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Glioblastoma remains a difficult cancer to treat successfully despite the multimodal therapeutic strategy of surgery, radiation therapy and chemotherapy with temozolomide (TMZ). From a combined radiation and drug screening platform, we identified potential combinations of HDAC inhibitor (HDACi) and MAPK/ERK kinase inhibitors (MEKi) with ionizing radiation as a novel therapy against glioblastoma. Our findings indicate that this combination strategy may potentially improve therapy that could benefit glioblastoma patients., Das Glioblastom ist trotz der multimodalen Therapiestrategie aus Operation, Strahlentherapie und Chemotherapie mit Temozolomid (TMZ) nach wie vor eine schwer zu behandelnder Krebsart. Auf der Grundlage einer kombinierten Bestrahlungs- und Arzneimittel-Screening-Plattform haben wir potenzielle Kombinationen von HDAC-Inhibitoren (HDACi) und MAPK/ERK-Kinase-Inhibitoren (MEKi) mit ionisierender Strahlung als neuartige Therapie gegen Glioblastom identifiziert. Unsere Ergebnisse deuten darauf hin, dass diese Kombinationsstrategie das Potenzial hat, die Therapie zu verbessern, von der Glioblastom-Patienten profitieren könnten.

The growing frequency of diagnostic and therapeutic medical procedures based on minimally invasive techniques of interventional radiology, has raised concerns about the occupational radiation doses to medical professionals. In this study, the first step towards a small x-ray radiation detector is made, to incorporate the benefits of conventional passive dosimeters with the real-time capabilities of electronic personal dosimeters., Die zunehmende Häufigkeit diagnostischer und therapeutischer auf minimalinvasiven Techniken der interventionellen Radiologie basierenden medizinischen Verfahren hat Besorgnis hinsichtlich der berufsbedingten Strahlungsdosen für medizinische Fachkräfte erregt. In dieser Studie wurde der erste Schritt in Richtung eines kleinen Röntgenstrahlungsdetektors gemacht, um die Vorteile herkömmlicher passiver Dosimeter mit der Echtzeitfähigkeit elektronischer Dosimeter zu verbinden.

This study provides evidence for the involvement of the lncRNA Gm12606 in the cellular radiation response, and in particular confirms a very strong role in the ageing process of mouse mesenchymal stem cells (mMSCs). Knockdown of Gm12606 strongly impaired transcription of the nearby Ink4a/Arf/Ink4b locus, suggesting a cis-mediated mechanism. Thus, mMSCs from bone marrow of Gm12606 exon1-deficient homozygous mice resulted in a significantly lower percentage of cellular senescence., Diese Studie liefert Beweise für die Beteiligung der lncRNA Gm12606 an der zellulären Strahlenantwort und bestätigt insbesondere eine sehr starke Rolle im Alterungsprozess von mesenchymalen Stammzellen der Maus (mMSCs). Der Knockdown von Gm12606 beeinträchtigte die Transkription des nahegelegenen Ink4a/Arf/Ink4b-Lokus stark, was auf einen cis-vermittelten Mechanismus hindeutet. So führten mMSCs aus dem Knochenmark von homozygoten Mäusen mit Gm12606-Exon1-Deletion zu einem deutlich geringeren Prozentsatz an zellulärer Seneszenz.

The Marine Corps’ Expeditionary Advanced Base Operations (EABO) concept places small, distributed forces within a contested environment to achieve strategic effects. However, current sustainment platforms and infrastructure lack the ability to provide required support in the context of EABO. As such, the Marine Corps must develop a novel resilient and robust distribution network capable of providing responsive sustainment to forces conducting EABO. To solve this problem, we develop a two-stage stochastic mixed integer linear program that seeks to minimize the cost of instantiating and operating a sustainment network across a range of possible in-context scenarios. Among the network’s constraints are demand, cost, capacity, risk, and supply considerations. Of these constraints, demand introduces the most uncertainty. Fluctuations in demand come from a variety of factors to include intensity of conflict, attrition, and other combat dynamics. Through the explicit and judicious modeling of such uncertainty, our model provides solutions that are robust to a wide range of demand scenarios. By implementing our model in a notional operational scenario in the South China Sea, we provide results and insights that ultimately assist the Marine Corps by providing an analytical basis for determining an optimal network comprised of locations, capacities, and prepositioning quantities for sustaining forces conducting EABO in the western Pacific., Outstanding Thesis, Captain, United States Marine Corps, Approved for public release. Distribution is unlimited.

Consider a stochastic duel with many players. Each player chooses an opponent to shoot at, makes a hit after a random amount of time that follows an exponential distribution, and is killed as soon as being hit for the first time. The duel continues until all but one player is killed, and the lone survivor is declared the winner. The goal of each player is to decide which opponent to target at any given time in order to maximize their winning probability. We develop an algorithm to compute each player’s optimal strategy and winning probability. In particular, the strongest player—the one having the largest kill rate—need not be the most likely to win, and it is not necessarily optimal for each player to shoot at their strongest opponent. We also consider a variation of the game in which players arrive sequentially to select their own kill rates, knowing the selections made by players who arrived earlier. In this sequential-move game with three players, the first player wants to be mediocre and the third player has the best chance to win. Our findings enable further understanding of military conflicts that involve three or more adversaries in the same area of operations., Outstanding Thesis, Major, United States Marine Corps, Approved for public release. Distribution is unlimited.

This work investigated the effects of low-dose radiation in clinically relevant situations on the brain in a mouse model. The results show that a single low-dose radiation exposure has a strong and sustained effect on the hippocampus at the molecular and structural level. Indications of increased inflammation and cell death were measured at a dose of 0.5 Gy, while lower doses trigger a protective effect. These results contribute to a better understanding of the long-term effects of clinically relevant radiation., Diese Arbeit untersuchte die Auswirkungen von niedrig dosierter Strahlung in klinisch relevanten Situationen auf das Gehirn im Mausmodell. Die Ergebnisse zeigen, dass eine einmalige niedrig dosierte Strahlenexposition eine starke und anhaltende Wirkung auf den Hippocampus auf molekularer und struktureller Ebene hat. Es wurden Hinweise auf eine erhöhte Entzündung und Zelltod bei einer Dosis von 0,5 Gy gemessen, während niedrigere Dosen einen protektiven Effekt auslösen. Diese Ergebnisse tragen dazu bei, die Langzeiteffekte klinisch relevanter Strahlung besser zu verstehen.

Diese Arbeit befasst sich mit der Fragestellung ab welcher Dosis von niedrigen ionisierenden Strahlen ein Risiko für eine Katarakt entsteht. Die verwendeten Dosen betrugen 0 Gy (Scheinbestrahlung/Kontrollen); 0,063 Gy; 0,125 Gy und 0,5 Gy. Es wurden jeweils die Zeitpunkte 4 und 24 h, sowie 12, 18 und 24 Monate nach der Bestrahlung untersucht. Für die Versuche wurden Wildtyp-Mäuse und Ercc2+/--Mäusen eingesetzt., This thesis examines an experimental evidence to determine if low doses of ionizing radiation lead to the formation of cataracts. Doses used were 0 Gy (sham irradiation, controls), 0.063 Gy, 0.125 Gy and 0.5 Gy. Eyes were examined at 4 h, 24 h and 12, 18 and 24 months after irradiation. For this purpose wild-type and Ercc2+/-- mice were used.

Mutations of AIP are associated with a subset of aggressive pituitary adenomas (PAs) that are commonly resistant to therapy. In the present study a novel subset of miRNAs that were differentially expressed between AIPmut+ and AIPmut- human PAs was identified. Functional characterization of two candidate miRNAs in vitro revealed that overexpression of miR-34a increased pro-tumorigenic behavior of PA cells. Gnai2 was validated as a direct target of miR-34a and its protein levels were reduced in AIPmut+ patients. The regulation of Gnai2 by miR-34a is a novel mechanism, which might help to explain AIP-associated tumorigenesis., AIP-Mutationen gehen mit äußerst aggressiven Hypophysenadenomen (HAs) einher, die häufig resistent gegenüber Therapien sind. Die vorgelegte Studie konnte eine Gruppe von miRNAs identifizieren, die zwischen AIPmut+ and AIPmut- Tumoren differenziell exprimiert sind. Funktionelle Charakterisierung zweier Kandidaten zeigte, dass die Überexpression von miR-34a tumorigenes Verhalten von HA Zellen fördert. Gnai2 wurde als direktes Zielgen von miR-34a identifiziert und die Protein Expression war in AIPmut+ Patienten reduziert. Die Regulation von Gnai2 durch miR-34a ist ein neuer Mechanismus, der helfen könnte die AIP-assoziierte Tumorentstehung zu erklären.

This study provides evidence for the involvement of the lncRNA Gm12606 in the cellular radiation response, and in particular confirms a very strong role in the ageing process of mouse mesenchymal stem cells (mMSCs). Knockdown of Gm12606 strongly impaired transcription of the nearby Ink4a/Arf/Ink4b locus, suggesting a cis-mediated mechanism. Thus, mMSCs from bone marrow of Gm12606 exon1-deficient homozygous mice resulted in a significantly lower percentage of cellular senescence., Diese Studie liefert Beweise für die Beteiligung der lncRNA Gm12606 an der zellulären Strahlenantwort und bestätigt insbesondere eine sehr starke Rolle im Alterungsprozess von mesenchymalen Stammzellen der Maus (mMSCs). Der Knockdown von Gm12606 beeinträchtigte die Transkription des nahegelegenen Ink4a/Arf/Ink4b-Lokus stark, was auf einen cis-vermittelten Mechanismus hindeutet. So führten mMSCs aus dem Knochenmark von homozygoten Mäusen mit Gm12606-Exon1-Deletion zu einem deutlich geringeren Prozentsatz an zellulärer Seneszenz.

The Ground-Based Anti-Ship Missile (GBASM) is a critical capability at the center of the Marine Corps’ concept of Expeditionary Advanced Base Operations and Force Design 2030 initiatives. This research formulates stochastic models for the evaluation of the efficiency and effectiveness of varying GBASM battery configurations in the context of a duel with a surface ship. The models produced are discrete-time Markov chains that model duels between a Blue GBASM battery and a Red surface ship. The models are parameterized to account for varying factors including lethality of Blue and Red, and evaluate salvos based on the number of GBASM delivery platforms and the number of missiles shot per platform. The primary output of this research is a modeling framework that allows an analyst to robustly analyze GBASM systems. Insights from the models reinforce Wayne Hughes’ mantra of “fire effectively first,” and highlight the importance of Blue being able to mass fires into an effective salvo.

The U.S. Navy (USN) utilizes the Vertical Launch System (VLS) to store and launch both their offensive and defensive missiles. Since the number of VLS silos on a given ship is fixed, to maximize offensive capability the USN needs to minimize the number of interceptors required to combat incoming anti-surface missiles. Current firing policies may be overly conservative and expend too many interceptors per incoming threat, which results in a substantial fraction of VLS silos dedicated to defensive missiles. Decision makers need an analysis tool to explore the trade-off between missile consumption and probability of raid annihilation (PRA) for various firing policies and would also benefit from a prescriptive algorithm to help inform missile expenditure. This thesis provides a model to optimize VLS firing policy using a set of multiple interceptor types while accounting for range limitations, travel time, multi-interceptor salvos, battle damage assessment, and range dependent probability of kill. Additionally, the thesis derives analytical results for the optimal, lowest-cost allocation of interceptors in the single interceptor case, which, in turn, generates insight into how to structure sequential salvos., N81, Washington DC, Ensign, United States Navy, Approved for public release. Distribution is unlimited.

The Ground-Based Anti-Ship Missile (GBASM) is a critical capability at the center of the Marine Corps’ concept of Expeditionary Advanced Base Operations and Force Design 2030 initiatives. This research formulates stochastic models for the evaluation of the efficiency and effectiveness of varying GBASM battery configurations in the context of a duel with a surface ship. The models produced are discrete-time Markov chains that model duels between a Blue GBASM battery and a Red surface ship. The models are parameterized to account for varying factors including lethality of Blue and Red, and evaluate salvos based on the number of GBASM delivery platforms and the number of missiles shot per platform. The primary output of this research is a modeling framework that allows an analyst to robustly analyze GBASM systems. Insights from the models reinforce Wayne Hughes’ mantra of “fire effectively first,” and highlight the importance of Blue being able to mass fires into an effective salvo., HQMC Programs and Resources (P&R), Washington D.C., Captain, United States Marine Corps, Approved for public release. Distribution is unlimited.

The Marine Corps’ Expeditionary Advanced Base Operations (EABO) concept places small, distributed forces within a contested environment to achieve strategic effects. However, current sustainment platforms and infrastructure lack the ability to provide required support in the context of EABO. As such, the Marine Corps must develop a novel resilient and robust distribution network capable of providing responsive sustainment to forces conducting EABO. To solve this problem, we develop a two-stage stochastic mixed integer linear program that seeks to minimize the cost of instantiating and operating a sustainment network across a range of possible in-context scenarios. Among the network’s constraints are demand, cost, capacity, risk, and supply considerations. Of these constraints, demand introduces the most uncertainty. Fluctuations in demand come from a variety of factors to include intensity of conflict, attrition, and other combat dynamics. Through the explicit and judicious modeling of such uncertainty, our model provides solutions that are robust to a wide range of demand scenarios. By implementing our model in a notional operational scenario in the South China Sea, we provide results and insights that ultimately assist the Marine Corps by providing an analytical basis for determining an optimal network comprised of locations, capacities, and prepositioning quantities for sustaining forces conducting EABO in the western Pacific.

Intelligence is a critical tool in modern security operations that provides insight into current and future operational conditions. It is a concept that transfers to other applications where monitoring activities or situations is imperative, such as ecological research. As technological advances in the past decades lead to increased availability of potential intelligence, we concentrate on source selection to ensure the resulting intelligence is of high quality and fit for purpose. We wish to bring focus to the more varied nature of intelligence than what is currently reflected in models of its collection and evaluation. Therefore, we examine the intelligence collection and analysis process in two separate scenarios; one treats it as a ongoing strategic activity, in another intelligence collection is carried out with an investigative intent. The first problem we formulate concerns source selection with a random time delay in feedback, corresponding to the collection and evaluation time of the intelligence. Both the distributions of such time delay and the outcome of the intelligence evaluation are unknown, giving rise to the classic exploration-exploitation dilemma in a long-run setting. We develop promising approaches to accommodate the novel features of the model based on Gittins indices and the knowledge gradient, and examine the issues presented when incorporating structures of dependence between the time delay and the outcome of the evaluation. Next, we develop a novel intelligence collection problem rooted in tactical level source selection, aiming to piece together an intelligence picture comprised of multiple types of information, for example, where and when an attack is planned. We demonstrate that when all elements of the model are known, dynamic programming provides the optimal policy. When some elements are unknown, which introduces an exploration-exploitation aspect to the model, we find that in certain cases the ability to learn is severely limited.

Nonfunctioning PAs (NFPAs) count for 30-40% of all pituitary tumors and in most cases (80%) they originate from gonadotroph cell linage. Lacking of signs and symptoms of hormone hypersecretion allows these tumors to grow and reach the macroadenoma stage. In such cases, a complete surgical removal of tumor is not achieved and the tumors tend to recur with various tempo. Currently, radiotherapy is the main post-operative option but it is not curative. Gene expression array analysis of MENX rat pituitary adenomas (PAs) identified many genes deregulated in these tumors among them Angiopoietin-1 (Ang-1) and Ang-2, which have not been extensively studied in pituitary adenoma progression like other angiogenesis promoting factors such as Vegf. We observed that rat and human PAs express higher amounts of Ang-2 at protein and mRNA level compared to non-tumorous tissues or healthy controls. Moreover, this protein was also detected in supernatant of rat and human primary PA cultures/established cell lines and plasma of NFPA patients indicating that this ligand is secreted by PA cells into culture medium or circulating blood. We found also that Ang-2 specific receptor, Tie-2, is expressed and partially phosphorylated in PA cells. This receptor could be activated by rhANG-2 in Ang-2-silenced GH3 cells and subsequently we observed activation of corresponding downstream signaling molecules. Activated Ang-2/Tie-2 signaling supported cell proliferation and displayed anti-apoptotic effects in rat and human primary PA cells and established GH3 cell line and blocking of this pathway led to decreased cell proliferation and enhanced apoptosis. In vivo treatment of MENX rats with anti-angiogenic drug AMG386 suppressed cell proliferation and induced apoptosis after 2 weeks, which suggests that blocking of this pathway might be a potential therapy option for NFPA patients, Hypophysenadenome (PA`s) sind häufig auftretende, intrakraniale Tumore. Etwa ein Drittel dieser Tumore bilden die nicht-funktionelle Hypophysenadenome (NFPA`s), die in 80% der Fälle aus gonadotropen Zellen bestehen. Da sie keine aktiven Hormone sezernieren, werden sie häufig relativ spät, im Makroadenoma-Stadium, diagnostiziert. Dadurch ist eine komplette chirurgische Entfernung oft erschwert und Rezidive können entstehen. Diese Adenome sprechen selten auf klassische medikamentöse Behandlungen an. Im Rahmen dieser Arbeit konnten wir zeigen, dass die Expression von Angiopoietin-1 (Ang-1) und Angiopoietin-2 (Ang-2) in Hypophysenadenomen des MENX ratstenmodels dysreguliert ist. Im Speziellen fanden wir, dass die Menge an Ang-2 sowohl in Ratten- als auch humanen NPFA auf mRNA- und Proteinebene erhöht war. Ang-2 wurde von primären Hypophysentumorkulturen aus Ratte und Mensch ins Zellkulturmedium sekretiert. Eine erhöhte Konzentration an Ang-2 konnte nachfolgend auch in Plasmaproben von NFPA-Patienten nachgewiesen werden. Im Rahmen dieser Arbeit konnten wir zeigen, dass Ang-2 als ein alternativer Ligand für den Rezeptor Tie-2 fungieren kann. Dieser lag in den Hypophysenadenomen daher in einer aktivierten, phosphorylierten Form vor. Durch Stimulation mit rekombinantem ANG-2 Protein, konnten wir eine extrazelluläre Stimulierung des Rezeptors in GH3 Hypophysenzellkulturen nachweisen, welche wiederum im Stande war intrinsische Signalkaskaden zu aktivieren. Dieser aktive Ang-2/Tie-2 Signalweg zeigte proliferative und anti-apoptotische Wirkungen in GH3 Zellen, Ratten- und humanen Hypophysenadenomaprimärzellen. Unsere Beobachtungen zeigten weiterhin, dass anti-angiogene Behandlung von Hypophysentumoren im MENX ratstenmodel mit AMG386 die Proliferation in PA`s inhibierte und gleichzeitig Apoptose aktivierte. Diese Studie zeigte, dass eine Blockierung des Ang-2/Tie-2 Signalweg eine potentielle Therapiemöglichkeit für NFPA-Patienten darstellen könnte.

Exposure to Ionizing radiation is an inevitable part of human existence. Although life on earth evolved in an environment with a considerable amount of ionizing radiation, excessive exposure to ionizing radiation results in a range of cancerous and non-cancerous diseases. Recent clinical and experimental models have shown that radiation-induced cardiovascular diseases belong to the spectrum of radiation-induced non-cancer effects., Die Exposition durch ionisierende Strahlung ist ein unvermeidlicher Teil der menschlichen Existenz. Obwohl sich das Leben auf der Erde in einer hoch durch ionisierende Strahlung belasteten Umwelt entwickelte, führt eine übermäßige Exposition zu Krebs und weiteren Erkrankungen. Aktuelle klinische und experimentelle Studien haben gezeigt, dass strahlungsinduzierte kardiovaskuläre Herz-Kreislauf-Erkrankungen zu den nicht-karzinogenen strahlungsinduzierten Krankheiten gehören.

Ziel der Arbeit war die Untersuchung eines eventuellen Bestehens synergistischer Effekte zwischen ionisierender Strahlung durch das Radiopharmakon [18F]FDG und einem statischen Magnetfeld bei PET-MRT-Untersuchungen. Bei der klinisch-experimentellen Studie durchliefen die Probanden PET-CT-, PET-MRT- oder MRT-Untersuchungen. Mithilfe des gamma-H2AX-Assay wurden Doppelstrangbrüche zur Erhebung des genotoxischen Potentials ermittelt. Es konnten keine synergistischen Effekte festgestellt werden., The aim of this study was to investigate possible synergistic effects between ionizing radiation caused by the radiolabeled agent [18F]FDG and a static magnetic field throughout a PET-MRI examination. The probands of this clinical study went through either a PET-CT, PET-MRI, or an MRI examination. With the aid of the gamma-H2AX-Assay double strand breaks were measured to determine the genotoxic potential. No synergistic effects could be found.

Diese Arbeit befasst sich mit der Fragestellung ab welcher Dosis von niedrigen ionisierenden Strahlen ein Risiko für eine Katarakt entsteht. Die verwendeten Dosen betrugen 0 Gy (Scheinbestrahlung/Kontrollen); 0,063 Gy; 0,125 Gy und 0,5 Gy. Es wurden jeweils die Zeitpunkte 4 und 24 h, sowie 12, 18 und 24 Monate nach der Bestrahlung untersucht. Für die Versuche wurden Wildtyp-Mäuse und Ercc2+/--Mäusen eingesetzt., This thesis examines an experimental evidence to determine if low doses of ionizing radiation lead to the formation of cataracts. Doses used were 0 Gy (sham irradiation, controls), 0.063 Gy, 0.125 Gy and 0.5 Gy. Eyes were examined at 4 h, 24 h and 12, 18 and 24 months after irradiation. For this purpose wild-type and Ercc2+/-- mice were used.

Long-term effects of a single low-dose radiation exposure on adult mouse brain and behavior were analyzed to determine the influence of different doses (0.063, 0.125 and 0.5 Gy), time after exposure (4, 12 and 18 months), sex and genotype (wildtype and mutant). Persistent and delayed changes were observed on behavior and hippocampal cell populations, as well as contrasting effects of the highest and lowest dose. No influence of sex was found. Impact of the mutation was significant at older age., Die Langzeitwirkungen einer einzelnen niedrig dosierten Strahlenexposition (0, 0.063, 0.125 oder 0.5 Gy) auf das Gehirn und das Verhalten erwachsener Mäuse wurden analysiert. Anhaltende und verzögerte Veränderungen des Verhaltens und der Hippocampus-Zellpopulationen sowie kontrastierende Effekte der höchsten und niedrigsten Dosis traten auf. Ein Einfluss des Geschlechts wurde nicht festgestellt, genetische Prädisposition war erst im höheren Alter relevant.

This work investigated the effects of low-dose radiation in clinically relevant situations on the brain in a mouse model. The results show that a single low-dose radiation exposure has a strong and sustained effect on the hippocampus at the molecular and structural level. Indications of increased inflammation and cell death were measured at a dose of 0.5 Gy, while lower doses trigger a protective effect. These results contribute to a better understanding of the long-term effects of clinically relevant radiation., Diese Arbeit untersuchte die Auswirkungen von niedrig dosierter Strahlung in klinisch relevanten Situationen auf das Gehirn im Mausmodell. Die Ergebnisse zeigen, dass eine einmalige niedrig dosierte Strahlenexposition eine starke und anhaltende Wirkung auf den Hippocampus auf molekularer und struktureller Ebene hat. Es wurden Hinweise auf eine erhöhte Entzündung und Zelltod bei einer Dosis von 0,5 Gy gemessen, während niedrigere Dosen einen protektiven Effekt auslösen. Diese Ergebnisse tragen dazu bei, die Langzeiteffekte klinisch relevanter Strahlung besser zu verstehen.

Mutations of AIP are associated with a subset of aggressive pituitary adenomas (PAs) that are commonly resistant to therapy. In the present study a novel subset of miRNAs that were differentially expressed between AIPmut+ and AIPmut- human PAs was identified. Functional characterization of two candidate miRNAs in vitro revealed that overexpression of miR-34a increased pro-tumorigenic behavior of PA cells. Gnai2 was validated as a direct target of miR-34a and its protein levels were reduced in AIPmut+ patients. The regulation of Gnai2 by miR-34a is a novel mechanism, which might help to explain AIP-associated tumorigenesis., AIP-Mutationen gehen mit äußerst aggressiven Hypophysenadenomen (HAs) einher, die häufig resistent gegenüber Therapien sind. Die vorgelegte Studie konnte eine Gruppe von miRNAs identifizieren, die zwischen AIPmut+ and AIPmut- Tumoren differenziell exprimiert sind. Funktionelle Charakterisierung zweier Kandidaten zeigte, dass die Überexpression von miR-34a tumorigenes Verhalten von HA Zellen fördert. Gnai2 wurde als direktes Zielgen von miR-34a identifiziert und die Protein Expression war in AIPmut+ Patienten reduziert. Die Regulation von Gnai2 durch miR-34a ist ein neuer Mechanismus, der helfen könnte die AIP-assoziierte Tumorentstehung zu erklären.

This thesis research examines the problem of optimally routing a remotely piloted fuel bladder (RPB) to effectively serve distributed maritime forces. In response to changes in the global threat environment, the U.S. Navy is developing new concepts that involve distributed surface forces operating in large threat areas over prolonged periods at sea. An idea that has been identified to support increasingly distributed forces is the use of minimally manned or unmanned prepositioned bulk fuel storage systems as part of a larger fuel distribution network. While current U.S. defense maritime logistics forces can continue to be called upon to resupply surface forces, they were not designed to support distributed maritime operations. Doing so may, in turn, affect mission effectiveness and operational outcomes. The problem is modeled as a dynamic facility location problem—how to relocate the RPB over discrete-time periods relative to the locations of the distributed surface forces or supported units (SUs). A Markov decision process model is formulated and analyzed with the objective of minimizing the total cost to serve the SUs, whose movements can be stochastic in nature., Commander, Republic of Singapore Navy, Approved for public release. distribution is unlimited

Many discrete-event dynamic systems face changing underlying conditions over time. Manufacturing processes are one example of systems that can be well modeled using discrete-event simulation. System changes include cyclical changes due to natural queueing behavior and changes due to random variability, either of which can involve significant structural changes to the system. For example, machines can degrade in performance, work shift schedules can change, or resources can be reallocated in a state-dependent manner. The ability to detect such changes is an important part of concept drift, which attempts to determine when a model may be outdated due to changing conditions. This research aims to formally integrate discrete-event simulation with methods of concept drift using a military vehicle manufacturing case study. We use simulation modeling to build a comprehensive model of this notional system and collect time series output under a variety of conditions. These output time series of queueing data are used to fit a recurrent neural network that can be used to identify state changes of interest. This work has broader implications in developing methods for detecting unusual activities using concept drift.

Unmanned autonomous vehicles (UAV) have made significant contributions to reconnaissance and surveillance missions in past U.S. military campaigns. As the prevalence of UAVs increases, there have also been improvements in counter-UAV technology that make it difficult for UAVs to successfully obtain valuable intelligence within an area of interest. Hence, it has become important that modern UAVs can accomplish their missions while maximizing their chances of survival. In this work, we specifically study the problem of identifying a short path from a designated start to a goal, while collecting all rewards and avoiding adversaries that move randomly on the grid. We present a comparison of two methods to solve this problem: a Deep Q-Learning model and an online optimization framework. Our computational experiments, designed using simple grid-world environments with random adversaries, showcase how these approaches work and compare them in terms of performance, accuracy, and computational time., Lieutenant Junior Grade, United States Navy, Approved for public release. distribution is unlimited

Many discrete-event dynamic systems face changing underlying conditions over time. Manufacturing processes are one example of systems that can be well modeled using discrete-event simulation. System changes include cyclical changes due to natural queueing behavior and changes due to random variability, either of which can involve significant structural changes to the system. For example, machines can degrade in performance, work shift schedules can change, or resources can be reallocated in a state-dependent manner. The ability to detect such changes is an important part of concept drift, which attempts to determine when a model may be outdated due to changing conditions. This research aims to formally integrate discrete-event simulation with methods of concept drift using a military vehicle manufacturing case study. We use simulation modeling to build a comprehensive model of this notional system and collect time series output under a variety of conditions. These output time series of queueing data are used to fit a recurrent neural network that can be used to identify state changes of interest. This work has broader implications in developing methods for detecting unusual activities using concept drift., Civilian, Singapore Technologies - Engineering Land Systems, Singapore, Approved for public release. Distribution is unlimited.

The U.S. Navy (USN) utilizes the Vertical Launch System (VLS) to store and launch both their offensive and defensive missiles. Since the number of VLS silos on a given ship is fixed, to maximize offensive capability the USN needs to minimize the number of interceptors required to combat incoming anti-surface missiles. Current firing policies may be overly conservative and expend too many interceptors per incoming threat, which results in a substantial fraction of VLS silos dedicated to defensive missiles. Decision makers need an analysis tool to explore the trade-off between missile consumption and probability of raid annihilation (PRA) for various firing policies and would also benefit from a prescriptive algorithm to help inform missile expenditure. This thesis provides a model to optimize VLS firing policy using a set of multiple interceptor types while accounting for range limitations, travel time, multi-interceptor salvos, battle damage assessment, and range dependent probability of kill. Additionally, the thesis derives analytical results for the optimal, lowest-cost allocation of interceptors in the single interceptor case, which, in turn, generates insight into how to structure sequential salvos.

Overview: Vertical launch system (VLS) is the current method to fire missiles from surface naval vessels and nuclear submarines. With the transition to distributed maritime operations (DMO), the USN would like to increase the offensive capability of VLS. The appropriate mix of missiles in VLS is tied to the firing policy to counter an incoming threat. A common firing policy is shoot-shoot-look-shoot-shoot (SSLSS). The "look" is battle damage assessment (BDA) to determine the outcome of the first two shots. With enhanced technology, SSLSS might be overly conservative in using scarce resources for defensive measures. In this project we will focus on determining the optimal mix of missiles in a VLS and the corresponding firing policy. Research Questions: What VLS loadouts strike a proper balance between offensive and defensive postures? What defensive firing policy (e.g., Shoot-Shoot-Look-Shoot-Shoot, Shoot-Look-Shoot) is more effective in a given scenario? How important is BDA time in the solution? (i.e., under what BDA time-windows would a given solution remain optimal?) How can soft-kill weapons (chaff, flare, electronic counter-measures) enhance Blue's effectiveness? Research Plan: We will initially focus on simple models. For example: Red fires n homogenous missiles in its salvo and Blue has m homogenous defensive missiles to counter. We will consider variants with and without BDA. Later we will develop optimization models to examine the optimal VLS missile mix and corresponding firing policy. These will be based on the weapon target assignment problem, but incorporate constraints specific for the VLS context. Initially we will focus on what missiles should go on the VLS and how should Blue employ them. Deliverables: Final report, IPRs, poster, exec summary, algorithms

The Marine Corps is developing anti-surface warfare (ASuW) capabilities as part of its Expeditionary Advanced Base Operations (EABO) concept. The purpose is to provide additional sea-control and sea-denial capabilities as part of an integrated naval ground-based anti-ship missile system (GBASM). A key question concerning GBASM is what is the best mix of munitions to be deployed for the sea-control and sea-denial mission. Besides the obvious fire-effectiveness criterion and its impact on defense capabilities, issues of mobility, vulnerability and logistics should be addressed too within a Pacific Theater scenario. Leveraging existing literature on firing theory and target assignment models, we will develop a descriptive probabilistic model, and associated measures of effectiveness (MOEs), for scenario-dependent evaluation of various munitions' mixes. The descriptive models will be the base for a prescriptive model that will optimize munition mixes and tactical employments. The output of this research will be a methodology for assessing the effect of munitions' mixes on defensive and counter-fire capabilities in the possible presence of other weapons, and a method for optimizing these mixes. The research questions are: What are the MOEs for evaluating munition-mixes in the GBASM context? How to utilize the MOEs to determine optimal in-context (South China Sea) munition-mixes at the tactical level? How to utilize insights obtained from the tactical level to determine deployed mixes for a campaign at the operational level? Based on the answers for questions (2) and (3), what would be the optimal mix of munitions at the strategic level? The research plan will follow a hierarchical bottom up pattern. We first formulate a set of reference tactical scenarios defined by (1) type of threat (2) combat intensity (3) ranges and (4) environmental conditions. Next we will develop a combat model (e.g., stochastic Lanchester) that will take as inputs Blue and Red munitions' characte

Overview: Vertical launch system (VLS) is the current method to fire missiles from surface naval vessels and nuclear submarines. With the transition to distributed maritime operations (DMO), the USN would like to increase the offensive capability of VLS. The appropriate mix of missiles in VLS is tied to the firing policy to counter an incoming threat. A common firing policy is shoot-shoot-look-shoot-shoot (SSLSS). The "look" is battle damage assessment (BDA) to determine the outcome of the first two shots. With enhanced technology, SSLSS might be overly conservative in using scarce resources for defensive measures. In this project we will focus on determining the optimal mix of missiles in a VLS and the corresponding firing policy. Research Questions: What VLS loadouts strike a proper balance between offensive and defensive postures? What defensive firing policy (e.g., Shoot-Shoot-Look-Shoot-Shoot, Shoot-Look-Shoot) is more effective in a given scenario? How important is BDA time in the solution? (i.e., under what BDA time-windows would a given solution remain optimal?) How can soft-kill weapons (chaff, flare, electronic counter-measures) enhance Blue's effectiveness? Research Plan: We will initially focus on simple models. For example: Red fires n homogenous missiles in its salvo and Blue has m homogenous defensive missiles to counter. We will consider variants with and without BDA. Later we will develop optimization models to examine the optimal VLS missile mix and corresponding firing policy. These will be based on the weapon target assignment problem, but incorporate constraints specific for the VLS context. Initially we will focus on what missiles should go on the VLS and how should Blue employ them. Deliverables: Final report, IPRs, poster, exec summary, algorithms

The Marine Corps is developing anti-surface warfare (ASuW) capabilities as part of its Expeditionary Advanced Base Operations (EABO) concept. The purpose is to provide additional sea-control and sea-denial capabilities as part of an integrated naval ground-based anti-ship missile system (GBASM). A key question concerning GBASM is what is the best mix of munitions to be deployed for the sea-control and sea-denial mission. Besides the obvious fire-effectiveness criterion and its impact on defense capabilities, issues of mobility, vulnerability and logistics should be addressed too within a Pacific Theater scenario. Leveraging existing literature on firing theory and target assignment models, we will develop a descriptive probabilistic model, and associated measures of effectiveness (MOEs), for scenario-dependent evaluation of various munitions' mixes. The descriptive models will be the base for a prescriptive model that will optimize munition mixes and tactical employments. The output of this research will be a methodology for assessing the effect of munitions' mixes on defensive and counter-fire capabilities in the possible presence of other weapons, and a method for optimizing these mixes. The research questions are: What are the MOEs for evaluating munition-mixes in the GBASM context? How to utilize the MOEs to determine optimal in-context (South China Sea) munition-mixes at the tactical level? How to utilize insights obtained from the tactical level to determine deployed mixes for a campaign at the operational level? Based on the answers for questions (2) and (3), what would be the optimal mix of munitions at the strategic level? The research plan will follow a hierarchical bottom up pattern. We first formulate a set of reference tactical scenarios defined by (1) type of threat (2) combat intensity (3) ranges and (4) environmental conditions. Next we will develop a combat model (e.g., stochastic Lanchester) that will take as inputs Blue and Red munitions' characte

The recent widespread implementation of Automatic Dependent Surveillance–Broadcasting (ADS-B) systems on aircraft allows for improved monitoring and air traffic control management. As part of this monitoring, it is important to be able to detect unusual flight trajectories due to weather events, detection avoidance, aircraft malfunction, or other activities that may signal anomalous behavior. Given the large volume of ADS-B data available from aircraft around the world, the ability to automatically determine the shape of the trajectory and identify anomalous behavior is important to reduce the need for human identification and labeling. A neural network model is developed for multicategory classification of the shape of the trajectory using features derived from a large ADS-B data set such as bearing and curvature. The results suggest promise in differentiating common trajectory shapes using key factors, with the accuracy of the classifier being comparable to human accuracy.

Ziel der Arbeit war die Untersuchung eines eventuellen Bestehens synergistischer Effekte zwischen ionisierender Strahlung durch das Radiopharmakon [18F]FDG und einem statischen Magnetfeld bei PET-MRT-Untersuchungen. Bei der klinisch-experimentellen Studie durchliefen die Probanden PET-CT-, PET-MRT- oder MRT-Untersuchungen. Mithilfe des gamma-H2AX-Assay wurden Doppelstrangbrüche zur Erhebung des genotoxischen Potentials ermittelt. Es konnten keine synergistischen Effekte festgestellt werden., The aim of this study was to investigate possible synergistic effects between ionizing radiation caused by the radiolabeled agent [18F]FDG and a static magnetic field throughout a PET-MRI examination. The probands of this clinical study went through either a PET-CT, PET-MRI, or an MRI examination. With the aid of the gamma-H2AX-Assay double strand breaks were measured to determine the genotoxic potential. No synergistic effects could be found.

Long-term effects of a single low-dose radiation exposure on adult mouse brain and behavior were analyzed to determine the influence of different doses (0.063, 0.125 and 0.5 Gy), time after exposure (4, 12 and 18 months), sex and genotype (wildtype and mutant). Persistent and delayed changes were observed on behavior and hippocampal cell populations, as well as contrasting effects of the highest and lowest dose. No influence of sex was found. Impact of the mutation was significant at older age., Die Langzeitwirkungen einer einzelnen niedrig dosierten Strahlenexposition (0, 0.063, 0.125 oder 0.5 Gy) auf das Gehirn und das Verhalten erwachsener Mäuse wurden analysiert. Anhaltende und verzögerte Veränderungen des Verhaltens und der Hippocampus-Zellpopulationen sowie kontrastierende Effekte der höchsten und niedrigsten Dosis traten auf. Ein Einfluss des Geschlechts wurde nicht festgestellt, genetische Prädisposition war erst im höheren Alter relevant.

Ionizing radiation influences the intercellular exosome communication of squamous head and neck cancer. Exosomes obtained from irradiated cells induce pro-tumorigenic intracellular signaling cascades, increase cell survival, DNA repair, migration and chemotaxis as well as MMP-activity. As a consequence, exosomes may act as drivers of radioresistance and metastatic head and neck cancer progression during tumor radiotherapy., Ionisierende Strahlung beeinflusst die interzelluläre Exosomen-vermittelte Kommunikation von Plattenepithelkarzinomen. Exosomen aus bestrahlten Zellen induzieren pro-tumorigene intrazelluläre Signalkaskaden, erhöhen das Zellüberleben, die DNA-Reparatur, die Migration und die Chemotaxis sowie die MMP-Aktivität. Infolgedessen können Exosomen die Strahlenresistenz und die Ausbildung von Metastasen während der Strahlentherapie von Kopf- und Halstumorpatienten fördern.

The response of non-transformed mammary epithelial cells and breast cancer cells to anti-miR-21 treatment alone and in combination with radiation has been evaluated. The combined treatment led to a significant increase in apoptosis as well as reduced growth and viability of cancer cells compared to normal cells whose proliferation was not significantly affected. The absence of phosphorylated JNK1/2 was observed after miR-21 knockdown in MCF-10A cells. The response to the combined treatment differs between cancer and non-cancer cells, this may hold a significant therapy potential for the breast cancer patients., Die Wirkung von einer anti-miR-21 Behandlung wurde auf nicht-transformierte Brustepithelzellen (MCF-10A) und auf Brustkrebszellen (MDA-MB-361) untersucht und der Effekt der Therapie allein und in Kombination mit Bestrahlung überprüft. Unsere Ergebnisse zeigen, dass die kombinierte Behandlung in Krebszellen zu einem signifikanten Anstieg in Apoptose, reduziertem Wachstum und Zellvitalität führen, während die Proliferation von gesunden Brustzellen nicht signifikant beeinträchtigt wurde. Es konnte gezeigt werden, dass nach Behandlung von MCF-10A JNK1/2 nicht nur geringer exprimiert wird, sondern auch nicht mehr phosphoryliert wird. Der Behandlungseffekt unterscheidet sich zwischen nicht-transformierten Brustepithelzellen und Brustkrebszellen, wodurch die Einsatzmöglichkeit in der Therapie ein großes Potential für die Brustkrebspatienten birgt.

Motivated by situations arising in surveillance, search and monitoring, in this paper we study dynamic allocation of assets which tend to fail, requiring replenishment before being once again available for operation on one of the available tasks. We cast the problem as a closed-system continuous-time Markov decision process with impulsive controls, maximising the long-term time-average sum of per-task reward rates. We then formulate an open-system continuous-time approximative model, whose Lagrangian relaxation yields a decomposition (innovatively extending the restless bandits approach), from which we derive the corresponding Whittle index. We propose two ways of adapting the Whittle index derived from the open-system model to the original closed-system model, a naïve one and a cleverly modified one. We carry out extensive numerical performance evaluation of the original closed-system model, which indicates that the cleverly modified Whittle index rule is nearly optimal, being within 1.6% (0.4%, 0.0%) of the optimal reward rate 75% (50%, 25%) of the time, and significantly superior to uniformly random allocation which is within 22.0% (16.2%, 10.7%) of the optimal reward rate. Our numerical results also suggest that the Whittle index must be cleverly modified when adapting it from the open-system, as the naïve Whittle index rule is not superior to a myopic greedy policy.

To understand the molecular changes of DNA repair in Mesenchymal stem cells (MSCs) of murine and human origin, which take place during in-vivo (physiological) ageing and during in-vitro ageing in the course of massive stem cell expansion, we performed this project. Considering the importance of telomere stability for the maintenance of MSCs long-term repopulation potential and stemness, the DNA repair capacity was studied with a special interest for the telomere regions of MSCs., Um die molekularen Veränderungen der DNA-Reparatur in Mesenchymale Stammzellen (MSCs) murinen und menschlichen Ursprungs zu verstehen, die während des (physiologischen) Alterns in vivo und während des Alterns in vitro im Verlauf einer massiven Stammzellenexpansion stattfinden, haben wir dieses Projekt durchgeführt. In Anbetracht der Bedeutung der Telomerstabilität für die Aufrechterhaltung des langfristigen Repopulationspotentials und der Stammzellen von MSC wurde die DNA-Reparaturkapazität mit besonderem Fokus auf die Änderungen in der Struktur an den Telomeren von MSC untersucht.

This study aims to find out differences between T2D-MSCs and healthy-MSCs when exposed to 3 Gy radiation, and to generate MSCs with therapeutic potential from type 2 diabetes patients derived stem cells, thereby reducing cell heterogeneity and age-related impairment of stem cell potency., Das Ziel von dieser Studie ist sowohl den Unterschied zwischen T2D-MSCs and healthy-MSCs heraus zu finden, wenn sie under der Strahlung von 3 Gy sind, als auch die Generation von MSCs mit therapeutischen Potenzial aus den T2D Patienten stammenden Stammzellen. Dadurch werden die Zellheterogenität und die mit dem Alter gebundenen Beeinträchtigungen von Stammzellen-Potenz reduziert.

Nonfunctioning PAs (NFPAs) count for 30-40% of all pituitary tumors and in most cases (80%) they originate from gonadotroph cell linage. Lacking of signs and symptoms of hormone hypersecretion allows these tumors to grow and reach the macroadenoma stage. In such cases, a complete surgical removal of tumor is not achieved and the tumors tend to recur with various tempo. Currently, radiotherapy is the main post-operative option but it is not curative. Gene expression array analysis of MENX rat pituitary adenomas (PAs) identified many genes deregulated in these tumors among them Angiopoietin-1 (Ang-1) and Ang-2, which have not been extensively studied in pituitary adenoma progression like other angiogenesis promoting factors such as Vegf. We observed that rat and human PAs express higher amounts of Ang-2 at protein and mRNA level compared to non-tumorous tissues or healthy controls. Moreover, this protein was also detected in supernatant of rat and human primary PA cultures/established cell lines and plasma of NFPA patients indicating that this ligand is secreted by PA cells into culture medium or circulating blood. We found also that Ang-2 specific receptor, Tie-2, is expressed and partially phosphorylated in PA cells. This receptor could be activated by rhANG-2 in Ang-2-silenced GH3 cells and subsequently we observed activation of corresponding downstream signaling molecules. Activated Ang-2/Tie-2 signaling supported cell proliferation and displayed anti-apoptotic effects in rat and human primary PA cells and established GH3 cell line and blocking of this pathway led to decreased cell proliferation and enhanced apoptosis. In vivo treatment of MENX rats with anti-angiogenic drug AMG386 suppressed cell proliferation and induced apoptosis after 2 weeks, which suggests that blocking of this pathway might be a potential therapy option for NFPA patients, Hypophysenadenome (PA`s) sind häufig auftretende, intrakraniale Tumore. Etwa ein Drittel dieser Tumore bilden die nicht-funktionelle Hypophysenadenome (NFPA`s), die in 80% der Fälle aus gonadotropen Zellen bestehen. Da sie keine aktiven Hormone sezernieren, werden sie häufig relativ spät, im Makroadenoma-Stadium, diagnostiziert. Dadurch ist eine komplette chirurgische Entfernung oft erschwert und Rezidive können entstehen. Diese Adenome sprechen selten auf klassische medikamentöse Behandlungen an. Im Rahmen dieser Arbeit konnten wir zeigen, dass die Expression von Angiopoietin-1 (Ang-1) und Angiopoietin-2 (Ang-2) in Hypophysenadenomen des MENX ratstenmodels dysreguliert ist. Im Speziellen fanden wir, dass die Menge an Ang-2 sowohl in Ratten- als auch humanen NPFA auf mRNA- und Proteinebene erhöht war. Ang-2 wurde von primären Hypophysentumorkulturen aus Ratte und Mensch ins Zellkulturmedium sekretiert. Eine erhöhte Konzentration an Ang-2 konnte nachfolgend auch in Plasmaproben von NFPA-Patienten nachgewiesen werden. Im Rahmen dieser Arbeit konnten wir zeigen, dass Ang-2 als ein alternativer Ligand für den Rezeptor Tie-2 fungieren kann. Dieser lag in den Hypophysenadenomen daher in einer aktivierten, phosphorylierten Form vor. Durch Stimulation mit rekombinantem ANG-2 Protein, konnten wir eine extrazelluläre Stimulierung des Rezeptors in GH3 Hypophysenzellkulturen nachweisen, welche wiederum im Stande war intrinsische Signalkaskaden zu aktivieren. Dieser aktive Ang-2/Tie-2 Signalweg zeigte proliferative und anti-apoptotische Wirkungen in GH3 Zellen, Ratten- und humanen Hypophysenadenomaprimärzellen. Unsere Beobachtungen zeigten weiterhin, dass anti-angiogene Behandlung von Hypophysentumoren im MENX ratstenmodel mit AMG386 die Proliferation in PA`s inhibierte und gleichzeitig Apoptose aktivierte. Diese Studie zeigte, dass eine Blockierung des Ang-2/Tie-2 Signalweg eine potentielle Therapiemöglichkeit für NFPA-Patienten darstellen könnte.

After boot camp, Marines enroll in a military occupational specialty (MOS) school. Unfortunately, due to enlistment fluctuations, there may be significant backlogs at certain schools. These backlogs cause Marines to enter Marines Awaiting Training (MAT) status, where they wait for a spot in their school to become available. These waits can last several months and are an inefficient use of Marine Corps resources and manpower. The Automotive Maintenance Technician’s Basic Course (AMTBC) at Camp Johnson, North Carolina, in particular struggles with a seasonal influx of new students due to the recruiting cycle. Currently, all AMTBC students are trained based on their Armed Forces Active Duty Base Date (AFADBD), without regard to prior experience, and via a fixed-sequence curriculum. The current process results in a backlog of students following the high school graduation cycle. By modeling the current process, we identify possible modifications to the system to reduce wait times and increase throughput. We also identify means of enhancing the quality of training by increasing hands-on training time, and estimate the potential impacts these changes could have on fleet-wide vehicle readiness. Additional research is needed to identify specific cost-benefit trade-offs, but the insights gained by studying AMTBC may also be applicable to other MOS-producing schools in the Marine Corps.

The present state of the naval logistics system is efficient and effective at supplying forward-deployed naval forces; however, it is optimized for operations in uncontested environments. As the United States enters another era of great-power competition, it must determine the type of logistics system that is able to operate in a region where friendly forces do not have sea control. This study creates a network of logistics hubs in the Pacific theater. Using network science and prominent centrality measures, we examine the structure of a nominal Pacific theater logistics network for an array of logistic assets. In this thesis, we develop a maximum flow algorithm and apply it to our logistics network. Our proposed maximum flow algorithm optimizes vessel configuration and routing to satisfy as much demand as possible. We hope our study provides insights into the capabilities of the current logistics system and potential areas for improving logistics capabilities in contested environments.

The U.S. Marine Corps utilizes its Supply Management Units (SMU) to provide Class IX repair parts support for the Marine Expeditionary Forces. These SMUs work with the Defense Logistics Agency to maintain an inventory of Class IX items that meets customer demand. Each SMU calibrates the inventory levels for each of its repair parts by adjusting several parameters: reorder point (ROP), time between inventory inspections (TBI), and requisitioning objective (RO). ROP and TBI determine when the SMU should replenish its inventory, and the RO determines how much should be ordered. Although current practice has allowed the SMUs to meet customer demand, due to budget cycle pressure and inaccurate parameter setting, parts overages and shortages occur. These lead to issues such as returning unordered materiel for reduced credit, increased inventory overhead costs, and longer customer wait times. This thesis constructs a stochastic simulation model using Simio to investigate if there are more efficient inventory policies than the SMUs’ current practice. The research focuses on customer wait time and aims to provide recommendations on inventory policies to the SMUs., HQMC DC I&L, LP, http://archive.org/details/evaluatinginvent1094564872, Outstanding Thesis, Lieutenant Commander, United States Navy, Approved for public release; distribution is unlimited.

There is a recent abundance of flight trajectory data due to Automatic Dependent Surveillance-Broadcast (ADS-B) becoming a prevalent and required aviation traffic control system. Motivated by incidents like the September 11, 2001, attacks, the Department of Defense and civilian intelligence agencies have taken a renewed interest in being able to quickly flag and act on flight pattern behavior that is considered outside the norm. Due to the large volume of daily flights in the United States alone, it is almost impossible for human operators to monitor and analyze individual flights for anomalous behavior. The Department of Defense and civilian intelligence agencies stand to gain increased capability and capacity if given the ability to analyze and flag unusual flight trajectories in a matter of seconds. Anomalous behavior in many cases is determined by the overall shape of the flight pattern. This thesis uses calculated shape features to classify nine pre-determined categories of ADS-B flight trajectories using a Deep Sequential Neural Network. With a data set of 11,303 human-classified tracks, the network has performed with an overall accuracy of 71% and a categorical average F1 score of 0.33 on a validation set. It has also performed with 70% accuracy and a categorical average F1 score of 0.25 on a ten-fold cross validation. The proposed method shows promise in being able to select unusual shapes from straight trajectories and in some cases may be able to classify them., Ensign, United States Navy, Approved for public release. distribution is unlimited

This report examines the transport and delivery of logistics in contested environments within the context of great-power competition (GPC). Across the Department of Defense (DOD), it is believed that GPC will strain our current supply lines beyond their capacity to maintain required warfighting capability. Current DOD efforts are underway to determine an appropriate range of platforms, platform quantities, and delivery tactics to meet the projected logistics demand in future conflicts. This report explores the effectiveness of various platforms and delivery methods through analysis in developed survivability, circulation, and network optimization models. Among other factors, platforms are discriminated by their radar cross-section (RCS), noise level, speed, cargo capacity, and self-defense capability. To maximize supply delivered and minimize the cost of losses, the results of this analysis indicate preference for utilization of well-defended convoys on supply routes where bulk supply is appropriate and smaller, and widely dispersed assets on shorter, more contested routes with less demand. Sensitivity analysis on these results indicates system survivability can be improved by applying RCS and noise-reduction measures to logistics assets., Director, Warfare Integration (OPNAV N9I), Major, Israel Defence Forces, Civilian, Singapore Technologies Engineering Ltd, Singapore, Commander, Republic of Singapore Navy, Commander, United States Navy, Captain, Singapore Army, Lieutenant, United States Navy, Lieutenant, United States Navy, Major, Republic of Singapore Air Force, Captain, United States Marine Corps, Lieutenant, United States Navy, Lieutenant, United States Navy, Lieutenant, United States Navy, Lieutenant, United States Navy, Lieutenant, United States Navy, Captain, Singapore Army, Lieutenant Junior Grade, United States Navy, Captain, Singapore Army, Lieutenant Colonel, Republic of Singapore Air Force, Approved for public release. distribution is unlimited

The present state of the naval logistics system is efficient and effective at supplying forward-deployed naval forces; however, it is optimized for operations in uncontested environments. As the United States enters another era of great-power competition, it must determine the type of logistics system that is able to operate in a region where friendly forces do not have sea control. This study creates a network of logistics hubs in the Pacific theater. Using network science and prominent centrality measures, we examine the structure of a nominal Pacific theater logistics network for an array of logistic assets. In this thesis, we develop a maximum flow algorithm and apply it to our logistics network. Our proposed maximum flow algorithm optimizes vessel configuration and routing to satisfy as much demand as possible. We hope our study provides insights into the capabilities of the current logistics system and potential areas for improving logistics capabilities in contested environments., Outstanding Thesis, Lieutenant Junior Grade, United States Navy, Approved for public release. distribution is unlimited

The Navy-Marine Corps Team as informed by A Design for Maintaining Maritime Superiority 2.0 and the 38th Commandant of the Marine Corps’ Commandant’s Planning Guidance (CPG) is planning to conduct distributed maritime operations and expeditionary advanced base operations. These highly distributed and mobile operations require new material and operational solutions for the storage and distribution of bulk fuel to sustain forces in the area of responsibility. The challenge of conducting distributed operations in contested environments disrupts the employment of current Combat Logistics Force platforms. This study investigates the bulk fuel cache (BFC) concept of minimally manned or unmanned pre-positioned bulk fuel storage systems as an alternative method for sustaining forward deployed operations in contested environments. This study considers a facility location model with stochastic demand and dynamic location to establish a baseline of operating considerations and concepts for the integration of BFCs into the naval logistics enterprise. This study explores BFC quantity, capacity, location, and dynamic movement for optimal sustainment of a distributed maritime force and informs future planning and acquisitions efforts., Major, United States Marine Corps, Approved for public release. distribution is unlimited

The U.S. Marine Corps utilizes its Supply Management Units (SMU) to provide Class IX repair parts support for the Marine Expeditionary Forces. These SMUs work with the Defense Logistics Agency to maintain an inventory of Class IX items that meets customer demand. Each SMU calibrates the inventory levels for each of its repair parts by adjusting several parameters: reorder point (ROP), time between inventory inspections (TBI), and requisitioning objective (RO). ROP and TBI determine when the SMU should replenish its inventory, and the RO determines how much should be ordered. Although current practice has allowed the SMUs to meet customer demand, due to budget cycle pressure and inaccurate parameter setting, parts overages and shortages occur. These lead to issues such as returning unordered materiel for reduced credit, increased inventory overhead costs, and longer customer wait times. This thesis constructs a stochastic simulation model using Simio to investigate if there are more efficient inventory policies than the SMUs’ current practice. The research focuses on customer wait time and aims to provide recommendations on inventory policies to the SMUs.

We consider Monte Carlo simulation in a setting where the samples are subject to random censoring. Such censoring occurs in settings as varied and diverse as perimeter protection, survival analysis, and electro-magnetic spectrum monitoring. We introduce and analyze two estimators: one based on empirical likelihood methods and another rooted in control variates ideas. We show that the proposed estimators can dramatically reduce the estimator variance in relation to the crude Monte Carlo estimator while not sacrificing computational speed.

This thesis research examines the problem of optimally routing a remotely piloted fuel bladder (RPB) to effectively serve distributed maritime forces. In response to changes in the global threat environment, the U.S. Navy is developing new concepts that involve distributed surface forces operating in large threat areas over prolonged periods at sea. An idea that has been identified to support increasingly distributed forces is the use of minimally manned or unmanned prepositioned bulk fuel storage systems as part of a larger fuel distribution network. While current U.S. defense maritime logistics forces can continue to be called upon to resupply surface forces, they were not designed to support distributed maritime operations. Doing so may, in turn, affect mission effectiveness and operational outcomes. The problem is modeled as a dynamic facility location problem—how to relocate the RPB over discrete-time periods relative to the locations of the distributed surface forces or supported units (SUs). A Markov decision process model is formulated and analyzed with the objective of minimizing the total cost to serve the SUs, whose movements can be stochastic in nature.

After boot camp, Marines enroll in a military occupational specialty (MOS) school. Unfortunately, due to enlistment fluctuations, there may be significant backlogs at certain schools. These backlogs cause Marines to enter Marines Awaiting Training (MAT) status, where they wait for a spot in their school to become available. These waits can last several months and are an inefficient use of Marine Corps resources and manpower. The Automotive Maintenance Technician’s Basic Course (AMTBC) at Camp Johnson, North Carolina, in particular struggles with a seasonal influx of new students due to the recruiting cycle. Currently, all AMTBC students are trained based on their Armed Forces Active Duty Base Date (AFADBD), without regard to prior experience, and via a fixed-sequence curriculum. The current process results in a backlog of students following the high school graduation cycle. By modeling the current process, we identify possible modifications to the system to reduce wait times and increase throughput. We also identify means of enhancing the quality of training by increasing hands-on training time, and estimate the potential impacts these changes could have on fleet-wide vehicle readiness. Additional research is needed to identify specific cost-benefit trade-offs, but the insights gained by studying AMTBC may also be applicable to other MOS-producing schools in the Marine Corps., Major, United States Marine Corps, Approved for public release. distribution is unlimited