High-Speed Radhard Mega-Pixel CIS Camera for High-Energy Physics

This dissertation describes the schematic design, physical layout implementation, system-level hardware with FPGA firmware design, and testing of a camera-on-a-chip with a novel high-speed CMOS image sensor (CIS) architecture developed for a mega-pixel array. The novel features of the design include an innovative quadruple column-parallel readout (QCPRO) scheme with rolling shutter that increases pixel rate, its ability to program the frame rate and to tolerate Total Ionizing Dose effects (TID). Two versions of the architecture, a small (128 x 1,024 pixels) and large (768 x 1,024 pixels) version were designed and fabricated with a custom layout that does not include library parts. The designs achieve a performance of 20 to 4,000 frames per second (fps) and they tolerate up to 125 krads of radiation exposure. The high-speed CIS architecture proposes and implements a creative quadruple column-parallel readout (QCPRO) scheme to achieve a maximum pixel rate, 10.485 gigapixels/s. The QCPRO scheme consists of four readout blocks per column and to complete four rows of pixels readout process at one line time. Each column-level readout block includes an analog time-interleaving (ATI) sampling circuit, a switched-capacitor programmable gain amplifier (SC-PGA), a 10-bit successive-approximation register (SAR) ADC, two 10-bit memory banks. The column-parallel SAR ADC is area-efficient to be laid out in half of one pixel pitch, 10 um. The analog ATI sampling circuit has two sample-and-hold circuits. Each sampling circuit can independently complete correlated double sampling (CDS) operation. Furthermore, to deliver over 10^10 pixel data in one second, a high-speed differential Scalable Low-Voltage Signaling (SLVS) transmitter for every 16 columns is designed to have 1 Gbps/ch at 0.4 V. Two memory banks provide a ping-pong operation: one connecting to the ADC for storing digital data and the other to the SLVS for delivering data to the off-chip FPGA. Therefore, the proposed CIS architecture can achieve 10,000 frames per second for a 1,024 x 1,024 pixel array. The floor plan of the proposed CIS architecture is symmetrical having one-half of pixel rows to read out on top, and the other half read out on the bottom of the pixel array. The rolling shutter feature with multi-lines readout in parallel and oversampling technique relaxes the image artifacts for capturing fast-moving objects. The CIS camera can provide complete digital input control and digital pixel data output. Many other components are designed and integrated into the proposed CMOS imager, including the Serial Peripheral Interface (SPI), bandgap reference, serializers, phase-locked loops (PLLs), and sequencers with configuration registers. Also, the proposed CIS can program the frame rate for wider applications by modifying three parameters: input clock frequency, the region of interest, and the counter size in the sequencer. The radiation hardening feature is achieved by using the combination of enclosed geometry technique and P-type guard-rings in the 0.18 um CMOS technology. The peripheral circuits use P-type guard-rings to cut the TID-induced leakage path between device to device. Each pixel cell is radiation tolerant by using enclosed layout transistors. The pinned photodiode is also used to get low dark current, and correlated double sampling to suppress pixel-level fixed-pattern noise and reset noise. The final pixel cell is laid out in 20 x 20 um^2. The total area of the pixel array is 2.56 x 20.28 mm^2 for low-resolution imager prototype and 15.36 x 20.28 mm^2 for high-resolution imager prototype. The entire CIS camera system is developed by the implementation of the hardware and FPGA firmware of the small-format prototype with 128 x 1,024 pixels and 754 pads in a 4.24 x 25.125 mm^2 die area. Different testing methods are also briefly described for different test purposes. Measurement results validate the functionalities of the readout path, sequencer, on-chip PLLs, and the SLVS transmitters. The programmable frame rate feature is also demonstrated by checking the digital control outputs from the sequencer at different frame rates. Furthermore, TID radiation tests proved the pixels can work under 125 krads radiation exposure

Frequency Coupling Admittance Modeling of Quasi-PR Controlled Inverter and Its Stability Comparative Analysis under the Weak Grid

This paper intends to comparatively study the stabilities of grid-connected inverters with three closely related controllers: quasi-proportional resonance (quasi-PR), proportional integral (PI), and proportional resonance (PR) under the weak grid. Firstly, considering the influence of frequency coupling characteristic, a frequency coupling admittance model of quasi-PR controlled inverter is established. Then, the admittance characteristics of the quasi-PR, PI and PR controlled inverters are compared. Admittance characteristics of the PI and PR controlled inverters are similar while the quasi-PR controlled inverter is quite different: the amplitude of the quasi-PR controlled inverter is larger than that of the PI controlled inverter and the phase difference between the two inverters is obvious in the mid-high frequency areas, which are mainly caused by the resonance bandwidth of the quasi-PR controller. Furthermore, the stabilities of the quasi-PR, PI and PR controlled inverters are analyzed. The stabilities of the PI and PR controlled inverters are similar but the quasi-PR controlled inverter is more sensitive to weak grid and high inverter output power. To achieve the same system stability, the voltage outer-loop bandwidth of the quasi-PR controlled inverter should be designed narrower than that of the PI and PR controlled inverters. Finally, experiments verify the correctness of the analyses

Proteomic assessment of a cell model of spinal muscular atrophy

Background Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES) cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease. Results When ES cells were primed with Noggin/fibroblast growth factors (bFGF and FGF-8) in a more robust neural differentiation medium for 2 days before differentiation induction, the efficiency of in vitro motor neuron differentiation was improved from ~25% to ~50%. The differentiated ES cells expressed a pan-neuronal marker (neurofilament) and motor neuron markers (Hb9, Islet-1, and ChAT). Even though SMN-deficient ES cells had marked reduced levels of SMN (~20% of that in control ES cells), the morphology and differentiation efficiency for these cells are comparable to those for control samples. However, proteomics in conjunction with western blot analyses revealed 6 down-regulated and 14 up-regulated proteins with most of them involved in energy metabolism, cell stress-response, protein degradation, and cytoskeleton stability. Some of these activated cellular pathways showed specificity for either undifferentiated or differentiated cells. Increased p21 protein expression indicated that SMA ES cells were responding to cellular stress. Up-regulation of p21 was confirmed in spinal cord tissues from the same SMA mouse model from which the ES cells were derived. Conclusion SMN-deficient ES cells provide a cell-culture model for SMA. SMN deficiency activates cellular stress pathways, causing a dysregulation of energy metabolism, protein degradation, and cytoskeleton stability

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population

Electrophysiological Properties of Motor Neurons in a Mouse Model of Severe Spinal Muscular Atrophy: In Vitro versus In Vivo Development

We examined the electrophysiological activity of motor neurons from the mouse model of severe spinal muscular atrophy (SMA) using two different methods: whole cell patch clamp of neurons cultured from day 13 embryos; and multi-electrode recording of ventral horns in spinal cord slices from pups on post-natal days 5 and 6. We used the MED64 multi-electrode array to record electrophysiological activity from motor neurons in slices from the lumbar spinal cord of SMA pups and their unaffected littermates. Recording simultaneously from up to 32 sites across the ventral horn, we observed a significant decrease in the number of active neurons in 5–6 day-old SMA pups compared to littermates. Ventral horn activity in control pups is significantly activated by serotonin and depressed by GABA, while these agents had much less effect on SMA slices. In contrast to the large differences observed in spinal cord, neurons cultured from SMA embryos for up to 21 days showed no significant differences in electrophysiological activity compared to littermates. No differences were observed in membrane potential, frequency of spiking and synaptic activity in cells from SMA embryos compared to controls. In addition, we observed no difference in cell survival between cells from SMA embryos and their unaffected littermates. Our results represent the first report on the electrophysiology of SMN-deficient motor neurons, and suggest that motor neuron development in vitro follows a different path than in vivo development, a path in which loss of SMN expression has little effect on motor neuron function and survival

Wireless Power and Signal Transmission Based on Time-sharing Multiplexing for WPT System

In wireless power transfer (WPT) systems, wireless transmission of signals is particularly important for some practical applications. An effective approach of signal and energy synchronous transmission based on time-sharing multiplexing of the same coupled coil is proposed in this paper. Using the same coupled coil, the signal transmission is carried on when interruption of power transmission happens. To realize the proposed method, the relationship between power transmission time and signal transmission time is provided to obtain the optimal transmission process of the power and signal. Besides, the power transmission efficiency (PTE) and the signal transmission rate (STR) are analyzed. Finally, the effectiveness of the proposed method is verified by the experiment

Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia

Mixed phenotype acute leukemia (MPAL) is a rare hematological malignancy that lacks consensus on optimal management. We report for the first time two cases of treatment-naïve B/myeloid MPAL patients treated with a novel chemo-free regimen using venetoclax combined with hypomethylating agents, which successfully induced complete remission with tolerable toxicities

A Multi-Objective Input–Output Linear Model for Water Supply, Economic Growth and Environmental Planning in Resource-Based Cities

Water resource and environment capacity have become two of the most important restrictions for sustainable development in resource-based cities whose leading industries are the exploitation and processing of resources. Taking Ordos in China as an example, this article constructs an integrated model combining a multi-objective optimization model with input–output analysis to achieve the tradeoffs between economic growth, water utilization and environmental protection. This dynamic model includes socioeconomic, water supply–demand, water quality control, air quality control, energy consumption control and integrated policy sub-models. These six sub-models interact with each other. After simulation, this article proposes efficient solutions on industrial restructuring by maximizing the Gross Regional Product of Ordos from 394.3 in 2012 to 785.1 billion RMB in 2025 with a growth rate of 6.4% annually; and presents a water supply plan by maximizing the proportion of reclaimed water from 2% to 6.3% through sewage treatment technology selection and introduction, and effective water allocation. Meanwhile, the environmental impacts are all in line with the planning targets. This study illustrates that the integrated modeling is generic and can be applied to any region suffering uncoordinated development issues and can serve as a pre-evaluation approach for conducting early warning research to offer suggestions for government decision-making