Dresden, Techn. Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Dresden, Techn. Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Our sensory experiences are encoded in the patterns of activity of the neurons in our brain. While we know we are capable of sensing and responding to a constantly changing sensory environment, we often study neural activity by repeatedly presenting the same stimulus and analyzing the average neural response. It is not understood how the average neural response represents the dynamic neural activity that produces our perceptions. In this work, we use functional imaging of the rodent primary somatosensory cortex, specifically the whisker representations, and apply classic signal-detection methods to test the predictive power of the average neural response. Stimulus features such as intensity are thought to be perceptually separable from the average representation; however, we show that stimulus intensity cannot be reliably decoded from neural activity from only a single experience. Instead, stimulus intensity was encoded only across many experiences. We observed this probabilistic neural code in multiple classic sensory paradigms including complex temporal stimuli (pairs of whisker deflections) and multi-whisker stimuli. These data suggest a novel framework for the encoding of stimulus features in the presence of high-neural variability. Specifically we suggest that our brains can compensate for unreliability by encoding information redundantly across cortical space. This thesis predicts that a somatosensory stimulus is not encoded identically each time it is experienced; instead, our brains use multiple redundant pathways to create a reliable sensory percept.

Regensburg, Univ., Diss., 2008.

Modern battle tanks are equipped with gun stabilization systems using gyro and encoder data to stabilize the gun barrel, although these systems are very sensitive and reliable, these systems assume the gun barrel as a rigid beam, and do not use information from

3 pp. / Problems and pests of cacti, agave, and yuccas / Barrel cactus and Saguaro (Carnegiea gigantea) are easily transplanted. Procedures for safely and succesfully moving these plants are discussed in this bulletin.

Between approximately 1850 and 1936, the barrel organ was one of the most commonly heard instruments in the streets of New York and the frequent subject of written, visual, and musical accounts created by middle class authors and artists. The instrument's loud, wheezy tunes inspired heated debates that began in the nineteenth century and were often aligned with the broader social upheavals caused by Italian immigration. Despite their frequent differences in perspective, most written accounts characterized organ grinders as poor, uneducated, Italian immigrants. Musical representations of street music developed a similar proclivity to emphasize Italian alterity. As early as the 1850s, it was common to quote popular dance idioms to evoke street music, a trend that continued well into the early twentieth century in Tin Pan Alley songs. These strophic songs offered more elaborate portrayals of organ grinders, mimicking the dialect of Italian immigrants through clipped, misspelled syllables. Street musicians declined in the twentieth century, but such stereotypes continued to resonate strongly within fictive musical portrayals. In Charles Ives' From Hanover Square North, the clashing quotations of a gospel hymn aurally signify the program's commuters and organ grinder, whose music animates the scene similar to a tableau found within Nathaniel Hawthorne's novel The House of Seven Gables. In contrast to Ives' idealistic conception of street music, Charles Cadman's opera The Willow Tree depicts a murderous street musician whose association with pleasant, Italian folk music does little to belie his unstable actions. Mayor Fiorello La Guardia's 1936 decision to stop licensing organ grinders created a controversy that may have influenced representations of organ grinders in Marc Blitzstein's I've Got the Tune and the animated short Organ Grinder's Swing. The 1936 controversy suggested that not only were middle class audiences concerned with unprecedented waves of Italian immigration, they were also worried about an urban soundscape increasingly saturated with noise. It was these twin problems that led a class of educated New Yorkers to create meaning by reverting to ethnic, class-based stereotype.

The de novo design of peptides is a central area of research in chemical biology. Although it is now possible to design helical peptide structures from first principle, designing â-sheets remains a challenge. Significant advances in this area have been made by using molecular scaffolds, which stabilize â-sheets through intramolecular H-bonding involving the scaffold or which direct supramolecular assembly of the conjugate. In my thesis, I have made use of novel strategies, using ferrocene (Fc) as a central scaffold for controlling the secondary structure of peptides. This approach has been highly successful. Four major new strategies are introduced and described in this thesis: <p>a) Cyclization of Fc-peptide conjugates of the type Fc[CO-Xxx-CSA]2 (Xxx = Gly, Ala, Val, Leu) and Fc[CO-Gly-Xxx-CSA]2 (Xxx = Val, Ile; CSA = cysteamine) leads to the clean formation of novel cyclic bioorganometallic conjugates, which exhibit strong intramolecular hydrogen bonding interactions that restrict the mobility of the podand peptide chains. In the latter system, this intermolecular hydrogen bonding interaction was exploited for the design of a novel â-barrel-like structure. For Fc[CO-Gly-Val-CSA]2 and Fc[CO-Gly-Ile-CSA]2 discrete cyclic supramolecular assemblies were formed in which the individual molecules assemble along the rims of the molecules, resulting in the formation of tubular peptide superstructures that possess a central cavity and are filled with water molecules. <p>b) Prior to my work, work by Hirao and Metzler-Nolte clearly showed that the two podand peptide chains in Fc-peptide conjugates are pointing away from each other. This would indicate that extended â-sheets cannot be formed by simply extending the podand peptide chains. In my work, I clearly demonstrate that, in contrast to earlier results, it is possible to use the Fc scaffold to stabilize â-sheet-like interactions in longer peptide chains. Two systems are described in this thesis Fc[CO-Gly-Val-Cys(Bz)-OMe]2 and Fc[CO-Gly-Ile-Cys(Bz)-OMe]2. In both the cases, amino acids are employed that have a high propensity for â-sheet formation. Both Fc-peptide conjugates exhibit strong interstrand hydrogen bonding, resembling that found in â-sheets.<p>c) In this work, I have demonstrated the use of ferrocene amino acid (Fca) to control the structure in peptides. In contrast to previous work by Metzler-Nolte, my work is largely focusing on the design of a repetitive Fca-peptide motif. It is proposed that this repetition will enable strong interactions between the peptide portions of the conjugate, resulting in the formation of an extended structure. To this effect, a series of Fca-conjugates of the type Boc-[Fca-Ala]n-OMe (n = 1-4) was synthesized and fully characterized. All systems display the expected interaction between the Ala residues having a 12-membered hydrogen bonded ring. Such a structural motif resembles that found in naturally occurring â-helical structures of the spike-region of some viral proteins. <p>d) I have also demonstrated the use of a novel Fc-derivative, Fc[NH-Boc]2, to control the structure of podand amino acid chains. Fc-diamine was synthesized by the convenient carbazide route giving this useful scaffold in high yield. This material was converted into its peptide conjugate and the resulting conjugate displays the elusive 14-membered hydrogen bonding ring. <p>Thus, in my work, I have provided a new complementary tool for peptide design that will undoubtedly find applications for the design of de novo proteins in the near future.

The de novo design of peptides is a central area of research in chemical biology. Although it is now possible to design helical peptide structures from first principle, designing â-sheets remains a challenge. Significant advances in this area have been made by using molecular scaffolds, which stabilize â-sheets through intramolecular H-bonding involving the scaffold or which direct supramolecular assembly of the conjugate. In my thesis, I have made use of novel strategies, using ferrocene (Fc) as a central scaffold for controlling the secondary structure of peptides. This approach has been highly successful. Four major new strategies are introduced and described in this thesis: <p>a) Cyclization of Fc-peptide conjugates of the type Fc[CO-Xxx-CSA]2 (Xxx = Gly, Ala, Val, Leu) and Fc[CO-Gly-Xxx-CSA]2 (Xxx = Val, Ile; CSA = cysteamine) leads to the clean formation of novel cyclic bioorganometallic conjugates, which exhibit strong intramolecular hydrogen bonding interactions that restrict the mobility of the podand peptide chains. In the latter system, this intermolecular hydrogen bonding interaction was exploited for the design of a novel â-barrel-like structure. For Fc[CO-Gly-Val-CSA]2 and Fc[CO-Gly-Ile-CSA]2 discrete cyclic supramolecular assemblies were formed in which the individual molecules assemble along the rims of the molecules, resulting in the formation of tubular peptide superstructures that possess a central cavity and are filled with water molecules. <p>b) Prior to my work, work by Hirao and Metzler-Nolte clearly showed that the two podand peptide chains in Fc-peptide conjugates are pointing away from each other. This would indicate that extended â-sheets cannot be formed by simply extending the podand peptide chains. In my work, I clearly demonstrate that, in contrast to earlier results, it is possible to use the Fc scaffold to stabilize â-sheet-like interactions in longer peptide chains. Two systems are described in this thesis Fc[CO-Gly-Val-Cys(Bz)-OMe]2 and Fc[CO-Gly-Ile-Cys(Bz)-OMe]2. In both the cases, amino acids are employed that have a high propensity for â-sheet formation. Both Fc-peptide conjugates exhibit strong interstrand hydrogen bonding, resembling that found in â-sheets.<p>c) In this work, I have demonstrated the use of ferrocene amino acid (Fca) to control the structure in peptides. In contrast to previous work by Metzler-Nolte, my work is largely focusing on the design of a repetitive Fca-peptide motif. It is proposed that this repetition will enable strong interactions between the peptide portions of the conjugate, resulting in the formation of an extended structure. To this effect, a series of Fca-conjugates of the type Boc-[Fca-Ala]n-OMe (n = 1-4) was synthesized and fully characterized. All systems display the expected interaction between the Ala residues having a 12-membered hydrogen bonded ring. Such a structural motif resembles that found in naturally occurring â-helical structures of the spike-region of some viral proteins. <p>d) I have also demonstrated the use of a novel Fc-derivative, Fc[NH-Boc]2, to control the structure of podand amino acid chains. Fc-diamine was synthesized by the convenient carbazide route giving this useful scaffold in high yield. This material was converted into its peptide conjugate and the resulting conjugate displays the elusive 14-membered hydrogen bonding ring. <p>Thus, in my work, I have provided a new complementary tool for peptide design that will undoubtedly find applications for the design of de novo proteins in the near future.

Proteins have a wide array of essential functions: from serving as enzymatic catalysts to protecting the immune system as antibodies. Proteins spontaneously self-organize into specific, folded structures determined by their amino acid sequences and the interaction between molecular forces. Since the 3-dimensional structure into which they fold often relates to the specific function of the protein, much effort has been directed towards methods to predict the folded structure from a given sequence, with the hope of being able to understand protein functions from sequence information. The protein folding problem can be summarized as the attempt to understand the relationship between a protein sequence and a protein's geometric shape, or fold. Thus, there are two principal problems: given a sequence, what 3-dimensional form will the protein take (forward problem), and given a particular fold, what sequence or sequences code for that form (the inverse problem). In this work, models that represent folds as continuous structures are explored. Models of the two prevalent motifs in protein folds, α helices and β barrels, are developed using axially deformed tubes and surfaces of revolution. These models are then analyzed and used to develop coordinate models of known and unknown structures.