Dissertations / Theses on the topic 'Sensitive manipulation'

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 161-172).
This thesis presents an effective alternative to the traditional approach to robotic manipulation. In our approach, manipulation is mainly guided by tactile feedback as opposed to vision. The motivation comes from the fact that manipulating an object implies coming in contact with it, consequently, directly sensing physical contact seems more important than vision to control the interaction of the object and the robot. In this work, the traditional approach of a highly precise arm and vision system controlled by a model-based architecture is replaced by one that uses a low mechanical impedance arm with dense tactile sensing and exploration capabilities run by a behavior-based architecture. The robot OBRERO has been built to implement this approach. New tactile sensing technology has been developed and mounted on the robot's hand. These sensors are biologically inspired and present more adequate features for manipulation than those of state of the art tactile sensors. The robot's limb was built with compliant actuators, which present low mechanical impedance, to make the interaction between the robot and the environment safer than that of a traditional high-stiffness arm. A new actuator was created to fit in the hand size constraints.
(cont.) The reduced precision of OBRERO's limb is compensated by the capability of exploration given by the tactile sensors, actuators and the software architecture. The success of this approach is shown by picking up objects in an unmodelled environment. This task, simple for humans, has been a challenge for robots. The robot can deal with new, unmodelled objects. OBRERO can come gently in contact, explore, lift, and place the object in a different location. It can also detect slippage and external forces acting on an object while it is held. Each one of these steps are done by using tactile feedback. This task can be done with very light objects with no fixtures and on slippery surfaces.
by Eduardo Rafael Torres Jara.
Ph.D.

"This thesis presents an extension of sensitive manipulation which transforms tactile sensors away from end effectors and closer to whole body sensory feedback. Sensitive manipulation is a robotics concept which more closely replicates nature by employing tactile sensing to interact with the world. While traditional robotic arms are specifically designed to avoid contact, biological systems actually embrace and intentionally contact the environment. This arm is inspired by these biological systems and therefore has compliant joints and a tactile shell surrounding the two primary links of the arm. The manipulator has also been designed to be capable of both industrial and humanoid style manipulation. There are an untold number of applications for an arm with increased tactile feedback primarily in dynamic environments such as in industrial, humanoid, and prosthetic applications. The arm developed for this thesis is intended to be a desktop research platform, however, one of the most influential applications for increased tactile feedback is in prosthetics which are operate in ever changing and contact ridden environments while continuously interacting with humans. This thesis details the simulation, design, analysis, and evaluation of a the first four degrees of freedom of a robotic arm with particular attention given to the design of modular series elastic actuators in each joint as well as the incorporation of a shell of tactile sensors. "

This thesis designed and realized a two-degree of freedom wrist and two finger manipulator that completes the six-degree of freedom Sensitive Manipulation Platform, the arm of which was previously developed. This platform extends the previous research in the field of robotics by covering not only the end effector with deformable tactile sensors, but also the links of the arm. Having tactile sensors on the arm will improve the dynamic model of the system during contact with its environment and will allow research in contact navigation to be explored. This type of research is intended for developing algorithms for exploring dynamic environments. Unlike traditional robots that focus on collision avoidance, this platform is designed to seek out contact and use it to gather important information about its surroundings. This small desktop platform was designed to have similar proportions and properties to a small human arm. These properties include compliant joints and tactile sensitivity along the lengths of the arms. The primary applications for the completed platform will be research in contact navigation and manipulation in dynamic environments. However, there are countless potential applications for a compliant arm with increased tactile feedback, including prosthetics and domestic robotics. This thesis covers the details behind the design, analysis, and evaluation of the two degrees of the Wrist and two two-link fingers, with particular attention being given to the integration of series elastics actuators, the decoupling of the fingers from the wrist, and the incorporation of tactile sensors in both the forearm motor module and fingers.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1994.
Includes bibliographical references (p. 255-277).
by Christopher John Lindblad.
Ph.D.

In the European Union an environmental risk assessment is required for the registration of new chemicals, biocides, pesticides and pharmaceuticals. In order to avoid the release of potential hazardous substances, various ecotoxicity tests are performed, including acute and chronic fish tests. As a consequence of the new program of the European Union “Registration, Evaluation and Authorisation of Chemicals” (REACH) the number of animal experiments for environmental risk assessment is expected to increase remarkably within the next years. On the other hand there is a strong societal demand for reducing the number of animal tests by using alternative in vitro models. According to EU directives, investigations using non-human vertebrate embryos are considered pain free in vitro methods and are therefore accepted as alternatives to animal experiments. For the acute fish test, the Danio rerio embryo test (DarT) has been established as a replacement method and included in national regulations at least for waste water (German Waste Water Dues Law). However, no alternatives for chronic fish tests are currently available. The overall goal of this thesis was to work towards such a replacement by extending DarT zu Gene-DarT. Toxicants will initially interact at the molecular level with consequences for physiology, fitness and survival. The analysis of gene expression patterns may unravel elements of these molecular events before any phenotypic changes are visible. The hypothesis of this thesis therefore was that chemical-sensitive genes in embryos exposed in a conventional DarT may indicate toxic impact of substances at sub-acute concentrations and thus enhance the sensitivity of the embryo toxicity test. Furthermore, unlike the conventional DarT-endpoints, gene expression analysis will provide insights into mechanistic processes underlying toxicity. The 3,4-dichloroaniline (3,4-DCA), which is used as a reference compound in the DarT, was selected as model chemical in this thesis. In a first step, differentially expressed genes in embryos exposed to 3,4-DCA were identified by microarray technology and RT-PCR techniques. Six dose-dependent significant differentially expressed genes were identified. These genes were involved in biotransformation pathways (cyp1a, ahr2), stress response (nrf2, maft, ho-1) and cell cycle control (fzr1). Differential expression upon 3,4-DCA exposure was detected below the LOEC (lowest observed effect concentration = 6.2 µM) of survival or developmental disorders of the embryo test (0.78 µM and above). For the validation of stage specific sensitivity, genes were also analysed in post-hatched stages. Extension of exposure to post-hatched stages resulted in a differential expression at lower concentrations as for the embryonic stages, indicating an improved sensitivity due to stage-specific sensitivity or exposure time. To confirm the adaptive function of the 3,4-DCA-sensitive genes, embryonic mRNA abundance was experimentally manipulated by knock down and overexpression. By injection of sense (mRNA) or antisense (siRNA) RNA in one-cell-stages of embryos, the transcript levels of genes were transiently enhanced or repressed in embryos exposed to 3,4-DCA. mRNA injection of the genes cyp1a, ho-1 and nrf2 reduced the number of embryos with 3,4-DCA-induced malformations. In contrast, siRNA injections for the same genes led to an increase in the severity and frequency of developmental disorders. The results clearly indicate the adaptive functions of the investigated genes or their corresponding proteins. This study demonstrates that the analysis of chemical-sensitive gene expression shows the potential to increase the sensitivity of conventional toxicity tests. The analysis of gene expression also provides additional mechanistic information for toxic action, e.g. in the presented study, the involvement of Ah-receptor regulated pathways as an adaptive response. Furthermore, the presented data indicate that functional manipulations, using mRNA and siRNA-injection, are suitable to evaluate the role of differentially expressed genes for toxicity.

In the European Union an environmental risk assessment is required for the registration of new chemicals, biocides, pesticides and pharmaceuticals. In order to avoid the release of potential hazardous substances, various ecotoxicity tests are performed, including acute and chronic fish tests. As a consequence of the new program of the European Union “Registration, Evaluation and Authorisation of Chemicals” (REACH) the number of animal experiments for environmental risk assessment is expected to increase remarkably within the next years. On the other hand there is a strong societal demand for reducing the number of animal tests by using alternative in vitro models. According to EU directives, investigations using non-human vertebrate embryos are considered pain free in vitro methods and are therefore accepted as alternatives to animal experiments. For the acute fish test, the Danio rerio embryo test (DarT) has been established as a replacement method and included in national regulations at least for waste water (German Waste Water Dues Law). However, no alternatives for chronic fish tests are currently available. The overall goal of this thesis was to work towards such a replacement by extending DarT zu Gene-DarT. Toxicants will initially interact at the molecular level with consequences for physiology, fitness and survival. The analysis of gene expression patterns may unravel elements of these molecular events before any phenotypic changes are visible. The hypothesis of this thesis therefore was that chemical-sensitive genes in embryos exposed in a conventional DarT may indicate toxic impact of substances at sub-acute concentrations and thus enhance the sensitivity of the embryo toxicity test. Furthermore, unlike the conventional DarT-endpoints, gene expression analysis will provide insights into mechanistic processes underlying toxicity. The 3,4-dichloroaniline (3,4-DCA), which is used as a reference compound in the DarT, was selected as model chemical in this thesis. In a first step, differentially expressed genes in embryos exposed to 3,4-DCA were identified by microarray technology and RT-PCR techniques. Six dose-dependent significant differentially expressed genes were identified. These genes were involved in biotransformation pathways (cyp1a, ahr2), stress response (nrf2, maft, ho-1) and cell cycle control (fzr1). Differential expression upon 3,4-DCA exposure was detected below the LOEC (lowest observed effect concentration = 6.2 µM) of survival or developmental disorders of the embryo test (0.78 µM and above). For the validation of stage specific sensitivity, genes were also analysed in post-hatched stages. Extension of exposure to post-hatched stages resulted in a differential expression at lower concentrations as for the embryonic stages, indicating an improved sensitivity due to stage-specific sensitivity or exposure time. To confirm the adaptive function of the 3,4-DCA-sensitive genes, embryonic mRNA abundance was experimentally manipulated by knock down and overexpression. By injection of sense (mRNA) or antisense (siRNA) RNA in one-cell-stages of embryos, the transcript levels of genes were transiently enhanced or repressed in embryos exposed to 3,4-DCA. mRNA injection of the genes cyp1a, ho-1 and nrf2 reduced the number of embryos with 3,4-DCA-induced malformations. In contrast, siRNA injections for the same genes led to an increase in the severity and frequency of developmental disorders. The results clearly indicate the adaptive functions of the investigated genes or their corresponding proteins. This study demonstrates that the analysis of chemical-sensitive gene expression shows the potential to increase the sensitivity of conventional toxicity tests. The analysis of gene expression also provides additional mechanistic information for toxic action, e.g. in the presented study, the involvement of Ah-receptor regulated pathways as an adaptive response. Furthermore, the presented data indicate that functional manipulations, using mRNA and siRNA-injection, are suitable to evaluate the role of differentially expressed genes for toxicity.

Thesis (PhD)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Introduction Cisplatin has been widely used to treat solid tumours and much success has come from the use of this drug in the treatment of head and neck, ovarian, testicular, cervical and small-cell lung cancers. However, the success of cisplatin treatment is limited due to its dose-limiting toxicity and its resulting side-effects, such as nephro- and ototoxicity. The devastating side-effects induced by cisplatin treatment provided the platform for this study whereby the aim was to lower the concentration of cisplatin while maintaining its cancer-specific cytotoxic action. Equally concerning is, cisplatin resistance which is becoming increasingly common, and this radically limits the clinical efficacy and utility of the drug. Adjuvant therapy has thus become necessary in an attempt to possibly curb or lessen the extent of cisplatin resistance. Due to the large body of evidence implicating the importance of autophagy in cancer, the prospect of targeting this mechanism has generally been accepted. Various chemotherapy agents induce autophagy in cancer cells; however the effect of cisplatin on autophagic induction has not been very well explored. We thus hypothesise that the manipulation of the autophagic pathway will sensitise cancer cells to a low concentration of cisplatin treatment. Furthermore, due to the functional interaction between Bcl-2 and Beclin-1 and its role in the regulation of autophagy, ratio analysis of Beclin-1 to Bcl-2 as means of detecting the role of autophagy within the cell under homeostatic and treatment/stress conditions has been conducted. Additionally, Bcl-2 has a prominent role in the malignant cell and it’s over-expression has been found to confer resistance in a variety of cancerous cell lines. We therefore hypothesise that the silencing of Bcl-2 prior to cisplatin treatment will sensitise cervical cancer cells to apoptosis and increase the Beclin-1/Bcl-2 ratio in favour of apoptosis. Materials and Methods Three human cervical cell lines were used: a non-cancerous ectocervical epithelial cell line (Ect1/E6E7) and two cancerous cervical cell lines (HeLa and CaSki). In order to determine a concentration of cisplatin that was non-toxic to the non-cancerous Ect1/E6E7 cell line, a dose-response was performed. With the use of an autophagy inhibitor (bafilomycin A1) and an autophagy inducer (rapamycin), autophagic flux capacities were assessed in each cell line through the Western blotting technique. In order to assess whether the chosen concentration of cisplatin induced autophagy, flow cytometry with the use of a Lysotracker™ dye was utilised, as well as analysis of autophagy protein levels (LC-3 II, Beclin-1 and p62). Autophagy modulation was achieved through two methods: pharmacological modulation with use of two recognised agents, namely bafilomycin A1 and rapamycin, and biological manipulation with the use of ATG5 and mTOR mRNA silencing. The effects of different treatment regimes on cell death was assessed with the use of PARP and caspase-3 cleavage through Western blotting, caspase-3/-7 activity (Caspase-Glo®), PI inclusion, LDH release and MTT reductive capacity. Additionally the effects of these treatment regimes on cell-cycle progression were also analysed. Beclin-1 and Bcl-2 expression was determined through Western blotting and immunocytochemistry before and after treatment with cisplatin in HeLa and CaSki cells. To assess the reliance of the cervical cancer cells on Bcl-2 after cisplatin treatment, Bcl-2 knock-down was achieved through RNA interference, where after the Beclin-1/Bcl-2 ratio was assessed as well as apoptosis with the use of cleaved PARP analysis (Western blotting) and Caspase-Glo©. For the ex vivo analysis, biopsies were collected from patients undergoing routine colposcopy screenings and hysterectomies at Tygerberg Hospital, Tygerberg, Western Cape. A total of 10 normal, 29 low-grade squamous intraepithelial lesions (LSIL), 33 high-grade squamous intraepithelial lesions (HSIL) and 13 carcinoma biopsies were collected for analysis, where after the expression profiles of two autophagy markers (mTOR and LC-3 II), as well as one anti-apoptotic marker (Bcl-2) were assessed. Protein levels were analysed through Western blot and confirmed through immunohistochemistry. Results Dose-response curves revealed that 15 μM of cisplatin did not induce cell death in the normal cervical epithelial cell line (Ect1/E6E7) and was therefore utilised through-out the remainder of the study. It was additionally determined that the CaSki cells were more resistant to cisplatin treatment when compared to the HeLa and Ect1/E6E7 cells. Autophagic flux analysis revealed that, although all three cell lines were cervix derived, their autophagic flux capacities differed. It was observed that the chosen concentration of cisplatin was able to induce autophagy in all three cell lines, with the HeLa cells demonstrating a particularly pronounced response. Autophagy modulation in conjunction with cisplatin treatment revealed the following: Autophagy inhibition with bafilomycin A1 lead to significant increases in caspase-3 and PARP cleavage and LDH release in both cervical cancer cell lines. The inhibition of autophagy through silencing of ATG5 induced caspase-3 cleavage and agrees with results obtained from pharmacological inhibition of autophagy with bafilomycin A1. In addition to autophagic induction, a low concentration of cisplatin induced the up-regulation of Bcl-2, which when silenced significantly improved cisplatin-induced apoptosis in both cervical cancer cell lines. Analysis of the expression profiles of mTOR and LC-3 in normal, pre-malignant (LSIL and HSIL) and cancerous cervical tissue revealed that autophagy is significantly up-regulated in HSILs and carcinoma of the cervix. Additionally, Bcl-2 expression is significantly increased in cervical carcinoma tissue, which agrees with results from other studies. Conclusion Autophagic flux capacities between the three cell lines investigated, derived from the same organ, differ significantly. This should be taken into consideration when autophagic modulation is being used as an adjuvant treatment. With regard to chemotherapy treatment in cervical cells, a low-concentration of cisplatin significantly induces autophagy in malignant and non-malignant cervix-derived cell lines where it serves a pro-survival mechanism. Inhibition of autophagy with bafilomycin A1 and ATG5 siRNA confirmed this survival effect in both cancerous cell lines where apoptosis was significantly increased. Interestingly, rapamycin pre-treatment together with cisplatin did not induce significant levels of apoptosis in HeLa cells where autophagy induction may have provided additional protection from the cytotoxic effects of cisplatin. Therefore the inhibition of autophagy through pharmacological and biological inhibition improves the cytotoxicity of a low concentration of cisplatin and provides a promising new avenue for the future treatment of cervical cancer. Bcl-2 up-regulation in response to cisplatin treatment also serves as a protective mechanism by which cervical cancer cells survive. The extent of apoptotic cell death observed after biological inhibition of Bcl-2 reiterates the fact that this response may be exploited in order to favour the use of lower concentrations of cisplatin. Analysis of clinical specimens emphasised the value of the in vitro work: Cervical cancer biopsies had increased expression of both LC-3 II and Bcl-2, indicating autophagy induction and apoptosis inhibition, respectively. Thus two novel methods of improving cisplatin cytotoxicity have been demonstrated in the following study. Treatment regimens may administer more frequently and prolonged due to the minimal side-effects that accompanies low-dose cisplatin treatment.
AFRIKAANSE OPSOMMING: Inleiding Sisplatien word algemeen gebruik vir die behandeling van soliede gewasse. Baie sukses is reeds deur die gebruik van díe middel behaal in die behandeling van kop en nek, ovariale, terstikulêre, servikale en klein-sel kankers. Die sukses van Sisplatien-behandeling word wel ingeperk deur die dosis-beperkende toksisiteit en die gevolglike newe-effekte soos nefrotoksisiteit. Hierdie verwoestende newe-effekte wat deur sisplatien behandelings geïnduseer word, het as die platform vir hierdie studie gedien. Die doel was om die sisplatien konsentrasies te verlaag, maar terselfdertyd die kankerspesifieke sitotoksisiteit te behou. Nog ʼn punt van kommer is dat sisplatien-weerstandigheid aan die toeneem is, wat die kliniese effektiwiteit en gebruik van hierdie middel geweldig beperk. Byvoegmiddels het dus noodsaaklik geraak in die poging om die sisplatien-weerstandigheid te verhoed. As gevolg van verskeie bewyse wat die belangrikheid van outofagie in kanker impliseer, is die vooruitsig om hierdie meganisme te teiken, algemeen aanvaar. Verskeie chemoterapeutiese middels induseer outofagie in kanker selle, hoewel die effek van Sisplatien op outofagiese induksie nog nie goed ondersoek is nie. Ons hipotese is dus dat die manipulasie van die outofagiese pad die kankerselle sensitiseer tot ʼn lae konsentrasie van sisplatien. Verder, as gevolg van die funksionele interaksie tussen Bcl-2 en Beclin-1, en hul rol in die regulering van outofagie, is verhouding-analises van Beclin-1 tot Bcl-2 uitgevoer met die doel om die rol van outofagie in die sel onder homeostatiese en behandeling/stres kondisies te bepaal. Verder is Bcl-2 bekend daarvoor om ʼn prominente rol te speel in kwaadaardige selle, en die ooruitdrukking daarvan is gevind om weerstandigheid aan te help in ʼn verskeidenheid van kankeragtige sellyne. Ons hipotetiseer dus dat geenonderdrukking van Bcl-2 voor die behandeling met sisplatien die servikale kanker selle sal sensitiseer tot apoptose en ʼn verhoging in die verhouding van Beclin-1/Bcl-2 veroorsaak, wat in die guns van apoptose is. Materiale en Metodes Drie menslike servikale sellyne was gebruik: ʼn nie-kankeragtige servikale epiteel sellyn (Ect/E6E7) en twee kankeragtige servikale sellyne (HeLa en CaSki). Om ʼn konsentrasie van sisplatien te bepaal wat nie-toksies tot die nie-kankeragtige Ect1/E6E7 sellyn is, was ʼn dosisrespons uitgevoer. Met die gebruik van ʼn outofagiese inhibeerder (bafilomycin A1) en ʼn outofagiese induseerder (rapamycin), is die outofagiese-fluks kapasiteite van elke sellyn deur die Western Blotting tegniek geassesseer. Om te bepaal of die gekose konsentrasie van sisplatien outofagie induseer, is vloeisitometrie met ʼn Lysotracker™ kleurstof gebruik, sowel as analises op outofagie proteïenvlakke (LC-3 II, Beclin-1 en p62). Outofagie modulering is behaal deur twee metodes: farmakologiese modulering met twee erkende middels, naamlik bafilomycin A1 en rapamycin, en biologiese manipulasie met die gebruik van ATG5 en mTOR geenonderdrukking. Die effekte van die verskillende behandeling skedules op seldood was geassesseer deur gebruik te maak van PARP en kaspase-3 splitsing deur Western Blotting, kaspase-3/-7 aktiwiteit deur Caspase-Glo ®, PI-insluiting, LDH vrystelling en MTT reduserende kapasiteit. Verder is die effekte van hierdie behandeling skedules op selsiklus progressie ook geanaliseer. Beclin-1 en Bcl-2 uitdrukking was ook bepaal deur Western Blotting en immunohistochemie voor en na behandeling met sisplatien in HeLa en CaSki selle. Om die afhanklikheid van die servikale kankerselle op Bcl-2 na sisplatien behandelings te toets, is Bcl-2 onderdruk deur RNA-inmenging, waarna Beclin-1/Bcl-2 verhouding geassesseer is, sowel as opoptose deur die gebruik van gesplitste PARP analises (Western Blotting) en Caspase-Glo©. Vir die ex vivo analises is biopsies vanaf pasiënte wat roetine kolposkopie en histerektomies ondergaan, verkry (Tygerberg Hospitaal, Tygerberg, Westelike Provinsie). ʼn Totaal van 10 normale, 29 lae-graad plaveisel intraepiteel letsels (LSIL), 33 hoe-graad plaveisel intraepiteel letsels (HSIL) en 13 karsinoom biopsies is verkry vir analises. Die uitdrukkingsprofiel van twee outofagiese merkers (mTOR en LC-3 II), asook een merker vir apoptose (Bcl-2), was geassesseer. Proteïen vlakke was ook deur Western Blotting geanaliseer en deur immunohistochemie bevestig. Resultate Dosisrespons kurwes het getoon dat 15 μM sisplatien nie seldood in die normale sellyn (Ect1/E6E7) geïnduseer het nie, en was daarom gebruik deur die res van hierdie studie. Verder is daar ook gevind dat CaSki selle meer weerstandig tot sisplatien behandelings is wanneer vergelyk word met die HeLa en Ect1/E6E7 selle. Outofagiese-fluks analises het getoon dat, alhoewel al drie sellyne vanaf die serviks afkomstig is, daar verskille is in hul outofagiese-fluks kapasiteit. Daar is ook waargeneem dat die gekose konsentrasie van sisplatien in staat was om outofagie te induseer in al drie sellyne, met HeLa selle wat die mees merkbare respons getoon het. Modulering van outofagie in samewerking met sisplatien behandelings het die volgende onthul: inhibisie van outofagie deur bafilomycin A1 het gelei tot ʼn beduidende verhoging in kaspase-3, PARP splitsing en LDH vrylating in beide servikale kankersellyne. Geenonderdrukking van ATG5 induseer kaspase-3 splitsing en stem ooreen met resultate wat verkry is deur farmakologiese inhibisie van outofagie met bafilomycin A1. Bykomend tot outofagiese indusering, het ʼn lae konsentrasie sisplatien die opregulering van Bcl-2 geïnduseer. Wanneer Bcl-2 geenonderdrukking in hierdie scenario toegepas was, het dit ʼn beduidende verbetering in sisplatien-geïnduseerde apoptose in beide servikale kankersellyne getoon. Analises van die uitdrukkingsprofiel van mTOR en LC-3 in normale, pre-maligne (LSIL en HSIL) en kankeragtige servikale weefsel, het getoon dat outofagie beduidend opgereguleer is in HSILs en servikale karsinome. Verder is Bcl-2 uitdrukking ook gevind om beduidend verhoog te wees in servikale karsinoomweefsel, wat ooreenstem met resultate verkry in ander studies. Gevolgtrekking Outofagiese-fluks kapasiteite tussen die drie sellyne, afkomstig van dieselfde orgaan, toon beduidende verskille. Hierdie bevinding moet in ag geneem word wanneer outofagiese-modulering as ʼn bevorderingsbehandeling gebruik word. Met betrekking tot chemoterapie behandeling in servikale selle; ʼn lae konsentrasie van sisplatien veroorsaak ʼn beduidende indusering van outofagie in kwaadaardige en nie-kwaadaardige serviks-afkomstige sellyne, en dien as ʼn oorlewingsmeganisme. Inhibisie van outofagie met bafilomycin A1 en ATG5 siRNA het hierdie beskermings effek bevestig, aangesien apoptose beduidend verhoog was in beide kankersellyne. Interessant genoeg het rapamycin pre-behandeling tesame met sisplatien nie beduidende vlakke van apoptose in HeLa selle geïnduseer nie. Outofagie induksie mag dalk addisionele beskerming teen die sitotoksiese effekte van sisplatien gebied het. Daarom het die inhibisie van outofagie deur farmakologiese en biologiese inhibering die sitotoksisiteit van ʼn lae konsentrasie sisplatien bevorder, wat ʼn belowende bevinding is vir die toekomstige behandeling van servikale kanker. Bcl-2 opregulering as gevolg van sisplatien behandelings dien ook as beskermings meganisme waarby servikale kankerselle oorleef. Die mate van apoptotiese seldood wat waargeneem word na biologiese inhibering van Bcl-2, wys weer op die feit dat hierdie respons uitgebuit kan word vir die gebruik van laer konsentrasies van sisplatien. Analises van die kliniese monsters het ook die waarde van die in vitro werk versterk: Servikale kanker biopsies het verhoogde uitdrukking van beide LC-3 II en Bcl-2 getoon, wat aandui dat outofagie geïnduseer en apoptose geïnhibeer word. Daar is dus twee nuwe metodes vir die verbetering van sisplatien-toksisiteit in hierdie studie gedemonstreer. Behandeling regimes kan meer gereeld en vir langer tydperke toegepas word, aangesien die newe-effekte van lae-dosis sisplatien behandelings minimaal is.
MRC for funding

The electronic and geometrical structure of single difluoro-bora-1,3,5,7-tetraphenyl-aza-dipyrromethene (aza-BODIPY) molecules adsorbed on the Au(111) surface is investigated by low temperature scanning tunneling microscopy and spectroscopy in conjunction with ab initio density functional theory simulations of the density of states and of the interaction with the substrate. Our DFT calculations indicate that the aza-BODIPY molecule forms a chemical bond with the Au(111) substrate, with distortion of the molecular geometry and significant charge transfer between the molecule and the substrate. Nevertheless, most likely due to the low corrugation of the Au(111) surface, diffusion of the molecule is observed for applied bias in excess of 1 V
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

The electronic and geometrical structure of single difluoro-bora-1,3,5,7-tetraphenyl-aza-dipyrromethene (aza-BODIPY) molecules adsorbed on the Au(111) surface is investigated by low temperature scanning tunneling microscopy and spectroscopy in conjunction with ab initio density functional theory simulations of the density of states and of the interaction with the substrate. Our DFT calculations indicate that the aza-BODIPY molecule forms a chemical bond with the Au(111) substrate, with distortion of the molecular geometry and significant charge transfer between the molecule and the substrate. Nevertheless, most likely due to the low corrugation of the Au(111) surface, diffusion of the molecule is observed for applied bias in excess of 1 V.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

We present the design, analysis and construction of a biologicallyinspired tactile sensor. The sensor can measure normal and lateralforces, conform to the surfaces with which it comes in contact andincrease the friction of the surface for a good grasp.The sensor is built using a simple process and the applied forcesare read using standard electronics. These features make thesensors ideal for mass production.We are motivated to build tactile sensors that are useful forrobotic manipulation given that the current ones do not have thefeatures that we consider necessary. The sensors presented in thispaper have been designed to deal with these issues. They have beendesigned and implemented in the fingers of the humanoid robotObrero.

碩士
國立臺灣大學
應用力學研究所
93
It is becoming gradually obvious that the high-throughput recognition and quantification of bio-molecules are of great importances in biomedical detection and disease diagnosis. With the growing interest and fast development in bio-nanotechnology, bio-sensing tools have been moving towards miniaturization, high sensitivity, and great promise in low-cost as well. A novel electric field-manipulated biosensor of label-free biomolecular recognition based on the nano-mechanics transduction in a micro-fabricated cantilever has been developed. Use of inherent protein charge not in an isoelectric point state is proven to be driven in an electric field, commonly seen in electrophoreses processes. Several electric field-manipulated experiments were conducted between the electrodes of -10V, +10V, and no voltage applications. It was found that the sensing area of the electrode with -10 volt was collectively deposited with the net positive protein IgG1 in a buffer solution of pH ~ 5. The significant surface stresses arise in sensing area as a negative electrode, while most proteins are, in contrast, repelled out of the sensing area applied in positive electrode. With the protein isoelectric point characteristics, the attraction and repulsion of proteins have been demonstrated in manipulation under electric fields across the electrodes with the device sensing element. In protein attraction demonstration, the device is capable of highly sensitive antigen detection by collecting most antibodies in a far dilute concentration. In addition, both use of attraction and repulsion in manipulation show the potential of selective deposition and local repulsion in specific sensing surface among multiple disparate sensing agents.

碩士
國立成功大學
化學工程學系碩博士班
95
In this study, cadmium sulfide quantum dots (CdS QDs) were used as a sensitizer of dye-sensitized Solar Cells (DSSCs). CdS QDs were deposited on the titania photoelectrodes using chemical bath deposition (CBD). Here, we focused on the discussion of cell efficiency for different structure titania photoelectrodes with micro/nano mutilayer porous structure made by spin coating method.From the experimental results, the assembly of the larger size titania particles (PT-501-A, 100nm) on the outer layer was not only with larger holes and scattering effect, but also with contribution to photocurrent by CdS QDs deposited on the larger size particles. In the different structures, ITO/6.5μm P25/3.7μm PT-501A（100nm）/CBD3 has the highest cell efficiency (1.14%). Therefore, micro/nano multilayer structure design of porous titania photoelectrodes was also suitable for improving cell performance of quantum dots dye-sensitized Solar Cells, attributed to the effect of scattering particles in enhancing the light harvesting efficiency.

碩士
國立臺灣科技大學
材料科學與工程系
104
Nano-manipulation is considered to be very important foundation research in nanotechnology. With the development of technology, the products have become the trend of miniaturization of materials that size from microns to nanometers. Therefore, the dispersion techniques urgently need to promote in order to approach the current demand. In this thesis, there are two parts describing the polymeric dispersants to achieve the nanohybrids of graphene platelets/-particle/-tubes nanomaterials or complexes will be prepared via the geometric shape in-homogeneity factor dispersing method and the corresponding functions including hydrophilic/hydrophobic dispersing properties. According to their functions, it could be searched possible applications, such as superhydrophobic surface and electrodes in dye-sensitized solar cells. The content of study is described as follow: In this study, the first part we report the micro-/nano- manipulation of highly surface roughness by star-shaped highly hydrophobic polymeric dispersants finely stabilized the nanohybrids of carbon black (CB), carbon nanotubes (CNTs), and reduced graphene oxide (rGO). The star-shaped organic dispersant, namely a polyisobutylene-imide copolymer (PIB-imide), was synthesized via amidation and imidation reactions of polyisobutylene-g-succinic anhydride (PIB-SA) and poly(oxypropylene)-triamine (Jeffamine T403) of approximately 440 average molecular weight (Mw). The dispersion mechanism between the carbon materials and the PIB-imide through non-covalent interactions such as hydrophobic effect. Furthermore, the hybrid films exhibiting a highly water-droplet contact angle of 158o and the sliding angle of 2o. Adding PMMA enhance the mechanism of micro/nanostructure also exhibiting a highly water-droplet CA of 152o and SA of 3o. The organic/inorganic nanohybrids are proven to be a convenient method for mimicking Lotus leaf surfaces and potential useful for manufacturing superhydrophobic coating. The second part choosing of reduced-grapheme oxide. Graphene has excellent electrical conductivity and catalytic properties. Adding an organic dispersant to help graphene dispersed and fabrication grapheme-carbon nanotubes and grapheme-carbon black composite electrode optimization of counter electrodes replace expensive platinum electrodes in dye-sensitized solar cells.