<p>Hallsta paper mill uses large amounts of water during the pulp and paper making processes. The wastewater is treated in two separate activated sludge processes referred to as BIO 1 and BIO 2. The main aim is to reduce the organic substance content, measured as COD (Chemical Oxygen Demand) before the wastewater is released into the environment. Since the effluent produced is very rich in organic substances, the addition of nitrogen (N) and phosphorus (P) are necessary to give satisfactory treatment results. Problems with sludge bulking sometimes occur which lead to increased levels of suspended matter and nutrients in the effluent. Periods of high concentration of phosphorus is also of great concern. The aim of this study is to investigate the causality behind the sludge bulking, with the help of scientific literature and analysis of previously compiled data using multivariate data analysis. COD and nutrients present in the influent will also be surveyed to identify variations in concentration caused by the paper making process.</p><p>The scientific literature points toward low nitrogen and phosphorus levels as the major causes of the bulking sludge, as this leads to increased growth of filamentous bacteria to the detriment of the preferred flocculating species. A full scale experiment was conducted in an attempt to evaluate sufficient dosage levels of N and P to reduce this problem. The experiment has produced stabile results with low percentages of suspended organic matter and nutrients.</p><p>Evaluation of the previously collected data using Multivariate Data Analysis did not lead to any correlation between variables being found, other than the impact of sludge concentration on COD-reduction. No relevant explanation to periods of high phosphorus levels could be found neither in the scientific literature nor in the multivariate data analysis.</p><p>Bleaching of the paper pulp, with hydrogen peroxide and lye, results in a subsequent increase in COD concentration in the wastewater. The study shows an increased COD in the water approximately 12 hours after the increased dosing of these bleaching agents. Also the amounts of easily degradable COD increases following increased dosage of hydrogen peroxide and lye. The content of easily accessible phosphorus in the influent represents a minimum of 25 % and 20 % of the amount theoretically required for BIO1 and BIO2 respectively. The influent levels of nitrogen represents 33 % and 100 % for BIO1 and BIO2 respectively.</p><p>From this study it has been possible to deduce that a controlled dosage of nutrients in relation to the incoming level of COD, is of great importance to the efficient treatment of COD rich effluent in the systems under investigation at Hallsta Papermill.</p> / <p>Vid Hallsta Pappersbruk används stora mängder vatten vid tillverkningen av massa och papper. Det förorenade processvattnet renas i två separata anläggningar, BIO1 och BIO2, båda med biologisk rening av typen aktivt slam. Avloppsvattnets höga halter av kolföreningar, vilka analyseras som COD (Chemical Oxygen Demand), kräver extra tillsats av kväve och fosfor för att erhålla tillfredsställande reningsresultat. I den biologiska reningen uppstår periodvis problem med slamsvällning, något som resulterar i höga utsläpp av suspenderat material och organiskt bundna näringsämnen. Även perioder med höga fosforutsläpp förekommer. Syftet med examensarbetet är att genom litteraturstudier och analys av historiska data, med hjälp av multivariat dataanalys, utreda orsakerna till problemen. Även en kartläggning av variationerna i inkommande avloppsvatten med avseende på COD och lättillgängliga näringsämnen genomförs.</p><p>Utifrån information från litteraturen tyder problemen med slamsvällning ofta på bristande tillgång på kväve och fosfor vilket bland annat kan resultera i kraftig tillväxt av filamentösa bakterier. För att komma till rätta med problemen startades ett styrt försök med beräknade optimala doseringskvoter. Försöket resulterade i stabil drift för båda anläggningarna med låga utsläppsnivåer av både suspenderat material och näringsämnen.</p><p>Resultatet från utvärderingen av driftsdata med multivariat analys visar att slamhalten har betydelse för COD-reduktionen i BIO1. Någon förklaring till problemen med höga fosforutsläpp har inte framkommit vare sig ur litteraturstudie eller multivariat dataanalys.</p><p>Vid alkalisk oxiderande blekning av termomekanisk pappersmassa ökar den totala COD-koncentrationen i avloppsvattnet i samband med höjd dosering av blekkemikalier. Studien visar att en ökad COD-koncentration kan observeras i vattnet in till BIO1 ca 12 timmar efter förhöjd dosering av blekkemikalier. Samtidigt ökar andelen lättnedbrytbart COD till följd av ökad blekningsgrad. Kartläggningen av inkommande vatten visar att mängden lättillgängligt kväve i avloppsvattnet in till biologierna motsvarar ca 33 % och 100 % av det teoretiskt beräknade behovet för BIO1 respektive BIO2. För fosfor uppgår motsvarande till minst 25 % respektive 20 % för BIO1 och BIO2.</p><p>Under examensarbetets gång har det kunnat konstateras att dosering av närsalter i förhållande till inkommande mängd COD är av stor vikt för en väl fungerande rening av det COD-rika avloppsvattnet vid Hallsta Pappersbruk.</p>

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Prior studies have demonstrated the effect of diazoxide in protecting against apoptosis via mitochondrial KATP channel opening in vitro. The current investigations are designed to determine if sildenafil, a phosphodiesterase-5 inhibitor and known mitochondrial KATP channel opener, would protect against chronic doxorubicin cardiomyopathy both in vivo and in vitro.Male ICR mice were randomized to 1 of 4 treatments: saline, sildenafil (0.7 mg/kg IP), doxorubicin (5 mg/kg IP), and sildenafil (0.7 mg/kg IP)+doxorubicin. Apoptosis was determined using the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling and in situ oligo ligation methods. Desmin distribution was determined via immunofluorescence. Bcl-2 was analyzed by Western blot. Left ventricular function was measured in Langendorff mode. Electrocardiographical analysis measured changes indicative of doxorubicin cardiotoxicity (ST-prolongation). In vitro studies using adult ventricular cardiomyocytes were exposed to doxorubicin (1 μM), sildenafil (1 μM) with or without NG-nitro-L-arginine methyl ester (L-NAME; 100 μM), or 5-hydroxydecanoate (5-HD; 100 μM) 1 hour before doxorubicin and incubated for 18 hours. Doxorubicin-treated mice demonstrated increased apoptosis and desmin disruption, which was attenuated in the sildenafil+doxorubicin group. Bcl-2 decreased in the doxorubicin group but was maintained at basal levels in the sildenafil+doxorubicin group. Left ventricular developed pressure and rate pressure product were significantly depressed in the doxorubicin group but attenuated in the sildenafil+doxorubicin group. ST-interval significantly increased in the doxorubicin group over 8 weeks. In the sildenafil+doxorubicin group, ST-interval remained unchanged from baseline. Doxorubicin significantly increased apoptosis, caspase-3 activation, and disruption of mitochondrial membrane potential in vitro,. In contrast, sildenafil significantly protected against doxorubicin cardiotoxicity; however, protection was abolished by both L-NAME and 5-HD. Cell viability studies using spectrophotometer and flow cytometric techniques demonstrated that sildenafil did not affect the antitumor efficacy of doxorubicin in PC-3 cells in vitro. In fact, flow cytometry data indicate that sildenafil, when combined with doxorubicin, was synergistic in the antineoplastic action of doxorubicin. Prophylactic treatment with sildenafil prevented apoptosis and left ventricular dysfunction in a chronic model of doxorubicin-induced cardiomyopathy. Moreover, these studies provide relevant clinical data on the safety and efficacy of sildenafil, leading the way for clinical trials in humans receiving doxorubicin chemotherapy.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Neste trabalho foi desenvolvido um estudo sistemático dos mecanismos de difusão responsáveis pelo switching de resistência em memórias resistivas. Essas memórias possuem estrutura semelhante a de um capacitor, a qual sofre uma transição de resistência induzida pela aplicação de um campo elétrico. A transição é provocada pela formação de filamentos condutivos no interior da matriz semicondutora. Os filamentos podem ser constituídos por metal originado de um dos eletrodos (ECM) ou por regiões do óxido deficientes em oxigênio (VCM), geradas pela difusão de vacâncias de oxigênio. Dispositivos de TiO2 foram construídos e sua resposta elétrica foi adquirida através de medidas elétricas do tipo I-V para diferentes metais de eletrodo. Técnicas de análise por feixe de íons, como retroespalhamento Rutherford por micro-feixe e perfilometria com reação nuclear ressonante, foram usadas para detalhamento dos processos de difusão. Constatou-se uma dependência do comportamento elétrico em função do método de deposição da camada semicondutora, sua espessura e os parâmetros da medida de tensão. No caso do filamento ser composto por átomos de metal, espectros de micro-RBS foram adquiridos para identificar a sua estrutura no interior do óxido. Ainda, observaram-se bolhas na superfície do eletrodo superior dos dispositivos com difusão de vacâncias de oxigênio após o tratamento elétrico. Nesse mesmo contexto, foi medida a difusividade e energia de ativação da difusão de oxigênio em filmes finos de TiOy. / In this work we developed a systematic study of diffusion mechanisms which are responsible for resistance switching in resistive memories. The structure of these memories is similar to a capacitor which suffers resistance transition induced by electrical field. The transition is caused by the formation of conductive filaments inside the semiconductor matrix. The filaments may be constituted by metal from one of the electrodes (ECM) or by oxygen deficient areas (VCM), generated from oxygen vacancies diffusion. Devices of TiO2 have been built and its electrical response was acquired through electrical measurements (I-V) for different electrode metals. Ion beam techniques such as micro-probe Rutherford Backscattering and Nuclear Reaction Profiling were used to detail the diffusion processes. It was observed a dependence in the electrical behaviour with the semiconductor layer deposition method, its thickness and bias measurement parameters. In the case which filaments are composed by metal atoms, measurements of micro-RBS were performed to identify its structure inside the oxide. Also, bubbles have been observed over the surface of top electrode in devices with oxygen vacancies diffusion after the electrical treatment. In this context, it was measured diffusivity and activation energy for oxygen diffusion in thin TiOy films.

Patients with giant axonal neuropathy (GAN) exhibit loss of motor and sensory function and typically live for less than 30 years. GAN is caused by autosomal recessive mutations leading to low levels of gigaxonin, a ubiquitously-expressed cytoplasmic protein whose cellular roles are poorly understood. GAN pathology is characterized by aggregates of intermediate filaments (IFs) in multiple tissues. Disorganization of the neuronal intermediate filament (nIF) network is a feature of several neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease and axonal Charcot-Marie-Tooth disease. In GAN such changes are often striking: peripheral nerve biopsies show enlarged axons with accumulations of neurofilaments; so called "giant axons." Interestingly, IFs also accumulate in other cell types in patients. These include desmin in muscle fibers, GFAP (glial fibrillary acidic protein) in astrocytes, and vimentin in multiple cell types including primary cultures of biopsied fibroblasts. These findings suggest that gigaxonin may be a master regulator of IFs, and understanding its function(s) could shed light on GAN as well as the numerous other diseases in which IFs accumulate. However, an interaction between gigaxonin and IFs has not been detected and how IF accumulation is triggered in the absence of functional gigaxonin has not been determined. To address these questions I undertook a proteomic screen to identify the normal binding partners of gigaxonin. Prominent among them were several classes of IFs, including the neurofilament subunits whose accumulation leads to the axonal swellings for which GAN is named. Strikingly, human motor neurons (MNs) differentiated from GAN iPSCs recapitulate this key phenotype. Accumulation of nIFs can be rescued by reintroduction of gigaxonin, by viral delivery or genetic correction. GAN iPS-MNs do not display survival vulnerability in the presence of trophic factors, but do display increased cell death in the presence of oxidative stress. Preliminary experiments suggest that in iPS-MNs nIFs are degraded by contributions from both the proteasome and lysosome. Gigaxonin interacts with the autophagy protein p62 which has been implicated in the clearance of ubiquitin aggregates by the lysosome, and this interaction is greatly enhanced in conditions of oxidative stress. My data provide the first direct link between gigaxonin loss and IF aggregation, and suggest that gigaxonin may be a substrate adaptor for the degradation of IFs by autophagy, pointing to future approaches for reversing the phenotype in human patients.

Les impulsions laser ultra-brèves (fs) et ultra-intenses (TW) forment, au cours de leur propagation non-linéaire dans l'atmosphère, des structures auto-guidées, d'une centaine de microns de diamètre, appelées filaments. Ces filaments résultent d'un équilibre dynamique entre l'effet Kerr qui focalise le faisceau et la défocalisation due plasma généré au sein de ceux-ci.<br /><br /> Au cours de mon travail de thèse, nous avons mesuré que le spectre de lumière blanche issue de l'automodulation de phase et de la génération de troisième harmonique s'étend de l'ultra-violet (230 nm) à l'infrarouge (4,5 µm). De même, la propagation dans l'air, sous différentes conditions (pluie, brouillard, turbulence), des faisceaux térawatts femtosecondes a été caractérisée afin de développer des applications atmosphériques.<br /> <br /> Il nous a ainsi été possible de développer le Lidar à lumière blanche pour réaliser des mesures préliminaires d'ozone et d'aérosols simultanément.<br /> <br /> De même, grâce à la propagation fortement non-linéaire du faisceau qui permet de transporter des hautes intensités sur de longue distance, nous avons pu détecter et identifier, à distance, des aérosols biologiques et des cibles solides (LIBS) en induisant in situ des effets non-linéaires.<br /> <br />Enfin, nous avons montré que le déclenchement et le guidage de décharges de haute tension par une impulsion laser femtoseconde sous la pluie reste possible avec une efficacité comparable à l'atmosphère sèche. D'autre part, une configuration à double impulsion laser augmente l'efficacité de déclenchement des décharges. Ces résultats nous rapprochent de la perspective de déclenchement et guidage de foudre par laser.

L'objet de cette thèse est l'étude de l'implication des filaments intermédiaires (cytosquelette) dans une fonction mécanique, et plus particulièrement, dans la fonction de mécanotransduction s'exerçant via un mécanisme de réorganisation de la structure du réseau en réponse aux changements mécaniques extracellulaires. Cette problématique est appréhendée selon deux optiques complémentaires, l'une déductive et l'autre inductive. La première traite de la caractérisation structurale des réseaux cytosquelettiques par des méthodes d'analyse d'images. La caractérisation de l'architecture des réseaux cytosquelettiques se définit comme une représentation simplifiée des réseaux suivie d'une quantification de leur architecture. Cette méthodologie, développée pour spécifier l'architecture de réseaux d'objets curvilignes, se compose de trois approches découlant d'une observation hiérarchisée des réseaux. Elle est utilisée, pour caractériser d'une part la variabilité intracellulaire de l'architecture des réseaux cytosquelettiques, et d'autre part les variations architecturales des réseaux cytosquelettiques de cellules exposées à des conditions mécaniques différentes. La seconde présente un modèle intégro-différentiel d'édification du réseau de cytokératine, s'appuyant sur l'hypothèse selon laquelle l'organisation structurale d'un réseau spécifique de cytosquelette dépend de sa fonction biologique. Ce modèle a été conçu dans le but de valider l'hypothèse, émise et observée lors de l'étape de caractérisation, d'implication des réseaux de filaments intermédiaires dans la mécanotransduction par variations architecturales. Du modèle mathématique d'organisation structurale du réseau de cytokératine d'une cellule épithéliale induite par les contraintes mécaniques est dérivé un modèle de simulation tridimensionnel. Ce modèle de simulation permet d'obtenir des exemples d'architecture de réseau de cytokératine pour des contraintes mécaniques données.

The biological function and the technological applications of semiflexible polymers, such as DNA, actin filaments and carbon nanotubes, strongly depend on their rigidity. Semiflexible polymers are characterized by their persistence length, the definition of which is the subject of the first part of this thesis. Attractive interactions, that arise e.g.~in the adsorption, the condensation and the bundling of filaments, can change the conformation of a semiflexible polymer. The conformation depends on the relative magnitude of the material parameters and can be influenced by them in a systematic manner. In particular, the morphologies of semiflexible polymer rings, such as circular nanotubes or DNA, which are adsorbed onto substrates with three types of structures, are studied: (i) A topographical channel, (ii) a chemically modified stripe and (iii) a periodic pattern of topographical steps. The results are compared with the condensation of rings by attractive interactions. Furthermore, the bundling of two individual actin filaments, whose ends are anchored, is analyzed. This system geometry is shown to provide a systematic and quantitative method to extract the magnitude of the attraction between the filaments from experimentally observable conformations of the filaments. / Die biologische Funktion und die technologischen Anwendungen semiflexibler Polymere, wie DNA, Aktinfilamente und Nanoröhren aus Kohlenstoff, werden wesentlich von deren Biegesteifigkeit bestimmt. Semiflexible Polymere werden charakterisiert durch ihre Persistenzlänge, mit deren Definition sich der erste Teil dieser Arbeit befasst. Anziehende Wechselwirkungen, wie sie z.B. bei der Adsorption, der Kondensation und der Bündelung von Filamenten auftreten, können die Konformation eines semiflexiblen Polymers verändern. Die Konformation ist dabei abhängig von der relativen Größe der Materialparameter und kann durch diese gezielt beeinflusst werden. Im Einzelnen werden hier die Morphologien semiflexibler Polymerringe, wie z.B. DNA oder ringförmiger Nanoröhren, untersucht, die auf drei verschieden strukturierten Substraten adsorbieren: (i) Ein topographischer Kanal, (ii) ein chemisch modifizierter Streifen und (iii) ein periodisches Muster topographischer Oberflächenstufen. Die Ergebnisse werden mit der Kondensation von Ringen durch anziehende Wechselwirkungen verglichen. Des Weiteren wird die Bündelung zweier Aktinfilamente, deren Enden verankert sind, untersucht. Diese Systemgeometrie liefert eine systematische Methode, um die Stärke der Anziehung zwischen den Filamenten aus experimentell beobachtbaren Konformationen zu berechnen.

In dieser Arbeit werden Knickinstabilitäten von Filamenten in biologischen Systemen untersucht. Das Zytoskelett von Zellen ist aus solchen Filamenten aufgebaut. Sie sind für die mechanische Stabilität der Zelle verantwortlich und spielen eine große Rolle bei intrazellulären Transportprozessen durch molekulare Motoren, die verschiedene Lasten wie beispielsweise Organellen entlang der Filamente des Zytoskeletts transportieren. Filamente sind semiflexible Polymere, deren Biegeenergie ähnlich groß ist wie die thermische Energie, so dass sie auch als elastische Balken auf der Nanoskala gesehen werden können, die signifikante thermische Fluktuationen zeigen. Wie ein makroskopischer elastischer Balken können auch Filamente eine mechanische Knickinstabilität unter Kompression zeigen. Im ersten Teil dieser Arbeit wird untersucht, wie diese Instabilität durch thermische Fluktuationen der Filamente beeinflusst wird. In Zellen können Kompressionskräfte durch molekulare Motoren erzeugt werden. Das geschieht zum Beispiel während der Zellteilung in der mitotischen Spindel. Im zweiten Teil der Arbeit untersuchen wir, wie die stochastische Natur einer von Motoren generierten Kraft die Knickinstabilität von Filamenten beeinflusst. Zunächst stellen wir kurz das Problem von Knickinstabilitäten auf der makroskopischen Skala dar und führen ein Modell für das Knicken von Filamenten oder elastischen Stäben in zwei Raumdimensionen und in Anwesenheit thermischer Fluktuationen ein. Wir präsentieren eine analytische Lösung für Knickinstabilitäten in Anwesenheit thermischer Fluktuationen, die auf einer Renormierungsgruppenrechnung im Rahmen des nichtlinearen Sigma-Models basiert. Wir integrieren die kurzwelligen Fluktuationen aus, um eine effektive Theorie für die langwelligen Moden zu erhalten, die die Knickinstabilität bestimmen. Wir berechnen die Änderung der kritischen Kraft für die Knickinstabilität und zeigen, dass die thermischen Fluktuationen in zwei Raumdimensionen zu einer Zunahme der kritischen Kraft führen. Außerdem zeigen wir, dass thermische Fluktuationen im geknickten Zustand zu einer Zunahme der mittleren projizierten Länge des Filaments in Richtung der wirkenden Kraft führen. Als Funktion der Konturlänge des Filaments besitzt die mittlere projizierte Länge eine Spitze an der Knickinstabilität, die durch thermische Fluktuationen abgerundet wird. Unser Hauptresultat ist die Beobachtung, dass ein geknicktes Filament unter dem Einfluss thermischer Fluktuationen gestreckt wird, d.h. dass seine mittlere projizierte Länge in Richtung der Kompressionskraft auf Grund der thermischen Fluktuationen zunimmt. Unsere analytischen Resultate werden durch Monte-Carlo Simulationen der Knickinstabilität semiflexibler Filamente in zwei Raumdimensionen bestätigt. Wir führen auch Monte-Carlo Simulationen in höheren Raumdimensionen durch und zeigen, dass die Zunahme der projizierten Länge unter dem Einfluss thermischer Fluktuationen weniger ausgeprägt ist und stark von der Wahl der Randbedingungen abhängt. Im zweiten Teil der Arbeit formulieren wir ein Modell für die Knickinstabilität semiflexibler Filamente unter dem Einfluss molekularer Motoren. Wir untersuchen ein System, in dem sich eine Gruppe von Motoren entlang eines fixierten Filaments bewegt, und dabei ein zweites Filament als Last trägt. Das Last-Filament wird gegen eine Wand gedrückt und knickt. Während des Knickvorgangs können die Motoren, die die Kraft auf das Filament generieren, stochastisch von dem Filament ab- und an das Filament anbinden. Wir formulieren ein stochastisches Model für dieses System und berechnen die “mean first passage time“, d.h. die mittlere Zeit für den Übergang von einem Zustand, in dem alle Motoren gebundenen sind zu einem Zustand, in dem alle Motoren abgebunden sind. Dieser Übergang entspricht auch einem Übergang aus dem gebogenen zurück in einen ungebogenen Zustand des Last-Filaments. Unser Resultat zeigt, dass für genügend kurze Mikrotubuli die Bewegung der Motoren von der durch das Last-Filament generierten Kraft beeinflusst wird. Diese Ergebnisse können in zukünftigen Experimenten überprüft werden. / We study buckling instabilities of filaments in biological systems. Filaments in a cell are the building blocks of the cytoskeleton. They are responsible for the mechanical stability of cells and play an important role in intracellular transport by molecular motors, which transport cargo such as organelles along cytoskeletal filaments. Filaments of the cytoskeleton are semiflexible polymers, i.e., their bending energy is comparable to the thermal energy such that they can be viewed as elastic rods on the nanometer scale, which exhibit pronounced thermal fluctuations. Like macroscopic elastic rods, filaments can undergo a mechanical buckling instability under a compressive load. In the first part of the thesis, we study how this buckling instability is affected by the pronounced thermal fluctuations of the filaments. In cells, compressive loads on filaments can be generated by molecular motors. This happens, for example, during cell division in the mitotic spindle. In the second part of the thesis, we investigate how the stochastic nature of such motor-generated forces influences the buckling behavior of filaments. In chapter 2 we review briefly the buckling instability problem of rods on the macroscopic scale and introduce an analytical model for buckling of filaments or elastic rods in two spatial dimensions in the presence of thermal fluctuations. We present an analytical treatment of the buckling instability in the presence of thermal fluctuations based on a renormalization-like procedure in terms of the non-linear sigma model where we integrate out short-wavelength fluctuations in order to obtain an effective theory for the mode of the longest wavelength governing the buckling instability. We calculate the resulting shift of the critical force by fluctuation effects and find that, in two spatial dimensions, thermal fluctuations increase this force. Furthermore, in the buckled state, thermal fluctuations lead to an increase in the mean projected length of the filament in the force direction. As a function of the contour length, the mean projected length exhibits a cusp at the buckling instability, which becomes rounded by thermal fluctuations. Our main result is the observation that a buckled filament is stretched by thermal fluctuations, i.e., its mean projected length in the direction of the applied force increases by thermal fluctuations. Our analytical results are confirmed by Monte Carlo simulations for buckling of semiflexible filaments in two spatial dimensions. We also perform Monte Carlo simulations in higher spatial dimensions and show that the increase in projected length by thermal fluctuations is less pronounced than in two dimensions and strongly depends on the choice of the boundary conditions. In the second part of this work, we present a model for buckling of semiflexible filaments under the action of molecular motors. We investigate a system in which a group of motors moves along a clamped filament carrying a second filament as a cargo. The cargo-filament is pushed against the wall and eventually buckles. The force-generating motors can stochastically unbind and rebind to the filament during the buckling process. We formulate a stochastic model of this system and calculate the mean first passage time for the unbinding of all linking motors which corresponds to the transition back to the unbuckled state of the cargo filament in a mean-field model. Our results show that for sufficiently short microtubules the movement of kinesin-I-motors is affected by the load force generated by the cargo filament. Our predictions could be tested in future experiments.