Magnetic Resonance Imaging in patients with ICDs and Pacemakers

Magnetic resonance (MR) imaging has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MR imaging. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. This review summarizes the potential hazards of the device-MR environment interaction, and presents updated information regarding in-vivo and in-vitro experiments. Recent reports on patients with implantable pacemakers and ICDs who underwent MR scan shows that under certain conditions patients with these implanted systems may benefit from this imaging modality. The data presented suggests that certain modern pacemaker and ICD systems may indeed be MR safe. This may have major clinical implications on current imaging practice

QnAs with David Baltimore

At the age of 37, David Baltimore accomplished what many researchers dream of but few achieve: reversing an entrenched dogma, eventually leading to a new view of life. In the early 1970s, Baltimore, a member of the National Academy of Sciences and a professor of biology at the California Institute of Technology, discovered reverse transcriptase—an enzyme found in some tumor viruses whose genetic code is written in the RNA alphabet. He found that reverse transcriptase can copy RNA into DNA, indicating that some viruses replicate via a DNA intermediate. The finding, which won Baltimore and others the 1975 Nobel Prize in Physiology or Medicine, enriched biologists’ views on the direction of flow of genetic information in cells. Baltimore was the keynote speaker at the Sackler Colloquium, “Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes,” held in September 2010. Here, he offers PNAS readers his perspectives on reverse transcription

Signals involved in protein intracellular sorting

“…Confusion appears to occur just after the articulation of a major conceptual advance that served to greatly clarify a problem of exceptional importance.”- Ira Mellman, 1996. What could be more fitting than the domain of protein trafficking to elucidate the above statement made by one of the several pioneers in the field? Ever since the pioneering groundwork laid down by Blobel and colleagues, emphasising protein translocation across intracellular membranes, the field of protein trafficking has been a playground of debates, dogma-reversals and rediscoveries. The possession of a valid cellular address tag is the basic requirement for the delivery of a given protein at its intracellular destination. However, the complexity involved in the foray of proteins from their site of synthesis to their site of function is within the scope of no comprehensive treatise. In this thesis, the work done on two individual transport steps of two different proteins has been summarised. In the first part of this thesis, the trafficking of the cation-dependent (CD-) mannose 6- phosphate receptor (MPR) has been studied. The CD-MPR cycles between the TGN and the plasma membrane, through the early and late endosomal compartments. It performs the important function of transport of lysosomal enzymes to lysosomes, a process which ensures the correct biogenesis of lysosomes. However, it is important that the receptor itself be excluded from lysosomes and safely retrieved to the TGN from late endosomes in order to avoid degradation in lysosomes. This is essential to ensure that the CD-MPR is available to support several rounds of lysosomal enzyme transport. This retrieval step has been shown to depend on a pair of aromatic residues F18W19 in the cytoplasmic tail of the receptor. Mutation of the residues to alanines has been shown to result in massive mislocalisation of the CD-MPR in lysosomes, the W19 residue being more crucial to this function and the F18 residue playing a contributory role. The retrieval has also been shown to take place in a Rab9 dependent manner using the cytosolic adaptor protein TIP47 (Tail Interacting Protein of 47 kDa). TIP47 specifically interacts with the diaromatic motif to effect this transport step. In this study, we demonstrated a strict requirement for di-aromaticity at the positions 18 and 19 of the cytosolic tail of the CDMPR both for correct intracellular sorting in vivo and optimal TIP47 interaction in vitro, thus demonstrating the significance of the di-aromatic motif in endosomal sorting and establishing the highly specific nature of this interaction. This also established a paradigm for the CD-MPR as a representative member of a generic family of diaromatic motif containing proteins. The second part of this thesis deals with the trafficking of the human mannose 6- phosphate uncovering enzyme (UCE). The recognition of the mannose 6-phosphate tag on lysosomal enzymes by the MPRs is facilitated by UCE which exposes the recognition signal on the lysosomal enzymes in a two-step enzymatic reaction: the first starts in the cis-Golgi and is mediated by a phosphotransferase and the second, mediated by UCE, occurs in the TGN. At steady state, UCE is mostly localised to the TGN and it cycles between the TGN and the plasma membrane. It is rapidly internalised from the surface in a clathrin dependent endocytic pathway and the internalisation has been shown to be mediated by a critical tyrosine-488 residue in its cytoplasmic tail. The transmembrane domain and first 11 residues of the cytoplasmic tail of UCE have been shown to be involved in its TGN retention. In this study, we identified the residues involved in TGN exit of UCE using a combination of biochemical and confocal immunofluorescence methods. Using a high dimensional neural network capable of identifying differences between images not visible to the eye, we determined that the residues 492QEMN were involved in TGN exit of UCE. The same method was also used to analyse the individual contribution of each amino acid in the sequence and it was found that residue Q492 is the most important to the exit function while residues M494 and N495 also contribute. The identification of a trans-Golgi network exit signal in its cytoplasmic tail elucidates the trafficking pathway of uncovering enzyme, a crucial player in lysosomal biogenesis. With these two analyses, we contributed to a better understanding of signal sequences involved in intracellular protein trafficking of two related proteins both involved in lysosomal biogenesis

Architectural Techniques to Enable Reliable and Scalable Memory Systems

High capacity and scalable memory systems play a vital role in enabling our desktops, smartphones, and pervasive technologies like Internet of Things (IoT). Unfortunately, memory systems are becoming increasingly prone to faults. This is because we rely on technology scaling to improve memory density, and at small feature sizes, memory cells tend to break easily. Today, memory reliability is seen as the key impediment towards using high-density devices, adopting new technologies, and even building the next Exascale supercomputer. To ensure even a bare-minimum level of reliability, present-day solutions tend to have high performance, power and area overheads. Ideally, we would like memory systems to remain robust, scalable, and implementable while keeping the overheads to a minimum. This dissertation describes how simple cross-layer architectural techniques can provide orders of magnitude higher reliability and enable seamless scalability for memory systems while incurring negligible overheads.Comment: PhD thesis, Georgia Institute of Technology (May 2017

Magnetic Resonance Imaging in patients with ICDs and Pacemakers

Magnetic resonance (MR) imaging has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MR imaging. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. This review summarizes the potential hazards of the device-MR environment interaction, and presents updated information regarding in-vivo and in-vitro experiments. Recent reports on patients with implantable pacemakers and ICDs who underwent MR scan shows that under certain conditions patients with these implanted systems may benefit from this imaging modality. The data presented suggests that certain modern pacemaker and ICD systems may indeed be MR safe. This may have major clinical implications on current imaging practice

QnAs with John P. Grotzinger. Interview by Prashant Nair.

In late November 2011, the National Aeronautics and Space Administration (NASA) plans to launch its robotic explorer to scour Mars for signs of the planet’s ability to support life. The Mars Science Laboratory (MSL) spacecraft is scheduled to lift off from Cape Canaveral Air Force Station in Florida, shuttling Curiosity, an SUV-sized rover with a hefty scientific payload, to the red planet’s surface. John Grotzinger, a member of the National Academy of Sciences and professor of geology at the California Institute of Technology, helps oversee the mission. He became involved in the quest after studying how changes in the Earth’s environment helped influence animal diversity in some parts of our planet. Here, Grotzinger discusses the MSL with PNAS

A Study on Barriers and Practices of Supply Chain Social Sustainability in Indian and North American Energy and Manufacturing Sectors

The paper paves a way to understand supply chain social sustainability practices and their associated barriers to implementation in the Indian and North American energy and manufacturing sectors. A systematic literature review and 4-point Likert scale survey provide clarity on the barriers and their perception from an industrial perspective. Findings from this study highlight that while the criticality of barriers differs with industry and geographies, some barriers are common to all. The study also highlights an approach needed for these sectors by identifying the most common barriers by providing a clear path on what practices can bring about the most impact in resolution. 20 barriers are identified, of which 3 show a stark difference in perception on its criticality against current published research work.  The paper also identifies the top barriers along with the practices that make it most easy to implement. 11 common barriers that exist in the target industries of the two countries are identified and 6 easiest-to-resolve barriers are revealed, analyzing the maximum number of mitigation practices available. The paper concludes by identifying eight most impactful social sustainability practices that can help resolve the maximum number of implementation barriers and highlights avenues for further research in the field

The Dirty Secret of SSDs: Embodied Carbon

Scalable Solid-State Drives (SSDs) have revolutionized the way we store and access our data across datacenters and handheld devices. Unfortunately, scaling technology can have a significant environmental impact. Across the globe, most semiconductor manufacturing use electricity that is generated from coal and natural gas. For instance, manufacturing a Gigabyte of Flash emits 0.16 Kg CO$_2$ and is a significant fraction of the total carbon emission in the system. We estimate that manufacturing storage devices has resulted in 20 million metric tonnes of CO$_2$ emissions in 2021 alone. To better understand this concern, this paper compares the sustainability trade-offs between Hard Disk Drives (HDDs) and SSDs and recommends methodologies to estimate the embodied carbon costs of the storage system. In this paper, we outline four possible strategies to make storage systems sustainable. First, this paper recommends directions that help select the right medium of storage (SSD vs HDD). Second, this paper proposes lifetime extension techniques for SSDs. Third, this paper advocates for effective and efficient recycling and reuse of high-density multi-level cell-based SSDs. Fourth, specifically for hand-held devices, this paper recommends leveraging elasticity in cloud storage.Comment: In the proceedings of the 1st Workshop on Sustainable Computer Systems Design and Implementation (HotCarbon 2022

Diagnosis: The Buck Starts Here, the Role of Diagnosis in Three Areas of Modern Medicine

This thesis examines the role of diagnosis—traditional and molecular—in three areas of medicine: personalized cancer treatment, treatment of infectious diseases and treatment of controversial disorders lacking unambiguous physiological bases. The thesis uses a mix of statistics, expert interviews and patient anecdotes to address in the form of three feature stories three aspects pertinent to the role of diagnosis in modern medicine. The first story addresses the challenges to developing diagnostic markers for truly personalized cancer therapy. The second story features a recent advance in molecular diagnostics that has transformed the treatment of infectious diseases, especially hitherto-unknown viral infections. The third story illustrates the plight of patients suffering from disorders whose very existence is controversial and for which doctors are unable to provide clear-cut diagnoses

FLuID: Mitigating Stragglers in Federated Learning using Invariant Dropout

Federated Learning (FL) allows machine learning models to train locally on individual mobile devices, synchronizing model updates via a shared server. This approach safeguards user privacy; however, it also generates a heterogeneous training environment due to the varying performance capabilities across devices. As a result, straggler devices with lower performance often dictate the overall training time in FL. In this work, we aim to alleviate this performance bottleneck due to stragglers by dynamically balancing the training load across the system. We introduce Invariant Dropout, a method that extracts a sub-model based on the weight update threshold, thereby minimizing potential impacts on accuracy. Building on this dropout technique, we develop an adaptive training framework, Federated Learning using Invariant Dropout (FLuID). FLuID offers a lightweight sub-model extraction to regulate computational intensity, thereby reducing the load on straggler devices without affecting model quality. Our method leverages neuron updates from non-straggler devices to construct a tailored sub-model for each straggler based on client performance profiling. Furthermore, FLuID can dynamically adapt to changes in stragglers as runtime conditions shift. We evaluate FLuID using five real-world mobile clients. The evaluations show that Invariant Dropout maintains baseline model efficiency while alleviating the performance bottleneck of stragglers through a dynamic, runtime approach