Real-time monitoring of protein conformational changes using a nano-mechanical sensor.

Proteins can switch between different conformations in response to stimuli, such as pH or temperature variations, or to the binding of ligands. Such plasticity and its kinetics can have a crucial functional role, and their characterization has taken center stage in protein research. As an example, Topoisomerases are particularly interesting enzymes capable of managing tangled and supercoiled double-stranded DNA, thus facilitating many physiological processes. In this work, we describe the use of a cantilever-based nanomotion sensor to characterize the dynamics of human topoisomerase II (Topo II) enzymes and their response to different kinds of ligands, such as ATP, which enhance the conformational dynamics. The sensitivity and time resolution of this sensor allow determining quantitatively the correlation between the ATP concentration and the rate of Topo II conformational changes. Furthermore, we show how to rationalize the experimental results in a comprehensive model that takes into account both the physics of the cantilever and the dynamics of the ATPase cycle of the enzyme, shedding light on the kinetics of the process. Finally, we study the effect of aclarubicin, an anticancer drug, demonstrating that it affects directly the Topo II molecule inhibiting its conformational changes. These results pave the way to a new way of studying the intrinsic dynamics of proteins and of protein complexes allowing new applications ranging from fundamental proteomics to drug discovery and development and possibly to clinical practice.

The Influence of Process Conditions on the Deresination Efficiency in Mechanical Pulp Washing

The aim of this thesis was to produce information for the estimation of the flow balance of wood resin in mechanical pulping and to demonstrate the possibilities for improving the efficiency of deresination in practice. It was observed that chemical changes in wood resin take place only during peroxide bleaching, a significant amount of water dispersed wood resin is retained in the pulp mat during dewatering and the amount of wood resin in the solid phase of the process filtrates is very small. On the basis of this information there exist three parameters related to behaviour of wood resin that determine the flow balance in the process: 1. The liberation of wood resin to the pulp water phase 2. Theretention of water dispersed wood resin in dewatering 3. The proportion of wood resin degraded in the peroxide bleaching The effect of different factors on these parameters was evaluated with the help of laboratory studies and a literature survey. Also, information related to the values of these parameters in existing processes was obtained in mill measurements. With the help of this information, it was possible to evaluate the deresination efficiency and the effect of different factors on this efficiency in a pulping plant that produced low-freeness mechanical pulp. This evaluation showed that the wood resin content of mechanical pulp can be significantly decreased if there exists, in the process, a peroxide bleaching and subsequent washing stage. In the case of an optimal process configuration, as high as a 85 percent deresination efficiency seems to be possible with a water usage level of 8 m3/o.d.t.

Studies on integrating kinematic design method with mechanical systems simulation techniques

Theultimate goal of any research in the mechanism/kinematic/design area may be called predictive design, ie the optimisation of mechanism proportions in the design stage without requiring extensive life and wear testing. This is an ambitious goal and can be realised through development and refinement of numerical (computational) technology in order to facilitate the design analysis and optimisation of complex mechanisms, mechanical components and systems. As a part of the systematic design methodology this thesis concentrates on kinematic synthesis (kinematic design and analysis) methods in the mechanism synthesis process. The main task of kinematic design is to find all possible solutions in the form of structural parameters to accomplish the desired requirements of motion. Main formulations of kinematic design can be broadly divided to exact synthesis and approximate synthesis formulations. The exact synthesis formulation is based in solving n linear or nonlinear equations in n variables and the solutions for the problem areget by adopting closed form classical or modern algebraic solution methods or using numerical solution methods based on the polynomial continuation or homotopy. The approximate synthesis formulations is based on minimising the approximation error by direct optimisation The main drawbacks of exact synthesis formulationare: (ia) limitations of number of design specifications and (iia) failure in handling design constraints- especially inequality constraints. The main drawbacks of approximate synthesis formulations are: (ib) it is difficult to choose a proper initial linkage and (iib) it is hard to find more than one solution. Recentformulations in solving the approximate synthesis problem adopts polynomial continuation providing several solutions, but it can not handle inequality const-raints. Based on the practical design needs the mixed exact-approximate position synthesis with two exact and an unlimited number of approximate positions has also been developed. The solutions space is presented as a ground pivot map but thepole between the exact positions cannot be selected as a ground pivot. In this thesis the exact synthesis problem of planar mechanism is solved by generating all possible solutions for the optimisation process ¿ including solutions in positive dimensional solution sets - within inequality constraints of structural parameters. Through the literature research it is first shown that the algebraic and numerical solution methods ¿ used in the research area of computational kinematics ¿ are capable of solving non-parametric algebraic systems of n equations inn variables and cannot handle the singularities associated with positive-dimensional solution sets. In this thesis the problem of positive-dimensional solutionsets is solved adopting the main principles from mathematical research area of algebraic geometry in solving parametric ( in the mathematical sense that all parameter values are considered ¿ including the degenerate cases ¿ for which the system is solvable ) algebraic systems of n equations and at least n+1 variables.Adopting the developed solution method in solving the dyadic equations in direct polynomial form in two- to three-precision-points it has been algebraically proved and numerically demonstrated that the map of the ground pivots is ambiguousand that the singularities associated with positive-dimensional solution sets can be solved. The positive-dimensional solution sets associated with the poles might contain physically meaningful solutions in the form of optimal defectfree mechanisms. Traditionally the mechanism optimisation of hydraulically driven boommechanisms is done at early state of the design process. This will result in optimal component design rather than optimal system level design. Modern mechanismoptimisation at system level demands integration of kinematic design methods with mechanical system simulation techniques. In this thesis a new kinematic design method for hydraulically driven boom mechanism is developed and integrated in mechanical system simulation techniques. The developed kinematic design method is based on the combinations of two-precision-point formulation and on optimisation ( with mathematical programming techniques or adopting optimisation methods based on probability and statistics ) of substructures using calculated criteria from the system level response of multidegree-of-freedom mechanisms. Eg. by adopting the mixed exact-approximate position synthesis in direct optimisation (using mathematical programming techniques) with two exact positions and an unlimitednumber of approximate positions the drawbacks of (ia)-(iib) has been cancelled.The design principles of the developed method are based on the design-tree -approach of the mechanical systems and the design method ¿ in principle ¿ is capable of capturing the interrelationship between kinematic and dynamic synthesis simultaneously when the developed kinematic design method is integrated with the mechanical system simulation techniques.

Torque vibration model of axial-flux surface-mounted permanent magnet synchronous machine

In order that the radius and thus ununiform structure of the teeth and otherelectrical and magnetic parts of the machine may be taken into consideration the calculation of an axial flux permanent magnet machine is, conventionally, doneby means of 3D FEM-methods. This calculation procedure, however, requires a lotof time and computer recourses. This study proves that also analytical methods can be applied to perform the calculation successfully. The procedure of the analytical calculation can be summarized into following steps: first the magnet is divided into slices, which makes the calculation for each section individually, and then the parts are submitted to calculation of the final results. It is obvious that using this method can save a lot of designing and calculating time. Thecalculation program is designed to model the magnetic and electrical circuits of surface mounted axial flux permanent magnet synchronous machines in such a way, that it takes into account possible magnetic saturation of the iron parts. Theresult of the calculation is the torque of the motor including the vibrations. The motor geometry and the materials and either the torque or pole angle are defined and the motor can be fed with an arbitrary shape and amplitude of three-phase currents. There are no limits for the size and number of the pole pairs nor for many other factors. The calculation steps and the number of different sections of the magnet are selectable, but the calculation time is strongly depending on this. The results are compared to the measurements of real prototypes. The permanent magnet creates part of the flux in the magnetic circuit. The form and amplitude of the flux density in the air-gap depends on the geometry and material of the magnetic circuit, on the length of the air-gap and remanence flux density of the magnet. Slotting is taken into account by using the Carter factor in the slot opening area. The calculation is simple and fast if the shape of the magnetis a square and has no skew in relation to the stator slots. With a more complicated magnet shape the calculation has to be done in several sections. It is clear that according to the increasing number of sections also the result will become more accurate. In a radial flux motor all sections of the magnets create force with a same radius. In the case of an axial flux motor, each radial section creates force with a different radius and the torque is the sum of these. The magnetic circuit of the motor, consisting of the stator iron, rotor iron, air-gap, magnet and the slot, is modelled with a reluctance net, which considers the saturation of the iron. This means, that several iterations, in which the permeability is updated, has to be done in order to get final results. The motor torque is calculated using the instantaneous linkage flux and stator currents. Flux linkage is called the part of the flux that is created by the permanent magnets and the stator currents passing through the coils in stator teeth. The angle between this flux and the phase currents define the torque created by the magnetic circuit. Due to the winding structure of the stator and in order to limit the leakage flux the slot openings of the stator are normally not made of ferromagnetic material even though, in some cases, semimagnetic slot wedges are used. In the slot opening faces the flux enters the iron almost normally (tangentially with respect to the rotor flux) creating tangential forces in the rotor. This phenomenon iscalled cogging. The flux in the slot opening area on the different sides of theopening and in the different slot openings is not equal and so these forces do not compensate each other. In the calculation it is assumed that the flux entering the left side of the opening is the component left from the geometrical centre of the slot. This torque component together with the torque component calculated using the Lorenz force make the total torque of the motor. It is easy to assume that when all the magnet edges, where the derivative component of the magnet flux density is at its highest, enter the slot openings at the same time, this will have as a result a considerable cogging torque. To reduce the cogging torquethe magnet edges can be shaped so that they are not parallel to the stator slots, which is the common way to solve the problem. In doing so, the edge may be spread along the whole slot pitch and thus also the high derivative component willbe spread to occur equally along the rotation. Besides forming the magnets theymay also be placed somewhat asymmetric on the rotor surface. The asymmetric distribution can be made in many different ways. All the magnets may have a different deflection of the symmetrical centre point or they can be for example shiftedin pairs. There are some factors that limit the deflection. The first is that the magnets cannot overlap. The magnet shape and the relative width compared to the pole define the deflection in this case. The other factor is that a shifting of the poles limits the maximum torque of the motor. If the edges of adjacent magnets are very close to each other the leakage flux from one pole to the other increases reducing thus the air-gap magnetization. The asymmetric model needs some assumptions and simplifications in order to limit the size of the model and calculation time. The reluctance net is made for symmetric distribution. If the magnets are distributed asymmetrically the flux in the different pole pairs will not be exactly the same. Therefore, the assumption that the flux flows from the edges of the model to the next pole pairs, in the calculation model from one edgeto the other, is not correct. If it were wished for that this fact should be considered in multi-pole pair machines, this would mean that all the poles, in other words the whole machine, should be modelled in reluctance net. The error resulting from this wrong assumption is, nevertheless, irrelevant.

Effect of Mechanical and Geometric Mismatching on Fatigue and Damage of Welded Joints

The future of high technology welded constructions will be characterised by higher strength materials and improved weld quality with respect to fatigue resistance. The expected implementation of high quality high strength steel welds will require that more attention be given to the issues of crack initiation and mechanical mismatching. Experiments and finite element analyses were performed within the framework of continuum damage mechanics to investigate the effect of mismatching of welded joints on void nucleation and coalescence during monotonic loading. It was found that the damage of undermatched joints mainly occurred in the sandwich layer and the damageresistance of the joints decreases with the decrease of the sandwich layer width. The damage of over-matched joints mainly occurred in the base metal adjacent to the sandwich layer and the damage resistance of the joints increases with thedecrease of the sandwich layer width. The mechanisms of the initiation of the micro voids/cracks were found to be cracking of the inclusions or the embrittled second phase, and the debonding of the inclusions from the matrix. Experimental fatigue crack growth rate testing showed that the fatigue life of under-matched central crack panel specimens is longer than that of over-matched and even-matched specimens. Further investigation by the elastic-plastic finite element analysis indicated that fatigue crack closure, which originated from the inhomogeneousyielding adjacent to the crack tip, played an important role in the fatigue crack propagation. The applicability of the J integral concept to the mismatched specimens with crack extension under cyclic loading was assessed. The concept of fatigue class used by the International Institute of Welding was introduced in the parametric numerical analysis of several welded joints. The effect of weld geometry and load condition on fatigue strength of ferrite-pearlite steel joints was systematically evaluated based on linear elastic fracture mechanics. Joint types included lap joints, angle joints and butt joints. Various combinations of the tensile and bending loads were considered during the evaluation with the emphasis focused on the existence of both root and toe cracks. For a lap joint with asmall lack-of-penetration, a reasonably large weld leg and smaller flank angle were recommended for engineering practice in order to achieve higher fatigue strength. It was found that the fatigue strength of the angle joint depended strongly on the location and orientation of the preexisting crack-like welding defects, even if the joint was welded with full penetration. It is commonly believed that the double sided butt welds can have significantly higher fatigue strength than that of a single sided welds, but fatigue crack initiation and propagation can originate from the weld root if the welding procedure results in a partial penetration. It is clearly shown that the fatigue strength of the butt joint could be improved remarkably by ensuring full penetration. Nevertheless, increasing the fatigue strength of a butt joint by increasing the size of the weld is an uneconomical alternative.

Neuro-mechanical and metabolic adjustments to the repeated anaerobic sprint test in professional football players.

PURPOSE: This study aimed to determine the neuro-mechanical and metabolic adjustments in the lower limbs induced by the running anaerobic sprint test (the so-called RAST). METHODS: Eight professional football players performed 6 × 35 m sprints interspersed with 10 s of active recovery on artificial turf with their football shoes. Sprinting mechanics (plantar pressure insoles), root mean square activity of the vastus lateralis (VL), rectus femoris (RF), and biceps femoris (BF) muscles (surface electromyography, EMG) and VL muscle oxygenation (near-infrared spectroscopy) were monitored continuously. RESULTS: Sprint time, contact time and total stride duration increased from the first to the last repetition (+17.4, +20.0 and +16.6 %; all P < 0.05), while flight time and stride length remained constant. Stride frequency (-13.9 %; P < 0.001) and vertical stiffness decreased (-27.2 %; P < 0.001) across trials. Root mean square EMG activities of RF and BF (-18.7 and -18.1 %; P < 0.01 and 0.001, respectively), but not VL (-1.2 %; P > 0.05), decreased over sprint repetitions and were correlated with the increase in running time (r = -0.82 and -0.90; both P < 0.05). Together with a better maintenance of RF and BF muscles activation levels over sprint repetitions, players with a better repeated-sprint performance (lower cumulated times) also displayed faster muscle de- (during sprints) and re-oxygenation (during recovery) rates (r = -0.74 and -0.84; P < 0.05 and 0.01, respectively). CONCLUSION: The repeated anaerobic sprint test leads to substantial alterations in stride mechanics and leg-spring behaviour. Our results also strengthen the link between repeated-sprint ability and the change in neuromuscular activation as well as in muscle de- and re-oxygenation rates.

Kiinnirullaimen dynamiikan ja värähtelyjen simulointi

Diplomityössä tutkittiin kaupallisen monikappaledynamiikkaohjelmiston soveltuvuutta kiinnirullaimen dynamiikan ja värähtelyjen tutkimiseen. Erityisen kiinnostuneita oltiin nipin kuvauksesta sekä nipissä tapahtuvista värähtelyistä. Tässä diplomityössä mallinnettiin kiinnirullaimen ensiö- ja toisiokäytöt sekä tampuuritela. Malli yhdistettiin myöhemmin Metso Paper Järvenpäässä rinnakkaisena diplomityönä tehtyyn malliin, joista muodostui kahteen ratkaisijaan perustuva simulointimalli. Simulointimalli rakennettiin käyttämään kahta erillistä ratkaisijaa, joista toinen on mekaniikkamallin rakentamisessa käytetty ADAMS-ohjelmisto ja toinen säätöjärjestelmää ja hydraulipiirejä kuvaava Simulink-malli. Nipin mallintamiseksi tampuuritela ja rullaussylinteri mallinnettiin joustaviksi käyttäen keskitettyjen massojen menetelmää. Siirtolaitteissa sekä runkorakenteissa tapahtuvat joustot kuvattiin yhden vapausasteen jousi-vaimennin voimilla kuvattuina järjestelminä. Tässä diplomityössä on myös keskitytty esittelemään ADAMS-ohjelmiston toimintaa ohjeistavasti sekä käsittelemään parametrisen mallintamisen etuja. Työssä havaittiin monikappaledynamiikan soveltuvuus kiinnirullaimen dynamiikan sekä dynaamisten voimien aiheuttamien värähtelyjen tutkimiseen. Suoritetuista värähtelymittauksista voitiin tehdä vain arvioita. Mallin havaittiin vaativan lisätutkimusta ja kehitystyötä

Development of rotating drum under mechanical and thermal load

A variable temperature field sets exacting demands to the structure under mechanical load. Most of all the lifetime of the rotating drum structure depends on temperature differences between parts inside the drum. The temperature difference was known because of the measurements made before. The list of demands was created based on customers’ needs. The limits of this paper were set to the inner structure of the drum. Creation of ideas for the inner structure was started open minded. The main principle in the creation process was to create new ideas for the function of the product with the help of sub-functions. The sub-functions were created as independent as possible. The best sub-functions were combined together and the new working principles were created based on them. Every working principle was calculated separately and criticized at the end of the calculation process. The main objective was to create the new kind of structure, which is not based too much to the old, inoperative structure. The affect of own weight of the inner structure to the stress values was quite small but it was also taken into consideration when calculating the maximum stress value of the structure. Because of very complex structures all of the calculations were made with the help of the ProE – Mechanica software. The fatigue analyze was made also for the best structure solution.

Purchasing Process Performance Definition and Improvement in the Mechanical Wood Industry

Tämän tutkimuksen ensisijaisena tavoitteena oli määrittää Schauman Wood Oy:n ostoprosessin suorituskyvyn nykytila yrityksen Suomen yksiköissä. Nykytila-arviointi suoritettiin uusien ja käytössä olevien mittaustulosten avulla. Tutkimuksessa verrattiin kymmenen tuotantolaitoksen ostoprosesseja keskenään. Keskeinen tutkimusongelma oli ostoprosessin suorituseroja aikaansaavien tekijöiden selvittäminen eri yksiköissä. Tutkimuksen tavoitteena oli saavuttaa yhtenäisemmät toimintatavat yrityksessä sekä laajentaa konsernin osto-organisaation hyödyntämistä hankintatoimessa. Tavoitteena oli ostoprosessin virtaviivaistaminen ja tehokkaamman seurantajärjestelmän kehittäminen. Ostotoimintojen suorituskyvyn jatkuva parantaminen perustuu osittain uusien mittareiden avulla saatavaan informaatioon ja täsmällisempään seurantaan. Sisäistä benchmarkingia käytettiin työkaluna suorituskyky-eroavaisuuksien määrittelyssä. Tietoa erilaisista toimintatavoista kerättiin haastattelemalla yrityksen ostajia ja tehdaspalvelupäälliköitä eri tehdaspaikkakunnilla. Sisäisen benchmarkingin avulla määriteltiin toimintatapa eroavaisuudet sekä kehitettiin seurantakortti, jossa jokaista yksikköä verrataan parhaaseen ja eniten kehittyneeseen yksikköön. Työn tuloksina muodostui ehdotuksia ostotoiminnon uusiksi mittareiksi. Uudet mittarit ovat tehokkuusmittareita, jotka kuvaavat resurssien käytön tehokkuutta sekä auttavat seuraamaan ostoprosessin tilaa entistä paremmin. Uusien mittareiden tavoitteena on myös vähentää mittareiden manipulaatiomahdollisuutta. Työn ulkopuolelle rajattiin informaatioteknologiajärjestelmien tietotekninen osuus. Eräs yrityksen tuotantolaitoksista rajattiin myös työn ulkopuolelle, koska sen ostoprosessit ovat huomattavasti kehittymättömämpiä kuin Schauman Woodin muiden tehtaiden ostoprosessit. Kyseisen yksikön kehittämisen tulee lähteä aivan ruohonjuuritasolta. Tutkimuksen teoriaosuus on kerätty alan ammattikirjallisuudesta ja tutkimuksen aihetta käsittelevistä uudehkoista tieteellisistä alan artikkeleista. Teorian tarkoituksena on tukea empiiristä osuutta sekä antaa lukijalle uusia näkemyksiä ostotoiminnan monista mahdollisuuksista. Tutkimuksen tuloksia ovat nykytila-analyysi, ehdotukset uusista ostotoiminnan mittareista sekä ehdotus MRO-tuotteiden ulkoistamiskokeilusta. Yrityksen ostotoiminnan tulisi kehittyä operatiivisesta tasosta kohti strategisempaa oston tasoa. Johdon sitoutuminen hankintatoimen kehityshankkeisiin on erityisen tärkeää, lisäksi hankintatoimi tulisi nähdä strategisempana osa-alueena yrityksessä. Hankintatoimen kehittämisen avulla yrityksen kustannustehokkuutta voidaan lisätä merkittävästi.

Traumatic injuries after mechanical cardiopulmonary resuscitation (LUCAS?2): a forensic autopsy study.

AIM: The aim of our study was to compare traumatic injuries observed after cardiopulmonary resuscitation (CPR) by means of standard (manual) or assisted (mechanical) chest compression by Lund University Cardiopulmonary Assist System, 2nd generation (LUCAS?2) device. METHODS: A retrospective study was conducted including cases from 2011 to 2013, analysing consecutive autopsy reports in two groups of patients who underwent medicolegal autopsy after unsuccessful CPR. We focused on traumatic injuries from dermal to internal trauma, collecting data according to a standardised protocol. RESULTS: The study group was comprised of 26 cases, while 32 cases were included in the control group. Cardiopulmonary resuscitation performed by LUCAS?2 was longer than manual CPR performed in control cases (study group: mean duration 51.5 min; controls 29.4 min; p = 0.004). Anterior chest lesions (from bruises to abrasions) were described in 18/26 patients in the LUCAS?2 group and in 6/32 of the control group. A mean of 6.6 rib fractures per case was observed in the LUCAS?2 group, but this was only 3.1 in the control group (p = 0.007). Rib fractures were less frequently observed in younger patients. The frequency of sternal factures was similar in both groups. A few trauma injuries to internal organs (mainly cardiac, pulmonary and hepatic bruises), and some petechiae (study 46 %; control 41 %; p = 0.79) were recorded in both groups. CONCLUSION: LUCAS?2-CPR is associated with more rib fractures than standard CPR. Typical round concentric skin lesions were observed in cases of mechanical reanimation. No life-threatening injuries were reported. Petechiae were common findings.

On the Analysis and Control of a Linear Synchronous Servomotor with a Flexible Load

Industry's growing need for higher productivity is placing new demands on mechanisms connected with electrical motors, because these can easily lead to vibration problems due to fast dynamics. Furthermore, the nonlinear effects caused by a motor frequently reduce servo stability, which diminishes the controller's ability to predict and maintain speed. Hence, the flexibility of a mechanism and its control has become an important area of research. The basic approach in control system engineering is to assume that the mechanism connected to a motor is rigid, so that vibrations in the tool mechanism, reel, gripper or any apparatus connected to the motor are not taken into account. This might reduce the ability of the machine system to carry out its assignment and shorten the lifetime of the equipment. Nonetheless, it is usually more important to know how the mechanism, or in other words the load on the motor, behaves. A nonlinear load control method for a permanent magnet linear synchronous motor is developed and implemented in the thesis. The purpose of the controller is to track a flexible load to the desired velocity reference as fast as possible and without awkward oscillations. The control method is based on an adaptive backstepping algorithm with its stability ensured by the Lyapunov stability theorem. As a reference controller for the backstepping method, a hybrid neural controller is introduced in which the linear motor itself is controlled by a conventional PI velocity controller and the vibration of the associated flexible mechanism is suppressed from an outer control loop using a compensation signal from a multilayer perceptron network. To avoid the local minimum problem entailed in neural networks, the initial weights are searched for offline by means of a differential evolution algorithm. The states of a mechanical system for controllers are estimated using the Kalman filter. The theoretical results obtained from the control design are validated with the lumped mass model for a mechanism. Generalization of the mechanism allows the methods derived here to be widely implemented in machine automation. The control algorithms are first designed in a specially introduced nonlinear simulation model and then implemented in the physical linear motor using a DSP (Digital Signal Processor) application. The measurements prove that both controllers are capable of suppressing vibration, but that the backstepping method is superior to others due to its accuracy of response and stability properties.