Kendall Square Research Articles

PASTE, Don't Cut: Genome Editing Tool Looks Beyond CRISPR and Prime

PASTE, Don't Cut: Genome Editing Tool Looks Beyond CRISPR and Prime

Innovation District Space and Element Identification Framework: Empirical Research from Shenzhen, China

Science and technology and skills have increasingly become the driving force to lead the development of knowledge economy. With the changes in the demand for knowledge workers and the location of enterprises, a new type of innovation space—innovation districts—has emerged. Countries have begun to identify and nurture innovation districts. Therefore, how to accurately identify innovation districts in cities has become an important research topic. The existing research on identifying innovation districts is mainly based on a qualitative description method at the element level. However, whether there are other potential innovation districts in urban space can be identified by quantitative identification. Therefore, the purpose of this paper is to establish an innovation district identification framework and a case study of the framework. The identification framework includes spatial identification and factor identification. In spatial identification, the identification index system is constructed based on the spatial location, range limit, and the surrounding area of innovative assets. In factor identification, the identification index system is constructed based on innovative assets, physical assets, and network assets, and Kendall Square and Boston innovation districts are used as the reference basis to determine whether the identified districts meet the standards of the constructed innovation districts. In empirical case research, spatial identification identified the Gaoxin South District (GXSD) spatial range. In factor identification, it was found that GXSD does not fully meet the standard of innovation district identification. This paper argues that the framework is essential for urban managers, planners, and urban designers to identify and evaluate high-quality innovation districts.

Estimating Pedestrian Flows on Street Networks

Problem, research strategy, and findings City governments and planners alike commonly seek to increase pedestrian activity on city streets as part of broader sustainability, community building, and economic development strategies. Though walkability has received ample attention in planning literature, most planners still lack practical methods for predicting how development proposals could affect pedestrian activity on specific streets or public spaces at different times of the day. Cities typically require traffic impact assessments (TIAs) but not pedestrian impact assessments. In this study I present a methodology for estimating pedestrian trip generation and distribution between detailed origins and destinations in both existing and proposed built environments. Using the betweenness index from network analysis, I introduce a number of methodological improvements that allow the index to model pedestrian trips with parameters and constraints to account for pedestrian behavior in different settings. I demonstrate its application in the Kendall Square area of Cambridge (MA), where estimated foot traffic is compared during lunch and evening peak periods with observed pedestrian counts. Takeaway for practice The proposed approach can be particularly useful for TIAs, neighborhood plans, and large-scale development projects, where pedestrian flow estimates can be used to guide pedestrian infrastructure and safety improvements and public space investments or for locating pedestrian priority streets during the COVID-19 pandemic.

A Material Perspective of Wood, Smoke, and BBQ

For those of us who have attempted to barbecue (BBQ), wood matters. Smoking delicious meats is effectively a chemical process that involves control over combustion of organic materials. Here, we get joint insight from a local pitmaster and a materials scientist.

Bayer readies cancer R&D site in Cambridge

Last fall, Bayer announced it would lay off 12,000 employees worldwide. In a tiny offset, the firm is now making plans for a cancer research center in Cambridge, Massachusetts. Bayer will pay the Massachusetts Institute of Technology about $100 million for a 12-year lease of nearly 5,800 m2 of lab and office space in a new building in Kendall Square, the city’s biotech hub. Bayer has 20 employees in Cambridge and plans to add 75 to the new site when it opens in 2021. The number could double to 150 the following year.

Realizing the Value of Industry-University Innovation Alliances

OverviewIn response to increasing market pressures over the past decade, corporate expectations for measurable results from engagement with universities have climbed. The trend has developed away from one-off cooperation with individual researchers and toward sustained cross-institutional collaborations that produce research that is integrated into the full span of the corporate innovation process. This trend is most visible in the emergence of corporate innovation centers adjacent to major universities, such as Kendall Square in Cambridge and Tech Square in Atlanta. This shift has called for a rethinking of the balance between academic and corporate roles and practices in these relationships. We describe five key practices universities and corporate partners can implement to support successful, sustained industry-university innovation alliances, developed from Georgia Tech’s experience in engaging with 25 corporate partners.

Can mRNA disrupt the drug industry?

On a brisk morning in April, dozens of investors filed into a Marriott hotel conference hall in Kendall Square, the biotech hub of Cambridge, Mass., for the first Moderna Therapeutics platform science day. They gathered hoping to get a rare, inside look at the science behind what the start-up had long claimed to be a disruptive drug platform: carefully designed molecules called messenger RNA that prompt the body to make its own medicine. The concept has attracted billions in funding, but the company had largely kept details of how the technique works under wraps. “Why are we so passionate about messenger RNA?” Moderna President Stephen Hoge asked the attentive audience. “It starts with the question of life,” he explained. “And in fact, all life that we know flows through messenger RNA. ... In our language, mRNA is the software of life.” Cells use mRNA to translate the static genes of

Anderson-Fabry disease.

Anderson-Fabry disease.

BMS fosters biotech in Kendall Square

Bristol-Myers Squibb has become a sponsor at LabCentral, a shared laboratory space in Cambridge, Mass., for biotech start-ups. The sponsorship will allow BMS to nominate two start-ups each year for a spot at LabCentral’s Kendall Square facilities; winners of the two so-called Golden Tickets will receive underwritten bench space for one scientist for one year and a priority spot on the waiting list for more space. BMS’s support of start-ups in the Boston area comes as the company builds a research facility in Kendall Square set to open in early 2018.

Profile of alisporivir and its potential in the treatment of hepatitis C

Two classes of hepatitis C antiviral agents currently exist, ie, direct-acting antivirals and host-targeting antivirals. Direct-acting antivirals target viral proteins including NS3/NS4A protease, NS5B polymerase and NS5A protein, while host-targeting antivirals target various host proteins critical for replication of the hepatitis C virus (HCV). Alisporivir is the most advanced host-targeting antiviral in clinical development. Alisporivir blocks HCV replication by neutralizing the peptidyl-prolyl isomerase activity of the abundant host cytosolic protein, cyclophilin A. Due to its unique mechanism of antiviral action, alisporivir is pangenotypic, provides a high barrier for development of viral resistance, and does not permit cross-resistance to direct-acting antivirals. Alisporivir has an excellent pharmacokinetic and safety profile. Phase I and II clinical studies have demonstrated that alisporivir causes a dramatic reduction in viral loads in HCV-infected patients. Alisporivir was shown to be highly potent in treatment-naïve and treatment-experienced patients with genotype 1 as well as in those with genotypes 2 or 3. Low viral breakthrough rates were observed and the most frequent clinical and laboratory adverse events associated with alisporivir in combination with pegylated interferon-alpha and ribavirin were similar to those associated with pegylated interferon-alpha and ribavirin used alone. A laboratory abnormality observed in some patients receiving alisporivir is hyperbilirubinemia, which is related to transporter inhibition and not to liver toxicity. The most recent clinical results suggest that alisporivir plus other direct-acting antivirals should provide a successful treatment option for difficult-to-treat populations, such as nonresponders to prior interferon-alpha therapy and patients with cirrhosis. In conclusion, alisporivir represents an attractive candidate component of future interferon-free regimens.

Covalent Modifiers: An Orthogonal Approach to Drug Design

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCovalent Modifiers: An Orthogonal Approach to Drug DesignMichele H. Potashman* and Mark E. Duggan*§View Author Information Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, Massachusetts 02139* To whom correspondence should be addressed. For M.H.P.: phone, (617) 444-5010; fax, (617) 577-9288; e-mail, [email protected]. For M.E.D.: phone, (617) 583-1983; e-mail, [email protected]§Current address: Link Medicine Inc., 161 First Street, Cambridge, MA 02142.Cite this: J. Med. Chem. 2009, 52, 5, 1231–1246Publication Date (Web):February 9, 2009Publication History Received11 July 2008Published online9 February 2009Published inissue 12 March 2009https://doi.org/10.1021/jm8008597Copyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views15725Altmetric-Citations275LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (985 KB) Get e-AlertsSUBJECTS:Adducts,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts

Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new roles for protein glycosylation in eukaryotes

To further understand the roles of protein glycosylation in eukaryotes, we globally identified glycan-containing proteins in yeast. A fluorescent lectin binding assay was developed and used to screen protein microarrays containing over 5000 proteins purified from yeast. A total of 534 yeast proteins were identified that bound either Concanavalin A (ConA) or Wheat-Germ Agglutinin (WGA); 406 of them were novel. Among the novel glycoproteins, 45 were validated by mobility shift upon treatment with EndoH and PNGase F, thereby extending the number of validated yeast glycoproteins to 350. In addition to many components of the secretory pathway, we identified other types of proteins, such as transcription factors and mitochondrial proteins. To further explore the role of glycosylation in mitochondrial function, the localization of four mitochondrial proteins was examined in the presence and absence of tunicamycin, an inhibitor of N-linked protein glycosylation. For two proteins, localization to the mitochondria is diminished upon tunicamycin treatment, indicating that protein glycosylation is important for protein function. Overall, our studies greatly extend our understanding of protein glycosylation in eukaryotes through the cataloguing of glycoproteins, and describe a novel role for protein glycosylation in mitochondrial protein function and localization.

Toward the green city through revitalizing major obsolescent urban lands

The author, an architect and urban designer, has played a leading role on a broad range of assignments in highly diverse urban settings in North America and Europe. Much of his work focuses on the rejuvenation of downtowns, waterfronts, neighborhoods, and campus master planning. His projects include the award-winning Saint Paul on the Mississippi Development Framework, the Brooklyn Bridge Park on the East River in New York, the East River waterfront in Lower Manhattan, the Fan Pier in Boston, the Southwest and Southeast Waterfronts in Washington, DC, the Vision Plan for Washington DC, Kendall Square and North Point/Lechmere Square in Cambridge, the Downtown Hartford Economic and Urban Design Action Strategy and the Downtown Master Plan for Fort Lauderdale. Current efforts include the " Big Picture for the Big Dig": the Rose Kennedy Greenway in Boston, the renewal of Regent Park, a major public housing project in Toronto; the implementation of the Convention District Master Plan in San Juan, P.R., and Urban Design advice for the Cincinnati Center City Development Corp (3CDC). In each city, with each project, his strategic, consensus-building approach has led to coordinated planning and a renewed focus on urban design. The text that follows is an edited and revised version of a paper presented at the international symposion on"The Natural City, " Toronto, 23-25 June, 2004, sponsored by the University of Toronto's Division of the Environment, Institute for Environmental Studies, and the World Society for Ekistics.

CTK: configurable object abstractions for multiprocessors

The Configuration Toolkit (CTK) is a library for constructing configurable object based abstractions that are part of multiprocessor programs or operating systems. The library is unique in its exploration of runtime configuration for attaining performance improvements: 1) its programming model facilitates the expression and implementation of program configuration; and 2) its efficient runtime support enables performance improvements by the configuration of program components during their execution. Program configuration is attained without compromising the encapsulation or the reuse of software abstractions. CTK programs are configured using attributes associated with object classes, object instances, state variables, operations, and object invocations. At runtime, such attributes are interpreted by policy classes, which may be varied separately from the abstractions with which they are associated. Using policies and attributes, an object's runtime behavior may be varied by: 1) changing its performance or reliability while preserving the implementation of its functional behavior, or 2) changing the implementation of its internal computational strategy. CTK's multiprocessor implementation is layered on a Cthreads-compatible programming library, which results in its portability to a wide variety of uni- and multiprocessor machines, including a Kendall Square KSR-2 Supercomputer, SGI machines, various SUN workstations, and as a native kernel on the GP1000 BBN Butterfly multiprocessor. The platforms evaluated in the paper are the KSR and SGI machines.

High-Performance Computational Chemistry: Hartree-Fock Electronic Structure Calculations on Massively Parallel Processors

The parallel performance of the NWChem version 1.2α parallel direct-SCF code has been characterized on five massively parallel supercomputers (IBM SP, Kendall Square KSR-2, CRAY T3D and T3E, and Intel Touchstone DELTA) using single-point energy calculations on seven molecules of varying size (up to 389 atoms) and composition (first-row atoms, halogens, and transition metals). The authors compare the performance using both replicated-data and distributed-data algorithms and the original McMurchie-Davidson and recently incorporated TEXAS integrals packages.

Oral Etomidate

Genzyme Corporation; One Kendall Square; Cambridge, MassachusettsIn Reply:-Thank you for your interest in our publication, “Oral Transmucosal Etomidate (OTET) in Volunteers. [1]” We agree that oral administration may be an effective route of etomidate administration. As noted in our article, it was impossible to distinguish how much absorption of etomidate from OTET occurred via the transmucosal route versus the gastrointestinal route. Further study is needed to elucidate this. However, work with animals in our lab has shown that etomidate is highly permeable through the canine buccal mucosa. [2]It is likely that a significant proportion of etomidate from OTET will be absorbed by the transmucosal route. Therefore, we would expect the onset of effect to be quicker with OTET compared to the oral solution. Again, this hypothesis needs further study. We agree with Dr. Lauretti that etomidate is distasteful. We noted in our article that the taste of OTET became significantly worse with increasing dose. Further development of OTET will necessitate flavor modification.James B. Streisand, M.D.Genzyme Corporation; One Kendall Square; Cambridge, Massachusetts(Accepted for publication June 13, 1998.)

Computing global virtual time in shared-memory multiprocessors

Global virtual time (GVT) is used in the Time Warp synchronization mechanism to perform irrevocable operations such as I/O and to reclaim storage. Most existing algorithms for computing GVT assume a message-passing programming model. Here, GVT computation is examined in the context of a shared-memory model. We observe that computation of GVT is much simpler in shared-memory multiprocessors because these machines normally guarantee that no two processors will observe a set of memory operations as occurring in different orders. Exploiting this fact, we propose an efficient, asynchronous, shared-memory GVT algorithm and prove its correctness. This algorithm does not require message acknowledgments, special GVT messages, or FIFO delivery of messages, and requires only a minimal number of shared variables and data structures. The algorithm only requires one round of interprocessor communication to compute GVT, in contrast to many message-based algorithms that require two. An efficient implementatin is described that eliminates the need for a processor to explicitly compute a local minimum for time warp systems using a lowest-timestamp-first scheduling policy in each processor. In addition, we propose a new mechanism called on-the-fly fossil collection that enables efficient storage reclamation for simulations containing large numbers, e.g., hundreds of thousand or even millions of simulator objects. On-the-fly fossil collection can be used in time warp systems executing on either shared-memory or message-based machines. Performance measurements of the GVT algorithm and the on-the-fly fossil collection mechanism on a Kendall Square Research KSR-2 machine demonstrate that these techniques enable frequent GVT and fossil collections, e.g., every millisecond, without incurring a significant performance penalty

The Recent Revolution in High Performance Computing

Recent events in the high-performance computing industry have concerned scientists and the general public regarding a crisis or a lack of leadership in the field. That concern is understandable considering the industry's history from 1993 to 1996. Cray Research, the historic leader in supercomputing technology, was unable to survive financially as an independent company and was acquired by Silicon Graphics. Two ambitious new companies that introduced new technologies in the late 1980s and early 1990s—Thinking Machines and Kendall Square Research—were commercial failures and went out of business. And Intel, which introduced its Paragon supercomputer in 1994, discontinued production only two years later.During the same time frame, scientists who had finished the laborious task of writing scientific codes to run on vector parallel supercomputers learned that those codes would have to be rewritten if they were to run on the next-generation, highly parallel architecture. Scientists who are not yet involved in high-performance computing are understandably hesitant about committing their time and energy to such an apparently unstable enterprise.However, beneath the commercial chaos of the last several years, a technological revolution has been occurring. The good news is that the revolution is over, leading to five to ten years of predictable stability, steady improvements in system performance, and increased productivity for scientific applications. It is time for scientists who were sitting on the fence to jump in and reap the benefits of the new technology.

Adaptive memory management and optimism control in time warp

It is widely believed that the Time Warp protocol for parallel discrete event simulation is prone to two potential problems: an excessive amount of wasted, rolled back computation resulting from “rollback thrashing” behaviors, and inefficient use of memory, leading to poor performance of virtual memory and/or multiprocessor cache systems. An adaptive mechanism is proposed based on the Cancelback memory management protocol for shared-memory multiprocessors that dynamically controls the amount of memory used in the simulation in order to maximize performance. The proposed mechanism is adaptive in the sense that it monitors the execution of the Time Warp program, and using simple models, automatically adjusts the amount of memory used to reduce Time Warp overheads (fossil collection, Cancelback, the amount of rolled back computation, etc.) to a manageable level. We describe an implementation of this mechanism on a shared memory, Kendall Square Research KSR-1, multiprocessor and demonstrate its effectiveness in automatically maximizing performance while minimizing memory utilzation, for several synthetic and benchmark discrete event simulation applications. We also demonstrate the adaptive ability of the mechanism by showing that it “tracks” the time-varying nature of a communication network simulation.

Matrix partitioning on a virtual shared memory parallel machine

The general problem considered in the paper is partitioning of a matrix operation between processors of a parallel system in an optimum load-balanced way without potential memory contention. The considered parallel system is defined by several features the main of which is availability of a virtual shared memory divided into segments. If partitioning of a matrix operation causes parallel access to the same memory segment with writing data to the segment by at least one processor, then contention between processors arises which implies performance degradation. To eliminate such situation, a restriction is imposed on a class of possible partitionings, so that no two processors would write data to the same segment. On the resulting class of contention-free partitionings, a load-balanced optimum partitioning is defined as satisfying independent minimax criteria. The main result of the paper is an algorithm for finding the optimum partitioning by means of analytical solution of respective minimax problems. The paper also discusses implementation and performance issues related to the algorithm, on the basis of experience at Kendall Square Research Corporation, where the partitioning algorithm was used for creating high-performance parallel matrix libraries.