Orientador: Pedro Cunha de Holanda / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-12T10:44:00Z (GMT). No. of bitstreams: 1 Boriero_DanielFrancisco_M.pdf: 4969339 bytes, checksum: 948e129914cf07a208b25eb26a168a96 (MD5) Previous issue date: 2008 / Resumo: Necessário na maioria das teorias para atribuir massa aos neutrinos e explicar o fenômeno de oscilação de sabores, o neutrino de mão direita, estéril em SU(2)L U(1)Y, é um candidato natural a matéria escura não bariônica. Cosmologicamente produzido via oscilação não ressonante de quiralidade do neutrino de mão esquerda e situado na categoria "Warm" de matéria escura, está atualmente desfavorecido como candidato a formar a totalidade da matéria escura. Apresentamos um cenário subdominante, no qual o neutrino estéril formaria apenas uma fração fs do total da matéria escura. Através da análise do sinal negativo do decaimento radiativo em raios-x difusos e ausência de supressão em estruturas de Lyman-a aplicadas na previsão de abundância gerada pelo modelo de massa n MSM, obtemos o limite de fs £ 0,65(2 s) em modelo cosmológico composto L (Ws +C)DM. Com esse resultado mostramos que o neutrino estéril ainda é um candidato viável para uma componente relativística da matéria escura, possível solução para o excesso de potência em pequena escala do modelo puramente "Cold". / Abstract: Needed in the most theories to confer mass to neutrinos and explain avour oscillations, the right-handed neutrino, sterile in SU(2)L U(1) Y , is a natural non-baryonic dark matter candidate. Cosmologicaly produced by non-resonant oscillattion with left-handed neutrinos and situated in the Warm regime, it's currently disfavored as composing the total dark matter. We present subdominant scenario where the sterile neutrino would compose only a fraction fs of the total dark matter, to constrain the model are utilized negative signals from diffuse X-Ray background and suppression from Lyman- a large scale structure applied to nMSM sterile neutrino theoretical production. We found the limit fs £ 0.65 (2 s) for a composed cosmological model L (Ws + C)DM. This result shows that the sterile neutrino is still a viable candidate for a relativistic component of dark matter and a possible solution to solve the excess power problem of the standard LCDM model in small scales. / Mestrado / Fisica das Particulas Elementares e Campos ; Cosmologia / Mestre em Física

Orientador: Orlando Luis Goulart Peres / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-24T13:21:19Z (GMT). No. of bitstreams: 1 BastoGonzalez_VictorSaul_D.pdf: 37659795 bytes, checksum: f4492cea9594ac4fbffc288a0c46526a (MD5) Previous issue date: 2014 / Resumo: Motivados pelos indícios experimentais da existência de um quarto neutrino, que surge nos dados de oscilações coletados nos experimentos de aparecimento e desaparecimento de neutrinos, e pela possibilidade teórica de explicar a pequena massa dos neutrinos através de dimensões extras grandes, fizemos análises em procura de vestígios destas duas motivações nos experimentos IceCube e KATRIN. A existência deste quarto neutrino implicaria 1) que existem mais neutrinos que os três tipos de neutrinos do Modelo Padrão da física de partículas, 2) que as interações deste novo neutrino não são descritas pelo Modelo Padrão, 3) que os parâmetros da mistura dos três tipos de neutrinos do Modelo Padrão seriam afetados pela mistura com este novo neutrino e 4) que a diferença dos quadrados das massas, ?m^{2}, associada a este neutrino seria grande, ?m^{2} ~1 eV^{2}. Usando os dados de neutrinos atmosféricos de IceCube, podemos indagar pela existência do quarto neutrino, pois para, ?m^{2} ~1 eV^{2} acontece uma conversão de sabor devida ao efeito de matéria sobre o neutrino no intervalo de energias analisado no IceCube. Assim, este efeito de matéria permite-nos pôr limites sobre os parâmetros que governam as oscilações de neutrinos estéreis. O experimento KATRIN procurará medir a massa do neutrino. Esta medida será feita analisando a cinemática dos elétrons emitidos no decaimento beta do Trítio que é uma medida independente do modelo físico, pois está fundamentada na conservação da energia. A presença de estados mais pesados, como os que existem quando neutrinos estéreis estão presentes, nos permitirá vincular estes neutrinos estéreis. Especificamente, analisamos em KATRIN indícios de um e dois neutrinos estéreis e também de dimensões extras grandes / Abstract: Motivated by the experimental evidence of the existence of a fourth neutrino, which arises from the data collected of neutrino oscillations in appearance and disappearance experiments, and by the theoretical possibility to explain the smallness of the mass of the neutrinos through large extra dimensions, we performed analyses in search of seeking indication of these two motivations in the IceCube and KATRIN experiments. The existence of this fourth neutrino would imply 1) that there are more types of neutrinos than the three types of neutrinos present in the Standard Model of particle physics, 2) that this new neutrino interactions are not described by the Standard Model, 3) that the parameters of the three neutrinos mixing would be affected by mixing with this new type of neutrino, and 4) that the squared-mass difference , ?m^{2} associated with this new neutrino would be large, , ?m^{2} ~1 eV^{2}. Using the atmospheric neutrino data from IceCube, we can investigate the existence of the fourth neutrino because a flavor conversion happens in the limit , ?m^{2} ~1 eV^{2} due to the effect of matter on the neutrino in the range of energies analyzed in the IceCube. Thus, this matter effect allows us to constrain the parameters that govern the sterile neutrino oscillations. The KATRIN experiment will seek to measure the neutrino mass. This measure will be performed by analyzing the kinematics of electrons emitted in the tritium beta decay, which is an independent measure of the physical model because it is based on energy conservation. The presence of heavier states such as those that exist when sterile neutrinos are present, will allow us to constrain these sterile neutrinos. Specifically, we analyze in KATRIN evidence of one and two sterile neutrinos and also of large extra dimensions / Doutorado / Física / Doutor em Ciências

No description available.

Inom sjukvården är det viktigt att material finns tillgängligt när operationer och ingrepp ska genomföras för att patienter ska få den vård de behöver. För att materialbrist inte ska uppstå krävs bra planering och hantering av material. Det finns ett flertal olika materialstyrningsmetoder som syftar till att undvika materialbrist och uppnå låga kostnader. I dagsläget ligger Ögonkliniken på sjukhusområdet på Universitetssjukhuset i Linköping men då lokalerna är gamla ska kliniken flytta till nya lokaler på Garnisonen, ett område utanför sjukhusområdet. I och med flytten kommer ett nytt materialflöde att uppstå för Ögonklinikens steriliserade material. Detta då Ögonkliniken innan flytten steriliserade allt sitt material själva på avdelningen och efter flytten kommer materialet istället att skickas till Sterilcentralen som ligger på sjukhusområdet för sterilisering. Syftet med studien är därför att skapa en bättre förståelse för det framtida materialflödetmellan Ögonkliniken och Sterilcentralen genom att analysera lämpligheten i olika materialstyrningsmetoder för Ögonklinikens verksamhet. Målet med studien är att kartlägga det framtida materialflödet samt att beräkna mängden material som behöver finnas i flödet för att materialbrist inte ska uppstå för Ögonkliniken. För att besvara syftet utgår studien från fyra frågeställningar: Vilka processer och aktiviteter kommer det framtida flödet att bestå av? Vilka karaktäristiska drag har Ögonklinikens sterila material? Givet de karaktäristiska drag som identifierats i fråga 2, vilken materialstyrningsmetod är mest lämplig? Vilka andra effektermedför valet av materialstyrningsmetodför det framtida flödet? För att kunna besvara frågeställningarna har information och data samlats in genom litteraturstudie, sekundärdata och intervjuer. Sekundärdata som samlats in är efterfrågedata,antal diskprocesser, antal autoklavkörningar och antal omkörda processer och körningar. Det framtida flödet kommer bestå av fyra parter; Ögonkliniken, Sterilcentralen, Stångåbuss och Inre Logistik. Intervjuer har genomförts med samtliga parter, där de har svarat på semistrukturerade intervjufrågor. Studien resulterar i en kartläggning över det framtida flödet, där processer och aktiviteter som flödet kommer bestå av illustreras. Det sterila materialet identifieras ha kort ledtid, ojämn efterfråganoch antingen fast eller varierande beställningsintervall samt beställningskvantitet. Kanban anses vara den mest lämpliga materialstyrningsmetoden att använda för Ögonkliniken. Detta för att kanban lämpar sig bäst för det sterila materialets karaktäristiska drag. De effekter som ett kanbansystem medför är att beställningspunkt och beställningskvantitet bestäms samt att kostnaderna och kapitalbindning kan hållas låga. Dock är inte de transporter som finns idag anpassade för ett kanbansystem, vilket leder till att detta kan behöva åtgärdas för att få ett fungerande kanbansystem. För att ett kanbansystem ska fungera behöver materialet transporteras direkt när behovet uppstår och i dagsläget fungerar inte de avtalade transporter på detta sätt. Då de avtalade transporterna går specifika tider istället. / It is crucial that sterile material is available when surgeries and other medical procedures need to be performed so that the patients receive the required healthcare. To ensure that shortfalls of required material do not occur good planning and efficient material management is required. There are several different material planning methods that can be used to avoid shortfall of material. As of today, Ögonkliniken is located within the hospital area at the university hospital in Linköping. However, Ögonkliniken is being relocated to new facilities located at Garnisonen, which is an area outside of the hospital area.The relocation is due to that the current facilities are old and worn down. Ögonkliniken handled their own sterile material and the sterilization process in their current facilities. When the relocation is complete the used sterile material will be transportedto Sterilcentralen, which is located within the hospital area, for sterilization. After sterilization,the material must be transported back to Ögonkliniken. Hence, a new material flow will emerge because of the relocation. The purpose of this study is to gain a better understanding of the new materialflow. This is achieved by analyzing different material planning methods and whether they are suited for Ögonkliniken.The aim of the study is to map the future material flow and to calculate the amount of materialt hat needs to be present in the flow to avoid material shortages at Ögonkliniken. To fulfill the purpose of the study four research questions have been formulated: What activities will the material flow consist of? What specific features does Ögonklinikens sterilized material have? Given the specific features that have been identified in question 2, which material planning method is best suited? What other impacts does the chosen material planning method result in for the future material flow? Toanswer the questions, information and data have been collected through literature study, secondary data and interviews. The secondary data that have been collected are statistics over number of preformed operations, number of washing processes, number of sterilization processes and number of processes that needed to be reprocessed. The future material flow will consist of four departments: Ögonklinken, Sterilcentralen, Stångåbuss and Inre Logistik. All departments have been interviewed where they have been asked semi structured questions. The sterile material has been identified with the following specific features, short lead time, irregular demand and either fixed or varying order interval and order quantity. The best suited material planning method for Ögonkliniken is the Kanban system. This is due to that the sterile material’s specific features match with the method. An implementation of a Kanban system will result in routines for when and what volume should be ordered. The system also allows for the cost of purchased material to be low. However, the way the transports are set up today does not suit a Kanban system. Therefore, the transports may have to be adapted so that the Kanban system will function well. For the Kanban system to work transportation of material must occur when the demand appears and today the transports only allow material to be picked up at specific times.

Le travail présenté dans cette thèse porte sur la recherche de neutrino stérile à l'aide de désintégrations β dans les expériences SOX et TRISTAN. Le neutrino stérile est une particule hypothétique, solidement établi théoriquement, qui ne prendrait part à aucune interaction fondamentale, gravité mise à part. Étant entendu que le neutrino stérile se mélange avec les neutrinos actifs connus, l'existence de ces premiers peut être étudiée directement en laboratoire. L'expérience SOX a été conçue pour explorer l'existence d'un neutrino stérile d'une masse autour de l'électronvolt (eV). Un neutrino stérile avec une telle masse permettrait d'expliquer plusieurs anomalies observées à courte distance de sources (quelques mètres) lors de mesures d'oscillations de neutrinos de basses énergies (quelques MeV). SOX avait pour projet d'utiliser le détecteur de neutrinos solaire déjà existant Borexino, et d'observer un signal d'oscillation vers le stérile à l'intérieur même du volume actif du détecteur. La source radioactive de 5.5 PBq et positionnée à 8.5 m du centre du détecteur, émettrait des antineutrinos électroniques via la désintégration β du ¹⁴⁴Ce et du ¹⁴⁴Pr. Une des clés de l'observation de cette oscillation, est la connaissance précise de l'activité de la source. Une telle activité peut être déterminée en mesurant la chaleur dégagée par la source. C'est la raison pour laquelle l'INFN Genova et la TUM ont développé conjointement un calorimètre dédié. La chaleur dégagée par la radioactivité est alors captée par un échangeur puis transmise à un circuit d'eau étroitement contrôlé. Le calorimètre a été assemblé, optimisé puis étalonné avec succès. La perte de chaleur du circuit fut déterminée lors des mesures d'étalonnage grâce à un chauffage électrique. Des variations des conditions expérimentales et une isolation thermique sophistiquée ont permis d'opérer avec des pertes de chaleur négligeables. Il a ainsi été démontré que la puissance thermique de la source pouvait être estimée, en 5 jours seulement, avec une précision supérieure à 0,2%. Malheureusement, le programme SOX a dû être annulé. Le projet TRISTAN, quant à lui, tend à démontrer l'existence d'un neutrino stérile avec une masse de l'ordre du kilo-électronvolt (keV). Si le neutrino stérile à l'eV tente d'apporter une réponse aux différentes anomalies observées lors de mesures d'oscillation, le neutrino stérile au keV, en tant que potentiel candidat matière noire. Le projet TRISTAN cherche à mesurer l'empreinte de ce nouvel état de masse sur le spectre du tritium dans le cadre de l'expérience KATRIN. Cette dernière vise à déterminer la masse effective du neutrino (actif) en mesurant l'extrémité du spectre de tritium avec une excellente résolution et un faible taux de comptage. Une fois la mesure achevée, le détecteur de KATRIN sera modifié afin d'effectuer une mesure différentielle et intégrale de l'ensemble du spectre en tritium: c'est le projet TRISTAN. Le détecteur actuel sera remplacé par un nouveau détecteur de silicium à dérive (SDD) de 3500 pixels permettant une résolution de 3% à 6 keV et pouvant supporter un taux de comptage montant jusqu'à 10⁸ coups par seconde, activité maximum attendue. Un prototype a été testé avec succès et une première mesure de tritium a été réalisé au spectromètre de masse neutrino Troitsk afin d'étudier les erreurs systématiques et de développer des méthodes d'analyses pertinentes. Un premier ajustement cohérent du spectre tritium différentiel acquis lors de cette installation, a démontré la faisabilité du projet. TRISTAN lui-même est toujours en cours de développement mais les caractérisations du détecteur et les études de systématiques sont plus qu'encourageantes pour la poursuite du projet. La première investigation de neutrino stérile avec le détecteur de TRISTAN sur le site de KATRIN est prévue après la mesure de masse, en cours à Karlsruhe, aux alentours de 2024. / The work presented in this thesis is about the sterile neutrino search with the two experiments SOX and TRISTAN based on the β-decay. Sterile neutrinos are theoretically well motivated particles that do not participate in any fundamental interaction except for the gravitation. With the help of these particles one could elegantly explain the origin of the neutrino mass, dark matter and the matter-antimatter asymmetry in the universe. As sterile neutrinos can mix with the known active neutrinos, they could be discovered in laboratory searches. The SOX experiment was designed to search for a sterile neutrino with a mass in the eV-range. This particular mass range is motivated by several anomalous observations at short-baseline neutrino experiments that could be explained by an additional oscillation with a length in the order of meters that arises from an eV-scale sterile neutrino. For SOX it was planned to use the existing Borexino solar neutrino detector to search for an oscillation signal within the detector volume. The neutrinos are emitted from a 5.5 PBq electron-antineutrino source made of the β-decaying isotopes ¹⁴⁴Ce and ¹⁴⁴Pr, located at 8.5 m distance from the detector center. For the analysis of the signal it is crucial to know the source activity. This parameter is determined by measuring the decay heat of the source with a thermal calorimeter that was developed by TUM and INFN Genova. The decay heat is measured through the temperature increase of a well-defined water flow in a heat exchanger that surrounds the source. The calorimeter was assembled, optimized and characterized. Heat losses were determined through calibration measurements with an electrical heat source. Adjustable measurement conditions and an elaborate thermal insulation allowed an operation with negligible heat losses. It was proven that the power of a decaying source can be measured with <0.2% uncertainty in a single measurement that lasts ~5 days. Unfortunately the SOX experiment was canceled after a technological problem rendered the source production with the required activity and purity impossible. The TRISTAN project is an attempt to discover sterile neutrinos with masses in the order of keV. In contrast to eV-scale sterile neutrinos that are motivated by several anomalies observed in terrestrial experiments, the existence of sterile neutrinos with masses in the keV range could resolve cosmological and astrophysical issues, as they are dark matter candidates. The TRISTAN project is an extension of the KATRIN experiment to search for the signature of keV-scale sterile neutrinos in the tritium β-spectrum. KATRIN itself is attempting to determine the effective neutrino mass by measuring the end point of the tritium spectrum at low counting rates. The KATRIN setup will be modified after the neutrino mass measurements are finished to conduct a differential and integral measurement of the entire tritium spectrum. This project is called TRISTAN. The current detector will be replaced by a novel 3500-pixel silicon drift detector system that has an outstanding energy resolution of a few hundred eV and can handle rates up to 10⁸ counts per second as they occur when the entire spectrum is scanned. Prototype detectors were successfully tested and first tritium data was taken at the Troitsk ν-mass spectrometer to study systematic effects and develop analysis methods. A successful fit of the differential tritium spectrum proved the feasibility of this approach. TRISTAN itself is still at an early stage, but the detector development and systematic studies are well on track and delivered so far encouraging results. The sterile neutrino search is scheduled after the KATRIN neutrino mass program is finished in ~2024.

No description available.

While cognitive impairment is common in peripheral diseases such as chronic kidney disease (CKD), mechanistic insights and effective therapies are lacking. Multiple toxins accumulating as a consequence of CKD have been identified, yet the consequences for cellular crosstalk in the brain and the mechanisms underlying the associated neuronal dysfunction remain largely elusive. In the case of CKD, more than 100 uremic toxins have been identified. Renal transplantation largely reverses the cognitive impairment associated with CKD, demonstrating that cognitive impairment in CKD can be reversed. This indicates that pharmaceutical approaches to target cognitive impairment in association with CKD may be feasible. However, it is unlikely that targeting a single toxin will be sufficient to combat neuronal dysfunction associated with peripheral diseases such as CKD, given the large number of toxins involved and since the pattern of accumulating toxins varies among affected patients. Rather than identifying single toxins, identifying a common mechanism inducing neuronal dysfunction and thus impairing cognition may identify new and feasible therapeutic approaches. One commonality of peripheral diseases such as liver or renal failure is sterile inflammation. Sterile inflammation has been linked with neurodegenerative diseases and associated cognitive impairment and inflammasome activation is one hallmark of chronic pathologies in the brain. Mutations in the inflammasome component NLRP3 show clinical manifestations of cryopyrin- associated periodic syndromes (CAPS), which are characterized by skin rash, fever and joint pain. Further, abnormal and constant NLRP3 signaling has been associated with some chronic and degenerative diseases such as Alzheimer’s disease (AD), atherosclerosis, arthritis or cancer. A causative function of the NLRP3 inflammasome for neurodegenerative processes is supported by preclinical studies. These pre-clinical studies used whole body knock out mice to demonstrate that deficiencies of NLRP3, caspase-1 or the primary receptor for IL-1β, IL-1R1, protect mice from neurodegenerative processes. While providing important insights into the role of the NLRP3-inflammasome in neurodegenerative processes, these studies did not identify the relevant cell types in which the inflammasome is activated, the mechanisms underlying inflammasome activation and the consequences thereof, e.g. for intracerebral cross-talk. In addition, whether sterile inflammation triggered by the NLRP3 inflammasome impairs cognition in the setting of primarily peripheral diseases such as CKD remains unknown. To address these open questions, I used a mouse model of CKD, in which I detected NLRP3 inflammasome in brains. Interestingly, despite inflammasome activation in the brain, microglial caspase-1 deficiency did not improve cerebral inflammation and cognition in CKD mice. I identified noncanonical IL-1β maturation in microglia in CKD conditions, which was cathepsin c – caspase-8 mediated. Restoring K+ homeostasis in microglia or genetic inhibition of neuronal IL-1R1 signaling abolished CKD-induced cognitive impairment. Mechanistically, noncanonical IL-1β maturation and secretion from microglia promotes via IL-1R signaling cognitive impairment in neurons. This identifies a molecular mechanism of sterile CNS inflammation and the associated intercellular signaling pathway, which may be therapeutically amendable. Microglial K+ dyshomeostasis and noncanonical microglial IL-1β maturation may be druggable targets in some forms of cognitive impairment.:Content 2 List of abbreviations 5 Graphical abstract 8 2 Introduction 9 2.1 Chronic kidney disease and cognition 11 2.2 Microglia cells 13 2.3 The inflammasome, potassium dyshomeostasis in brain cells and thallium autometallography 15 2.4 Sterile inflammation in neurodegenerative diseases 17 3 Aims of the study 19 4 Materials and Methods 20 4.1 Reagents 20 4.2 Mice 27 4.3 CKD mouse model (5/6 nephrectomy model) 30 4.4 Evans Blue extravasation assay 32 4.5 2-photon microscopy 32 4.6 Analysis of mice 33 4.7 In vivo interventions 33 4.8 Histology and immunohistochemical analysis 34 4.9 Cell culture 34 4.10 Dextran permeability assay 35 4.11 Thallium-AMG (TlAMG), ex vivo and in vitro 36 4.12 Protein extraction and Western blotting 38 4.13 IL-1β ELISA 38 4.14 Reverse Transcriptase Polymerase Chain Reaction (RT–PCR) 38 4.15 Proximity ligation assay (PLA) 39 4.16 Behavioral analysis 39 4.17 Cathepsin c substrate assay 40 4.18 snRNA-Seq 41 4.19 Statistical Analysis 42 5 Results 43 5.1 Chronically impaired renal function leads to cognitive decline 43 5.2 Blood brain barrier (BBB) disruption in chronic kidney disease 44 5.3 Potassium dyshomeostasis in brain cells in CKD 45 5.4 CKD leads to microglia activation 46 5.5 Priming of microglia in CKD depends on potassium dyshomeostasis and its restoration improves cognition in CKD 49 5.6 TRAM34 ameliorates potassium dyshomeostasis and behavior in CKD 51 5.7 Uremia-induced cognitive impairment depends on microglia- neuron crosstalk via IL-1R1 52 5.8 Deciphering the microglial molecular pathway in CKD 56 5.9 Microglia activation in CKD is independent of NLRP3 56 5.10 Microglial IL-1β maturation occurs independently of the NLRP3-Caspase-1 inflammasome in CKD 57 5.11 The role of caspase- 8 in microglia activation in CKD 60 5.12 Lysosomal cathepsin c promotes microglia activation pivotal for caspase-8 activation 62 5.13 Broader implication of the pathway in other chronic peripheric diseases 63 5.14 Microglia inflammasome activation and IL-1β release is sufficient to induce cognitive impairment 64 5.15 Tables 66 6 Discussion 69 7 Summary 75 8 Zusammenfassung 80 9 References 86 10 Declaration about the independent preparation of the work 97 11 Presentation of own contribution 98 12 Curriculum vitae 99 13 Publications 104 14 Acknowledgments 106

No description available.

The neutrino is, by its nature, an elusive particle that requires massive detectors with small backgrounds to capture a handful of events. Nevertheless, neutrino experiments stand at the heart of the current mysteries of particle physics and astrophysics. These include the origin and size of neutrino mass, the existence of additional types of neutrinos, CP violation and the matter--antimatter asymmetry, the amount of metals in the Sun's core, and the existence of non-nuclear energy sources in the Sun. This dissertation concerns the the use of a novel detector technology, the Raghavan Optical Lattice (ROL), in the Low-Energy Neutrino Spectrometer (LENS) and Neutrino Lattice (NuLat) experiments. LENS will measure the solar neutrino luminosity and the Sun's core metallicity using a ROL with indium-loaded liquid scintillator. NuLat will probe the existence of light sterile neutrinos with masses of $ \sim 1\,\mathrm{eV} $ using a ROL made from $ ^{6}\mathrm{Li} $-loaded plastic scintillator. For LENS we present an overview of the experiment and the present the ROL construction results from the LENS R\andD program. In particular we will present results from the micro- and mini-LENS prototypes. For both LENS and NuLat we present the development of an event reconstruction algorithm for ROLs and we apply these to the expected signals for these experiments. For NuLat we present an overview of the experiment including its theory of operation and its sensitivity to sterile neutrino oscillations. Finally, we present work toward the full-sized NuLat detector through bench-top tests and construction of the NuLat demonstrator. / Ph. D.

Nuclear reactors have played an essential role in developing our current understanding of neutrinos. The precision measurement of these high-flux, pure-flavor and controllable artificial neutrino sources shed lights on a wide range of fundamental questions in physics. Specifically, the Reactor Antineutrino Anomaly hints that there may exist a novel eV-scale sterile neutrino, which requires new physics beyond the Standard Model. Performing reactor neutrino spectrum measurements at very-short baseline will improve our imperfect understanding of antineutrino emission from fissile material. CHANDLER is a new-generation neutrino experiment aiming for reactor antineutrino spectrum measurements, to test the eV-scale sterile neutrino oscillation hypothesis unambiguously. The second prototype detector, MiniCHANDLER, was deployed 25 meters from a $2.9~GW_{th}$ commercial nuclear reactor in North Anna, Virginia. To fight against the overwhelming background arising from its surface-level deployment, CHANDLER detectors adopt a novel design using lithium-6 ($^6$Li) loaded zinc sulfide (ZnS) scintillator to tag neutron capture events, which significantly improves the IBD detection efficiency. The use of the Raghavan optical lattice brings enormous enhancement of light collection towards high energy resolution, which unlocks reconstruction of event topology to further suppress backgrounds. The ability of measuring reactor antineutrino spectra enables the potential application of CHANDLER technology in nuclear nonproliferation. This thesis features the prototype detectors instrumentation, data analysis development and Monte Carlo study for the CHANDLER experiment during 2016 to 2020. The detector calibration and energy reconstruction with vertical muon forms a core piece of this thesis. We report our observation of IBD spectrum with 5.5$sigma$ significance with a four month deployment of the minimal shielded MiniCHANDLER prototype at North Anna. The application of separation cuts and topological selections in the analysis are instrumental for a segmented plastic scintillator detector. We also present our results from the proton scintillation quenching measurement at Triangle Universities Nuclear Laboratory, with the deployment of the first prototype detector, MicroCHANDLER, at a neutron beam. / Doctor of Philosophy / The sterile neutrino is a hypothetical particle yet to be observed, whose existence is suggested by a number of physics experiments with strong theoretical motivation. Due to the low chance of a neutrino interacting with matter, most neutrino detectors use a special process called inverse beta decay (IBD) to detect them. The CHANDLER experiment set out to measure antineutrinos produced by a reactor in the vicinity of its core. We found a significant signal of antineutrinos from our four-month deployment. This thesis details the technology and analysis that enables neutrino detection and improves detection efficiency. We also shows how we squeeze out the maximum information available to us from raw data, through the process called reconstruction. Other research topics related to the CHANDLER detector RandD are also included in this thesis.