No description available.

Rising global antibiotic resistance has caused concerns over sources and pathways for the spread of contributing factors. Majority of the antimicrobials used in the U.S. are involved in veterinary medicine, primarily with livestock rearing. Animal manure land application integrates livestock farming and agroecosystems. This manure contains antibiotic resistant elements (AREs) (resistant bacteria, resistance genes, and veterinary antibiotics) that contribute towards antimicrobial resistance. Altering manure application techniques can reduce surface runoff of other contaminants such as excess N and P, pesticides, and hormones, that can impact water quality. Conventional tillage practices in the U.S. has reduced or stopped, making subsurface injection of manure a promising option when compared to surface application. Our research compared manure application methods, manure application seasons, cropping system, and manure-rainfall time gaps to gauge the impact on AREs in the environment. Two field-scale rainfall simulation studies were conducted along with one laboratory study. Using the injection method lowered concentrations of manure associated AREs entering surface runoff. When manure was surface applied and rainfall occurred 7 d after application, 9-30 times less resistant fecal coliform bacteria (FCB) entered surface runoff when compared to 1 d time gap for that broadcast method. Within a day of manure application, antibiotic resistance gene (ARG) profiles in soil began to differ from each other based on manure application and soil ARG richness in all manure-amended soil increased compared to the background. Runoff from injection plots contained 52 ARGs with higher abundance compared to runoff from surface applied plots. ARGs in the former were more correlated to soil and more correlated to manure in the latter. The highest antibiotic concentrations were in the injection slit soil of those plots. Antibiotic concentrations in samples corresponded positively to concentrations of resistant FCB and ARGs, and there was a positive correlation between resistant FCB and their associated ARGs (Spearman's ρ = 0.43-0.63). A CRIISPR-Cas12a assay for quantification of ARGs in environmental samples was just as precise as conventional methods. There is also potential for in-situ detection. These combined results can hopefully help farmers improve manure management practices that mitigate spread of AREs to surrounding water, crops, and soil. / Doctor of Philosophy / Rising global antibiotic resistance cause concerns over sources and pathways for the spread of contributing factors. Most of the antimicrobials used in the U.S. are involved in veterinary medicine, especially with livestock rearing. Overuse of antibiotics that are medically important to human medicine compromises the effectiveness of our medicines. Animal manure contains antibiotic resistant elements (AREs) such as resistant bacteria, resistance genes, and antibiotics) that contribute towards resistance issues. Once these AREs enter the environment, they can be taken up by crops, runoff into surface water or leached into ground water, or even reside within the animal products we consume. Altering manure application techniques is beneficial for nutrient conservation but also potentially for reducing ARE spread. With our research, we compared manure application methods, manure application seasons, cropping systems, and manure-rainfall time gaps to find ways to balance the need for manure application and the spread of resistance. We used two field-scale rainfall simulation studies along with one laboratory study. Overall, using the injection method resulted in significantly lower concentrations of manure associated AREs entering surface runoff. When manure was surface applied and rainfall occurred 7 d after application, less resistant fecal coliform bacteria (FCB) entered surface runoff when compared to the 1 d time gap for broadcast methods. Within a day of manure application, antibiotic resistance gene (ARG) profiles in soil began to differ from each other and soil ARG totals in all manure applied soil increased compared to the background. Runoff from injection plots contained more soil ARGs and runoff from surface applied plots containing more manure associated ARGs. The subsurface injection method also caused highest antibiotic concentrations in the injection slit soil of those plots. High antibiotic concentrations in samples generally meant high concentrations of resistant FCB and ARGs, and resistant FCB were also found with their associated ARGs as well. A CRISPR-Cas12a assay for quantification of ARGs in environmental samples was just as precise as conventional methods. There is also potential for onsite detection. These combined results can hopefully help farmers improve manure management practices that mitigate spread of AREs to surrounding water, crops, and soil.

This dissertation combines studies of aeolian bedforms and aeolian dune-field patterns to create a comprehensive set of tools that can be used in tandem (or separately) to extract information about climate change and landscape evolution, and to identify the controls on formation for specific modern dune fields or ancient aeolian sequences. The spatial distribution of surface processes, erosion/deposition rates, and lee face sorting on aeolian dunes are each a function of the incident angle. This correlation between stratification style and incidence angle can be used to develop a “toolbox” of methods based on measurements of key suites of parameters found in ancient aeolian deposits. Information obtained from the rock record can be used as input data for different kinds of numerical models. Regional-scale paleowind conditions can be used to validate paleoclimate and global circulation models. Understanding the natural variability in the Earth’s climate throughout its history can help predict future climate change. Reconstructed wind regimes and bedform morphologies can be used in numerical models of aeolian dune-field pattern evolution to simulate patterns analogous to those reconstructed from ancient aeolian systems. Much of the diversity of aeolian dune-field patterns seen in the real world is a function of the sediment supply and transport capacity, which in turn determine the sediment availability of the system. Knowledge of the sediment supply, availability, and transport capacity of aeolian systems can be used to predict the amount of sand in the system and where it might have migrated. This information can be extremely useful for development and production of oil and gas accumulations, where a discovery has been made but the spatial extent of the aeolian reservoir is unknown. / text

Congenital myasthenic syndromes (CMS) are a group of heterogeneous disorders caused by mutations in genes encoding for proteins that are essential for neuromuscular transmission. All CMS share the clinical feature of fatigable muscle weakness. The differential diagnosis of CMS is wide, with a range of diseases going from autoimmune myasthenia gravis to muscle disorders. In this thesis, it was shown that measuring antibodies to clustered acetylcholine receptors (AChRs) by cell-based assay is helpful in the differential diagnosis of CMS. The findings of the current investigations showed that mutations in COL13A1, encoding the Collagen Type XIII α1 chain, were responsible for the symptoms of several patients with previously undefined myasthenias. In addition, this work described the clinical and complementary features of a novel CMS subtype due to mutations in the glycosylation pathway gene GMPPB. Investigations on a novel MUSK missense mutation (p.Ala617Val) uncovered previously unrecognised mechanisms of how levels of MuSK phosphorylation are critical to maintain synaptic structure, and guided suitable treatment for the patient. The study on the clinical and molecular basis of stridor, a novel clinical feature recently identified in patients with DOK7-CMS, prompted the identification of a novel DOK7 isoform, which warrants further investigation to elucidate its role in AChR clustering. Finally, the therapy of patients with severe AChR-deficiency was optimised thanks to a case series study that showed a robust improvement following the addition of β2-adrenergic agonists to their long-term treatment regime that included pyridostigmine.

Effect of architecture at nanoscale on the macroscopic properties of polymer materials has long been a field of major interest, as evidenced by inhomogeneities in networks, multimodal network topologies, etc. The primary purpose of this research is to establish the architecture-property relationship of polymer networks by studying the physical and mechanical responses of a series of topologically different PTHF networks. Monodispersed allyl-terminated PTHF precursors were synthesized through ¡°living¡± cationic polymerization and functional end-capping. Model networks of various crosslink densities and inhomogeneities levels (unimodal, bimodal and clustered) were prepared by endlinking precursors via thiol-ene reaction. Thermal characteristics, i.e., glass transition, melting point, and heat of fusion, of model PTHF networks were investigated as functions of crosslink density and inhomogeneities, which showed different dependence on these two architectural parameters. Study of freezing point depression (FPD) of solvent confined in swollen networks indicated that the size of solvent microcrystals is comparable to the mesh size formed by intercrosslink chains depending on crosslink density and inhomogeneities. Relationship between crystal size and FPD provided a good reflection of the existing architecture facts in the networks. Mechanical responses of elastic chains to uniaxial strains were studied through SANS. Spatial inhomogeneities in bimodal and clustered networks gave rise to ¡°abnormal butterfly patterns¡±, which became more pronounced as elongation ratio increases. Radii of gyration of chains were analyzed at directions parallel and perpendicular to stretching axis. Dependence of Rg on ¦Ë was compared to three rubber elasticity models and the molecular deformation mechanisms for unimodal, bimodal and clustered networks were explored. The thesis focused its last part on the investigation of evolution of free volume distribution of linear polymer (PE) subjected to uniaxial strain at various temperatures using a combination of MD, hard sphere probe method and Voronoi tessellation. Combined effects of temperature and strain on free volume were studied and mechanism of formation of large and ellipsoidal free volume voids was explored.

No description available.

The thesis consists of three parts. In the first part, we introduce the notion of device-cache-aware schedulers. Modern disk subsystems have many megabytes of memory for various purposes such as prefetching and caching. Current disk scheduling algorithms make decisions oblivious of the underlying device cache algorithms. In this thesis, we propose a scheduler architecture that is aware of underlying device cache. We also describe how the underlying device cache parameters can be automatically deduced and incorporated into the scheduling algorithm. In this thesis, we have only considered adaptive caching algorithms as modern high end disk subsystems are by default configured to use such algorithms. We implemented a prototype for Linux anticipatory scheduler, where we observed, compared with the anticipatory scheduler, upto 3 times improvement in query execution times with Benchw benchmark and upto 10 percent improvement with Postmark benchmark. The second part deals with implementing cooperative caching for the Redhat Global File System. The Redhat Global File System (GFS) is a clustered shared disk file system. The coordination between multiple accesses is through a lock manager. On a read, a lock on the inode is acquired in shared mode and the data is read from the disk. For a write, an exclusive lock on the inode is acquired and data is written to the disk; this requires all nodes holding the lock to write their dirty buffers/pages to disk and invalidate all the related buffers/pages. A DLM (Distributed Lock Manager) is a module that implements the functions of a lock manager. GFS’s DLM has some support for range locks, although it is not being used by GFS. While it is clear that a data sourced from a memory copy is likely to have lower latency, GFS currently reads from the shared disk after acquiring a lock (just as in other designs such as IBM’s GPFS) rather than from remote memory that just recently had the correct contents. The difficulties are mainly due to the circular relationships that can result between GFS and the generic DLM architecture while integrating DLM locking framework with cooperative caching. For example, the page/buffer cache should be accessible from DLM and yet DLM’s generality has to be preserved. The symmetric nature of DLM (including the SMP concurrency model) makes it even more difficult to understand and integrate cooperative caching into it (note that GPFS has an asymmetrical design). In this thesis, we describe the design of a cooperative caching scheme in GFS. To make it more effective, we also have introduced changes to the locking protocol and DLM to handle range locks more efficiently. Experiments with micro benchmarks on our prototype implementation reveal that, reading from a remote node over gigabit Ethernet can be upto 8 times faster than reading from a enterprise class SCSI disk for random disk reads. Our contributions are an integrated design for cooperative caching and lock manager for GFS, devising a novel method to do interval searches and determining when sequential reads from a remote memory perform better than sequential reads from a disk. The third part deals with selecting a primary network partition in a clustered shared disk system, when node/network failures occur. Clustered shared disk file systems like GFS, GPFS use methods that can fail in case of multiple network partitions and also in case of a 2 node cluster. In this thesis, we give an algorithm for fault-tolerant proactive leader election in asynchronous shared memory systems, and later its formal verification. Roughly speaking, a leader election algorithm is proactive if it can tolerate failure of nodes even after a leader is elected, and (stable) leader election happens periodically. This is needed in systems where a leader is required after every failure to ensure the availability of the system and there might be no explicit events such as messages in the (shared memory) system. Previous algorithms like DiskPaxos are not proactive. In our model, individual nodes can fail and reincarnate at any point in time. Each node has a counter which is incremented every period, which is same across all the nodes (modulo a maximum drift). Different nodes can be in different epochs at the same time. Our algorithm ensures that per epoch there can be at most one leader. So if the counter values of some set of nodes match, then there can be at most one leader among them. If the nodes satisfy certain timeliness constraints, then the leader for the epoch with highest counter also becomes the leader for the next epoch (stable property). Our algorithm uses shared memory proportional to the number of processes, the best possible. We also show how our protocol can be used in clustered shared disk systems to select a primary network partition. We have used the state machine approach to represent our protocol in Isabelle HOL logic system and have proved the safety property of the protocol.

Plug nozzle, a passive altitude adaptive nozzle, for futuristic SSTO applications, exhibits greater efficiency as compared to conventional nozzles over a wide range of altitudes. The plug nozzle comprises of a primary nozzle and a contoured plug; an under–expanded jet exiting the primary nozzle is allowed to further expand over the plug surface for altitude adaptation. At design condition the flow expands correctly to the ambient conditions on the full length plug surface, while at off design conditions the flow adapts to the ambient conditions through wave interactions within the nozzle core jet. Based on thrust to weight considerations, the full length plug is truncated and this results in a base flow rich in flow physics. In addition, the base flow exhibits an interesting transitional behaviour from open wake to a closed wake because of the wave interactions within the nozzle core jet. The plug surface flow can further exhibit flow complexities because of wave interactions resulting from the shear layer emanating from the splitter plates, in case of clustered plug flows. Considering these flow complexities, the design of the plug nozzles and analysing the associated flows can be a challenge to the aerodynamic community. An attempt has been made in understanding this class of flows in this thesis. This objective has been accomplished using both experimental and computational tools. In the present work, both the linear and annular plug nozzle geometries have been analysed for a wide range of pressure ratios spanning from 5to 80. The linear and annular nozzles have been designed for similar flow conditions and their respective design pressure ratios are 60and 66. From the experimental and computational results, it has been shown that the computational solver performs well in predicting the wave interactions on the plug surface. In addition the limitations of the computational solver in predicting the plug base flows in general has been brought out. This limitation in itself need not be considered as a serious handicap in the design and analysis of plug nozzle flows; this is because the plug base contribution to the thrust is very minimal, as has been brought out in this thesis. Apart from this the high quality experimental data generated is also of immense value to the CFD community as this also serves as a valuable data base for CFD code validation. For analysis, the plug flow field has been categorized into three different regimes based on the primary nozzle lip expansion fan extent. The flow field is categorised based on the reflection of the primary nozzle lip expansion fan from plug surface, base region shear layer and symmetry line downstream of the base region recirculation bubble. This flow division is particularly helpful in understanding the base wake characteristics with increasing pressure ratio. The base lip pressure and the base pressure variation have been discussed with respect to the primary nozzle lip expansion fan extent. In the open wake regime (or for low pressure ratios) the wave interactions within the core jet flow impinge on the base region shear layer. Because of these interactions it is difficult to propose an empirical model for open wake base pressure. In the closed wake regime (for higher pressure ratios), the base region recirculation bubble is completely under the shower of primary nozzle lip expansion fan. Hence the base lip pressure and base pressure are frozen with respect to stagnation conditions. Based on these insights it was possible to propose empirical models for linear and annular closed wake base pressure. Along with these, a mathematical model defining a reference pressure ratio PR∗, beyond which the closed wake base pressure is expected to be more than the ambient pressure has also been proposed. This is expected to serve as a good design parameter. In case of linear plug flows, this also serves the purpose of base wake transition, for the cases considered in this thesis. The flow expansion process or the primary nozzle lip expansion fan extent was also useful in understanding the differences between the linear and annular plug nozzle flow fields. In a linear plug nozzle, the flow expands only in the streamwise direction while in an annular plug nozzle the flow expands both along the streamwise and azimuthal directions. The flow expands at a faster rate in case of annular nozzle as against linear nozzle. Hence differences are observed between the linear and annular nozzle on plug and base surfaces. On the annular plug surface more wave interactions are observed because of faster expansion. With regard to base characteristics, faster expansion in annular plug nozzle, with respect to linear nozzle, results in a lower base lip pressure, lower base pressure and higher wake transition pressure ratio. The realistic cluster plug configurations have also been considered for the present studies. The effects of clustering on the plug nozzle flow field have been brought out by considering two different linear cluster nozzles and one annular cluster nozzle. The differences in the flow field of a simple and cluster plug nozzle has been discussed. In case of simple plug nozzle wave interactions are observed only in the stream wise direction, while in case of cluster plug nozzle three dimensional wave interactions are observed because of the splitter plates. Along the splitter plate differential end conditions introduce a curved recompression shock on the plug surface. This recompression shock in turn induces a streamwise vortex and also a secondary shock. It has been observed that differences between the simple and cluster plug surface pressure field are because of three dimensional wave interactions. Regarding the base pressure, differences between the simple and cluster geometries were observed for shorter truncation plug lengths (20% length plug). While for longer plug lengths (more than 34% length) the effects of clustering were reduced on the base pressure. Regarding the transition pressure ratio, differences were observed between simple and clustered plug nozzles for all the plug lengths considered. In addition, the performance of the plug nozzles has been carried out. From the analysis it was found that the primary nozzle and plug surface are major contributors towards thrust. The base surface contributes only about 2– 3% of the thrust at design condition. Hence, from a design point of view, a computational solver can be a useful tool considering its efficacy on the plug surface and in the primary nozzle.

Plug nozzle, a passive altitude adaptive nozzle, for futuristic SSTO applications, exhibits greater efficiency as compared to conventional nozzles over a wide range of altitudes. The plug nozzle comprises of a primary nozzle and a contoured plug; an under–expanded jet exiting the primary nozzle is allowed to further expand over the plug surface for altitude adaptation. At design condition the flow expands correctly to the ambient conditions on the full length plug surface, while at off design conditions the flow adapts to the ambient conditions through wave interactions within the nozzle core jet. Based on thrust to weight considerations, the full length plug is truncated and this results in a base flow rich in flow physics. In addition, the base flow exhibits an interesting transitional behaviour from open wake to a closed wake because of the wave interactions within the nozzle core jet. The plug surface flow can further exhibit flow complexities because of wave interactions resulting from the shear layer emanating from the splitter plates, in case of clustered plug flows. Considering these flow complexities, the design of the plug nozzles and analysing the associated flows can be a challenge to the aerodynamic community. An attempt has been made in understanding this class of flows in this thesis. This objective has been accomplished using both experimental and computational tools. In the present work, both the linear and annular plug nozzle geometries have been analysed for a wide range of pressure ratios spanning from 5to 80. The linear and annular nozzles have been designed for similar flow conditions and their respective design pressure ratios are 60and 66. From the experimental and computational results, it has been shown that the computational solver performs well in predicting the wave interactions on the plug surface. In addition the limitations of the computational solver in predicting the plug base flows in general has been brought out. This limitation in itself need not be considered as a serious handicap in the design and analysis of plug nozzle flows; this is because the plug base contribution to the thrust is very minimal, as has been brought out in this thesis. Apart from this the high quality experimental data generated is also of immense value to the CFD community as this also serves as a valuable data base for CFD code validation. For analysis, the plug flow field has been categorized into three different regimes based on the primary nozzle lip expansion fan extent. The flow field is categorised based on the reflection of the primary nozzle lip expansion fan from plug surface, base region shear layer and symmetry line downstream of the base region recirculation bubble. This flow division is particularly helpful in understanding the base wake characteristics with increasing pressure ratio. The base lip pressure and the base pressure variation have been discussed with respect to the primary nozzle lip expansion fan extent. In the open wake regime (or for low pressure ratios) the wave interactions within the core jet flow impinge on the base region shear layer. Because of these interactions it is difficult to propose an empirical model for open wake base pressure. In the closed wake regime (for higher pressure ratios), the base region recirculation bubble is completely under the shower of primary nozzle lip expansion fan. Hence the base lip pressure and base pressure are frozen with respect to stagnation conditions. Based on these insights it was possible to propose empirical models for linear and annular closed wake base pressure. Along with these, a mathematical model defining a reference pressure ratio PR∗, beyond which the closed wake base pressure is expected to be more than the ambient pressure has also been proposed. This is expected to serve as a good design parameter. In case of linear plug flows, this also serves the purpose of base wake transition, for the cases considered in this thesis. The flow expansion process or the primary nozzle lip expansion fan extent was also useful in understanding the differences between the linear and annular plug nozzle flow fields. In a linear plug nozzle, the flow expands only in the streamwise direction while in an annular plug nozzle the flow expands both along the streamwise and azimuthal directions. The flow expands at a faster rate in case of annular nozzle as against linear nozzle. Hence differences are observed between the linear and annular nozzle on plug and base surfaces. On the annular plug surface more wave interactions are observed because of faster expansion. With regard to base characteristics, faster expansion in annular plug nozzle, with respect to linear nozzle, results in a lower base lip pressure, lower base pressure and higher wake transition pressure ratio. The realistic cluster plug configurations have also been considered for the present studies. The effects of clustering on the plug nozzle flow field have been brought out by considering two different linear cluster nozzles and one annular cluster nozzle. The differences in the flow field of a simple and cluster plug nozzle has been discussed. In case of simple plug nozzle wave interactions are observed only in the stream wise direction, while in case of cluster plug nozzle three dimensional wave interactions are observed because of the splitter plates. Along the splitter plate differential end conditions introduce a curved recompression shock on the plug surface. This recompression shock in turn induces a streamwise vortex and also a secondary shock. It has been observed that differences between the simple and cluster plug surface pressure field are because of three dimensional wave interactions. Regarding the base pressure, differences between the simple and cluster geometries were observed for shorter truncation plug lengths (20% length plug). While for longer plug lengths (more than 34% length) the effects of clustering were reduced on the base pressure. Regarding the transition pressure ratio, differences were observed between simple and clustered plug nozzles for all the plug lengths considered. In addition, the performance of the plug nozzles has been carried out. From the analysis it was found that the primary nozzle and plug surface are major contributors towards thrust. The base surface contributes only about 2– 3% of the thrust at design condition. Hence, from a design point of view, a computational solver can be a useful tool considering its efficacy on the plug surface and in the primary nozzle.

This thesis deals with the techniques of global illumination of the scene. The theoretical part discusses various techniques, focusing on processing in real-time using various optimization methods. It focuses to the technology of photon splatting using view sample cluster hierarchy. The main part is analysis, implenetation and measurement of mentioned method.