Enantioselective Total Synthesis of Macfarlandin C, a Spongian Diterpenoid Harboring a Concave-Substituted cis-Dioxabicyclo[3.3.0]octanone Fragment.

The enantioselective total synthesis of the rearranged spongian diterpenoid (-)-macfarlandin C is reported. This is the first synthesis of a rearranged spongian diterpenoid in which the bulky hydrocarbon fragment is joined via a quaternary carbon to the highly hindered concave face of the cis-2,8-dioxabicyclo[3.3.0]octan-3-one moiety. The strategy involves a late-stage fragment coupling between a tertiary carbon radical and an electrophilic butenolide resulting in the stereoselective formation of vicinal quaternary and tertiary stereocenters. A stereoselective Mukaiyama hydration that orients a pendant carboxymethyl side chain cis to the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave-substituted cis-dioxabicyclo[3.3.0]octanone fragment

The uncertain benefits of environmental reform in open economies

We compare the instantaneous and the long run effects of environmental reform in closed and open economies. Harmonization upward (decreasing distortions where they are most severe) or harmonization downward (increasing distortions where they are less severe), both tend to increase instantaneous world welfare. Environmental reform in a country with less severe distortions works against harmonization and may decrease welfare. Harmonization upward has more beneficial long-run effects than harmonization downward, and also provides higher expected instantaneous benefits if the current stock is uncertain. In the short run there is a conflict between environmental protection and reduction of unemployment, but in the long run the two goals are consistent

Pedestrian Detection with Wearable Cameras for the Blind: A Two-way Perspective

Blind people have limited access to information about their surroundings, which is important for ensuring one's safety, managing social interactions, and identifying approaching pedestrians. With advances in computer vision, wearable cameras can provide equitable access to such information. However, the always-on nature of these assistive technologies poses privacy concerns for parties that may get recorded. We explore this tension from both perspectives, those of sighted passersby and blind users, taking into account camera visibility, in-person versus remote experience, and extracted visual information. We conduct two studies: an online survey with MTurkers (N=206) and an in-person experience study between pairs of blind (N=10) and sighted (N=40) participants, where blind participants wear a working prototype for pedestrian detection and pass by sighted participants. Our results suggest that both of the perspectives of users and bystanders and the several factors mentioned above need to be carefully considered to mitigate potential social tensions.Comment: The 2020 ACM CHI Conference on Human Factors in Computing Systems (CHI 2020

Ubiquitous Memory Introspection (Preliminary Manuscript)

Modern memory systems play a critical role in the performance ofapplications, but a detailed understanding of the application behaviorin the memory system is not trivial to attain. It requires timeconsuming simulations of the memory hierarchy using long traces, andoften using detailed modeling. It is increasingly possible to accesshardware performance counters to measure events in the memory system,but the measurements remain coarse grained, better suited forperformance summaries than providing instruction level feedback. Theavailability of a low cost, online, and accurate methodology forderiving fine-grained memory behavior profiles can prove extremelyuseful for runtime analysis and optimization of programs.This paper presents a new methodology for Ubiquitous MemoryIntrospection (UMI). It is an online and lightweight mini-simulationmethodology that focuses on simulating short memory access tracesrecorded from frequently executed code regions. The simulations arefast and can provide profiling results at varying granularities, downto that of a single instruction or address. UMI naturally complementsruntime optimizations techniques and enables new opportunities formemory specific optimizations.In this paper, we present a prototype implementation of a runtimesystem implementing UMI. The prototype is readily deployed oncommodity processors, requires no user intervention, and can operatewith stripped binaries and legacy software. The prototype operateswith an average runtime overhead of 20% but this slowdown is only 6%slower than a state of the art binary instrumentation tool. We used32 benchmarks, including the full suite of SPEC2000 benchmarks, forour evaluation. We show that the mini-simulation results accuratelyreflect the cache performance of two existing memory systems, anIntel Pentium~4 and an AMD Athlon MP (K7) processor. We alsodemonstrate that low level profiling information from the onlinesimulation can serve to identify high-miss rate load instructions with a77% rate of accuracy compared to full offline simulations thatrequired days to complete. The online profiling results are used atruntime to implement a simple software prefetching strategy thatachieves a speedup greater than 60% in the best case

How to Do a Million Watchpoints: Efficient Debugging Using Dynamic Instrumentation

Application debugging is a tedious but inevitable chore in any software development project. An effective debugger can make programmers more productive by allowing them to pause execution and inspect the state of the process, or monitor writes to memory to detect data corruption. The latter is a notoriously difficult category of bugs to diagnose and repair especially in pointer-heavy applications. The debugging challenges will increase with the arrival of multicore processors which require explicit parallelization of the user code to get any performance gains. Parallelization in turn can lead to more data debugging issues such as the detection of data races between threads. This paper leverages the increasing efficiency of runtime binary interpreters to provide a new concept of Efficient Debugging using Dynamic Instrumentation, or EDDI. The paper demonstrates for the first time the feasibility of using dynamic instrumentation on demand to accelerate software debuggers, especially when the available hardware support is lacking or inadequate. As an example, EDDI can simultaneously monitor millions of memory locations, without crippling the host processing platform. It does this in software and hence provides a portable debugging environment. It is also well suited for interactive debugging because of the low associated overheads. EDDI provides a scalable and extensible debugging framework that can substantially increase the feature set of standard off the shelf debuggers.Singapore-MIT Alliance (SMA

Comprehensive analysis of the mouse renal cortex using two-dimensional HPLC – tandem mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Proteomic methodologies increasingly have been applied to the kidney to map the renal cortical proteome and to identify global changes in renal proteins induced by diseases such as diabetes. While progress has been made in establishing a renal cortical proteome using 1-D or 2-DE and mass spectrometry, the number of proteins definitively identified by mass spectrometry has remained surprisingly small. Low coverage of the renal cortical proteome as well as our interest in diabetes-induced changes in proteins found in the renal cortex prompted us to perform an in-depth proteomic analysis of mouse renal cortical tissue.</p> <p>Results</p> <p>We report a large scale analysis of mouse renal cortical proteome using SCX prefractionation strategy combined with HPLC – tandem mass spectrometry. High-confidence identification of ~2,000 proteins, including cytoplasmic, nuclear, plasma membrane, extracellular and unknown/unclassified proteins, was obtained by separating tryptic peptides of renal cortical proteins into 60 fractions by SCX prior to LC-MS/MS. The identified proteins represented the renal cortical proteome with no discernible bias due to protein physicochemical properties, subcellular distribution, biological processes, or molecular function. The highest ranked molecular functions were characteristic of tubular epithelium, and included binding, catalytic activity, transporter activity, structural molecule activity, and carrier activity. Comparison of this renal cortical proteome with published human urinary proteomes demonstrated enrichment of renal extracellular, plasma membrane, and lysosomal proteins in the urine, with a lack of intracellular proteins. Comparison of the most abundant proteins based on normalized spectral abundance factor (NSAF) in this dataset versus a published glomerular proteome indicated enrichment of mitochondrial proteins in the former and cytoskeletal proteins in the latter.</p> <p>Conclusion</p> <p>A whole tissue extract of the mouse kidney cortex was analyzed by an unbiased proteomic approach, yielding a dataset of ~2,000 unique proteins identified with strict criteria to ensure a high level of confidence in protein identification. As a result of extracting all proteins from the renal cortex, we identified an exceptionally wide range of renal proteins in terms of pI, MW, hydrophobicity, abundance, and subcellular location. Many of these proteins, such as low-abundance proteins, membrane proteins and proteins with extreme values in pI or MW are traditionally under-represented in 2-DE-based proteomic analysis.</p