Academic literature on the topic 'Dimers'

In this work, we study the use of asymmetric carbon nanotube (CNT) dimers for the contactless detection of foreign nano-particles. Asymmetric CNT dimers create a unique field distribution, through the electromagnetic coupling, which in turn generates two distinct resonances representing the bonding and anti-bonding modes. The presence of a foreign nano-particle (NP) in the vicinity of the CNT dimer perturbs the dimer’s field distribution and causes the bonding and anti-bonding resonances to shift by unequal amounts depending on the NP location. By studying the difference in the shift of the bonding and the anti-bonding resonances, we show that the NP relative location can be reconstructed. The computational experiments performed in this work show how asymmetric CNT dimers can be used for novel sensing applications.

ABSTRACT We have examined the antipneumococcal activities of novel quinolone dimers in which ciprofloxacin was tethered to itself or to pipemidic acid by linkage of C-7 piperazinyl rings. Symmetric 2,6-lutidinyl- and trans-butenyl-linked ciprofloxacin dimers (dimers 1 and 2, respectively) and a pipemidic acid-ciprofloxacin dimer (dimer 3) had activities against Streptococcus pneumoniae strain 7785 that were comparable to that of ciprofloxacin, i.e., MICs of 2, 1, and 4 to 8 μg/ml versus an MIC of 1 to 2 μg/ml, respectively. Surprisingly, unlike ciprofloxacin (which targets topoisomerase IV), several lines of evidence revealed that the dimers act through gyrase in S. pneumoniae. First, ciprofloxacin-resistant parC mutants of strain 7785 remained susceptible to dimers 1 to 3, whereas a gyrA mutation conferred a four- to eightfold increase in the dimer MIC but had little effect on ciprofloxacin activity. Second, dimer 1 selected first-step gyrA (S81Y or S81F) mutants (MICs, 8 to 16 μg/ml) that carried wild-type topoisomerase IV parE-parC genes. Third, dimers 1 and 2 promoted comparable DNA cleavage by S. pneumoniae gyrase and topoisomerase IV, whereas ciprofloxacin-mediated cleavage was 10-fold more efficient with topoisomerase IV than with gyrase. Fourth, the GyrA S81F and ParC S79F enzymes were resistant to dimers, confirming that the resistance phenotype is largely silent in parC mutants. Although a dimer molecule could bind very tightly by bridging quinolone binding sites in the enzyme-DNA complex, the greater potency of ciprofloxacin against gyrase and topoisomerase IV suggests that dimers 1 to 3 bind in a monomeric fashion. The bulky C-7 side chain may explain dimer targeting of gyrase and activity against efflux mutants. Tethered quinolones have potential as mechanistic tools and as novel antimicrobial agents.

The simulation of dimers formation during the low-temperature reconstruction of GaAs (001) surface terminated with Ga or As atoms was performed by the molecular dynamics method using the analytical Bond-Order Potential based on quantum mechanical theory incorporating both σ- and π- bonds between atoms. A decrease in values of potential energy of the atoms during formation of isolated surface dimer have been determined. It has been found that potential energy of an atom in As-dimer is several tenths of an eV lower than in Ga-dimer. Kinetics of the initial stages of Ga-dimers formation in the temperature range of 25 - 40 K was studied. It was found that the characteristic thermal activation energy of single isolated Ga-dimers formation is ~ 29 meV, which is lower than the same value for As-dimers (~ 38 meV). Time constants characterizing the average rate of transformation of one dimer into a chain of two dimers at temperature range of 28 - 37 K were estimated. Inverse values of these parameters for paired Ga- and As-dimers are in the ranges of 10^11 – 10^12 s^-1 and 10^9 – 10^10 s^-1, respectively, while corresponding parameters for the formation of single dimers are in the ranges of 4·10^6 – 10^8 s^-1 and 1.4·10^6 – 7.4·10^7 s^-1.

Insulin degrading enzyme (IDE) has been detected in the cerebrospinal fluid media and plays a role in encapsulating and degrading the amyloid β (Aβ) monomer, thus regulating the levels of Aβ monomers. The current work illustrates a first study by which IDE encapsulates polymorphic early-stage Aβ oligomers. The main goal of this study was to investigate the molecular mechanisms of IDE activity on the encapsulated early-stage Aβ dimers: fibril-like and random coil/α-helix dimers. Our work led to several findings. First, when the fibril-like Aβ dimer interacts with IDE-C domain, IDE does not impede the contact between the monomers, but plays a role as a ‘dead-end’ chaperone protein. Second, when the fibril-like Aβ dimer interacts with the IDE-N domain, IDE successfully impedes the contacts between monomers. Third, the inhibitory activity of IDE on random coil/α-helix dimers depends on the stability of the dimer. IDE could impede the contacts between monomers in relatively unstable random coil/α-helix dimers, but gets hard to impede in stable dimers. However, IDE encapsulates stable dimers and could serve as a ‘dead-end’ chaperone. Our results examine the molecular interactions between IDE and the dimers, and between the monomers within the dimers. Hence, this study provides insights into the inhibition mechanisms of the primary nucleation of Aβ aggregation and the basic knowledge for rational design to inhibit Aβ aggregation.

Are the dimer structures of active Ras isoforms similar? This question is significant since Ras can activate its effectors as a monomer; however, as a dimer, it promotes Raf's activation and MAPK (mitogen-activated protein kinase) cell signalling. In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. The active helical dimers formed by the allosteric lobe are isoform-specific: K-Ras4B-GTP favours the α3 and α4 interface; H-Ras-GTP favours α4 and α5. Both isoforms also populate a stable β-sheet dimer interface formed by the effector lobe; a less stable β-sandwich interface is sustained by salt bridges of the β-sheet side chains. Raf's high-affinity β-sheet interaction is promoted by the active helical interface. Collectively, Ras isoforms’ dimer conformations are not uniform; instead, the isoform-specific dimers reflect the favoured interactions of the HVRs (hypervariable regions) with cell membrane microdomains, biasing the effector-binding site orientations, thus isoform binding selectivity.

The synthesis and surface self-assembly behavior of two types of metal-porphyrin dimers is described. The first dimer type consists of two porphyrins linked via a rigid conjugated spacer, and the second type has an alkyne linker, which allows rotation of the porphyrin moieties with respect to each other. The conjugated dimers were equipped with two copper or two manganese centers, while the flexible dimers allowed a modular built-up that also made the incorporation of two different metal centers possible. The self-assembly of the new porphyrin dimers at a solid–liquid interface was investigated at the single-molecule scale using scanning tunneling microscopy (STM). All dimers formed monolayers, of which the stability and the internal degree of ordering of the molecules depended on the metal centers in the porphyrins. While in all monolayers the dimers were oriented coplanar with respect to the underlying surface (‘face-on’), the flexible dimer containing a manganese and a copper center could be induced, via the application of a voltage pulse in the STM setup, to self-assemble into monolayers in which the porphyrin dimers adopted a non-common perpendicular (‘edge-on’) geometry with respect to the surface.

ABSTRACT E-cadherin, an adhesive transmembrane protein of epithelial adherens junctions, forms two types of detergent-resistant dimers: adhesive dimers consisting of cadherin molecules derived from two neighboring cells and lateral dimers incorporating cadherins of the same cell. Both dimers depend on the integrity of the same residue, Trp156. While the relative amounts of these complexes are not certain, we show here that in epithelial A-431 cells, adhesive dimers may be a prevalent form. Inactivation of the calcium-binding sites, located between successive cadherin ectodomains, drastically reduced the amount of adhesive dimers and concomitantly increased the amount of lateral dimers. A similar interdependence of adhesive and lateral dimers was observed in digitonin-permeabilized cells. In these cells, adhesive dimers immediately disassembled after lowering the Ca2+ concentration below 0.1 mM. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime. These observations suggest that cadherin-mediated adhesion is based on the dynamic cycling of E-cadherin between monomeric and adhesive dimer states.

The adhesion receptor E-cadherin maintains cell–cell junctions by continuously forming short-lived adhesive dimers. Here mixed culture cross-linking and coimmunoprecipitation assays were used to determine the dynamics of adhesive dimer assembly. We showed that the amount of these dimers increased dramatically minutes after the inhibition of endocytosis by ATP depletion or by hypertonic sucrose. This increase was accompanied by the efficient recruitment of E-cadherin into adherens junctions. After 10 min, when the adhesive dimer amount had reached a plateau, the assembly of new dimers stalled completely. These cells, in a striking difference from the control, became unable to disintegrate both their intercellular contacts and adhesive dimers in response to calcium depletion. The same effects, but after a slightly longer time course, were obtained using acidic media, another potent approach inhibiting endocytosis. These data suggest that endocytosis is the main pathway for the dissociation of E-cadherin adhesive dimers. Its inhibition blocks the replenishment of the monomeric cadherin pool, thereby inhibiting new dimer formation. This suggestion has been corroborated by immunoelectron microscopy, which revealed cadherin-enriched coated pit-like structures in close association with adherens junctions.

A conformational analysis has been carried out for monoprotonated, unprotonated and deprotonated glycine dimers in the gas phase and an aqueous solution. MP2/6-311++(d,p), B3LYP/6-311++(d,p) and M06/6-311++(d,p) optimizations were performed for more than 200 initial conformations comprising nonionic (COOH–CH2–NH2) (N) and zwitterionic (COO−–CH2–NH3+) (Z) structures for neutral monomers. All the methods indicate that Z monomers are preferred over N ones for the neutral and deprotonated dimers in aqueous solutions, whereas the reverse trend is observed in the gas phase (including also protonated dimers). NC and ZC structures coexist in aqueous solutions for the protonated glycine dimer. The preferred geometries are significantly different depending on the media and total dimer charge. Moreover, several minima display close energies in each series (media and total dimer charge). New conformers, not previously reported, are found to be significantly populated in those conformational mixtures. Dimers containing Z monomers are associated with larger absolute solvation energies and are more prone than N-containing ones to experience protonation and deprotonation in the gas phase, whereas the reverse trend is observed in the aqueous solution. The Quantum Theory of Atoms in Molecules (QTAIM) analysis reveals that uncharged dimers display trifling electron density transfer between monomers, whereas it is significant in anionic and cationic dimers.

Four kinds of dimers from cyclic peptide [-(1R, 3S)-γ-Acc-D-Phe]3 were investigated using molecular modeling based on the density functional theory (DFT), molecular mechanics (MM) and molecular dynamics (MD). The equilibrium dimer structures reveal that these dimers can be divided into two different types according to stacking formation, in which one type dimer is more stable due to the effect of side chain groups. In each type of dimers, only one can transport CHCl3. When the terminal N-substituent methyl is introduced, the transport character is reversed. Analysis of 500 ps MD trajectory suggests that the inner and terminal sizes of the dimers are the main factor that affects the transport of CHCl3. The modeling results can provide a new way for designing and synthesizing cyclic peptide transport channels.

Controlling both energy and electron transfer processes is necessary for the performance of both light harvesting, and light emitting devices. The efficiency of both energy and electron transfer depends on the degree, or magnitude of the electronic coupling between molecules. In photosynthetic organisms such as plants and bacteria, long range energy transfer occurs between electronically coupled assemblies of chlorophyll molecules. The remarkable energy transfer efficiencies of light harvesting complexes employed in photosynthesis is intimately related to the orientation and intermolecular spacing between neighboring, identical chlorophyll molecules. In an attempt to develop inexpensive artificial light harvesting systems and devices researchers have synthesized an impressive catalogue of organic small molecules and polymers to generate free electrons and holes from absorbed light energy. The most commonly employed design principle for synthesizing both small molecule and polymer light absorbing systems is to link together an electron deficient (acceptor) molecule to an electron rich (donor) molecule through a conjugated linker. The conjugated bridge between donor and acceptor units enables charge transfer states that offer band-gap tuning and more easily separated electron/hole pairs. However, exciton migration in these synthetic donor-acceptor systems only partially mimics the assemblies of light harvesting molecules found in nature. As a result, exciton migration is limited to very short distances in synthetic light harvesting organic molecules. The following thesis presents a new approach for controlling the electronic coupling between neighboring identical molecules. By bridging two identical molecules about a sulfur atom, the electronic coupling between the two molecules can be increased by increasing the oxidation state of the “sulfur-bridge”. The broader implication of this work is that we may not need to use strongly coupled, conjugated donor-acceptor systems to achieve efficient charge separation and excitation migration. Instead, by using a non-conjugated linker, such as sulfur or perhaps even a saturated carbon atom, between molecules with identical electronic structure we may be able to enhance exciton transport in synthetic light harvesting assemblies.
Science, Faculty of
Chemistry, Department of
Graduate

We have obtained spectra of 10 vibrational bands of the Cs₂ (2)³∏_u ← ϰ³∑⁺₉ system. The molecules were formed in a supersonic free jet expansion, and were excited by light from a single mode CW dye laser. The total laser induced fluorescence was measured at 90° to the incident light and molecular beam, using a photomultiplier. Using a slit system to image a selected part of the interaction region, we have reduced the Doppler width to about 350MHz. We have been able to resolve the discrepancy between the different vibrational band positions given in two previous papers. Our vibrational bands show broad rotational contours, but we have not been able to resolve individual rotational lines. We have also obtained rotationally resolved spectra of the bandhead region of 22 vibrational bands of the Β¹∏₉ ← X¹∑⁺_u system. We found that the frequencies of the bandheads agreed with the bandhead positions deduced from the Dunham coefficients of a previous work. We have developed a theoretical model of the rotational structure and intensity distribution, taking into account optical pumping and the small solid angle subtended by the detector. By fitting this model to the experimental spectrum of the v' = 3,u∿ = 0 band using least squares optimization, we were able to extract rotational constants and line positions. We found that these line positions were in good agreement with those from the previous work. We have discussed how such spectroscopic data may be used in a determination of the s-wave scattering length of caesium, and we have reviewed the validity of the scattering length and other pararneterisations of low energy Cs-Cs interactions.

Thesis (M.S. in chemistry)--Washington State University, August 2009.
Title from PDF title page (viewed on Aug. 10, 2009). "Department of Chemistry." Includes bibliographical references (p. 53-55).

Thesis (Ph. D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 1997?
Includes copies of previously published articles. Includes bibliographical references (last 7 unnumbered leaves ).

Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.
Committee Chair: Sherrill, C. David; Committee Member: Bredas, Jean-Luc; Committee Member: Hud, Nicholas; Committee Member: Perry, Joseph.

This thesis is devoted to the study of orientifolds and dynamical supersymmetry breaking in configurations of D-branes on toric Calabi-Yau singularities, through the lens of dimer models. We first review the basic ingredients of string theory that led to the formulation of gauge/gravity dualities in terms of dimers. Then, we discuss the non-abelian anomaly cancellation conditions for the supersymmetric gauge theories arising on D-branes and provide necessary geometric criteria to determine whether an orientifold projection can be safely introduced. We also find a new realization of orientifold projection without fixed loci in dimer models and expand on its physical features. We argue that it exhausts the possibilities of orientifolding dimer models. In the subsequent part of the thesis, we investigate dynamical supersymmetry breaking vacua in the same class of models and their typical instability along N=2 Coulomb branches. This leads us to formulate a no-go theorem against their stability based on geometrical features of the singularity, and then to establish a precise way to circumvent it. We eventually find the first instance of stable dynamical supersymmetry breaking vacuum in string theory from D-branes on a toric Calabi-Yau singularity, the Octagon.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

Summary My PhD thesis is composed of two parts. A part deals with the characterization of alpha-synuclein (aS) dimers aggregation properties in respect to those of aS. The experimental work was conducted at CRIBI laboratory, at University of Padua, and constitutes the main project in which I was involved. During the third year of my PhD I spent six months at the Biopolymer Mass Spectrometry Laboratory of Imperial College in London. I conducted a glycomic analysis of mice tissues and a pilot study on expression and biosynthesis of mixed linked glucans emicellulose. Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterized by the loss of dopaminergic neurons in substantia nigra. The histological hallmarks of PD are intracellular inclusions, known as Lewy bodies (LBs), composed by filamentous and aggregated protein. The pathogenesis of the disease is still unclear, but a key step in the onset of PD is the aggregation of aS into amyloid fibrils, that deposit within LBs as the major component. Despite its importance in neurodegeneration, little is known about aS function, native physiological state and mechanism of aggregation. aS was recently described as a folded tetramer, but was generally considered a natively unfolded protein. aS is able to acquire alpha-helix conformation upon interaction with lipids and to convert to beta-structure in pathological processes. During the aggregation process, aS forms soluble oligomers, transient beta-structured intermediate between the physiological form of aS and amyloid fibrils. Dimerization of aS could represent a critical, rate-limiting step in the aggregation and amyloid formation of the protein. Therefore, we decided to study the aggregation of several different dimers of aS, produced through molecular biology techniques. A cysteine residue has been added at the N-terminal or at the C-terminal of aS, therefore producing a dimer N-N or C-C linked through a disulfide bond. A N-C dimer, formed two consecutive aS molecules, was obtained as a single polypeptide chain. During the project, another dimer, called DC dimer, was produced in order to further draw up the hydrophobic regions, and avoid the interferences of side chains within the molecule. DC is constituted by two consecutive central, highly amyloidogenic regions, containing aS residues from 1 to104 joined to residues from 29 to 140. The dimers represent a suitable tool for the study of intramolecular aS interaction pathway. Some remarkable differences define and limit the mobility freedom of the dimers respect to aS, hypothetically differentiating the fibrillation process of the four protein structures. The characterization of the dimers was performed using chemical and biophysical techniques in order to define their behaviour in solution as monomer. CD, IR and NMR spectroscopy studies show that all the dimers are unfolded. They undergo alpha-helical transition upon interaction with the detergent SDS. These results evidence that dimers strongly resemble aS conformational features. All the dimers were tested for the ability to form fibrils, by incubating the molecules under physiological buffer and at a protein concentration of 1 mg/ml. They show to be able to form fibrils, that are positive to Thioflavin T binding assay. Moreover, analysis of the structure of fibrils, conducted using circular dichroism (CD) and Fourier Transformed-IR (FTIR) spectroscopy, detects the structural transition from random to beta-sheet structure as attended for typical amyloid structure. Fibrils morphology was investigated by transmission electron microscopy (TEM) and atomic force microscopy (AFM) imaging. Fibrils derived from aS dimers are quite long, unbranched and formed by a single filament, a peculiar difference with aS fibril morphology. To identify which amino acids in the respective types of fibrils belong to the fibril core, proteolysis was performed. The rationale of this experiment reside in the fact that disordered regions of proteins are generally site of enzymatic attack and hydrolysis occurs at flexible chain region devoid of hydrogen-bonded secondary structure. Therefore, the prospects are to remove the flexible parts or tail from the amyloid core. Results showed that the core structures of the fibrils of the different molecules seems to be constituted by the same amino acidic region, which encompasses the segment 35-96, in analogy with previous studies. The kinetic of the process was analyzed by fluorescence techniques (ThT binding assay) and by evaluating the amount of protein present in fibrils on time. This calculation was indirectly performed measuring the absorbance of the supernatant obtained after centrifugation of each aliquot. NN and NC dimers show a slower kinetic of fibrillation than aS, while the rate of fibril formation of CC and DC dimers is faster than aS. Moreover, aggregation experiments on mixtures of aS in the presence of small amount of dimers were also conducted in order to check if the presence of dimer influence aS kinetic. Results evidenced the ability of CC dimer to affect the aggregation of aS. On the base of collected results, models of the dimer conformation within the fibrils are proposed. The research experience performed at Imperial College London gave me the possibility to learn and apply advanced techniques in mass spectrometry analysis of small organic compound, using GC-MS and MALDI-TOF spectrometers. N-acetylglucosaminyltransferase V (GlcNacT-V), encoded by the Mgat5 gene, is a medial Golgi enzyme which catalyzes the addiction of a beta-1,6-linked GlcNAc to the alpha-1,6 mannose of the trimannosyl N-glycan core. GlcNacT-V plays a pivotal role in the formation of tri- and tetra-antennary N-glycans on newly synthesized glycoprotein. This branch provides the preferred substrate for the enzymatic subsequent synthesis of polylactosamine chains and terminal modification including the Lewis antigens. In my study, glycomic analyses were performed to investigate possible changes in protein N-glycosylation in wild type conditions and in the absence of Mgat5 gene in C57B5 mice kidneys. In parallel, N-glycan profile of kidneys and spleens coming from mice treated with high fat diet GlcNAc supplementation were analyzed. Previous results demonstrate that the effects of GlcNAc salvage appear to increase flux to UDP-GlcNAc. Therefore we were interested to know whether this implementation affects N-glycan branching. Results show that Mgat5 deficient mouse kidney display less amount of tri-antennary and tetra-antennary structure compared to controls. However, GlcNAc dietary salvage has no apparent effect on N-linked glycosylation in the kidney and spleen, even if the experiments conducted on cell lines demonstrate that increased influx of UDP-GlcNAc resulted on increased N-glycan branching. Moreover, the performance of optimized glycome procedure allowed the identification of more tri-antennary glycan structures than the one reported on CFG (Consortium of Functional Glycomics) database.
Riassunto La mia tesi di dottorato è composta di due sezioni. Una sezione riguarda la caratterizzazione di dimeri di alpha-sinucleina (aS) in confronto con le proprietà di aS, sia in soluzione che in esperimenti di aggregazione. Il lavoro sperimentale è stato condotto nel laboratorio di Chimica delle Proteine (CRIBI Biotechnology Center), presso l’Università degli studi di Padova, e costituisce il progetto principale nel quale sono stata coinvolta. Durante il mio terzo anno di dottorato ho trascorso 6 mesi al laboratorio Biopolymer Mass Spectrometry Laboratory presso l’Imperial College a Londra. In questo laboratorio sono stata coinvolta in due progetti: uno studio di analisi glicomica di tessuti murini e un progetto pilota sulla biosintesi di emicellulosa mixed linked glucans (MLG). Il morbo di Parkinson è una malattia neurodegenerativa progressiva caratterizzata dalla perdita di neuroni dopaminergici nella substantia nigra. La principale caratteristica istologica della malattia è la presenza di inclusioni intracellulari, conosciute come corpi di Lewy, composti da aggregati proteici filamentosi. La patogenesi della malattia è ancora poco chiara, ma un passaggio chiave nello sviluppo della malattia è l’aggregazione di alpha-synuclein (aS) in fibrille amiloidi, che si accumulano dei corpi di Lewy e ne costituiscono il componente principale. Nonostante la sua importanza nella neurodegenerazione, si conoscono poco la funzione di aS, il suo stato nativo fisiologico e il meccanismo di aggregazione. aS è stata di recente descritta come un tetramero di proteine in alpha-elica, ma aS è stata generalmente descritta come una proteina natively unfolded. aS assume conformazione ad alpha-elica a seguito di interazione con lipidi e converte a struttura beta durante i processi patologici. Durante il processo di aggregazione, aS forma oligomeri solubili di struttura beta, transienti intermedi tra la forma fisiologica di aS e le fibrille amiloidi. La dimerizzazione di aS può rappresentare un fattore limitante nell’aggregazione e nella formazione di struttura amiloide. Pertanto, abbiamo deciso di studiare l’aggregazione di diversi dimeri di aS, prodotti mediante biologia molecolare. E’ stato aggiunto un residuo di cisteina all’ N- o al C- terminale di aS, producendo quindi dimeri NN o CC, legati attraverso un legame disolfuro. Un dimero NC, formato da due molecole consecutive di aS, è stato ottenuto come singola catena polipeptidica. Durante il progetto è stato prodotto un altro dimero, chiamato DC, disegnato in modo da avvicinare ulteriormente le regioni idrofobiche di aS, ed evitare le interferenze provocate dalle catene laterali, che vengono a trovarsi all’interno della molecola nei dimeri NN, CC ed NC. Il dimero DC contiene i residui 1-104 uniti al segmento 29-140 di aS, ed è quindi costituito da due regioni centrali di aS, altamente amilodoigeniche, disposte in modo consecutivo. I dimeri rappresentano uno strumento adatto per lo studio delle interazioni intramolecolari di aS. Alcune differenze sostanziali definiscono e limitano la libertà di movimento dei dimeri rispetto ad aS, ipoteticamente differenziando il processo di fibrillazione delle cinque strutture proteiche. La caratterizzazione dei dimeri è stata effettuata utilizzando tecniche biofisiche e chimiche al fine di definire il loro comportamento in soluzione come monomero. Studi di dicroismo circolare (CD), spettroscopia IR ed NMR hanno dimostrato che tutti i dimeri sono unfolded. Tutti effettuano transizione ad alpha-elica a seguito dell’interazione con il detergente SDS. Questi risultati provano che i dimeri hanno caratteristiche conformazionali simili ad aS. Successivamente, è stata esaminata la capacità dei dimeri di formare fibrille, incubando le molecole in tampone fisiologico alla concentrazione di 1 mg/ml. Tiutti sono in grado di formare fibrille, che sono positive al saggio di legame alla Tioflavina T (ThT), generalmente utilizzato per determinare la presenza di struttura amiloide. Inoltre, le analisi della struttura delle fibrille, condotte usando CD e spettroscopia IR in trasformata di Fourier (FT-IR), rilevano la presenza di transizione strutturale da random a struttura beta come ci si aspetta per fibrille amiloidi. La morfologia delle fibrille è stata studiata mediante microscopia elettronica a trasmissione (TEM) e microscopia di forza atomica (AFM). Le fibrille derivate dai dimeri di aS sono abbastanza lunghe, non ramificate e a singolo filamento, una differenza peculiare rispetto alle fibrille di aS, che si presentano twisted e formate da più filamenti. Per identificare quali amminoacidi di ciascun dimero fosse coinvolto nel core fibrillare sono sati eseguiti esperimenti di proteolisi. Il razionale di questo esperimento risiede nel fatto che le regioni non strutturate delle proteine sono in genere sito di attacco enzimatico, e l’idrolisi si verifica quindi in regioni flessibili, sprovviste di legani idrogeno intermolecolari che stabilizzano una struttura secondaria. Quindi lo scopo dell’esperimento è di rimuovere le parti flessibili dal core amyloide. I risultati hanno mostrato come le strutture core delle fibrille dei diversi dimeri sembrino essere costituite dalla stessa regione amminoacidica, che comprende il segmento 35-96, in analogia con studi precedenti su aS. La cinetica del processo è stata analizzata con tecniche di fluorescenza (saggio ThT) e valutando la quantità di proteine presenti nel tempo. Questo calcolo è stato effettuato indirettamente misurando l’assorbanza del surnatante ottenuto dopo ultracentrifugazione delle aliquote prelevate da miscele di aggregazione a diversi tempi. I dimeri NN ed NC hanno mostrato una cinetica di aggregazione più lenta rispetto ad aS, mentre il tasso di formazione delle fibrille di CC e DC è più veloce. Inoltre, esperimenti di aggregazione su miscele di aS in presenza di piccole quantità di dimeri sono stati condotti al fine di verificare se la presenza del dimero influenzasse la cinetica di aS. I risultati hanno evidenziato la capacità del dimero CC di influenzare l’aggregazione di aS. Sulla base dei risultati ottenuti, sono stati proposti dei modelli sulla conformazione dei dimeri all’interno delle fibrille. L’esperienza di ricerca svolta all’Imperial College London mi ha dato la possibilità di imparare e applicare tecniche avanzate di spettrometria di massa (MS) sull’analisi di composti organici, utilizzando gas cromatografia accoppiata ad MS (GC-MS) e spettrometri MALDI-TOF. L’enzima N-acetylglucosaminyltransferase V (GlcNAc-V), codificato dal gene Mgat 5, è un enzima del Golgi che catalizza l’addizione di un GlcNAc in posizione beta-1,6 a un mannosio alpha-1,6 della struttura di base degli zuccheri legati a residui amminici (N-glicani). GlcNAc-V svolge un ruolo fondamentale nella formazione di N-glicani a tre- e quattro-antenne su una proteina appena glicosilata. Queste ramificazioni forniscono il substrato favorito per la successiva sintesi enzimatica di catene poli-lactosamminiche e per le modificazioni terminali, compresi gli antigeni di Lewis. Ho svolto analisi glicomiche su tessuti renali murini per studiare possibili cambiamenti nella N-glicosilazione in topi wild type e knock out per il gene Mgat 5. In parallelo, è stato analizzato il profilo glicomico di tessuti renali e di milza di topi alimentati con una dieta ricca di GlcNAc. Risultati precedenti avevano dimostrato un aumento nel flussio di UDP-GlcNAc (substrato di GlcNAc-V), perciò eravamo interessati a determinare se il maggione apporto di zucchero influenzasse le glicosilazioni proteiche. I risultati hanno evidenziato come le glicoproteine dei topi ko per Mgat 5 hanno meno strutture a tre- e quattro-antenne nelle glicosilazioni rispetto ai controlli. L’apporto di GlcNAc nella dieta non ha alcun affetto apparente sulla struttura e composizione delle glicosilazioni dei tessuti analizzati, nonostante precedenti esperimenti condotti su linee cellulari abbiano avuto un diverso esito. Inoltre, le analisi che ho condotto hanno permesso di identificare glicosilazioni non ancora registrate nel database CFG (Consortium of Functional Glycomics) per i tessuti analizzati.

Two studies were carried out in an effort to gain a better understanding of how ketene dimers develop sizing. In the first study, eight ketene dimers with a range of melting points, vapor pressures, and molecular weights were evaluated for rate of sizing development. Ketene dimer melting point had a clear effect on the rate of sizing development. High melting ketene dimers initiated sizing at higher sheet moistures than low melting dimers. High melting dimers also developed their ultimate level of sizing faster than low melting ketene dimers. These results suggest that solid and liquid ketene dimers have different mechanisms of sizing development. Ketene dimer vapor pressure and molecular weight had no consistent effects on the rate of sizing development. Pseudo first order rate constants for sizing development were then measured for a high melting solid ketene dimer and a liquid ketene dimer over dryer temperatures ranging from 55 °C to 85 °C. The rate constants measured for the liquid ketene dimer increased steadily as dryer temperature increased. An Arrhenius plot of the rate constants obtained for the liquid ketene dimer yielded an activation energy of 11 kcal per mole for sizing development. These results are consistent with the hypothesis that the chemical reaction of the lactone ring is the rate determining step in sizing development for liquid ketene dimers. The high melting solid ketene dimer followed more complex kinetics and probably developed sizing by a combination of mechanisms. It is likely that the differing sizing responses measured for the solid and liquid ketene dimers are due to differing sizing contributions from the unreacted and hydrolyzed ketene dimers.

Intermediate filaments (IFs), in addition to microtubules (MTs) and microfilaments (MFs), are one of the three major components of the cytoskeleton in eukaryotic cells. As the basic building block of IFs, the properties of the IF dimmer re crucial to fully understand the molecular basis for the properties of the IF network in cells. However, the structure of IF dimers remains unknown, which has thus far prevented the elucidation of its nanomechanical properties, in particular molecular-level mechanisms of deformation. Here we present the development of a full atomistic molecular model of the vimentin dimmer, a coiled-coil structure consisting of four alpha-helixes (AHs). The structure is found to be stable in molecular dynamics simulation after an extensive equilibration process. After careful structure prediction, the behavior of the IF dimer under mechanical stress is investigated; including studies of changing the pulling velocity and a detailed analysis of the associated deformation and rupture mechanisms. Most notably, we observe a transition of AHs to beta-sheets (BSs) under mechanical deformation, as has been observed indirectly in earlier experimental studies. Our result helps to better understand the structure and fracture mechanism of this important protein filament.

D-dimers are specific derivatives of cross-linked fibrin. Their concentration may be used to conduct thrombolysis and predict its outcome. In this investigation we studied the relationship between D-dimer plasma levels during thrombolysis of deep leg vein thrombosis (DVT) and the phlebographic success.METHODS: 17 patients (9 males, 8 females, age range 17-56 years) were studied. All patients had DVT and were treated with either an acylated streptokinaseplasminogen complex (n=lO) or streptokinase (n=5) or both drugs successively (n=2) for 4.6 days on average. The thrombolytic effect was assessed by ascending phlebography and the patients were divided into 3 groups: A complete clearance, B partial clearance, C no change. The D-dimers were measured by a non-competitive EIA assay with a monoclonal antibody against a conformational epitope on the plasmin-resistant D-dimer, fragment of cross-linked fibrin.RESULTS: The table gives the mean D-dimer levels in the 3 groups of patients at 12 hours intervals.The statistical analysis (Newman-Keuls multiple range test) suggests that low D-dimer levels, especially over the first 36 hours are related to treatment failures.CONCLUSIONS: Despite some overlapping between successful and non-successful cases and lack of absolute specificity of the assay the D-dimer concentration may predict treatment failure in the first two days.

Abstract The combustion characteristics of PCU Alkene Dimers (C22H24) are evaluated as solid fuels in high speed flows, at conditions typical for ramjet operation (i.e., Mach 0.25, stagnation temperature and pressure of 300 K and 150 kPa, respectively). Samples of the dimer are binded into a solid layer with a styrene-polybutadiene copolymer (8% w/w) on the test chamber wall and convectively ignited by a gaseous flame in air. The goals of this research are of both practical and fundamental relevance: (i) determine the ability of the high energy fuel to increase practical devices’ performance, (ii) quantify and improve the combustion characteristics of the alkene dimers (i.e., ignition, flame stability, particulate formation), (iii) investigate the dynamics of the solid-gas interface combustion. To date, ignition times and rates of heat release were measured and the theoretical modelling was initiated. Preliminary results indicate that, in the present configuration, the dimer ignition times fall within the range reported in literature for other solid fuels. Large differences exist among different sets of data due primarily to nonsimilar geometrical configuration of the test. The dimer exhibits substantial rates of heat release in comparison with other solid fuels.

7-Azaindole (7AI) is one of a class of molecules that exhibit dual fluorescence as a result of excited-state tautomer formation. The tautomer is reached through a proton transfer from the initially excited "normal" form, the only form present in the ground electronic state. When isolated (in the gas phase or in non-hydroxylic solvents) 7AI does not tautomerize at an observable rate. However, in non-polar solvents, 7-azaindole forms dimers which enable the excited-state tautomerization to occur via a double proton transfer mechanism. Tautomerization in 7AI dimers has been studied for quite some time as a possible model for DNA mutagenesis [1]. Recent measurements have shown that the dimer the reaction is quite facile, occurring in ~1 ps at room temperature [2].

Mixed-valent transition metal dimers have become key systems for understanding many fundamental aspects of electron transfer dynamics.1 We have been interested in the mixed-valent dimer [(NC)5RuIICNRum(NH3)5]1- for which optical excitation into the metal-metal charge transfer (MMCT) band produces a state which is highly unstable with respect to back electron transfer.

In the present work we report the discovery of new families of solitary waves in a 1:N (N>1) granular dimers (a heavy bead followed and preceded by N light beads) wherein the Hertzian interaction law governs the interaction between spherical beads. We consider the dimer chain with zero precompression. The dynamics of such a dimer chain is governed by two system parameters, the stiffness ratio and the mass ratio between the light and the heavy beads. In particular we study in detail the solitary waves in 1:2 dimer chains [11]. The solitary waves in a 1:2 dimer are contrastingly different from that in a homogeneous chain and 1:1 dimer chain. Solitary waves realized in homogeneous and 1:1 dimer chains possess symmetric velocity waveforms. In contrast, in a 1:2 dimer chain we realize solitary waves that have symmetric velocity waveforms on the heavy beads, whereas that on the light beads is non-symmetric. The existence of families of solitary waves in these systems is attributed to the dynamical phenomenon to ‘anti-resonance’. This leads to the complete elimination of radiating waves in the trail of the propagating pulse. Anti-resonances are associated with certain symmetries of the velocity waveforms of the beads of the dimer. We conjecture that a countable infinity of family of solitary waves can be realized in 1:2 dimer chains. Interestingly, solitary waves in a general 1:N (N>2) dimer chain are far more difficult to realize. For the case of 1:2 dimers, we can vary the two parameters to satisfy conditions such that the oscillatory tails in the trail of the primary pulse of the two light beads decay to zero. In contrast, for a 1:N (N>2) dimer chain, we have the same two parameters but need to satisfy the decaying conditions on N light beads simultaneously. This leads to a mathematically ill-posed problem and as such rigorously no solitary waves can be realized in general.