Electrical and optical interconnects for high-performance computing

Technology scaling has enabled drastic growth in the computational and storage capacity of integrated circuits (ICs). This constant growth drives an increasing demand for high-bandwidth communication between and within ICs. In this dissertation we focus on low-power solutions that address this demand. We divide communication links into three subcategories depending on the communication distance. Each category has a different set of challenges and requirements and is affected by CMOS technology scaling in a different manner. We start with short-range chip-to-chip links for board-level communication. Next we will discuss board-to-board links, which demand a longer communication range. Finally on-chip links with communication ranges of a few millimeters are discussed.

Electrical signaling is a natural choice for chip-to-chip communication due to efficient integration and low cost. IO data rates have increased to the point where electrical signaling is now limited by the channel bandwidth. In order to achieve multi-Gb/s data rates, complex designs that equalize the channel are necessary. In addition, a high level of parallelism is central to sustaining bandwidth growth. Decision feedback equalization (DFE) is one of the most commonly employed techniques to overcome the limited bandwidth problem of the electrical channels. A linear and low-power summer is the central block of a DFE. Conventional approaches employ current-mode techniques to implement the summer, which require high power consumption. In order to achieve low-power operation we propose performing the summation in the charge domain. This approach enables a low-power and compact realization of the DFE as well as crosstalk cancellation. A prototype receiver was fabricated in 45nm SOI CMOS to validate the functionality of the proposed technique and was tested over channels with different levels of loss and coupling. Measurement results show that the receiver can equalize channels with maximum 21dB loss while consuming about 7.5mW from a 1.2V supply. We also introduce a compact, low-power transmitter employing passive equalization. The efficacy of the proposed technique is demonstrated through implementation of a prototype in 65nm CMOS. The design achieves up to 20Gb/s data rate while consuming less than 10mW.

An alternative to electrical signaling is to employ optical signaling for chip-to-chip interconnections, which offers low channel loss and cross-talk while providing high communication bandwidth. In this work we demonstrate the possibility of building compact and low-power optical receivers. A novel RC front-end is proposed that combines dynamic offset modulation and double-sampling techniques to eliminate the need for a short time constant at the input of the receiver. Unlike conventional designs, this receiver does not require a high-gain stage that runs at the data rate, making it suitable for low-power implementations. In addition, it allows time-division multiplexing to support very high data rates. A prototype was implemented in 65nm CMOS and achieved up to 24Gb/s with less than 0.4pJ/b power efficiency per channel. As the proposed design mainly employs digital blocks, it benefits greatly from technology scaling in terms of power and area saving.

As the technology scales, the number of transistors on the chip grows. This necessitates a corresponding increase in the bandwidth of the on-chip wires. In this dissertation, we take a close look at wire scaling and investigate its effect on wire performance metrics. We explore a novel on-chip communication link based on a double-sampling architecture and dynamic offset modulation technique that enables low power consumption and high data rates while achieving high bandwidth density in 28nm CMOS technology. The functionality of the link is demonstrated using different length minimum-pitch on-chip wires. Measurement results show that the link achieves up to 20Gb/s of data rate (12.5Gb/s/$\mu$m) with better than 136fJ/b of power efficiency.

Mechanisms of Transposable Element Repression by Piwi Proteins in the piRNA Pathway of Drosophila Germ Cells

The ability to reproduce is a defining characteristic of all living organisms. During reproduction, the integrity of genetic material transferred from one generation to the next is of utmost importance. Organisms have diverse strategies to ensure the fidelity of genomic information inherited between generations of individuals. In sexually reproducing animals, the piRNA pathway is an RNA-interference (RNAi) mechanism that protects the genomes of germ cells from the replication of ‘selfish’ genetic sequences called transposable elements (TE). When left unabated, the replication of TE sequences can cause gene disruption, double-stranded DNA breaks, and germ cell death that results in sterility of the organism. In Drosophila, the piRNA pathway is divided into a cytoplasmic and nuclear branch that involves the functions of three Piwi-clade Argonaute proteins—Piwi, Aubergine (Aub) and Argonaute-3 (Ago3)—which bind piwi-interacting RNA (piRNA) to form the effector complexes that represses deleterious TE sequences.

The work presented in this thesis examines the function and regulation of Piwi proteins in Drosophila germ cells. Chapter 1 presents an introduction to piRNA biogenesis and to the essential roles occupied by each Piwi protein in the repression of TE. We discuss the architecture and function of germ granules as the cellular compartments where much of the piRNA pathway operates. In Chapter 2, we present how Piwi in the nucleus co-transcriptionally targets genomic loci expressing TE sequences to direct the deposition of repressive chromatin marks. Chapter 3 examines the cytoplasmic function of the piRNA pathway, where we find that the protein Krimper coordinates Aub and Ago3 in the piRNA ping-pong pathway to adaptively target and destroy TE transcripts. Chapter 4 explores how interactions of Piwis with associated proteins are modulated by arginine methylation modifications. Lastly, in Chapter 5 I present evidence that the cytoplasmic branch of the piRNA pathway can potentially ‘cross-talk’ with the nuclear branch to transfer sequence information to better target and co-transcriptionally silence the genomic loci coding active TE sequences. Overall, the work presented in this thesis constitutes a part of the first steps in understanding the molecular mechanisms that protect germ cells from invasion by TE sequences.

DNA-mediated charge transport signaling within the cell

DNA possesses the curious ability to conduct charge longitudinally through the π-stacked base pairs that reside within the interior of the double helix. The rate of charge transport (CT) through DNA has a shallow distance dependence. DNA CT can occur over at least 34 nm, a very long molecular distance. Lastly, DNA CT is exquisitely sensitive to disruptions, such as DNA damage, that affect the dynamics of base-pair stacking. Many DNA repair and DNA-processing enzymes are being found to contain 4Fe-4S clusters. These co-factors have been found in glycosylases, helicases, helicase-nucleases, and even enzymes such as DNA polymerase, RNA polymerase, and primase across the phylogeny. The role of these clusters in these enzymes has remained elusive. Generally, iron-sulfur clusters serve redox roles in nature since, formally, the cluster can exist in multiple oxidation states that can be accessed within a biological context. Taken together, these facts were used as a foundation for the hypothesis that DNA-binding proteins with 4Fe-4S clusters utilize DNA-mediated CT as a means to signal one another to scan the genome as a first step in locating the subtle damage that occurs within a sea of undamaged bases within cells.

Herein we describe a role for 4Fe-4S clusters in DNA-mediated charge transport signaling among EndoIII, MutY, and DinG, which are from distinct repair pathways in E. coli. The DinG helicase is an ATP-dependent helicase that contains a 4Fe-4S cluster. To study the DNA-bound redox properties of DinG, DNA-modified electrochemistry was used to show that the 4Fe-4S cluster of DNA-bound DinG is redox-active at cellular potentials, and shares the 80 mV vs. NHE redox potential of EndoIII and MutY. ATP hydrolysis by DinG increases the DNA-mediated redox signal observed electrochemically, likely reflecting better coupling of the 4Fe-4S cluster to DNA while DinG unwinds DNA, which could have interesting biological implications. Atomic force microscopy experiments demonstrate that DinG and EndoIII cooperate at long range using DNA charge transport to redistribute to regions of DNA damage. Genetics experiments, moreover, reveal that this DNA-mediated signaling among proteins also occurs within the cell and, remarkably, is required for cellular viability under conditions of stress. Knocking out DinG in CC104 cells leads to a decrease in MutY activity that is rescued by EndoIII D138A, but not EndoIII Y82A. DinG, thus, appears to help MutY find its substrate using DNA-mediated CT, but do MutY or EndoIII aid DinG in a similar way? The InvA strain of bacteria was used to observe DinG activity, since DinG activity is required within InvA to maintain normal growth. Silencing the gene encoding EndoIII in InvA results in a significant growth defect that is rescued by the overexpression of RNAseH, a protein that dismantles the substrate of DinG, R-loops. This establishes signaling between DinG and EndoIII. Furthermore, rescue of this growth defect by the expression of EndoIII D138A, the catalytically inactive but CT-proficient mutant of EndoIII, is also observed, but expression of EndoIII Y82A, which is CT-deficient but enzymatically active, does not rescue growth. These results provide strong evidence that DinG and EndoIII utilize DNA-mediated signaling to process DNA damage. This work thus expands the scope of DNA-mediated signaling within the cell, as it indicates that DNA-mediated signaling facilitates the activities of DNA repair enzymes across the genome, even for proteins from distinct repair pathways.

In separate work presented here, it is shown that the UvrC protein from E. coli contains a hitherto undiscovered 4Fe-4S cluster. A broad shoulder at 410 nm, characteristic of 4Fe-4S clusters, is observed in the UV-visible absorbance spectrum of UvrC. Electron paramagnetic resonance spectroscopy of UvrC incubated with sodium dithionite, reveals a spectrum with the signature features of a reduced, [4Fe-4S]+1, cluster. DNA-modified electrodes were used to show that UvrC has the same DNA-bound redox potential, of ~80 mV vs. NHE, as EndoIII, DinG, and MutY. Again, this means that these proteins are capable of performing inter-protein electron transfer reactions. Does UvrC use DNA-mediated signaling to facilitate the repair of its substrates?

UvrC is part of the nucleotide excision repair (NER) pathway in E. coli and is the protein within the pathway that performs the chemistry required to repair bulky DNA lesions, such as cyclopyrimidine dimers, that form as a product of UV irradiation. We tested if UvrC utilizes DNA-mediated signaling to facilitate the efficient repair of UV-induced DNA damage products by helping UvrC locate DNA damage. The UV sensitivity of E. coli cells lacking DinG, a putative signaling partner of UvrC, was examined. Knocking out DinG in E. coli leads to a sensitivity of the cells to UV irradiation. A 5-10 fold reduction in the amount of cells that survive after irradiation with 90 J/m2 of UV light is observed. This is consistent with the hypothesis that UvrC and DinG are signaling partners, but is this signaling due to DNA-mediated CT? Complementing the knockout cells with EndoIII D138A, which can also serve as a DNA CT signaling partner, rescues cells lacking DinG from UV irradiation, while complementing the cells with EndoIII Y82A shows no rescue of viability. These results indicate that there is cross-talk between the NER pathway and DinG via DNA-mediated signaling. Perhaps more importantly, this work also establishes that DinG, EndoIII, MutY, and UvrC comprise a signaling network that seems to be unified by the ability of these proteins to perform long range DNA-mediated CT signaling via their 4Fe-4S clusters.

The oculomotor system: (1) Vertical-horizontal interaction and signal recognition, (2) Time delays and power spectra

In the first section of this thesis, two-dimensional properties of the human eye movement control system were studied. The vertical - horizontal interaction was investigated by using a two-dimensional target motion consisting of a sinusoid in one of the directions vertical or horizontal, and low-pass filtered Gaussian random motion of variable bandwidth (and hence information content) in the orthogonal direction. It was found that the random motion reduced the efficiency of the sinusoidal tracking. However, the sinusoidal tracking was only slightly dependent on the bandwidth of the random motion. Thus the system should be thought of as consisting of two independent channels with a small amount of mutual cross-talk.

These target motions were then rotated to discover whether or not the system is capable of recognizing the two-component nature of the target motion. That is, the sinusoid was presented along an oblique line (neither vertical nor horizontal) with the random motion orthogonal to it. The system did not simply track the vertical and horizontal components of motion, but rotated its frame of reference so that its two tracking channels coincided with the directions of the two target motion components. This recognition occurred even when the two orthogonal motions were both random, but with different bandwidths.

In the second section, time delays, prediction and power spectra were examined. Time delays were calculated in response to various periodic signals, various bandwidths of narrow-band Gaussian random motions and sinusoids. It was demonstrated that prediction occurred only when the target motion was periodic, and only if the harmonic content was such that the signal was sufficiently narrow-band. It appears as if general periodic motions are split into predictive and non-predictive components.

For unpredictable motions, the relationship between the time delay and the average speed of the retinal image was linear. Based on this I proposed a model explaining the time delays for both random and periodic motions. My experiments did not prove that the system is sampled data, or that it is continuous. However, the model can be interpreted as representative of a sample data system whose sample interval is a function of the target motion.

It was shown that increasing the bandwidth of the low-pass filtered Gaussian random motion resulted in an increase of the eye movement bandwidth. Some properties of the eyeball-muscle dynamics and the extraocular muscle "active state tension" were derived.

A measurement of inclusive quasi-elastic electron scattering cross sections at high momentum transfer

We have measured inclusive electron-scattering cross sections for targets of ^(4)He, C, Al, Fe, and Au, for kinematics spanning the quasi-elastic peak, with squared, four­ momentum transfers (q^2) between 0.23 and 2.89 (GeV/c)^2. Additional data were measured for Fe with q^2's up to 3.69 (GeV/c)^2 These cross sections were analyzed for the y-scaling behavior expected from a simple, impulse-approximation model, and are found to approach a scaling limit at the highest q^2's. The q^2 approach to scaling is compared with a calculation for infinite nuclear matter, and relationships between the scaling function and nucleon momentum distributions are discussed. Deviations from perfect scaling are used to set limits on possible changes in the size of nucleons inside the nucleus.

The deuteron-deuteron reaction and the stopping cross section of D_2O ice below 600 kev

The energy loss of protons and deuterons in D_2O ice has been measured over the energy range, E_p 18 - 541 kev. The double focusing magnetic spectrometer was used to measure the energy of the particles after they had traversed a known thickness of the ice target. One method of measurement is used to determine relative values of the stopping cross section as a function of energy; another method measures absolute values. The results are in very good agreement with the values calculated from Bethe’s semi-empirical formula. Possible sources of error are considered and the accuracy of the measurements is estimated to be ± 4%.

The D(dp)H^3 cross section has been measured by two methods. For E_D = 200 - 500 kev the spectrometer was used to obtain the momentum spectrum of the protons and tritons. From the yield and stopping cross section the reaction cross section at 90° has been obtained.

For E_D = 35 – 550 kev the proton yield from a thick target was differentiated to obtain the cross section. Both thin and thick target methods were used to measure the yield at each of ten angles. The angular distribution is expressed in terms of a Legendre polynomial expansion. The various sources of experimental error are considered in detail, and the probable error of the cross section measurements is estimated to be ± 5%.

Total cross section measurements for ^3He(^3He, 2p)^4He at low energies

Precise measurements of the total reaction cross section for ³He(³He,2p)⁴He He have been made in the range of center-of-mass energies between 1100 keV and 80 keV. A differentially pumped gas target modified to operate with a limited quantity of the target gas was employed to minimize the uncertainties in the primary energy and energy straggle. Beam integration inside the target gas was carried out by a calorimetric device which measures the total energy spent in a heat sink rather than the total charge in a Faraday cup. Proton energy spectra have been obtained using a counter telescope consisting of a gas proportional counter and a surface barrier detector and angular distributions of these protons have been measured at seven bombarding energies. Cross section factors, S(E), have been calculated from the total cross sections and fitted to a linear function of energy over different ranges of energy. For E_cm < 500 keV

S(E_cm) = S₀ + S₁ E_cm

where S₀ = (5.0 ^+0.6_-0.4) MeV - barns and S₁ = (-1.8 ± 0.5) barns.