Crystals that count! Physical principles and experimental investigations of DNA tile self-assembly

Algorithmic DNA tiles systems are fascinating. From a theoretical perspective, they can result in simple systems that assemble themselves into beautiful, complex structures through fundamental interactions and logical rules. As an experimental technique, they provide a promising method for programmably assembling complex, precise crystals that can grow to considerable size while retaining nanoscale resolution. In the journey from theoretical abstractions to experimental demonstrations, however, lie numerous challenges and complications.

In this thesis, to examine these challenges, we consider the physical principles behind DNA tile self-assembly. We survey recent progress in experimental algorithmic self-assembly, and explain the simple physical models behind this progress. Using direct observation of individual tile attachments and detachments with an atomic force microscope, we test some of the fundamental assumptions of the widely-used kinetic Tile Assembly Model, obtaining results that fit the model to within error. We then depart from the simplest form of that model, examining the effects of DNA sticky end sequence energetics on tile system behavior. We develop theoretical models, sequence assignment algorithms, and a software package, StickyDesign, for sticky end sequence design.

As a demonstration of a specific tile system, we design a binary counting ribbon that can accurately count from a programmable starting value and stop growing after overflowing, resulting in a single system that can construct ribbons of precise and programmable length. In the process of designing the system, we explain numerous considerations that provide insight into more general tile system design, particularly with regards to tile concentrations, facet nucleation, the construction of finite assemblies, and design beyond the abstract Tile Assembly Model.

Finally, we present our crystals that count: experimental results with our binary counting system that represent a significant improvement in the accuracy of experimental algorithmic self-assembly, including crystals that count perfectly with 5 bits from 0 to 31. We show some preliminary experimental results on the construction of our capping system to stop growth after counters overflow, and offer some speculation on potential future directions of the field.

Pertsonen-kudeaketaren kasu-azterketa: Burdiñola, S.Coop.

LABURPENA: Lan honetan Burdinola S.Coop.-ko pertsonen kudeaketa aztertuko da, giza baliabideen zuzendaritzaren ikuspuntutik, alegia. Horrela, organizazioetan giza baliabideek zenbaterainoko garrantzia daukaten erakutsi nahi da. Izan ere, alor horretan ezarritako helburu nahiz estrategiek erakundeko helburu orokorrak lortzea errazten dute. Hasteko lanean murgiltzeko balio duen sarrera labur bat, helburuak eta erabilitako metodologiaren zehaztapena egingo da. Ondoren, Burdinola kooperatiba aurkeztuko da eta segidan giza baliabideen ikuspuntutik kanpo zein barne analisia burutuko dira, azkenean AMIA matrize batean ideiak islatuz. Ildo beretik, giza baliabideen helburuak eta estrategiak diseinatuko dira, estrategien ikuskaritza eta ebaluazioa dakartenak loturik. Amaitzeko ondorio nagusienak planteatuko dira, erreferentzi bibliografiko eta eranskinez gain.

De menor a criança, de criança a filho: discursos de adoção

A presente tese teve como objetivo primordial cartografar e analisar algumas instituições e mitos que potencializaram, no contexto do estado do Rio de Janeiro, a emergência e a legitimação da prática da adoção-pronta. Por adoção-pronta, entendemos as solicitações de adoções que aportam nos Juizados da Infância e da Juventude como fato consumado, isto é, a criança a ser adotada já se encontra, concretamente, com os requerentes que pretendem regularizar uma situação instituída. Essa medida, via de regra, sustenta-se num tripé: uma mãe que entrega, um casal que acolhe e discursos de especialistas, dentre eles, psicólogos e assistentes sociais, que ratificam tal relação. A amostragem da pesquisa foi composta por dez processos de adoção-pronta, sendo cinco na vigência do Código de Menores e cinco sob a ótica do Estatuto da Criança e do Adolescente. A genealogia histórica de Foucault, as ferramentas da Análise Institucional bem como a Análise e a Ordem do Discurso de Orlandi e Foucault foram, nesse percurso, os recortes metodológicos priorizados. As análises permitiram constatar que são pobres, jovens, solteiras e empregadas domésticas as mulheres-mães que entregam seus filhos em adoção. Os que acolhem, em sua maioria, são legalmente casados, economicamente ativos, possuem filhos e, não mantém com a mãe biológica, laços de parentalidade. Os laudos técnicos, via de regra, têm colocado, na mãe pobre, a responsabilidade e a autonomia pelo ato de entrega e, portanto, vêm funcionando como instrumentos de produção e sustentação de subjetividades, tais como a de mãe desnaturada. Em síntese, as análises nos possibilitaram concluir que os discursos dos especialistas longe de afirmarem a ineficácia das políticas públicas como co-autoras dos processos de destituição do poder familiar, vêm afirmando a adoção-pronta como prática de repercussão pública, isto é, enquanto uma solução-alternativa ao quadro de pobreza de cidadania.

Interfacial recognition of human prostate-specific antigen by immobilized monoclonal antibody: effects of solution conditions and surface chemistry.

The specific recognition between monoclonal antibody (anti-human prostate-specific antigen, anti-hPSA) and its antigen (human prostate-specific antigen, hPSA) has promising applications in prostate cancer diagnostics and other biosensor applications. However, because of steric constraints associated with interfacial packing and molecular orientations, the binding efficiency is often very low. In this study, spectroscopic ellipsometry and neutron reflection have been used to investigate how solution pH, salt concentration and surface chemistry affect antibody adsorption and subsequent antigen binding. The adsorbed amount of antibody was found to vary with pH and the maximum adsorption occurred between pH 5 and 6, close to the isoelectric point of the antibody. By contrast, the highest antigen binding efficiency occurred close to the neutral pH. Increasing the ionic strength reduced antibody adsorbed amount at the silica-water interface but had little effect on antigen binding. Further studies of antibody adsorption on hydrophobic C8 (octyltrimethoxysilane) surface and chemical attachment of antibody on (3-mercaptopropyl)trimethoxysilane/4-maleimidobutyric acid N-hydroxysuccinimide ester-modified surface have also been undertaken. It was found that on all surfaces studied, the antibody predominantly adopted the 'flat on' orientation, and antigen-binding capabilities were comparable. The results indicate that antibody immobilization via appropriate physical adsorption can replace elaborate interfacial molecular engineering involving complex covalent attachments.

亲子依恋对大学生人际关系影响的性别效应

Parent-child attachment refers to the emotional bond that forms between parent and child, which has great influences on the child’s interpersonal development. Present study applied both correlation method and secure attachment memory activation method to investigate the “gender relation effects” of parent-child attachment’s influences on college students’ close relationships, general attachment representation, and emotion and social loneliness. The basic hypotheses on “gender relation” were set as: “same-sex” parent-child attachment has more influences on college students’ “same-sex” interpersonal relationships, while “opposite-sex” parent-child attachment has more influences on college students’ “opposite-sex” interpersonal relationships. Major findings includes: 1. There was weak correlation of attachment security between father-child and mother-child relationships. The findings indicated that, among college students, the security of “opposite-sex” parent-child attachment representation is higher to some extent than that of “same-sex” parent-child attachment representation. 2. There were significant correlations between parent-child attachment and college students’ attachment anxiety in close relationships. Major findings indicated that “opposite-sex” parent-child attachment security negatively predicts college students’ attachment anxiety in both “same-sex” and “opposite-sex” close relationships. 3. Gender relation effects were significant in the correlations between parent-child attachment and college students’ level of avoidant attachment representation. “Same-sex” parent-child attachment security positively predicted avoidant attachment level in college students’ “same-sex” close relationships, while “opposite-sex” parent-child attachment security positively predicted avoidant attachment level in “opposite-sex” close relationships. 4. Parent-child attachment security memory activation had significant influences on college students’ general attachment representation, in which gender relation effects indicated that: the memory activation of father-child attachment security significantly increases participants’ security of self-model in general attachment representation to “male others”; while the memory activation of mother-child attachment security significantly increase participants’ security of others-model in general attachment representation to “female others”. 5. For male college students, father-son attachment security negatively predicted their emotion and social loneliness. For female college students, father-daughter attachment security negatively predicted their emotion loneliness, while mother-daughter attachment security negatively predicted their social loneliness. Attachment security memory activation had significant influences on college students’ social loneliness, in which gender relation effects was confirmed in that only father-child attachment security memory activation significantly decreased male participants’ level of social loneliness. The results indicated that gender relation effects are significant in the influences of parent-child attachment on college students’ interpersonal relationship representations, especially when the level of avoidant of attachment in college students’ close relationships was predicted by parent-child attachment representation, and when the memory activation of parent-child attachment influenced college students’ general attachment representation. The present study confirmed to some extent that gender relation consistency exists in attachment representations among different interpersonal relations, and serves as a new model for analysis of gender differences in the research fields. In the present study, however, gender relation effects were not confirmed in all the interpersonal relationship representations, which indicated the complexity in the problems of gender differences in the research fields of close relationships.

Electromagnetic tracking and steering for catheter navigation

This thesis explores the use of electromagnetics for both steering and tracking of medical instruments in minimally invasive surgeries. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. Navigation to the peripheral regions of the lung is difficult due to physical dimensions of the bronchi and current methods have low successes rates for accurate diagnosis. Firstly, the potential use of DC magnetic fields for the actuation of catheter devices with permanently magnetised distal attachments is investigated. Catheter models formed from various materials and magnetic tip formations are used to examine the usefulness of relatively low power and compact electromagnets. The force and torque that can be exerted on a small permanent magnet is shown to be extremely limited. Hence, after this initial investigation we turn our attention to electromagnetic tracking, in the development of a novel, low-cost implementation of a GPS-like system for navigating within a patient. A planar magnetic transmitter, formed on a printed circuit board for a low-profile and low cost manufacture, is used to generate a low frequency magnetic field distribution which is detected by a small induction coil sensor. The field transmitter is controlled by a novel closed-loop system that ensures a highly stable magnetic field with reduced interference from one transmitter coil to another. Efficient demodulation schemes are presented which utilise synchronous detection of each magnetic field component experienced by the sensor. The overall tracking accuracy of the system is shown to be less than 2 mm with an orientation error less than 1°. A novel demodulation implementation using a unique undersampling approach allows the use of reduced sample rates to sample the signals of interest without loss of tracking accuracy. This is advantageous for embedded microcontroller implementations of EM tracking systems. The EM tracking system is demonstrated in the pre-clinical environment of a breathing lung phantom. The airways of the phantom are successfully navigated using the system in combination with a 3D computer model rendered from CT data. Registration is achieved using both a landmark rigid registration method and a hybrid fiducial-free approach. The design of a planar magnetic shield structure for blocking the effects of metallic distortion from below the transmitter is presented which successfully blocks the impact of large ferromagnetic objects such as operating tables. A variety of shielding material are analysed with MuMetal and ferrite both providing excellent shieling performance and an increased signal to noise ratio. Finally, the effect of conductive materials and human tissue on magnetic field measurements is presented. Error due to induced eddy currents and capacitive coupling is shown to severely affect EM tracking accuracy at higher frequencies.

Electron tomography of cryofixed, isometrically contracting insect flight muscle reveals novel actin-myosin interactions.

BACKGROUND: Isometric muscle contraction, where force is generated without muscle shortening, is a molecular traffic jam in which the number of actin-attached motors is maximized and all states of motor action are trapped with consequently high heterogeneity. This heterogeneity is a major limitation to deciphering myosin conformational changes in situ. METHODOLOGY: We used multivariate data analysis to group repeat segments in electron tomograms of isometrically contracting insect flight muscle, mechanically monitored, rapidly frozen, freeze substituted, and thin sectioned. Improved resolution reveals the helical arrangement of F-actin subunits in the thin filament enabling an atomic model to be built into the thin filament density independent of the myosin. Actin-myosin attachments can now be assigned as weak or strong by their motor domain orientation relative to actin. Myosin attachments were quantified everywhere along the thin filament including troponin. Strong binding myosin attachments are found on only four F-actin subunits, the "target zone", situated exactly midway between successive troponin complexes. They show an axial lever arm range of 77°/12.9 nm. The lever arm azimuthal range of strong binding attachments has a highly skewed, 127° range compared with X-ray crystallographic structures. Two types of weak actin attachments are described. One type, found exclusively in the target zone, appears to represent pre-working-stroke intermediates. The other, which contacts tropomyosin rather than actin, is positioned M-ward of the target zone, i.e. the position toward which thin filaments slide during shortening. CONCLUSION: We present a model for the weak to strong transition in the myosin ATPase cycle that incorporates azimuthal movements of the motor domain on actin. Stress/strain in the S2 domain may explain azimuthal lever arm changes in the strong binding attachments. The results support previous conclusions that the weak attachments preceding force generation are very different from strong binding attachments.

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics.

Muscle Logic: New Knowledge Resource for Anatomy Enables Comprehensive Searches of the Literature on the Feeding Muscles of Mammals.

BACKGROUND: In recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required. DEVELOPMENT AND TESTING OF THE ONTOLOGY: Here we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar. RESULTS AND SIGNIFICANCE: Our tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities.

Towards the sustainable use of Europe’s forests: a centre for European forest science! – Some missing catalytic elements?

The Symposium, “Towards the sustainable use of Europe’s forests”, with sub-title “Forest ecosystem and landscape research: scientific challenges and opportunities” lists three fundamental substantive areas of research that are involved: Forest management and practices, Ecosystem processes and functional ecology, and Environmental economics and sociology. This paper argues that there are essential catalytic elements missing! Without these elements there is great danger that the aimed-for world leadership in the forest sciences will not materialize. What are the missing elements? All the sciences, and in particular biology, environmental sciences, sociology, economics, and forestry have evolved so that they include good scientific methodology. Good methodology is imperative in both the design and analysis of research studies, the management of research data, and in the interpretation of research finding. The methodological disciplines of Statistics, Modelling and Informatics (“SMI”) are crucial elements in a proposed Centre of European Forest Science, and the full involvement of professionals in these methodological disciplines is needed if the research of the Centre is to be world-class. Distributed Virtual Institute (DVI) for Statistics, Modelling and Informatics in Forestry and the Environment (SMIFE) is a consortium with the aim of providing world-class methodological support and collaboration to European research in the areas of Forestry and the Environment. It is suggested that DVI: SMIFE should be a formal partner in the proposed Centre for European Forest Science.

Controlling the agenda at WWF - the multinationals' network

This paper by CEO, PSIRU and PSI details the continuing influence of water multinationals on the World Water Forum and its agenda.

Second Metatarsophalangeal joint Synovitis: Update

In podiatric clinics is very common to find inflamatory process in metatarsophalangeal joint capsule , plantar plate and collateral ligaments damage, but it is not clearly recognized. Many authors hipotetized with joint instability of multiple aetiology and his concomitant evolution in different stages with own joint disease. This pathology has more incidence in second metatarsophalangeal joint than third and others and it is a common etiology of metatarsal pain. Bad biomechanics alters forefoot function and can produce overload in capsular joint, decreasing mobility and getting worse the pathology.