Remembering Wonder

This is a booklet about research on alternative play and memorial structures

File Fragmentation over an Unreliable Channel

It has been recently discovered that heavy-tailed file completion time can result from protocol interaction even when file sizes are light-tailed. A key to this phenomenon is the RESTART feature where if a file transfer is interrupted before it is completed, the transfer needs to restart from the beginning. In this paper, we show that independent or bounded fragmentation guarantees light-tailed file completion time as long as the file size is light-tailed, i.e., in this case, heavy-tailed file completion time can only originate from heavy-tailed file sizes. If the file size is heavy-tailed, then the file completion time is necessarily heavy-tailed. For this case, we show that when the file size distribution is regularly varying, then under independent or bounded fragmentation, the completion time tail distribution function is asymptotically upper bounded by that of the original file size stretched by a constant factor. We then prove that if the failure distribution has non-decreasing failure rate, the expected completion time is minimized by dividing the file into equal sized fragments; this optimal fragment size is unique but depends on the file size. We also present a simple blind fragmentation policy where the fragment sizes are constant and independent of the file size and prove that it is asymptotically optimal. Finally, we bound the error in expected completion time due to error in modeling of the failure process

On-Command Regulation of Kinase Activity using Photonic Stimuli

The underlying role that many kinases play in complex cellular pathways as well as disease remains unclear. To better understand the role that kinases play in both health and disease states, the use of light as an external stimulus to modulate kinase activity with high spatiotemporal resolution has gained increasing interest over the years. Herein we highlight the progress made towards the development of light-responsive kinase enzymes and small molecule inhibitors. In these examples, photolabile caging groups and photoswitchable entities have been utilised to modulate either kinase activation or inhibition in a light-controlled manner

Ohm's Law in the Fast Lane: General Relativistic Charge Dynamics

Fully relativistic and causal equations for the flow of charge in curved spacetime are derived. It is believed that this is the first set of equations to be published that correctly describes the flow of charge, and evolution of the electromagnetic field, in highly dynamical relativistic environments on time scales much shorter than the collapse time ($GM/c^3$). The equations will be important for correctly investigating problems such as the dynamical collapse of magnetized stellar cores to black holes and the production of jets and gravitational waves. This system of equations, given the name of `charge dynamics', is analogous to those of hydrodynamics (which describe the flow of {\em mass} in spacetime rather than the flow of charge). The most important one in the system is the relativistic generalized Ohm's law, which is used to compute time-dependent four-current. Unlike previous equations for the current, this one ensures that charge drift velocities remain less than the speed of light, takes into account the finite current rise time, is expressed in a covariant form, and is suitable for general relativistic computations in an arbitrary metric. It includes the standard known effects (Lorentz force, Hall effect, pressure effect, and resistivity) and reduces to known forms of Ohm's law in the appropriate limits. In addition, the plasma particles are allowed to have highly relativistic drift velocities, resulting in an implicit equation for the `current beaming factor' $\gamma_q$.Comment: 23 pages, 0 figures; accepted for publication in the Astrophysical Journa

Design and development of photoswitchable DFG-Out RET kinase inhibitors

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline “head” constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC50) ratio in the cellular assay, tentatively assigned to stability issues. The corresponding stilbene compound gave a Z/E (IC50) ratio well above 100, consistent with that measured in the biochemical assay. Ultimately, a 7-azaindole based photoswitchable DFG-out kinase inhibitor was shown to display more than a 10-fold difference in bioactivity between the two isomers, in both a biochemical and a cell-based assay, as well as excellent stability even under reducing conditions

On Channel Failures, File Fragmentation Policies, and Heavy-Tailed Completion Times

It has been recently discovered that heavy-tailed completion times can result from protocol interaction even when file sizes are light-tailed. A key to this phenomenon is the use of a restart policy where if the file is interrupted before it is completed, it needs to restart from the beginning. In this paper, we show that fragmenting a file into pieces whose sizes are either bounded or independently chosen after each interruption guarantees light-tailed completion time as long as the file size is light-tailed; i.e., in this case, heavy-tailed completion time can only originate from heavy-tailed file sizes. If the file size is heavy-tailed, then the completion time is necessarily heavy-tailed. For this case, we show that when the file size distribution is regularly varying, then under independent or bounded fragmentation, the completion time tail distribution function is asymptotically bounded above by that of the original file size stretched by a constant factor. We then prove that if the distribution of times between interruptions has nondecreasing failure rate, the expected completion time is minimized by dividing the file into equal-sized fragments; this optimal fragment size is unique but depends on the file size. We also present a simple blind fragmentation policy where the fragment sizes are constant and independent of the file size and prove that it is asymptotically optimal. Both these policies are also shown to have desirable completion time tail behavior. Finally, we bound the error in expected completion time due to error in modeling of the failure process

FuSSI-Net: Fusion of Spatio-temporal Skeletons for Intention Prediction Network

Pedestrian intention recognition is very important to develop robust and safe autonomous driving (AD) and advanced driver assistance systems (ADAS) functionalities for urban driving. In this work, we develop an end-to-end pedestrian intention framework that performs well on day- and night- time scenarios. Our framework relies on objection detection bounding boxes combined with skeletal features of human pose. We study early, late, and combined (early and late) fusion mechanisms to exploit the skeletal features and reduce false positives as well to improve the intention prediction performance. The early fusion mechanism results in AP of 0.89 and precision/recall of 0.79/0.89 for pedestrian intention classification. Furthermore, we propose three new metrics to properly evaluate the pedestrian intention systems. Under these new evaluation metrics for the intention prediction, the proposed end-to-end network offers accurate pedestrian intention up to half a second ahead of the actual risky maneuver.Comment: 5 pages, 6 figures, 5 tables, IEEE Asilomar SS

Proinflammatory Protein Signatures in Cryptogenic and Large Artery Atherosclerosis Stroke

Objectives: The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle‐aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke. Materials & Methods: Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18–69 years and once from age‐matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C‐statistics. Results: We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ≥ 0.85). For both subtypes, RANTES, IL‐4, and IFN‐γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ≥ 0.76), and here eotaxin and MCP‐1 contributed the most. Conclusions: The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL‐4, and IFN‐γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP‐1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause