AzMMMan-ßgalactosidase was delivered as a model enzyme. It exhibited cytosolic activity in the transduced cells far higher than without shuttle. Aside from these encouraging options for protein delivery and modification, the linker might have broader use in the design of novel programmed, acid labile and biodegradable drug delivery systems. Targeted therapeutics could, after delivery into acidic tumor areas or upon cellular uptake into endosomes, be dismantled from their outer shell including targeting ligands. Besides drug delivery, the linker may also be of interest for other applications, such as reversible labeling of various biological and also chemical molecules. The developed linking strategy and the presented concepts for transduction shuttles may help to get a step closer in the design of an all-purpose protein delivery platform, applicable on bench as on bedside

Microkinetic Modeling of the Oxidation of Methane Over PdO Catalysts—Towards a Better Understanding of the Water Inhibition Effect

Water, which is an intrinsic part of the exhaust gas of combustion engines, strongly inhibits the methane oxidation reaction over palladium oxide-based catalysts under lean conditions and leads to severe catalyst deactivation. In this combined experimental and modeling work, we approach this challenge with kinetic measurements in flow reactors and a microkinetic model, respectively. We propose a mechanism that takes the instantaneous impact of water on the noble metal particles into account. The dual site microkinetic model is based on the mean-field approximation and consists of 39 reversible surface reactions among 23 surface species, 15 related to Pd-sites, and eight associated with the oxide. A variable number of available catalytically active sites is used to describe light-off activity tests as well as spatially resolved concentration profiles. The total oxidation of methane is studied at atmospheric pressure, with space velocities of 160,000 h−1 in the temperature range of 500–800 K for mixtures of methane in the presence of excess oxygen and up to 15% water, which are typical conditions occurring in the exhaust of lean-operated natural gas engines. The new approach presented is also of interest for modeling catalytic reactors showing a dynamic behavior of the catalytically active particles in general

UAS Literary & Arts Journal

Proof copy provided by Tidal Echoes.Tidal Echoes is an annual showcase of writers and artists with one thing in common: a life surrounded by the rainforests and waterways of Southeast Alaska.Davy Josh’s Note -- A Note from Chalise -- A Note from Emily Wall -- Brain Bucket -- Cephalic index -- A Gift of Fat for the Fire -- Our heroes have always been... -- Colorful Clouds -- Role Model -- Anchors -- Out My Window -- Adaptation -- Bookshelves -- In the Flow -- It’s a Small World Parade Float -- Sexy -- Death by Algebra -- Friend -- mirabile visu -- Exchange II -- F A D E -- Borne Alone -- Continuum -- The Week Before St. Valentine’s -- Bottled Up -- Untitled -- Early Morning Conspiracy Theory -- Westport -- Boulder Creek -- Jumping Off Rooftops -- Staying in the Room With Ernestine Hayes -- Blueberry -- After Neruda By Way of Bly (Tenure) -- Magic of Water -- Old Tom Steals the Light -- Old Tom Finds a Whale -- Research Project -- Guppy (boat) -- Arizona Spyder -- From Anthropomorphism to Zoomorphism -- Bus Stop -- December 1, 1955 -- Between Tides at Twilight -- Dementia -- Winter Ferry -- Coming into Auke Bay -- The Search for Jane Rogers -- Inlaid Tea Cups -- The Big Melt -- Kingsmill Reef -- Despite Man’s Best Efforts to Ruin It -- Roberts from Flume -- India Scarf -- Painted and Petrified -- Medicine Bag -- Merrill Field -- Deadly Kites -- Brazilian Ghetto -- Seattle Riff -- The Gospel Truth of My Gay Bird -- Signing the Divorce Papers -- Red Shades -- Holey Cow -- Untitled -- Series of Cedar Baskets -- A Conversation With Ranunculus -- Deconstruction -- Sandy Beach -- Threshold -- Oil and Honesty: An Interview with Artist and Professor David Woodie -- Mitkof #3 -- Still Life -- First Day of Fall -- Falling in the Garden -- After Finishing an Activities Report for the Dean -- Homage to Po Chü-I -- Nunc Dimittis -- Do Wise Men Have Bad Days? -- To the Plain Land -- Flood of ‘69 -- How a woman makes her own wine -- Untitled (translation from Russian) -- Existential Sestina -- It’s the knowing -- Blood and Guts -- Sometime Walking on the Beach -- Untitled -- Connecting the Pieces -- Hemlock -- Klawock Island -- Driven By the Tides -- Lunch -- The People -- Howling Dog -- Winter Cabin Lullaby -- Chain Gang -- A Review of Social Groups in Female Homo Sapiens as Exemplified by Mammary Restraint -- Apparatuses -- Douglas Island Bridge -- Going Home -- Author and Artist Biographie

UAS Literary & Arts Journal

Proof copy provided by Tidal Echoes.The 2016 edition of Tidal Echoes presents an annual showcase of writers and artists who share one thing in common: a life surrounded by the rainforests and waterways of Southeast Alaska.a heart is a heavy burden -- Editor’s Note -- Acknowledgements -- Always a Pause -- Untitled -- Mishima Teabowls -- Mint Tea and Red Wine -- The Dry Winter Scent of Prairies -- Northern Sunrise -- Musical Theory in a Falling Tree -- Jumbo Lookout -- The Shape of an Echo -- Wonderwall -- It’s Difficult [excerpt from the poem “Marissa”] -- Yéil x’us.eetí Raven Footprints -- táakw winter -- King Fisher -- Bear -- A Dandelion by its own Name -- Migrations -- Untitled -- They Named Her Driftwood -- Kissing in the Rain -- Waltz of the Flowers: Anna and Company -- Sun Catcher -- Porcelain Curtains -- The River -- Kathleen Lake -- A Living Tapestry -- Red Cedar Tlingit Haida Weave -- Skinned -- Survivor -- Auke Lake Lights -- Aurora Chasers -- Emma Afloat -- I Can’t Sleep -- The Ghost I’m Left With -- Framed Memories -- Tequila, Sweat, and Prayers -- The Alchemical Marriage -- A New New Hope -- each dream practice -- Clouds -- Seasons Change and the Waters Run On -- John Muir -- Salmon Speaks -- A Place That Holds Names -- Untitled -- Salmon Spirit Chest, Connected (box) -- The Language of Weaving: Featured Artist Dr. Teri Rofkar -- Nome, Alaska -- Drained -- I’m From -- Srevlla—The state of things where the spring snow is so soft that one sinks into it. -- Reflections -- Txamsem -- Post-Glacial Rebound -- Dressed in Garlands -- Learning the Dance -- Shamrocks -- When You See Me -- Water Spirit -- To Speak for Restraint, for Wildness, for Beauty: Featured Writer Aleria Jensen -- Young Eagle -- Untitled (detail) -- Baula -- Airport Dike Trail Evening -- Ninja Meatballs -- Untitled -- In the Wild Without Child: One Mother’s Invitation to Self -- Whale Tail Vista -- Questions for Anemones -- Yellow Cedarbark Wool on Starfish Pot -- Gleaming Orange and Pissed -- Through the Sky She Comes -- Love for the Honeybee -- The Last Speaker -- Juneau Fireweed -- Judy Plays the Tuba -- Illuminated Juneau -- Airport Dike Trail Moonlight -- Escape -- A Wooden Mother -- Black and Whites -- an excuse for staying indoors (a working title for a work in progress) -- Insecurities -- Lake Farm -- Yew Bear -- Rupture -- Mendenhall Glacier -- The Rookery -- Transient -- Laminaria -- Untitled -- Querencia -- Hoard -- Untitled -- Small Birds Sign -- Selfie at Two -- Entropy -- Goodbye -- Sitka Bridge -- My Remedy -- S1 -- Delta Symbols Static -- Falling -- Breathe Deeply -- Drum, drum away -- Eaglefest Dancer -- Wasichana -- Writer & Artist Biographie

Preserving cultural heritage: Analyzing the antifungal potential of ionic liquids tested in paper restoration

Early industrialization and the development of cheap production processes for paper have led to an exponential accumulation of paper-based documents during the last two centuries. Archives and libraries harbor vast amounts of ancient and modern documents and have to undertake extensive endeavors to protect them from abiotic and biotic deterioration. While services for mechanical preservation such as ex post de-acidification of historic documents are already commercially available, the possibilities for long-term protection of paper-based documents against fungal attack (apart from temperature and humidity control) are very limited. Novel processes for mechanical enhancement of damaged cellulosic documents use Ionic Liquids (IL) as essential process components. With some of these ILs having azolefunctionalities similar to well-known fungicides such as Clotrimazole, the possibility of antifungal activities of these ILs was proposed but has not yet been experimentally confirmed. We evaluated the potency of four ILs with potential application in paper restoration for suppression of fungal growth on five relevant paper-infesting molds. The results revealed a general antifungal activity of all ILs, which increased with the size of the non-polar group. Physiological experiments and ultimate elemental analysis allowed to determine the minimal inhibitory concentration of each IL as well as the residual IL concentration in process-treated paper. These results provide valuable guidelines for IL-applications in paper restoration processes with antifungal activity as an added benefit. With azoles remaining in the paper after the process, simultaneous repair and biotic protection in treated documents could be facilitated

HPC-GAP: engineering a 21st-century high-performance computer algebra system

Symbolic computation has underpinned a number of key advances in Mathematics and Computer Science. Applications are typically large and potentially highly parallel, making them good candidates for parallel execution at a variety of scales from multi-core to high-performance computing systems. However, much existing work on parallel computing is based around numeric rather than symbolic computations. In particular, symbolic computing presents particular problems in terms of varying granularity and irregular task sizes thatdo not match conventional approaches to parallelisation. It also presents problems in terms of the structure of the algorithms and data. This paper describes a new implementation of the free open-source GAP computational algebra system that places parallelism at the heart of the design, dealing with the key scalability and cross-platform portability problems. We provide three system layers that deal with the three most important classes of hardware: individual shared memory multi-core nodes, mid-scale distributed clusters of (multi-core) nodes, and full-blown HPC systems, comprising large-scale tightly-connected networks of multi-core nodes. This requires us to develop new cross-layer programming abstractions in the form of new domain-specific skeletons that allow us to seamlessly target different hardware levels. Our results show that, using our approach, we can achieve good scalability and speedups for two realistic exemplars, on high-performance systems comprising up to 32,000 cores, as well as on ubiquitous multi-core systems and distributed clusters. The work reported here paves the way towards full scale exploitation of symbolic computation by high-performance computing systems, and we demonstrate the potential with two major case studies

Application of alternative cell separation systems for the harvest of mammalian cell culture processes in a fully disposable single-use facility

In a fully disposable facility where the use of continuous disk-stack centrifuges are not preferred, harvest processes based on conventional depth filtration become more challenging with increasing single-use bioreactor (SUB) size and higher density culture. Lower filterability due to high volume and high cell density diminishes the efficiency of the depth filtration. In addition, the use of larger depth filtration systems is constrained by the facility footprint. To address the challenge described, several alternative single-use harvest technologies were evaluated. A disposable centrifuge with a small foot print, low consumable cost, and ease of operation was tested. In a study using a 1kL SUB for harvest, the disposable centrifuge was compared to a continuous disk-stack centrifuge, both followed by conventional depth filtration. The best operating conditions, as well as the edges of failures, were found for the disposable centrifuge. When compared to the disk-stack centrifuge results showed that the operation can be performed in a wide range without impacting depth filtration area requirements and less depth filter area was needed. In addition to testing a disposable centrifuge, flocculation was evaluated and compared, followed by the depth filtration. This was found to be another low-cost alternative process, while also occupying less facility space. The flocculation technology was tested with different cell lines and results showed significant improvement in filterability and reduction of depth filter area compared to full traditional depth filtration train

Direct hot embossing of microelements by means of photostructurable polyimide

While automatic hot embossing systems are available for large- and small-scale productions of polymeric devices, one of the process challenges remains to be the manufacturing of precise, durable, and yet inexpensive hot embossing stamps. The use of metallic stamps manufactured by electroplating a photoresist pattern or by precision milling and their replication into silicone molds with UV-lithography, electroplating, and molding techniques is state of the art. Yet, there have been few, if any, thriving attempts to directly emboss polymers by means of bare photoresists, and in particular polyimide-based photoresists, without transferring the photoresist patterns into a different stamp material. We conduct a proof-of-concept by developing hot embossing stamps based on photosensitive polyimide. We focus primarily on the reliability of the aforementioned stamps throughout the hot embossing cycle and the fidelity of pattern transfer onto polymeric films for different microstructural patterns. © 2016 Society of Photo-Optical Instrumentation Engineers (SPIE).DFG/CRC/Planar Optronic System