844 resultados para leave to deliver interrogatories
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Pós-graduação em Desenvolvimento Humano e Tecnologias - IBRC
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Pós-graduação em Agronomia (Energia na Agricultura) - FCA
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Human infections with EHEC such as O157:H7 have been a great concern for worldwide food-industry surveillance. This pathogen is commonly associated with bloody diarrhea that can evolve to the life-threatening hemolytic uremic syndrome. Animals are the natural reservoir where this pathogen remains asymptomatically, in steps of ingestion and colonization of the bowel. The bacterium is shed in the feces, contaminating the surroundings, including water and food that are directed for human consumption. A major player in this colonization process is intimin, an outer membrane adhesion molecule encoded by the E. coli attachment and effacement (eae) gene that has been shown to be essential for intimate bacterial attachment to eukaryotic host cells. In an attempt to reduce the colonization of animal reservoirs with EHEC O157:H7, we designed a vaccine model to induce an immune response against intimin gamma. The model is based on its recombinant expression in attenuated Salmonella, used as a suitable vaccine vector because of its recognized ability to deliver recombinant antigens and to elicit all forms of immunity: mucosal, systemic, and humoral responses. To test this model, mice were orally immunized with a S. enterica serovar Typhimurium strain carrying the pYA3137eaeA vector, and challenged with E. coli O157:H7. Here we show that immunization induced the production of high levels of specific IgG and IgA antibodies and promoted reduction in the fecal shedding of EHEC after challenge. The live recombinant vaccine reported herein may contribute to the efforts of reducing animal intestinal mucosa colonization.
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Over the last decade, Brazil has pioneered an innovative model of branchless banking, known as correspondent banking, involving distribution partnership between banks, several kinds of retailers and a variety of other participants, which have allowed an unprecedented growth in bank outreach and became a reference worldwide. However, despite the extensive number of studies recently developed focusing on Brazilian branchless banking, there exists a clear research gap in the literature. It is still necessary to identify the different business configurations involving network integration through which the branchless banking channel can be structured, as well as the way they relate to the range of bank services delivered. Given this gap, our objective is to investigate the relationship between network integration models and services delivered through the branchless banking channel. Based on twenty interviews with managers involved with the correspondent banking business and data collected on almost 300 correspondent locations, our research is developed in two steps. First, we created a qualitative taxonomy through which we identified three classes of network integration models. Second, we performed a cluster analysis to explain the groups of financial services that fit each model. By contextualizing correspondents' network integration processes through the lens of transaction costs economics, our results suggest that the more suited to deliver social-oriented, "pro-poor'' services the channel is, the more it is controlled by banks. This research offers contributions to managers and policy makers interested in understanding better how different correspondent banking configurations are related with specific portfolios of services. Researchers interested in the subject of branchless banking can also benefit from the taxonomy presented and the transaction costs analysis of this kind of banking channel, which has been adopted in a number of developing countries all over the world now. (C) 2011 Elsevier B.V. All rights reserved.
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Purpose: To evaluate the effectiveness and safety of postoperative low single-dose of beta-irradiation (beta-RT) in pterygium comparing conjunctival autograft (CAG) surgery with CAG plus adjuvant beta-RT in a randomized clinical trial. Methods: This trial was designed as a prospective, randomized, single-center study. Surgery was performed in all cases according to the CAG technique. One hundred and eight pterygia were post-operatively randomized to CAG + beta-RT or CAGalone. In the case of beta-RT, a (90) Sr eye applicator was used to deliver 10 Gy to the sclera surface at a dose rate of between 200 and 250 cGy/min. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. Results: Between February 2008 and September 2008, 116 eyes with primary pterygium were operated on according to the trial protocol. Adjuvant treatment was performed within 24 h post-operatively. Eight patients were lost to follow-up, resulting in 108 patients who could be analyzed. At a mean follow-up of 18 months (range, 8-33), in the 54 eyes randomized to receive CAG + beta-RT, 5 relapses occurred compared with 12 recurrences in the 54 eyes in CAG, for a crude control rate of 90.8 % vs. 78%; p = 0.032, respectively. The treatment complications as hyperemia, total dehiscence of the autograft and dellen were significantly more frequent in the CAG (p < 0.05). The arm of beta-RT resulted in better cosmetic results and improves of symptoms than CAG. Conclusions: A low single-dose of beta-RT of 10 Gy after CAG surgery was a simple, effective, and safe treatment that reduced the risk of primary pterygium recurrence, improved symptoms after surgery, resulting in a better cosmetic effect than only CAG. (C) 2012 Elsevier Inc.
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Abstract Background Particulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the other hand, cationic compounds and assemblies exhibit a general antimicrobial action. In this work, cationic nanoparticles built from drug, cationic lipid and polyelectrolytes are shown to be excellent and active carriers of amphotericin B against C. albicans. Results Assemblies of amphotericin B and cationic lipid at extreme drug to lipid molar ratios were wrapped by polyelectrolytes forming cationic nanoparticles of high colloid stability and fungicidal activity against Candida albicans. Experimental strategy involved dynamic light scattering for particle sizing, zeta-potential analysis, colloid stability, determination of AmB aggregation state by optical spectra and determination of activity against Candida albicans in vitro from cfu countings. Conclusion Novel and effective cationic particles delivered amphotericin B to C. albicans in vitro with optimal efficiency seldom achieved from drug, cationic lipid or cationic polyelectrolyte in separate. The multiple assembly of antibiotic, cationic lipid and cationic polyelctrolyte, consecutively nanostructured in each particle produced a strategical and effective attack against the fungus cells.
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Most amniotes vertebrates have an intromittent organ to deliver semen. The reptile Sphenodon and most birds lost the ancestral penis and developed a cloaca-cloaca mating. Known as hemipenises, the copulatory organ of Squamata shows unique features between the amniotes intromittent organ. They are the only paired intromittent organs across amniotes and are fully inverted and encapsulated in the tail when not in use. The histology and ultrastructure of the hemipenes of Crotalus durissus rattlesnake is described as the evolutionary implications of the main features discussed. The organization of hemipenis of Crotalus durissus terrificus in two concentric corpora cavernosa is similar to other Squamata but differ markedly from the organization of the penis found in crocodilians, testudinata, birds and mammals. Based on the available data, the penis of the ancestral amniotes was made of connective tissue and the incorporation of smooth muscle in the framework of the sinusoids occurred independently in mammals and Crotalus durissus. The propulsor action of the muscle retractor penis basalis was confirmed and therefore the named should be changed to musculus hemipenis propulsor.The retractor penis magnus found in Squamata has no homology to the retractor penis of mammals, although both are responsible for the retraction of the copulatory organ
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The wide use of e-technologies represents a great opportunity for underserved segments of the population, especially with the aim of reintegrating excluded individuals back into society through education. This is particularly true for people with different types of disabilities who may have difficulties while attending traditional on-site learning programs that are typically based on printed learning resources. The creation and provision of accessible e-learning contents may therefore become a key factor in enabling people with different access needs to enjoy quality learning experiences and services. Another e-learning challenge is represented by m-learning (which stands for mobile learning), which is emerging as a consequence of mobile terminals diffusion and provides the opportunity to browse didactical materials everywhere, outside places that are traditionally devoted to education. Both such situations share the need to access materials in limited conditions and collide with the growing use of rich media in didactical contents, which are designed to be enjoyed without any restriction. Nowadays, Web-based teaching makes great use of multimedia technologies, ranging from Flash animations to prerecorded video-lectures. Rich media in e-learning can offer significant potential in enhancing the learning environment, through helping to increase access to education, enhance the learning experience and support multiple learning styles. Moreover, they can often be used to improve the structure of Web-based courses. These highly variegated and structured contents may significantly improve the quality and the effectiveness of educational activities for learners. For example, rich media contents allow us to describe complex concepts and process flows. Audio and video elements may be utilized to add a “human touch” to distance-learning courses. Finally, real lectures may be recorded and distributed to integrate or enrich on line materials. A confirmation of the advantages of these approaches can be seen in the exponential growth of video-lecture availability on the net, due to the ease of recording and delivering activities which take place in a traditional classroom. Furthermore, the wide use of assistive technologies for learners with disabilities injects new life into e-learning systems. E-learning allows distance and flexible educational activities, thus helping disabled learners to access resources which would otherwise present significant barriers for them. For instance, students with visual impairments have difficulties in reading traditional visual materials, deaf learners have trouble in following traditional (spoken) lectures, people with motion disabilities have problems in attending on-site programs. As already mentioned, the use of wireless technologies and pervasive computing may really enhance the educational learner experience by offering mobile e-learning services that can be accessed by handheld devices. This new paradigm of educational content distribution maximizes the benefits for learners since it enables users to overcome constraints imposed by the surrounding environment. While certainly helpful for users without disabilities, we believe that the use of newmobile technologies may also become a fundamental tool for impaired learners, since it frees them from sitting in front of a PC. In this way, educational activities can be enjoyed by all the users, without hindrance, thus increasing the social inclusion of non-typical learners. While the provision of fully accessible and portable video-lectures may be extremely useful for students, it is widely recognized that structuring and managing rich media contents for mobile learning services are complex and expensive tasks. Indeed, major difficulties originate from the basic need to provide a textual equivalent for each media resource composing a rich media Learning Object (LO). Moreover, tests need to be carried out to establish whether a given LO is fully accessible to all kinds of learners. Unfortunately, both these tasks are truly time-consuming processes, depending on the type of contents the teacher is writing and on the authoring tool he/she is using. Due to these difficulties, online LOs are often distributed as partially accessible or totally inaccessible content. Bearing this in mind, this thesis aims to discuss the key issues of a system we have developed to deliver accessible, customized or nomadic learning experiences to learners with different access needs and skills. To reduce the risk of excluding users with particular access capabilities, our system exploits Learning Objects (LOs) which are dynamically adapted and transcoded based on the specific needs of non-typical users and on the barriers that they can encounter in the environment. The basic idea is to dynamically adapt contents, by selecting them from a set of media resources packaged in SCORM-compliant LOs and stored in a self-adapting format. The system schedules and orchestrates a set of transcoding processes based on specific learner needs, so as to produce a customized LO that can be fully enjoyed by any (impaired or mobile) student.
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Matita (that means pencil in Italian) is a new interactive theorem prover under development at the University of Bologna. When compared with state-of-the-art proof assistants, Matita presents both traditional and innovative aspects. The underlying calculus of the system, namely the Calculus of (Co)Inductive Constructions (CIC for short), is well-known and is used as the basis of another mainstream proof assistant—Coq—with which Matita is to some extent compatible. In the same spirit of several other systems, proof authoring is conducted by the user as a goal directed proof search, using a script for storing textual commands for the system. In the tradition of LCF, the proof language of Matita is procedural and relies on tactic and tacticals to proceed toward proof completion. The interaction paradigm offered to the user is based on the script management technique at the basis of the popularity of the Proof General generic interface for interactive theorem provers: while editing a script the user can move forth the execution point to deliver commands to the system, or back to retract (or “undo”) past commands. Matita has been developed from scratch in the past 8 years by several members of the Helm research group, this thesis author is one of such members. Matita is now a full-fledged proof assistant with a library of about 1.000 concepts. Several innovative solutions spun-off from this development effort. This thesis is about the design and implementation of some of those solutions, in particular those relevant for the topic of user interaction with theorem provers, and of which this thesis author was a major contributor. Joint work with other members of the research group is pointed out where needed. The main topics discussed in this thesis are briefly summarized below. Disambiguation. Most activities connected with interactive proving require the user to input mathematical formulae. Being mathematical notation ambiguous, parsing formulae typeset as mathematicians like to write down on paper is a challenging task; a challenge neglected by several theorem provers which usually prefer to fix an unambiguous input syntax. Exploiting features of the underlying calculus, Matita offers an efficient disambiguation engine which permit to type formulae in the familiar mathematical notation. Step-by-step tacticals. Tacticals are higher-order constructs used in proof scripts to combine tactics together. With tacticals scripts can be made shorter, readable, and more resilient to changes. Unfortunately they are de facto incompatible with state-of-the-art user interfaces based on script management. Such interfaces indeed do not permit to position the execution point inside complex tacticals, thus introducing a trade-off between the usefulness of structuring scripts and a tedious big step execution behavior during script replaying. In Matita we break this trade-off with tinycals: an alternative to a subset of LCF tacticals which can be evaluated in a more fine-grained manner. Extensible yet meaningful notation. Proof assistant users often face the need of creating new mathematical notation in order to ease the use of new concepts. The framework used in Matita for dealing with extensible notation both accounts for high quality bidimensional rendering of formulae (with the expressivity of MathMLPresentation) and provides meaningful notation, where presentational fragments are kept synchronized with semantic representation of terms. Using our approach interoperability with other systems can be achieved at the content level, and direct manipulation of formulae acting on their rendered forms is possible too. Publish/subscribe hints. Automation plays an important role in interactive proving as users like to delegate tedious proving sub-tasks to decision procedures or external reasoners. Exploiting the Web-friendliness of Matita we experimented with a broker and a network of web services (called tutors) which can try independently to complete open sub-goals of a proof, currently being authored in Matita. The user receives hints from the tutors on how to complete sub-goals and can interactively or automatically apply them to the current proof. Another innovative aspect of Matita, only marginally touched by this thesis, is the embedded content-based search engine Whelp which is exploited to various ends, from automatic theorem proving to avoiding duplicate work for the user. We also discuss the (potential) reusability in other systems of the widgets presented in this thesis and how we envisage the evolution of user interfaces for interactive theorem provers in the Web 2.0 era.
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A single picture provides a largely incomplete representation of the scene one is looking at. Usually it reproduces only a limited spatial portion of the scene according to the standpoint and the viewing angle, besides it contains only instantaneous information. Thus very little can be understood on the geometrical structure of the scene, the position and orientation of the observer with respect to it remaining also hard to guess. When multiple views, taken from different positions in space and time, observe the same scene, then a much deeper knowledge is potentially achievable. Understanding inter-views relations enables construction of a collective representation by fusing the information contained in every single image. Visual reconstruction methods confront with the formidable, and still unanswered, challenge of delivering a comprehensive representation of structure, motion and appearance of a scene from visual information. Multi-view visual reconstruction deals with the inference of relations among multiple views and the exploitation of revealed connections to attain the best possible representation. This thesis investigates novel methods and applications in the field of visual reconstruction from multiple views. Three main threads of research have been pursued: dense geometric reconstruction, camera pose reconstruction, sparse geometric reconstruction of deformable surfaces. Dense geometric reconstruction aims at delivering the appearance of a scene at every single point. The construction of a large panoramic image from a set of traditional pictures has been extensively studied in the context of image mosaicing techniques. An original algorithm for sequential registration suitable for real-time applications has been conceived. The integration of the algorithm into a visual surveillance system has lead to robust and efficient motion detection with Pan-Tilt-Zoom cameras. Moreover, an evaluation methodology for quantitatively assessing and comparing image mosaicing algorithms has been devised and made available to the community. Camera pose reconstruction deals with the recovery of the camera trajectory across an image sequence. A novel mosaic-based pose reconstruction algorithm has been conceived that exploit image-mosaics and traditional pose estimation algorithms to deliver more accurate estimates. An innovative markerless vision-based human-machine interface has also been proposed, so as to allow a user to interact with a gaming applications by moving a hand held consumer grade camera in unstructured environments. Finally, sparse geometric reconstruction refers to the computation of the coarse geometry of an object at few preset points. In this thesis, an innovative shape reconstruction algorithm for deformable objects has been designed. A cooperation with the Solar Impulse project allowed to deploy the algorithm in a very challenging real-world scenario, i.e. the accurate measurements of airplane wings deformations.
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Human reactions to vibration have been extensively investigated in the past. Vibration, as well as whole-body vibration (WBV), has been commonly considered as an occupational hazard for its detrimental effects on human condition and comfort. Although long term exposure to vibrations may produce undesirable side-effects, a great part of the literature is dedicated to the positive effects of WBV when used as method for muscular stimulation and as an exercise intervention. Whole body vibration training (WBVT) aims to mechanically activate muscles by eliciting neuromuscular activity (muscle reflexes) via the use of vibrations delivered to the whole body. The most mentioned mechanism to explain the neuromuscular outcomes of vibration is the elicited neuromuscular activation. Local tendon vibrations induce activity of the muscle spindle Ia fibers, mediated by monosynaptic and polysynaptic pathways: a reflex muscle contraction known as the Tonic Vibration Reflex (TVR) arises in response to such vibratory stimulus. In WBVT mechanical vibrations, in a range from 10 to 80 Hz and peak to peak displacements from 1 to 10 mm, are usually transmitted to the patient body by the use of oscillating platforms. Vibrations are then transferred from the platform to a specific muscle group through the subject body. To customize WBV treatments, surface electromyography (SEMG) signals are often used to reveal the best stimulation frequency for each subject. Use of SEMG concise parameters, such as root mean square values of the recordings, is also a common practice; frequently a preliminary session can take place in order to discover the more appropriate stimulation frequency. Soft tissues act as wobbling masses vibrating in a damped manner in response to mechanical excitation; Muscle Tuning hypothesis suggest that neuromuscular system works to damp the soft tissue oscillation that occurs in response to vibrations; muscles alters their activity to dampen the vibrations, preventing any resonance phenomenon. Muscle response to vibration is however a complex phenomenon as it depends on different parameters, like muscle-tension, muscle or segment-stiffness, amplitude and frequency of the mechanical vibration. Additionally, while in the TVR study the applied vibratory stimulus and the muscle conditions are completely characterised (a known vibration source is applied directly to a stretched/shortened muscle or tendon), in WBV study only the stimulus applied to a distal part of the body is known. Moreover, mechanical response changes in relation to the posture. The transmissibility of vibratory stimulus along the body segment strongly depends on the position held by the subject. The aim of this work was the investigation on the effects that the use of vibrations, in particular the effects of whole body vibrations, may have on muscular activity. A new approach to discover the more appropriate stimulus frequency, by the use of accelerometers, was also explored. Different subjects, not affected by any known neurological or musculoskeletal disorders, were voluntarily involved in the study and gave their informed, written consent to participate. The device used to deliver vibration to the subjects was a vibrating platform. Vibrations impressed by the platform were exclusively vertical; platform displacement was sinusoidal with an intensity (peak-to-peak displacement) set to 1.2 mm and with a frequency ranging from 10 to 80 Hz. All the subjects familiarized with the device and the proper positioning. Two different posture were explored in this study: position 1 - hack squat; position 2 - subject standing on toes with heels raised. SEMG signals from the Rectus Femoris (RF), Vastus Lateralis (VL) and Vastus medialis (VM) were recorded. SEMG signals were amplified using a multi-channel, isolated biomedical signal amplifier The gain was set to 1000 V/V and a band pass filter (-3dB frequency 10 - 500 Hz) was applied; no notch filters were used to suppress line interference. Tiny and lightweight (less than 10 g) three-axial MEMS accelerometers (Freescale semiconductors) were used to measure accelerations of onto patient’s skin, at EMG electrodes level. Accelerations signals provided information related to individuals’ RF, Biceps Femoris (BF) and Gastrocnemius Lateralis (GL) muscle belly oscillation; they were pre-processed in order to exclude influence of gravity. As demonstrated by our results, vibrations generate peculiar, not negligible motion artifact on skin electrodes. Artifact amplitude is generally unpredictable; it appeared in all the quadriceps muscles analysed, but in different amounts. Artifact harmonics extend throughout the EMG spectrum, making classic high-pass filters ineffective; however, their contribution was easy to filter out from the raw EMG signal with a series of sharp notch filters centred at the vibration frequency and its superior harmonics (1.5 Hz wide). However, use of these simple filters prevents the revelation of EMG power potential variation in the mentioned filtered bands. Moreover our experience suggests that the possibility of reducing motion artefact, by using particular electrodes and by accurately preparing the subject’s skin, is not easily viable; even though some small improvements were obtained, it was not possible to substantially decrease the artifact. Anyway, getting rid of those artifacts lead to some true EMG signal loss. Nevertheless, our preliminary results suggest that the use of notch filters at vibration frequency and its harmonics is suitable for motion artifacts filtering. In RF SEMG recordings during vibratory stimulation only a little EMG power increment should be contained in the mentioned filtered bands due to synchronous electromyographic activity of the muscle. Moreover, it is better to remove the artifact that, in our experience, was found to be more than 40% of the total signal power. In summary, many variables have to be taken into account: in addition to amplitude, frequency and duration of vibration treatment, other fundamental variables were found to be subject anatomy, individual physiological condition and subject’s positioning on the platform. Studies on WBV treatments that include surface EMG analysis to asses muscular activity during vibratory stimulation should take into account the presence of motion artifacts. Appropriate filtering of artifacts, to reveal the actual effect on muscle contraction elicited by vibration stimulus, is mandatory. However as a result of our preliminary study, a simple multi-band notch filtering may help to reduce randomness of the results. Muscle tuning hypothesis seemed to be confirmed. Our results suggested that the effects of WBV are linked to the actual muscle motion (displacement). The greater was the muscle belly displacement the higher was found the muscle activity. The maximum muscle activity has been found in correspondence with the local mechanical resonance, suggesting a more effective stimulation at the specific system resonance frequency. Holding the hypothesis that muscle activation is proportional to muscle displacement, treatment optimization could be obtained by simply monitoring local acceleration (resonance). However, our study revealed some short term effects of vibratory stimulus; prolonged studies should be assembled in order to consider the long term effectiveness of these results. Since local stimulus depends on the kinematic chain involved, WBV muscle stimulation has to take into account the transmissibility of the stimulus along the body segment in order to ensure that vibratory stimulation effectively reaches the target muscle. Combination of local resonance and muscle response should also be further investigated to prevent hazards to individuals undergoing WBV treatments.
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Die vorliegende Arbeit sollte weitere Erkenntnisse zum Abflussverhalten forstlich genutzter Standorte im Einzugsgebiet der Nahe liefern. Zu diesem Zweck wurde das 12,73 km² umfassenden Einzugsgebietes des Oberen Gräfenbaches als Untersuchungsgebiet ausgewählt, das im fast ausschließlich waldbestandenen Soonwald lokalisiert ist. Das Einzugsgebiet wurde ab 1999 mit einem hydrometeorologischen Messnetz ausgestattet. Zusammen mit Geländebeobachtungen des Abflussgeschehens und einer Aufnahme der physiogeographischen Gebietseigenschaften wurde eine Analyse des Abflussverhaltens möglich. Die Analysen umfassten die grundlegende quantitative Auswertung der erhobenen Zeitreihen mit Hilfe statistisch-mathematischer Verfahren und die Nachbildung der hydrologischen Prozesse mit Hilfe des Modells MMS/PRMS. Die räumliche Diskretisierung des Gebietes erfolgte dabei durch Ausweisung von Hydrological Response Units (HRUs). Die Nachbildung des Ist-Zustandes wurde durch Rechnung mehrerer Landnutzungsszenarien ergänzt. Die Untersuchungen zeigten die enorme Variabilität der Gebietsabflüsse bei insgesamt hohen Jahresabflussvolumina auf. Zwischen den einzelnen Hangbereichen bestehen dabei grundlegende Unterschiede, die sowohl die Abflussbildungsprozesse als auch den Abflussgang betreffen. Im Rahmen der Landnutzungsszenarien wurde aufbauend deutlich, dass sich eine Veränderung der forstlichen Bestandeszusammensetzung nur nachrangig auf die Abflussentstehung auswirkt.
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We deal with five problems arising in the field of logistics: the Asymmetric TSP (ATSP), the TSP with Time Windows (TSPTW), the VRP with Time Windows (VRPTW), the Multi-Trip VRP (MTVRP), and the Two-Echelon Capacitated VRP (2E-CVRP). The ATSP requires finding a lest-cost Hamiltonian tour in a digraph. We survey models and classical relaxations, and describe the most effective exact algorithms from the literature. A survey and analysis of the polynomial formulations is provided. The considered algorithms and formulations are experimentally compared on benchmark instances. The TSPTW requires finding, in a weighted digraph, a least-cost Hamiltonian tour visiting each vertex within a given time window. We propose a new exact method, based on new tour relaxations and dynamic programming. Computational results on benchmark instances show that the proposed algorithm outperforms the state-of-the-art exact methods. In the VRPTW, a fleet of identical capacitated vehicles located at a depot must be optimally routed to supply customers with known demands and time window constraints. Different column generation bounding procedures and an exact algorithm are developed. The new exact method closed four of the five open Solomon instances. The MTVRP is the problem of optimally routing capacitated vehicles located at a depot to supply customers without exceeding maximum driving time constraints. Two set-partitioning-like formulations of the problem are introduced. Lower bounds are derived and embedded into an exact solution method, that can solve benchmark instances with up to 120 customers. The 2E-CVRP requires designing the optimal routing plan to deliver goods from a depot to customers by using intermediate depots. The objective is to minimize the sum of routing and handling costs. A new mathematical formulation is introduced. Valid lower bounds and an exact method are derived. Computational results on benchmark instances show that the new exact algorithm outperforms the state-of-the-art exact methods.
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Clostridium difficile, der Auslöser der nosokomialen Antibiotika-assoziierten Durchfälle und der Pseudomembranösen Kolitis, besitzt zwei Hauptvirulenzfaktoren: die Toxine A und B. In vorangegangenen Veröffentlichungen wurde gezeigt, dass Toxin B durch einen zytosolischen Faktor der eukaryotischen Zielzelle während des Aufnahmeweges in die Zelle gespalten wird. Nur die N-terminale katalytische Domäne erreicht das Zytosol. Hierbei wurde davon ausgegangen, dass eine Protease der Zielzelle die Spaltung katalysiert. In dieser Arbeit konnte gezeigt werden, dass die Spaltung von Toxin B ein intramolekularer Prozess ist, der zytosolisches Inositolphosphat der Zielzelle als Kofaktor zur Aktivierung der intrinsischen Protease benötigt. Die Freisetzung der katalytischen Domäne durch Inositolphosphat-induzierte Spaltung ist nicht nur das Prinzip des Clostridium difficile Toxin B sondern auch des Toxin A, als auch des alpha Toxin von Clostridium novyi und das Letale Toxin von Clostridium sordellii. Der kovalente Inhibitor von Aspartatproteasen 1,2-epoxy-3-(p-nitrophenoxy)propan (EPNP), wurde dazu verwendet die intrinsische Protease von Toxin B zu blockieren und ermöglichte die Identifikation des katalytischen Zentrums. EPNP modifiziertes Toxin B verliert die intrinsische Proteaseaktivität und Zytotoxizität, aber wenn es direkt in das Zytosol der Wirtszelle injiziert ist, bleibt die Toxizität erhalten. Diese ist damit der erste Bericht eines bakteriellen Toxins, das eukaryotische Signale zur induzierten Autoproteolyse nutzt, um seine katalytisch-toxische Domäne in das Zytosol der Zielzelle freizusetzen. Durch diese Ergebnisse kann das Modell der Toxin-Prozessierung nun um einen weiteren entscheidenden Schritt vervollständigt werden.
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Beamforming entails joint processing of multiple signals received or transmitted by an array of antennas. This thesis addresses the implementation of beamforming in two distinct systems, namely a distributed network of independent sensors, and a broad-band multi-beam satellite network. With the rising popularity of wireless sensors, scientists are taking advantage of the flexibility of these devices, which come with very low implementation costs. Simplicity, however, is intertwined with scarce power resources, which must be carefully rationed to ensure successful measurement campaigns throughout the whole duration of the application. In this scenario, distributed beamforming is a cooperative communication technique, which allows nodes in the network to emulate a virtual antenna array seeking power gains in the order of the size of the network itself, when required to deliver a common message signal to the receiver. To achieve a desired beamforming configuration, however, all nodes in the network must agree upon the same phase reference, which is challenging in a distributed set-up where all devices are independent. The first part of this thesis presents new algorithms for phase alignment, which prove to be more energy efficient than existing solutions. With the ever-growing demand for broad-band connectivity, satellite systems have the great potential to guarantee service where terrestrial systems can not penetrate. In order to satisfy the constantly increasing demand for throughput, satellites are equipped with multi-fed reflector antennas to resolve spatially separated signals. However, incrementing the number of feeds on the payload corresponds to burdening the link between the satellite and the gateway with an extensive amount of signaling, and to possibly calling for much more expensive multiple-gateway infrastructures. This thesis focuses on an on-board non-adaptive signal processing scheme denoted as Coarse Beamforming, whose objective is to reduce the communication load on the link between the ground station and space segment.