2,358 research outputs found
Matthias Wagner : author profile
No full textThe author presented on this page has published his 10. article in Angewandte Chemie in the last 10 years
NeuroCarb : artificial neural networks for NMR structure elucidation of oligosaccharides
Get PDFRecombinant proteins and monoclonal antibodies offer great promise as therapeutics for hundreds
of diseases. Today, there are almost 400 biotechnology drugs in development for over 200 different
conditions. Many of these drugs are glycoproteins for which the correct glycosylation patterns are
important for their structure and function. Achieving and maintaining proper glycosylation is a major
challenge in biotechnology manufacturing. Most recombinant therapeutic glycoproteins are
produced in living cells. This method is used in an attempt to correctly match the glycosylation
patterns found in the natural human form of the protein and achieve optimal in vivo functionality.
However, utilizing cell systems to produce glycoproteins requires balancing the cells ability to
produce the protein with its ability to attach the appropriate carbohydrates. One limitation of this
approach is that the expression systems do not maintain complete glycosylation under high-volume
production conditions. This results in low yields of usable product and contributes to the cost and
complexity of producing these drugs. Incorrect glycosylation also affects the half-life of the drug.
Low production yields are a significant contributor to the critical worldwide shortage of
biotechnology manufacturing capacity.
To achieve higher production yields, the required quality standards to fulfill regulations by health
authorities, fast, accurate and preferably inexpensive analytical methods are required. Nowadays
the (routine) analysis of therapeutic glycoprotein is accomplished by analytical HPLC, MS or Lectin
blotting and in conjunction with chemical derivatization, exo-glycosidases treatment, and/or other
selective chemical cleavage reactions. The fact that different carbohydrates have very similar
molecular weights and physicochemical properties makes the analysis of glycosylation slow and
complex. Conventional glycoanalysis requires multiple steps to obtain the structure, sequence and
prevalence of all glycans in a glycoprotein sample. Complete analysis typically takes several days
and highly trained personnel. Therefore, the need for more efficient and rapid glycoanalysis
methodology is fundamental to the success of biotechnologically produced drugs.
With this demand in the back of one's mind, a 13C-NMR spectra analysis system for
oligosaccharides based on multiple Back-propagation neural networks was developed during this
thesis. Before the realization of the idea, some fundamental questions had to be posed:
1. Are the monosaccharide moieties, the anomeric configuration and the substitution pattern
of an oligosaccharide shown in a NMR (13C or 1H) spectrum?
2. What kind of NMR data provides this information better (1H or 13C-NMR)?
3. How can spectroscopic data be processed, compressed and transferred into a neural
network?
4. Which neural network architecture, learning algorithm and learning parameters lead to
optimal results?
Preliminary experiments showed that the six chemical shifts of a monosaccharide moiety (from
glucose, galactose and mannose) suffice to identify the monosaccharide itself, the anomeric
configuration (if the anomeric carbon atom is substituted) and the substitution position(s). The
experiments also revealed that these compounds could be almost completely separated by the help
of Counter-propagation neural networks.
The main goal of the neural network approach was to recognize every single monosaccharide
moiety in an oligosaccharide and train specialized separated networks for each monosaccharide
moiety group. Therefore, the neural networks should be trained with the 13C-NMR spectra of these
monosaccharide moieties. During the test phase, the whole spectrum of an oligosaccharide will be
presented to the network and the specialized networks should then only recognize the
monosaccharide moieties they are trained for.
Initial attempts to train a Back-propagation neural network to identify six methyl pyranoside
compounds failed. This lack of success was because the data set used was too small and an
uncompressed NMR spectrum leads to too many input neurons. Therefore, the data foundation was
changed and enlarged with 535 monosaccharide moieties (mostly galactose, glucose and
mannose) from literature and a special data compression (JCAMP-DX for NMR files) and parsing
software tool called ANN Pattern File Generator was developed. The entire dataset was normalized
and stored in a FileMaker 13C-NMR database. Further experiments with this new dataset, different
Back-propagation network layouts and training parameters still did not achieve the designated
recognition rate of unknown test compounds. The training performance of the neural networks
seems to be insensible against major changes of training parameters. Tests with a new and
enlarged dataset (1000 oligosaccharides and approx. 2500 monosaccharide moieties) with
Kohonen networks highlighted, that separate Kohonen networks for each monosaccharide type
yield to higher recognition rates than networks, which have to deal with all three monosaccharide
types at once.
This cognition was transferred to separate back propagation networks, which now showed
recognition rates higher than 90% for unknown compounds. This separated approach worked
excellent for disaccharides with two different monosaccharide moieties. Disaccharides with similar
or identical moieties cannot be identified because the designated neural network recognizes only
one monosaccharide at once. Out of this disadvantage, the so-called 'ensemble' or 'group of
experts' approach was developed. Here, one utilizes the fact, that no trained neural network shows
exactly the same recognition characteristics. Different neural networks respond differently to the
same test inputs. Twenty trained neural networks at a time were grouped into ensembles. All these
networks are trained to recognize the same monosaccharide moiety. After presenting a test input
(e.g. disaccharide) to this group of experts, one gets at the most extreme case, twenty different
recognition results. Afterwards, the results can be statistically analyzed. In the case of a
disaccharide with two monosaccharide moieties of the same carbohydrate (e.g. α-D-Glcp-1-4-β-DGlcp-
OMe), the analysis will deliver both monosaccharide compounds because some networks
recognized one and other networks the other part of the disaccharide.
The ensemble approach brought the final breakthrough of this thesis. Disaccharide recognition
rates in the range of 85 – 96% (depending on the monosaccharide moiety – glucose, galactose or
mannose) demonstrate the feasibility of the approach. The hit rates of the different ensembles can
certainly be improved by a more subtle choice of the members of each ensemble. An ongoing
diploma work shows a recognition improvement in this direction
Enduring Ambiguity: What Is European Literature? Matthias Nawrat in Conversation with Monika Woltig
Get PDFMatthias Nawrat is a Polish-German author living in Germany born in Opole, Poland. He moved with his family to Bamberg in 1989. He was awarded the Adelbert-von-ChamissoFörderpreis, was nominated for the Deutscher Buchpreis, received the Bremen Literature Prize and the Alfred Döblin Medaille. His most important novels were "Wir zwei allein" (2012), "Die vielen Tode unseres Opas Jurek" (2015), and "Der traurige Gast" (2019).Matthias Nawrat to niemiecki autor polskiego pochodzenia. Matthias Nawrat urodził się w Opolu i wraz z rodziną przeprowadził się w 1989 roku do Bambergu. Uzyskał Nagrodę im. Adelberta von Chamisso (Förderpreis), był nominowany do Niemieckiej Nagrody Książkowej (Deutscher Buchpreis), otrzymał Nagrodę Literacką miasta Bremy i Medal im. Alfreda Döblina. Najważniejsze teksty: "Wir zwei allein" (2012), "Die vielen Tode unseres Opas Jurek" (2015), "Der traurige Gast" (2019).Matthias Nawrat ist ein deutscher Autor polnischer Herkunft. Matthias Nawrat wurde im polnischen Opole geboren und siedelte 1989 mit seiner Familie nach Bamberg über. Er wurde mit dem Adelbert-von-Chamisso-Förderpreis ausgezeichnet, zum Deutschen Buchpreis nominiert und erhielt den Bremer Literaturpreis sowie die Alfred-Döblin-Medaille. Die wichtigsten Texte: "Wir zwei allein" (2012), "Die vielen Tode unseres Opas Jurek" (2015), "Der traurige Gast" (2019)
Baculus Militaris Compendiosus Infanterie Oder Officirers Stab Das ist Ein kurtzer Begrieff der Kriegs Lectionen bey dem Fußvolck gebräuchlich auch nötig : Bestehend in sechserley Exercitien 1. In der Partisan, halber Pique oder Jägerstock. 2. In der Fahn. 3. In der Pique. 4. In der Musqueten. 5. In der Musqueten mit der gabel oben und unten mit einer eiserner spitzen und in der mitten mit einem ein geschrobenen hacken. 6. In Hieb degen/ welcher bey dem fußvolck brauchlich / [Matthias Schlüter]
No full textJohn Matthias
Get PDFPoster promoting author John Matthias reading from his work in the Auditorium, Building 9, University of North Florida.
Poster dimensions: 26.7 cm x 41.8 cmhttps://digitalcommons.unf.edu/performances_print/1013/thumbnail.jp
Recognizing and marshalling the pre-publication error correction potential of open data for more reproducible science
No full textPatristical Ideas in the Works of Matthias of Janov
Get PDFANGLICKÁ ANOTACE Title: Patristical ideas in the works of Matthias of Janov The thesis treats of the identification of ideas of church fathers in the work and thinking of Matthias of Janov. The thesis consits of three main parts. First part deals with Matthias of Janov in broader context of church tradition. Major political and theological developments that could have an impact on Matthias theological work are presented in this section. Second part introduces life of Matthias of Janov and identifies his major theological contributions. In the third part of the thesis, following explanation of methodology used, the findings of the author are presented. Three areas were selected by the author and researched in view of the identification of possible influance of church fathers in the Matthias of Janov work: the idea of Antichrist, frequent eucharisty and condemnation of idolatry. The findings confirm a strong influance of Augustin and Hieronymus in particular and other early church fathers on the formation of the theology of Matthias of Janov in all three areas of the study. It was also noticed that through the church fathers Matthias of Janov was strongly influenced by neoplatonism which was documented on his idea of "The First Thruth" Key words: Matthias of Janov, church fathers, antichrist, eucharisty,..
Foreign Policy of King Matthias Corvinus from 1464 to 1490
Get PDFOvaj je članak drugi dio rada u kojem se istražuje vrlo kompleksna europska politika ugarsko-hrvatskoga kralja Matijaša Korvina. U ovom se dijelu razmatraju događaji od proljeća 1464. do 1490. godine. U prvom poglavlju članka autor obrađuje pokušaj organiziranja križarskoga pohoda Pija II. protiv Osmanlija 1464. i Matijaševe samostalne akcije radi učvršćivanja jugoistočnih granica kraljevstva. U drugom se poglavlju obrađuje razvoj Matijaševih odnosa s bivšim tastom Jurjem Podjebradskim koji je na kraju doveo do rata (1468–1471). U trećem je poglavlju dan kratak osvrt na pobunu plemstva protiv Matijaševe centralističke vladavine 1472. Četvrto se poglavlje bavi ratom za češko prijestolje (1471–1479) i ponovnim ratom protiv Fridrika III. (1477). U petom poglavlju autor daje kratki pregled Matijaševih odnosa s papinstvom, a u šestom pregled ratovanja s Osmanlijama tijekom sedamdesetih i osamdesetih godina XV. stoljeća. U sedmom poglavlju razmatraju se diplomatske akcije vezane uz traženje Matijaševe nove supruge te njegov brak s Beatricom Aragonskom. U osmom poglavlju autor se bavi Matijaševim ratom s Fridrikom III. za carsku titulu. Deveto je poglavlje posvećeno kraljevoj vanjskoj politici i diplomatskim aktivnostima s Venecijom i talijanskim državama tijekom osamdesetih godina. Deseto poglavlje daje pregled političkih aktivnosti tijekom posljednjih godina njegove vladavine. Jedanaesto poglavlje analizira Matijaševu vojsku. Rad završava kratkim pregledom posljednica kraljeve burne politike.This article is the second part of a longer paper in which the author reviews the very complex foreign policy of Hungarian-Croatian king Matthias Corvinus. In this paper the author analyses major events from Matthias’ coronation in the spring of 1464 until his sudden death in Vienna in the spring of 1490. The whole paper and analysis of events are based on research of various sources and literature. In the first chapter the author describes the failed attempt of Pope Pius II to organize a crusade against the Ottoman Empire in 1464 and Matthias’ own actions against the Turks with the main goal of strengthening his southeastern borders. In the second chapter the author analyses the conflict between Matthias and his ex-father-in-law, George of Poděbrady, and the war between them (1468–1471). In the third chapter the author gives a short overview of the uprising of magnates and the aristocracy against the central rule of King Matthias (1472). The fourth chapter deals with the war for the Bohemian throne from 1471 to 1479 and the war against Frederick III in 1477. In the next chapter the author gives a brief overview of the diplomatic relations between popes and Matthias Corvinus over a longer period of time, from 1464 to 1490. The main subject of the sixth chapter is the war against the Ottoman Empire during the seventh and eighth decade of the 15th century. In the seventh chapter the author describes Matthias’ search for his next wife and his marriage to Beatrice of Aragon. In the following chapter the author reviews Matthias’ new war against Frederick III for the title of the German Empire. The ninth chapter is a brief overview of Matthias’ foreign policy in the Italian states and Venice during the last decade of his life. The tenth chapter is dedicated to the final years of Matthias’ life. The next chapter analyses one of the most important segments of his foreign policy – his army. This article ends with short overview of the events which happened after the death of King Matthias and the consequences of his stormy policy
Achieving sustainable reorganization after bankruptcy: empirical evidence from formal proceedings of Austrian SMEs
No full textAuthor Matthias Baschinger, BScMasterarbeit Universität Linz 202
- …
