<p>To maintain homeostasis, T lymphocytes die through caspase&ndash;dependent apoptosis. However, blockage of caspase activity in T lymphocytes does not increase cell survival. The loss of caspase 8 activity leads to programmed necrosis (necroptosis) upon T cell receptor (TCR) stimulation in T lymphocytes. Necroptosis is correlated with excessive macroautophagy, an intracellular catabolic process characterized by the sequestration of cytoplasmic compartments through double&ndash;membrane vacuoles. Meanwhile, the proper induction of macroautophagy is required for T lymphocyte survival and function. Cellular caspase 8 (FLICE)&ndash;like inhibitory protein (c&ndash;FLIP) promotes survival in T lymphocytes. c&ndash;FLIP suppresses death receptor&ndash;induced apoptosis by modulating caspase 8 activation. Whether this modulation plays a role in the regulation of necroptosis has yet to be studied. Additionally, overexpression of c&ndash;FLIP reduces autophagy induction and promotes cell survival in cell lines. It remains unclear whether c&ndash;FLIP protects primary T lymphocytes by regulating the threshold at which autophagy occurs. In this study, c&ndash;FLIP isoform&ndash;specific conditional deletion models were used to study the role of c&ndash;FLIP in necroptosis and autophagy in primary T lymphocytes.</p><p>Our results showed that the long isoform of c&ndash;FLIP (c&ndash; FLIP_L) regulates necroptosis by inhibiting receptor interacting protein 1 (RIP&ndash;1). Upon TCR stimulation, c&ndash;FLIP_L&ndash;deficient T cells underwent RIP&ndash;1&ndash;dependent necroptosis. Interestingly, though previous studies have generally described necroptosis in the absence of caspase 8 activity and apoptosis, pro&ndash;apoptotic caspase 8 activity and the rate of apoptosis were also increased in c&ndash;FLIPL&ndash;deficient T lymphocytes. Moreover, c&ndash; FLIP_L&ndash;deficient T cells exhibited enhanced autophagy, which served a cytoprotective function. </p><p>Apoptosis can be induced by either death receptors on the plasma membrane (extrinsic pathway), or the damage of the genome and/or cellular organelles (intrinsic pathway). Previous studies in c&ndash;FLIP&ndash;deficient T lymphocytes suggested that c&ndash;FLIP promotes cell survival in the absence of death receptor signals. Independent of death receptor signaling, mitochondria sense apoptotic stimuli and mediate the activation of caspases. Whether c&ndash;FLIP regulates mitochondrion&ndash;dependent apoptotic signaling remains unknown. Here, by deleting the <italic>c&ndash;Flip <italic> gene in mature T lymphocytes, we showed a role for c&ndash;FLIP in the intrinsic apoptosis pathway. In naïve T cells stimulated with the apoptosis inducer, c&ndash;FLIP suppressed cytochrome c release from mitochondria. Bim&ndash;deletion rescued the enhanced apoptosis in c&ndash;FLIP&ndash;deficient T cells, while inhibition of caspase 8 did not. Different from activated T cells, there were no signs of necroptosis in c&ndash;FLIP&ndash;deficient naïve T cells. Together, our findings indicate that c&ndash;FLIP is a key regulator of apoptosis, necroptosis and autophagy in T lymphocytes.</p> / Dissertation

No description available.

One central question of neuroscience asks how a neural system can generate the diversity of complex behaviors needed to meet the range of possible demands placed on an organism by an ever changing environment. In many cases, it appears that animals assemble complex behaviors by recombining sets of simpler behaviors known as behavioral primitives. The crawling behavior of the nematode worm Caenorhabditis elegans represents a classic example of such an approach since worms use the simple behaviors of forward and reverse locomotion to assemble more complex behaviors such as search and escape. The relative simplicity and well-described anatomy of the worm nervous system combined with a high degree of genetic tractability make C. elegans an attractive organism with which to study the neural circuits responsible for assembling behavioral primitives into complex behaviors. Unfortunately, difficulty probing the physiological properties of central synapses in C. elegans has left this opportunity largely unfulfilled. In this dissertation we address this challenge by developing techniques that combine whole-cell patch clamp recordings with optical stimulation of neurons. We do this using transgenic worms that express the light-sensitive ion channel Channelrhodopsin-2 (ChR2) in putative pre-synaptic neurons and fluorescent protein reporters in the post-synaptic neurons to be targeted by electrodes. We first apply this new approach to probe C. elegans circuitry in chapter II where we test for connectivity between nociceptive neurons known as ASH required for sensing aversive stimuli, and premotor neurons required for generating backward locomotion, known as AVA. In chapter III we extend our analysis of the C. elegans locomotory circuit to the premotor neurons required for generating forward locomotion, known as AVB. We identify inhibitory synaptic connectivity between ASH and AVB and between the two types of premotor neurons, AVA and AVB. Finally, we use our observations to develop a biophysical model of the locomotory circuit in which switching emerges from the attractor dynamics of the network. Primitive selection in C. elegans may thus represent an accessible system to test kinetic theories of decision making. This dissertation includes previously published co-authored material.

Some techniques are presented to permit the implementation of asynchronous sequential circuits using standard flip-flops. An algorithm is presented for the RS flip-flop, and it is shown that any flow table may be realized using the algorithm (the flow table is assumed to be realizable using standard logic gates). The approach is shown to be directly applicable to synchronous circuits, and transition flip-flops (JK, D, and T) are analyzed using the ideas developed. Constraints are derived for the flow tables to meet to be realizable using transition flip-flops in asynchronous situations, and upper and lower bounds on the number of transition flip-flops required to implement a given flow table are stated.

A series of Basic Assembler Language subroutines were developed and made available to the FORTRAN IV language processor which makes list processing possible in a flexible and easily understood way. The subroutine will create and maintain list structures in the computer's core storage. The subroutines are sufficiently general to permit FORTRAN programmers to tailor list processing routines to their own individual requirements. List structure sizes are limited only by the amount of core storage available. (61 pages)

The successful synthesis of a family of donor-iridium complex-acceptor triads (T1–T6, pMV1 and mMV1) and their electrochemical and photophysical properties were presented in this work. Triarylamines (TAA) were used as donors and naphthalene diimide (NDI) as acceptor. A bis-cyclometalated phenylpyrazole iridium dipyrrin complex acts as a photosensitiser. In addition, a molecular structure of T1 was obtained by single crystal X-ray diffraction. Transient absorption spectroscopy experiments of these triads resembled that upon excitation a photoinduced electron transfer efficiently generates long-lived, charge-separated (CS) states. Thereby, the electron-transfer mechanism depends on the excitation energy. The presence of singlet and triplet CS states was clarified by magnetic-field dependent transient-absorption spectroscopy in the nanosecond time regime. It was demonstrated that the magnetic field effect of charge-recombination kinetics showed for the first time a transition from the coherent to the incoherent spin-flip regime. The lifetime of the CS states could be drastically prolonged by varying the spacer between the iridium complex and the NDI unit by using a biphenyl instead of a phenylene unit in T4. A mixed-valence (MV) state of two TAA donors linked to an iridium metal centre were generated upon photoexcitation of triad pMV1 and mMV1. The mixed-valence character in these triads was proven by the analysis of an intervalence charge-transfer (IV-CT) band in the (near-infrared) NIR spectral region by femtosecond pump-probe experiments. These findings were supported by TD-DFT calculations. The synthesis of dyads (D1–D4) was performed. Thereby the dipyrrin ligand was substituted with electron withdrawing groups. The electrochemical and photophysical characterisation revealed that in one case (D4) it was possible to generate a CS state upon photoexcitation. / In dieser Arbeit wurden die erfolgreiche Synthese einer Donor-Iridiumkomplex-Akzeptor-Familie (Triaden T1–T6, pMV1 und mMV1) und deren elektrochemischen und photophyiskalischen Eigenschaften vorgestellt. Als Donor wurden Triarylamine (TAA) verwendet, als Akzeptoreinheit diente ein Naphthalin-Diimid (NDI). Ein bis-cyclometallierter Phenylpyrazol-Iridium-Dipyrrin-Komplex übernahm die Aufgabe des Photosensibilisators. Die synthetischen Arbeiten konnten mit einer molekularen Struktur von T1 mittels Röntgenbeugung eines Einkristalls ergänzt werden. Bei Photoanregung der Triaden mit transienter Absorptions-Spektroskopie wurde die sehr effiziente Bildung von langlebigen, ladungsgetrennten (CS) Zuständen beobachtet. Es wurde zudem herausgefunden, dass der Elektronentransfer (ET)-Mechanismus von der verwendeten Anregungswellenlänge abhängt. Der Nachweis von Singulett und Triplett CS-Zuständen wurde mittels magnetfeldabhängiger, transienter Absorptions-Spektroskopie erbracht. Eine Analyse des Magnetfeldeffekts der Ladungsrekombinations-Kinetik zeigte zum ersten Mal einen Übergang von einem kohärenten zu einem inkohärenten Spinumkehrprozess. Die Lebenszeit des CS-Zustandes ließ sich dramatisch verlängern indem die Phenylen- durch eine Biphenyl-Brückeneinheit zwischen dem Iridiumkomplex und dem NDI ersetzt wurde. Gemischvalente Zustände konnten mittels photinduziertem Elektronentransfer in den Triaden pMV1 und mMV1 erzeugt werden. Im Fall von pMV1 wurde eine intensive Intervalenz-Ladungstransfer (IV-CT) Bande im nahinfraroten Spektralbereich mittels Femtosekunden transienter Anregungs-Abfrage-Spektroskopie beobachtet werden. Die Analyse dieser IV-CT Bande wurde mit TD-DFT Rechnungen vervollständigt. Die Synthese von Dyaden (D1–D4) wurde erfolgreich durchgeführt, dabei wurde der Dipyrrin-Ligand mit elektronenziehenden Substituenten versehen. Die spektroskopische und elektrochemische Analyse erbrachte nach erfolgter Lichtanregung in einem Fall (D4) ebenfalls einen CS-Zustand.

A key feature of recent agricultural extension programs has been the focus on increased participation for local, rural communities in the overall decision-making process. This move towards increasing community participation has raised expectations in terms of communication: communication between central research facilities and rural communities, between rural communities and central research facilities, and amongst the rural communities themselves. In order to provide effective communication along each of these channels, attention is turning to the extension trainers deployed in the field. For extension trainers this emerging communication role is distinct from, and supplementary to, the conventional technical training function. The thesis highlights the lack of effective training in communication skills in existing extension training programs. It identifies the flip chart as the most widely used visual aid for farmer training, and the overhead projector as the most widely used visual aid for in-service training. The thesis develops a comprehensive set of training competencies and content for teaching those two technologies, derived from individual task analyses and an extensive literature review. A range of strategic alternatives for the delivery of those competencies in a developing country are then formulated and examined. Central to the different strategies considered is the use of interactive multimedia as a key delivery technology. Two proprietary CDROMs have been designed and produced specifically to the support training in the design and production skills for overhead projector and flip chart technologies. The design, content and production of the CDROMs is described, and both technical and user evaluations are presented. The two CDROMs have been field-tested in Sri Lanka, across a broad range of strategic alternatives. The outcome is a set of guidelines and specific structures for training programs in overhead projector and flip chart technologies. The guidelines are generic and broadly applicable. The case studies also indicate a particular subset of preferred strategies for the future deployment of interactive multimedia-based training in developing countries. Most specifically, the thesis indicates a balance between and the need for mix of interactive multimedia modules along with face-to-face training support / Doctor of Philosophy (PhD)

In recent years, even though the light output of GaN-based LED continues to increase, the brightness (~20 lm/W) is still low compared to conventional lighting systems and it is necessary to further improve the light extraction of LEDs. In this study, we utilize flip-chip technique, photoresist microlenses, reflectors and thermoelectric cooler to increase the light extraction of GaN MQW LED. Electroluminescence (EL) and power angular distribution are used to measure the light output intensity of LED. From temperature dependent current-voltage (I-V-T) characteristics, the charge carrier transport mechanisms at different biased regions are also investigated. In the results, back emission of LED with SiO2/Al reflector has maximum light intensity ( 3.28£gW ) , which is higher than front emission one ( 2.73£gW ) in vertical emitting area ( at 90 angles). LED with P.R. microlenses (refractive index, n=1.62) on backside could improve the light extraction of LED (about 1.2 times) as well. The enhancement of light output is duo to the reduction of light absorption from the metal contact and Fresnel¡¦s transmission losses at GaN (n=2.4)/air (n=1) interface. Finally, we fabricate a high brightness LED with above light enhancement design. EL intensity of LED is increased about 1.25 times than conventional one. Therefore, we can manufacture a LEDs array with above designs to obtain high light output for future solid-state illumination.

To calculate the characteristics of electronic parts is divided by 1.Chip. 2.Assembly, i.e. package. 3. PCB (Printed Circuit Board). Analizing the electrical characteristics of package needs consideration from all system can distinguish the influence of function. Although the analysis method may be change but we can get the characteristics results from the parameters of circuit element (i.e. Resistance, Inductance, Capacitance). Different measurement or modeling technology can prove that the list data is correct. That moisture in plastic packages can cause cracking or delamination during the surface mount assembly process. During this process, the packages are heated to 220-240¢J. At these temperatures, any moisture present in the plastic vaporizes and exerts stresses in the package, which can cause delamination between the mold compound and the leadframe or die. The mismatch in thermal expansion coefficients of the package¡¦s components also induces stresses. If these combined stresses are greater than the fracture strength of the plastic, cracks will form. The susceptibility of a package to cracking depends on: 1.amount of absorbed moisture, 2.die size, 3.package design, 4.mold compound characteristics, 5.solder reflow temperature profile. Widely, flip chip technology is defined as mounting the chip to a substrate with any kind of materials and methods, as long as the chip surface (active area) is facing to the substrate. The advantages of FC-BGA is¡G1.Efficient use of PCB area. 2.Area array access for high I/O device. 3.Allow for finer pitches. 4.Fewer joints. 5.Better performance of high frequency application. 6.FC is and will be lowest cost.

Abstract The thesis is aimed to analyze the flip chip in chip scale package (CSP) by finite element method incorporated with software ANSYS due to thermally cyclic loading. The coefficient of thermal expansion (CTE) of underfill and different mechanical properties of four kinds underfill-A, B, C, D and with/without metal cap are considered as parameters. The effects of above-mentioned parameters on package¡¦s displacement, strain and stress fields are studied. The results show that the maximum equivalent strain and stress take place at the interface between chip and underfill far away from the center of the whole package and on the top of the most outside solder bump in the solder joint. The larger the CTE of underfill is, the larger the maximum equivalent strain and stress are. Package with metal cap can reduce the displacement to almost half or more of that without cap, but increase the values of maximum equivalent strain and stress. No matter with metal cap or not, the underfill D is the best choice. Hence, the underfill material properties possess lower CTE and larger Young¡¦s modulus than those of solder bump.