Academic literature on the topic 'Sensitive manipulation'

Object grasping and manipulation in robotics has been largely approached using visual feedback. Human studies on the other hand have demonstrated the importance of tactile and force feedback to guide the interaction between the fingers and the objects. Inspired by these observations, we propose an approach that consists in guiding a robot’s actions mainly by tactile feedback, with remote sensing such as vision, used only as a complement. Directly sensing the interaction forces between the object, the environment, and the robot’s hand enables it to obtain information relevant to the task that can be used to perform it more reliably. This approach (that we call sensitive manipulation) requires important changes in the hardware and in the way the robot is programmed. At the hardware level, we exploit compliant actuators and novel sensors that allow to safely interact and detect the environment. We developed strategies to perform manipulation tasks that take advantage of these new sensing and actuation capabilities. In this paper, we demonstrate that using these strategies the humanoid robot Obrero can safely find, reach and grab unknown objects that are neither held in place by a fixture nor placed in a specific orientation. The robot can also make insertions by “feeling” the hole without specialized mechanisms such as a remote center of compliance (RCC).

We studied the behavioural effect of increasing the frequency of handling in Red-winged Blackbird (Agelaius phoeniceus), a species that is weight sensitive to captivity. Manipulations consisted in weighing groups of birds every 1, 3, 6, and 9 days, and measuring their food consumption, activity level, and behaviour. Results show that the more frequently the birds are manipulated, the less active they become, the less food they consume, and the more weight they lose. On the day of the manipulation, all birds reacted similarly, regardless of the frequency of manipulation for their group. They remained inactive for extended periods of time after being manipulated, probably because of the stress induced. The next day, they fed as much or more than the day before the manipulation. The longer the time interval between manipulations, the better their weight recovery. If stresses were at too close a time interval from one another, the birds constantly lost weight. Spacing manipulations, whatever they are, would be a reasonable solution to avoid the expression of disturbed behaviours and the loss of weight in captive wild birds used in behavioral studies.

Manipulating the light emission direction and boosting its directivity have essential importance in integrated nanophotonic devices. Here, we theoretically propose a single dielectric silicon nanoblock as an efficient, multifunctional and ultracompact all-dielectric nanoantenna to direct light into a preferential direction. Unidirectional scattering of a plane wave as well as switchable directive emission fed by a localized emitter are demonstrated within the nanoantenna. The high directionalities are revealed to originate from a variety of mechanisms that can coexist within a single nanoblock, which contribute to the far-field radiation patterns of the outcoming light, thanks to the wealth of multipolar electric and magnetic resonances. The efficient beam redirections are also observed, which are sensitive to the local configurations of the emitter antenna coupled system. The designed antenna, with extreme geometry simplicity, ultracompact and low-loss features, could be favorable for highly sensitive sensing as well as applications in optical nanocircuits.

SUMMARYAs various robots are anticipated to coexist with humans in the near future, safe manipulation in unknown, cluttered environments becomes an important issue. Manipulation in an unknown environment, however, has been proven to be NP-Hard and the risk of unexpected human--robot collision hampers the dawning of the era of human--robot coexistence. We propose a non-contact-based sensitive skin as a means to provide safe manipulation hardware and interleaving planning between the workspace and the configuration space as software to solve manipulation problems in unknown, crowded environments. Novelty of the paper resides in demonstration of real time and yet complete path planning in an uncertain and crowded environment. To that end, we introduce the framework of the sensor-based interleaving planner (SBIP) whereby search completeness and safe manipulation are both guaranteed in cluttered environments. We study an interleaving mechanism between sensation in a workspace and execution in the corresponding configuration space for real-time planning in uncertain environments, thus the name interleaving planner implies.Applications of the proposed system include manipulators of a humanoid robot, surgical manipulators, and robotic manipulators working in hazardous and uncertain environments such as underwater, unexplored planets, and unstructured indoor spaces.

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

Area-specific knowledge is indispensable for studying political development, but this can also lead to “blindspots” when conducting historical research if one’s horizons are limited to conventionally defined “areas.” Focusing on the 19th century, the author argues that the compartmentalization of the study of European and American political development has restricted our understanding of both. Particularly in struggles over democratization, pre-democratic elites in both regions saw their fates as linked and adopted similar strategies. In fact, one such strategy—the manipulation of electoral systems to limit working-class influence—was a mainstay of European politics, but first emerged in the American context. This finding illustrates the benefits of a comparative area studies (CAS) framework. A context-sensitive comparison of European and American political development offers a new perspective on the question of institutional endogeneity in Europe, while offering a new take on the question of “why no workers’ parties in the United States?”

This introductory chapter lays the conceptual foundation for the book, defining the citizen marketer approach to political activism and its close connection to the concept of the citizen consumer, as well as its embeddedness in the viral marketing model that is currently being employed by both commercial marketers and myriad political institutions and organizations. The discussion further delineates the persuasion framework of citizen media participation and how it differs from and overlaps with other major frameworks in the existing scholarship. The chapter then turns to an examination of the broader context of promotional culture and the “marketplace of ideas” and how their critiques sensitize us to the risks of trivialization and manipulation that are posed by the citizen marketer approach. Finally, it defines two key concepts, selective forwarding and curatorial agency, which describe the peer-to-peer circulation of preexisting media content as a means of publicizing and promoting political ideas.

Almost one-third of adult Americans will have an anxiety disorder in their lifetime, with enormous personal, societal, and financial costs. Among the most disabling of these disorders are post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social anxiety disorder, generalized anxiety disorder, and panic disorder. Although there are evidence-based treatments for these disorders, as many as 50% of patients do not respond, and there is a considerable need for new therapies. This chapter proposes that the excessive generalization seen in patients with pathological anxiety is due to impaired hippocampal functioning, specifically a deficit in the neural process of pattern separation, which relies upon the dentate gyrus and is sensitive to neurogenesis. Preclinical findings indicate that stimulating DG neurogenesis improves pattern separation and reduces anxiety behaviors in mice. As a result the authors hypothesize that pharmacological or environmental manipulations aimed at stimulating neurogenesis will be beneficial for the treatment of anxiety disorders.

The possibility of using photo-stimulus to control flow in microfluidics devices is very appealing as light can provide contactless stimulation, is biocompatible and can be applied in a non-invasive and highly precise manner. One of the most popular ways to achieve photo-control flow in microfluidic channels is throughout the use of photo-responsive molecules. We review here the different principles and strategies of using photo-responsive molecules to induce or control liquid motion using light, which include the use of photo-controlled polymeric actuators, photo-sensitive coatings, or photo-sensitive surfactants. We further analyse the capability of these approaches to induce flow control throughout the photo-operation of valves, photo-control of electro-osmotic flows or photo-manipulation of discrete microliter-sized droplets.

This chapter discusses perceptions of Moscow’s ‘fifth column’ in the Irish state. While the communist party amounted to little more than an insignificant cult, not all communists declared themselves openly. Significantly, other political strands, particularly the IRA, were seen to be susceptible to communist manipulation. During the Cold War this gave rise to exaggerated fears about communism and its agents. Dublin officials co-operated with the British, and the Americans, in combating communists and their left-wing republican allies. In Northern Ireland, the Communist Party (CPNI) remained extremely weak, but retained influence of some significance within trade union officialdom. And, in Britain, the Connolly Association attempted to organise Irish exiles under the tutelage of the Communist Party of Great Britain (CPGB). The US embassy in Dublin was sensitive to any suggestion of communist activity; Irish and American officials placed intelligence co-operation on a formal footing in 1954.

Social engineering is a process that cyber criminals use to psychologically manipulate an unsuspecting person into divulging sensitive details. Social engineering is an extremely powerful tool that can be deployed to exploit the human's element of security and inherently psychological manipulation. According to a security industry survey, social engineering tops the list of the 10 most popular hacking methods. The first step in any social engineering attack is to collect information about the attacker's target. A social networking site is an online platform that allows users to create a public profile and interact with other users on the website. They are also a hotbed for social engineering cyber attacks to personal information; they are a relevant source of wealth of personal and organisational information that can be found within these social environments. This article defines social engineering and some techniques of social engineering attacks based on social networking sites, drawbacks on a users' privacy, and arising implications.