A structural analysis of G-quadruplex/ligand interactions

This focused review article discusses in detail, all available high-resolution small molecule ligand/G-quadruplex structural data derived from crystallographic and NMR based techniques, in an attempt to understand key factors in ligand binding and to highlight the biological importance of these complexes. In contrast to duplex DNA, G-quadruplexes are four-stranded nucleic acid structures folded from guanine rich repeat sequences stabilized by the stacking of guanine G-quartets and extensive Watson-Crick/Hoogsteen hydrogen bonding. Thermally stable, these topologies can play a role in telomere regulation and gene expression. The core structures of G-quadruplexes form stable scaffolds while the loops have been shown, by the addition of small molecule ligands, to be sufficiently adaptable to generate new and extended binding platforms for ligands to associate, either by extending G-quartet surfaces or by forming additional planar dinucleotide pairings. Many of these structurally characterised loop rearrangements were totally unexpected opening up new opportunities for the design of selective ligands. However these rearrangements do significantly complicate attempts to rationally design ligands against well defined but unbound topologies, as seen for the series of napthalene diimides complexes. Drawing together previous findings and with the introduction of two new crystallographic quadruplex/ligand structures we aim to expand the understanding of possible structural adaptations available to quadruplexes in the presence of ligands, thereby aiding in the design of new selective entities. (C) 2011 Elsevier Masson SAS. All rights reserved.

An Inconvenient Truth: Barriers to Truth Recovery in the Aftermath of Institutional Child Abuse in Ireland

Contemporary settled democracies, including the United States, England and Wales and Ireland, have witnessed a string of high profile cases of institutional child abuse in both church and state settings. Set against the broader literature on transitional justice, this analysis argues that there are significant barriers to truth recovery within the particular context of historical institutional abuse by the clergy in the Republic of Ireland. In the main, I argue that the frameworks of the inquiries and commissions into historical institutional child abuse are not conducive to truth recovery or the search for justice in dealing with the legacy of an abusive past. It is the church-state relationship which makes the Irish situation noteworthy and unique. The Catholic Church and child care institutions are especially self-protective, secretive and closed by nature and strongly discourage the drawing of attention to any deficiencies in organisational procedures. The nature of the public inquiry process also means that there is often a rather linear focus on accountability and apportioning blame. Collectively, such difficulties inhibit fuller systemic investigation of the veracity of what actually happened and, in turn, meaningful modification of child care policies. The article concludes by offering some thoughts on implications for transitional justice discourses more broadly as well as the residual issues for Ireland and other settled democracies in terms of moving on from the legacy of institutional child abuse.

Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale

The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. While G-quartet stems have been well characterised, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 µs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.

In All The Worlds

This is a sequence of miniature pieces (totalling 30 minutes of music) for viola d'amore and string quartet, commissioned by Garth Knox for performance with Quatuor Bela (Paris.) Premiere will take place in Paris, November 2013.

Load Balanced Scalable Byzantine Agreement through Quorum Building, with Full Information

We address the problem of designing distributed algorithms for large scale networks that are robust to Byzantine faults. We consider a message passing, full information model: the adversary is malicious, controls a constant fraction of processors, and can view all messages in a round before sending out its own messages for that round. Furthermore, each bad processor may send an unlimited number of messages. The only constraint on the adversary is that it must choose its corrupt processors at the start, without knowledge of the processors’ private random bits.

A good quorum is a set of O(logn) processors, which contains a majority of good processors. In this paper, we give a synchronous algorithm which uses polylogarithmic time and Õ(vn) bits of communication per processor to bring all processors to agreement on a collection of n good quorums, solving Byzantine agreement as well. The collection is balanced in that no processor is in more than O(logn) quorums. This yields the first solution to Byzantine agreement which is both scalable and load-balanced in the full information model.

The technique which involves going from situation where slightly more than 1/2 fraction of processors are good and and agree on a short string with a constant fraction of random bits to a situation where all good processors agree on n good quorums can be done in a fully asynchronous model as well, providing an approach for extending the Byzantine agreement result to this model.

Sound Synthesis for Contact-Driven Musical Instruments via Discretisation of Hamilton's Equations

Physical modelling of musical instruments involves studying nonlinear interactions between parts of the instrument. These can pose several difficulties concerning the accuracy and stability of numerical algorithms. In particular, when the underlying forces are non-analytic functions of the phase-space variables, a stability proof can only be obtained in limited cases. An approach has been recently presented by the authors, leading to unconditionally stable simulations for lumped collision models. In that study, discretisation of Hamilton’s equations instead of the usual Newton’s equation of motion yields a numerical scheme that can be proven to be energy conserving. In this paper, the above approach is extended to collisions of distributed objects. Namely, the interaction of an ideal string with a flat barrier is considered. The problem is formulated within the Hamiltonian framework and subsequently discretised. The resulting nonlinearmatrix equation can be shown to possess a unique solution, that enables the update of the algorithm. Energy conservation and thus numerical stability follows in a way similar to the lumped collision model. The existence of an analytic description of this interaction allows the validation of the model’s accuracy. The proposed methodology can be used in sound synthesis applications involving musical instruments where collisions occur either in a confined (e.g. hammer-string interaction, mallet impact) or in a distributed region (e.g. string-bridge or reed-mouthpiece interaction).

Full characterization of the quantum linear-zigzag transition in atomic chains

A string of repulsively interacting particles exhibits a phase transition to a zigzag structure, by reducing the transverse trap potential or the interparticle distance. Based on the emergent symmetry Z2 it has been argued that this instability is a quantum phase transition, which can be mapped to an Ising model in transverse field. An extensive Density Matrix Renormalization Group analysis is performed, resulting in an high-precision evaluation of the critical exponents and of the central charge of the system, confirming that the quantum linear-zigzag transition belongs to the critical Ising model universality class. Quantum corrections to the classical phase diagram are computed, and the range of experimental parameters where quantum effects play a role is provided. These results show that structural instabilities of one-dimensional interacting atomic arrays can simulate quantum critical phenomena typical of ferromagnetic systems.

Energy conserving schemes for the simulation of musical instrument contact dynamics

Collisions are an innate part of the function of many musical instruments. Due to the nonlinear nature of contact forces, special care has to be taken in the construction of numerical schemes for simulation and sound synthesis. Finite difference schemes and other time-stepping algorithms used for musical instrument modelling purposes are normally arrived at by discretising a Newtonian description of the system. However because impact forces are non-analytic functions of the phase space variables, algorithm stability can rarely be established this way. This paper presents a systematic approach to deriving energy conserving schemes for frictionless impact modelling. The proposed numerical formulations follow from discretising Hamilton׳s equations of motion, generally leading to an implicit system of nonlinear equations that can be solved with Newton׳s method. The approach is first outlined for point mass collisions and then extended to distributed settings, such as vibrating strings and beams colliding with rigid obstacles. Stability and other relevant properties of the proposed approach are discussed and further demonstrated with simulation examples. The methodology is exemplified through a case study on tanpura string vibration, with the results confirming the main findings of previous studies on the role of the bridge in sound generation with this type of string instrument.

Identifying PV module mismatch faults by a thermography-based temperature distribution analysis

Photovoltaic (PV) solar power generation is proven to be effective and sustainable but is currently hampered by relatively high costs and low conversion efficiency. This paper addresses both issues by presenting a low-cost and efficient temperature distribution analysis for identifying PV module mismatch faults by thermography. Mismatch faults reduce the power output and cause potential damage to PV cells. This paper first defines three fault categories in terms of fault levels, which lead to different terminal characteristics of the PV modules. The investigation of three faults is also conducted analytically and experimentally, and maintenance suggestions are also provided for different fault types. The proposed methodology is developed to combine the electrical and thermal characteristics of PV cells subjected to different fault mechanisms through simulation and experimental tests. Furthermore, the fault diagnosis method can be incorporated into the maximum power point tracking schemes to shift the operating point of the PV string. The developed technology has improved over the existing ones in locating the faulty cell by a thermal camera, providing a remedial measure, and maximizing the power output under faulty conditions.

Coupled Effects of a Perturbation in a Complex Structure Observed with SDO/AIA, SDO/HMI and ROSA/HARDcam

We study properties of intensity fluctuations in NOAA Active Region 11250 observed on 13 July 2011 starting at UT 13:32. Included are data obtained in the EUV bands of the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory (SDO/AIA) as well as nearly simultaneous observations of the chromosphere made, at much higher spatial and temporal resolution, with the Rapid Oscillations in the Solar Atmosphere (ROSA) and Hydrogen-Alpha Rapid Dynamics camera (HARDcam) systems at the Dunn Solar Telescope. A complex structure seen in both the ROSA/HARDcam and SDO data sets comprises a system of loops extending outward from near the boundary of the leading sunspot umbra. It is visible in the ROSA Ca II K and HARDcam Hα images, as well as the SDO 304 Å, 171 Å and 193 Å channels, and it thus couples the chromosphere, transition region and corona. In the ground-based images the loop structure is 4.1 Mm long. Some 17.5 Mm, can be traced in the SDO/AIA data. The chromospheric emissions observed by ROSA and HARDcam appear to occupy the inner, and apparently cooler and lower, quarter of the loop. We compare the intensity fluctuations of two points within the structure. From alignment with SDO/HMI images we identify a point "A" near the loop structure, which sits directly above a bipolar magnetic feature in the photosphere. Point "B" is characteristic of locations within the loops that are visible in both the ROSA/HARDcam and the SDO/AIA data. The intensity traces for point A are quiet during the first part of the data string. At time ~ 19 min they suddenly begin a series of impulsive brightenings. In the 171 Å and 193 Å coronal lines the brightenings are localized impulses in time, but in the transition region line at 304 Å they are more extended in time. The intensity traces in the 304 Å line for point B shows a quasi-periodic signal that changes properties at about 19 min. The wavelet power spectra are characterized by two periodicities. A 6.7 min period extends from the beginning of the series until about 25 minutes, and another signal with period ~3 min starts at about 20 min. The 193 Å power spectrum has a characteristic period of 5 min, before the 20 min transition and a 2.5 min periodicity afterward. In the case of HARDcam Hα data a localized 4 min periodicity can be found until about 7 min, followed by a quiet regime. After ~20 min a 2.3 min periodicity appears. Interestingly a coronal loop visible in the 94 Å line that is centrally located in the AR, running from the leading umbra to the following polarity, at about time 20 min undergoes a strong brightening beginning at the same moment all along 15 Mm of its length. The fact that these different signals all experience a clear-cut change at time about 20 min suggests an underlying organizing mechanism. Given that point A has a direct connection to the photospheric magnetic bipole, we conjecture that the whole extended structure is connected in a complex manner to the underlying magnetic field. The periodicities in these features may favor the wave nature rather than upflows and interpretations will be discussed.

Evaluating environmental enrichment options for commercial broiler chickens

Implications Provision of environmental enrichment in line with that required by welfare-based quality assurance schemesdoes not always appear to lead to clear improvements in broiler chicken welfare. This research perhaps serves to highlightthe deficit in information regarding the ‘real world’ implications of enrichment with perches, string and straw bales.

Introduction Earlier work showed that provision of natural light and straw bales improved leg health in commercial broilerchickens (Bailie et al., 2013). This research aimed to determine if additional welfare benefits were shown in windowedhouses by increasing straw bale provision (Study 1), or by providing perches and string in addition to straw bales (Study 2).

Material and methods Commercial windowed houses in Northern Ireland containing ~23,000 broiler chickens (placed inhouses as hatched) were used in this research which took place in 2011. In Study 1 two houses on a single farm wereassigned to one of two treatments: (1) 30 straw bales per house (1 bale/44m2), or (2) 45 straw bales per house (1bale/29m2). Bales of wheat straw, each measuring 80cm x 40cm x 40cm were provided from day 10 of the rearing cycle,as in Bailie et al. (2013). Treatments were replicated over 6 production cycles (using 276,000 Ross 308 and Cobb birds),and were swapped between houses in each replicate. In Study 2, four houses on a single farm were assigned to 1 of 4treatments in a 2 x 2 factorial design. Treatments involved 2 levels of access to perches (present (24/house), or absent), and2 levels of access to string (present (24/house), or absent), and both types of enrichment were provided from the start of thecycle. Each perch consisted of a horizontal, wooden beam (300 cm x 5 cm x 5cm) with a rounded upper edge resting on 2supports (15 cm high). In the string treatment, 6 pieces of white nylon string (60 cm x 10 mm) were tied at their mid-pointto the wire above each of 4 feeder lines. Thirty straw bales were also provided per house from day 10. This study wasreplicated over 4 production cycles using 368,000 Ross 308 birds. In both studies behaviour was observed between 0900and 1800 hours in weeks 3-5 of the cycle. In Study 1, 8 focal birds were selected in each house each week, and generalactivity, exploratory and social behaviours recorded directly for 10 minutes. In Study 2, 10 minute video recordings weremade of 6 different areas (that did not contain enrichment) of each house each week. The percentage of birds engaged inlocomotion or standing was determined through scan sampling these recordings at 120 second intervals. Four perches andfour pieces of string were filmed for 25 mins in each house that contained these enrichments on one day per week. The totalnumber of times the perch or string was used was recorded, along with the duration of each bout. In both studies, gaitscores (0 (perfect) to 5 (unable to walk)) and latency to lie (measured in seconds from when a bird had been encouraged tostand) were recorded in 25 birds in each house each week. Farm and abattoir records were also used in both studies todetermine the number of birds culled for leg and other problems, mortality levels, slaughter weights, and levels of pododermatitis and hock burn. Data were analysed using SPSS (version 20.0) and treatment and age effects on behaviouralparameters were determined in normally distributed data using ANOVA (‘Straw bale density*week’, or‘string*perches*week’ as appropriate), and in non-normally distributed data using Kuskall-Wallace tests (P<0.05 forsignificance) . Treatment (but not age) effects on performance and health data were determined using the same testsdepending on normality of data.

Results Average slaughter weight, and levels of mortality, culling, hock burn and pododermatitis were not affected bytreatment in either study (P<0.05). In Study 1 straw bale (SB) density had no significant effect on the frequency orduration of behaviours including standing, walking, ground pecking, dust bathing, pecking at bales or aggression, or onaverage gait score (P>0.05). However, the average latency to lie was greater when fewer SB were provided (30SB 23.38s,45SB 18.62s, P<0.01). In Study 2 there was an interaction between perches (Pe) and age in lying behaviour, with higherpercentages of birds observed lying in the Pe treatment during weeks 4 and 5 (week 3 +Pe 77.0 -Pe 80.9, week 4 +Pe 79.5 -Pe 75.2, week 5 +Pe 78.4 -Pe 76.2, P<0.02). There was also a significant interaction between string (S) and age inlocomotory behaviour, with higher percentages of birds observed in locomotion in the string treatment during week 3 butnot weeks 4 and 5 (week 3 +S 4.9 -S 3.9, week 4 +S 3.3 -S 3.7, week 5 +S 2.6 -S 2.8, P<0.04). There was also aninteraction between S and age in average gait scores, with lower gait scores in the string treatment in weeks 3 and 5 (week3: +S 0.7, -S 0.9, week 4: +S 1.5, -S 1.4, week 5: +S 1.9, -S 2.0, P<0.05). On average per 25 min observation there were15.1 (±13.6) bouts of perching and 19.2 (±14.08) bouts of string pecking, lasting 117.4 (±92.7) and 4.2 (±2.0) s for perchesand string, respectively.

Conclusion Increasing straw bale levels from 1 bale/44m2 to 1 bale/29m2 floor space does not appear to lead to significantimprovements in the welfare of broilers in windowed houses. The frequent use of perches and string suggests that thesestimuli have the potential to improve welfare. Provision of string also appeared to positively influence walking ability.However, this effect was numerically small, was only shown in certain weeks and was not reflected in the latency to lie.Further research on optimum design and level of provision of enrichment items for broiler chickens is warranted. Thisshould include measures of overall levels of activity (both in the vicinity of, and away from, enrichment items).

CD4+ T Cells Targeting Dominant and Cryptic Epitopes from Bacillus anthracis Lethal Factor

Anthrax is an endemic infection in many countries, particularly in the developing world. The causative agent, Bacillus anthracis, mediates disease through the secretion of binary exotoxins. Until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. There is, however, growing recognition that cellular immune responses involving IFNγ producing CD4+ T cells also contribute significantly to a protective memory response. An established concept in adaptive immunity to infection is that during infection of host cells, new microbial epitopes may be revealed, leading to immune recognition of so called 'cryptic' or 'subdominant' epitopes. We analyzed the response to both cryptic and immunodominant T cell epitopes derived from the toxin component lethal factor and presented by a range of HLA-DR alleles. Using IFNγ-ELISpot assays we characterized epitopes that elicited a response following immunization with synthetic peptide and the whole protein and tested their capacities to bind purified HLA-DR molecules in vitro. We found that DR1 transgenics demonstrated T cell responses to a greater number of domain III cryptic epitopes than other HLA-DR transgenics, and that this pattern was repeated with the immunodominant epitopes, as a greater proportion of these epitopes induced a T cell response when presented within the context of the whole protein. Immunodominant epitopes LF457-476 and LF467-487 were found to induce a T cell response to the peptide, as well as to the whole native LF protein in DR1 and DR15, but not in DR4 transgenics. The analysis of Domain I revealed the presence of several unique cryptic epitopes all of which showed a strong to moderate relative binding affinity to HLA-DR4 molecules. However, none of the cryptic epitopes from either domain III or I displayed notably high binding affinities across all HLA-DR alleles assayed. These responses were influenced by the specific HLA alleles presenting the peptide, and imply that construction of future epitope string vaccines which are immunogenic across a wide range of HLA alleles could benefit from a combination of both cryptic and immunodominant anthrax epitopes.

Interacção entre estruturas intervalares e estruturas espectrais, na música instrumental/vocal

A presente tese apresenta-se num formato bipartido, sendo a primeira parte uma investigação teórica e a segunda parte um conjunto de composições originais que procuram estabelecer, directa e indirectamente, uma relação com a temática investigada. A investigação incide sobre as diferentes relações que se podem estabelecer entre estruturas intervalares e estruturas espectrais, a partir de um conjunto representativo de obras de diferentes compositores. As obras originais da segunda parte configuram um objecto final de análise e reflexão. As composições que integram a segunda parte da tese são: Inês – sete miniaturas sobre A Castro, para soprano e orquestra, sobre excertos de “Castro”, de António Ferreira; Um sino contra o tempo, para flauta, clarinete, percussão e piano; Terra, para orquestra de cordas; Dor e Amor, para voz, flauta, clarinete, percussão, harpa, piano, violino, viola e violoncelo, sobre poemas de Nuno Júdice; e Ode a Gaia, para soprano solo, coro misto e electrónica, a partir de textos de diversos autores e épocas, desde Homero a Fernando Pessoa. Esta investigação surge a partir da convicção de que é possível e enriquecedor para a composição a coexistência e o estabelecimento de uma relação entre estruturas que valorizam as qualidades dos intervalos que as constituem e estruturas de tipo espectral. Se o pensamento intervalar pode ser relacionado com princípios de estruturação ligados a toda uma tradição musical, desde a música modal, à tonal e à atonal, o pensamento espectral relaciona-se com o estudo do fenómeno sonoro e do timbre e é integrado mais tardiamente no séc. XX como um possível modelo estruturante na composição. A investigação sobre as obras seleccionadas, sobretudo de compositores que colocam o fenómeno da percepção num plano central, procura diferentes interacções entre os dois tipos de estrutura, interrogando-se sobre em que medida é que essa interacção influencia ou é mesmo determinante para o resultado musical final. São analisadas diferentes aplicações, tais como: a procura de qualidades acústicas na criação de estruturas intervalares, a criação de timbres particulares para linhas estruturantes, a manipulação tímbrica de estruturas verticais, a inter-relação de camadas intervalares e espectrais na textura musical de forma sincrónica e diacrónica, e o surgimento de material intervalar a partir de estruturas espectrais. Os principais resultados passam pela confirmação de que o pensamento intervalar é compatível com o pensamento espectral e vice-versa, podendo-se concluir que são essenciais diferentes funções para os dois tipos de estrutura na textura musical e que quer as estruturas intervalares quer as espectrais se relacionam com diferentes aspectos da percepção, tendo, assim, uma influência determinante no resultado musical final, na eficácia da escuta e na sua fruição.

Estudo da degradação de fibras óticas sob o efeito de potências elevadas

Os sistemas de comunicações óticas têm evoluído rapidamente e, como consequência, a potência dos sinais óticos propagados na fibra tem vindo a aumentar. A propagação de sinais de elevada potência pode resultar na degradação e/ou destruição da fibra ótica. O presente trabalho tem como objetivo o estudo do impacto da propagação de sinais óticos com elevadas potências na degradação e redução do tempo de vida útil das fibras óticas. Estudou-se este tipo de degradação das fibras óticas a dois níveis: degradação do revestimento de fibras sujeitas a curvaturas apertadas e ignição e propagação do efeito rastilho que leva a destruição da fibra ótica. Para a concretização deste estudo, caracterizou-se experimentalmente o aumento de temperatura no revestimento de fibras óticas sujeitas a curvaturas de diâmetro reduzido e na presença de sinais com elevada potência. Tendo-se desenvolvido um modelo analítico para descrever o aquecimento do revestimento da fibra. No âmbito do efeito rastilho em fibra ótica, estudou-se experimentalmente, em diversos tipos de fibra, as principais propriedades deste fenómeno, nomeadamente, a potência ótica de limiar necessária para a sua ignição e propagação, a velocidade de propagação e as características da cadeia de bolhas formada no núcleo da fibra ótica durante a propagação deste efeito. Desenvolveu-se, ainda, um modelo teórico para simular a propagação do efeito rastilho, tendo sido validado e complementado através de resultados experimentais. Por fim, desenvolveram-se e implementaram-se técnicas para detetar e interromper a propagação do efeito rastilho, como forma de limitar a extensão de fibra destruída e proteger os equipamentos óticos da rede.

Salivary proteomics and peptidomics of type 1 diabetes Mellitus

A Diabetes Mellitus (DM) compreende um conjunto de desordens metabólicas comuns caracterizadas por hiperglicemia, que afeta diferentes órgãos do organismo. Ao longo do tempo, ocorrem danos microvasculares no glomérulo renal, retina e nervos periféricos, bem como doença macrovascular nas artérias. A composição da saliva também é afetada pela DM, com consequências na homeostasia oral. No entanto, o proteoma e o peptidoma salivar têm sido pouco explorados na DM tipo 1 e nas suas complicações crónicas. Tendo em conta o crescente interesse na saliva como fluido diagnóstico, o objetivo principal deste trabalho foi avaliar os eventos proteolíticos subjacentes à DM tipo 1 e às suas complicações microvasculares, bem como, caracterizar as alterações induzidas pela DM tipo 1 no proteoma e peptidoma salivar. A DM tipo 1 e particularmente as complicações microvasculares associadas modulam o perfil proteolítico dos fluidos biológicos, com diferenças significativas de atividade observadas na urina e saliva, atribuídas principalmente ao complexo Metaloproteinase da Matriz (MMP)-9/lipocalina associada à gelatinase de neutrófilos, aminopeptidase N, azurocidina e calicreína 1. O aumento da atividade proteolítica observado na saliva total dos diabéticos resultou no aumento da percentagem de péptidos, principalmente de um número acrescido de fragmentos de colagénio do tipo I, refletindo possivelmente um estado inflamatório crónico dos tecidos orais e periodontais. O peptidoma também corrobora uma maior suscetibilidade das proteínas salivares, especificamente, das proteínas ricas em prolina básicas (bPRP) 1, bPRP2 e proteínas ricas em prolina ácidas (aPRP) à proteólise, evidenciando a geração de fragmentos de proteínas associadas à ligação a bactérias. A análise do proteoma salivar baseada em iTRAQ mostrou uma sobre-expressão de L-plastina, fator do adenocarcinoma do pâncreas e das proteínas S100-A8 e S100-A9, enfatizando a importância do sistema imune inato na patogénese da DM tipo 1 e das complicações microvasculares associadas. A análise integrada de todas as proteínas expressas diferencialmente entre os pacientes diabéticos com ou sem complicações microvasculares e indivíduos saudáveis foi realizada com o STRING, onde se observam três conjuntos funcionalmente ligados, um compreende a interação entre o colagénio tipo I, colagénio tipo II e MMP-9, um segundo conjunto envolve a MMP-2 e o colagénio de tipo I e um terceiro conjunto composto por proteínas salivares e inflamatórias. Estes conjuntos estão associados com as vias Kegg de interação recetor-matriz extracelular, de adesão focal e migração transendotelial dos leucócitos. Por outro lado, a análise do proteoma e peptidoma salivar destacou potenciais biomarcadores para o diagnóstico e prognóstico da DM tipo 1 e das suas complicações.