95 research outputs found
The Military Technical Revolution:
The conduct of war changed dramatically between World War II and Operation Desert Storm. The major differences resulted from a revolution in military technology. As we look ahead ten years to the world of the year 2003, we need to examine this Military Technical Revolution (MTR) to project how the next war will be different from Desert Storm. An analysis of technological changes since World War II indicates that the MTR has undergone three distinct phases, which started at different times, stand today at different stages, and accordingly will culminate (or have already} at different times
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The kinetics of adenovirus DNA replication
Methods have been developed to measure the time required to
complete replication of an adenovirus DNA molecule and the time
between rounds of replication of the viral genomes. These methods
show that 22 minutes are required to complete replication of an
adenovirus DNA molecule at 37° C and that this time is constant
throughout infection. The rate limiting step in DNA replication is
initiation of a round of replication. The initiation rate decreases
over infection and shows saturable kinetics corresponding to a
maximum of 50, 000 replication sites per cell. The size of the pool
of adenovirus DNA molecules actively replicating is approximately
constant over infection, and the DNA molecules in the pool are preferentially
replicated. By use of the measured rate parameters
based on the strand displacement mechanism of DNA replication
(R. L. Lechner and T. J. Kelly, Jr. , 1977. Cell, 12, 1007) several
types of experiments were computer simulated to show that this
mechanism and measured rate parameters are consistent quantitatively
with experimental data. A mechanism is proposed for
generation of defective adenovirus DNA inherent in normal replication
Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors
The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates
Maternal 25-Hydroxyvitamin D and Preterm Birth in Twin Gestations
To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24â28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies
Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells
Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells.ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to GâąACAâą âą âąTGTâąC. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and ÎČ were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types.Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
Glycosylation is a topic of intense current interest in the
development of biopharmaceuticals because it is related
to drug safety and efficacy. This work describes results of
an interlaboratory study on the glycosylation of the Primary
Sample (PS) of NISTmAb, a monoclonal antibody
reference material. Seventy-six laboratories from industry,
university, research, government, and hospital sectors
in Europe, North America, Asia, and Australia submit-
Avenue, Silver Spring, Maryland 20993; 22Glycoscience Research Laboratory, Genos, Borongajska cesta 83h, 10 000 Zagreb, Croatia;
23Faculty of Pharmacy and Biochemistry, University of Zagreb, A. KovacË icÂŽ a 1, 10 000 Zagreb, Croatia; 24Department of Chemistry, Georgia
State University, 100 Piedmont Avenue, Atlanta, Georgia 30303; 25glyXera GmbH, Brenneckestrasse 20 * ZENIT / 39120 Magdeburg, Germany;
26Health Products and Foods Branch, Health Canada, AL 2201E, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9 Canada;
27Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama Higashi-Hiroshima 739â8530 Japan; 28ImmunoGen,
830 Winter Street, Waltham, Massachusetts 02451; 29Department of Medical Physiology, Jagiellonian University Medical College,
ul. Michalowskiego 12, 31â126 Krakow, Poland; 30Department of Pathology, Johns Hopkins University, 400 N. Broadway Street Baltimore,
Maryland 21287; 31Mass Spec Core Facility, KBI Biopharma, 1101 Hamlin Road Durham, North Carolina 27704; 32Division of Mass
Spectrometry, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongwon-gu, Cheongju Chungbuk, 363â883 Korea
(South); 33Advanced Therapy Products Research Division, Korea National Institute of Food and Drug Safety, 187 Osongsaengmyeong 2-ro
Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 363â700, Korea (South); 34Center for Proteomics and Metabolomics, Leiden
University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; 35Ludger Limited, Culham Science Centre, Abingdon,
Oxfordshire, OX14 3EB, United Kingdom; 36Biomolecular Discovery and Design Research Centre and ARC Centre of Excellence for Nanoscale
BioPhotonics (CNBP), Macquarie University, North Ryde, Australia; 37Proteomics, Central European Institute for Technology, Masaryk
University, Kamenice 5, A26, 625 00 BRNO, Czech Republic; 38Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse
1, 39106 Magdeburg, Germany; 39Department of Biomolecular Sciences, Max Planck Institute of Colloids and Interfaces, 14424
Potsdam, Germany; 40AstraZeneca, Granta Park, Cambridgeshire, CB21 6GH United Kingdom; 41Merck, 2015 Galloping Hill Rd, Kenilworth,
New Jersey 07033; 42Analytical R&D, MilliporeSigma, 2909 Laclede Ave. St. Louis, Missouri 63103; 43MS Bioworks, LLC, 3950 Varsity Drive
Ann Arbor, Michigan 48108; 44MSD, Molenstraat 110, 5342 CC Oss, The Netherlands; 45Exploratory Research Center on Life and Living
Systems (ExCELLS), National Institutes of Natural Sciences, 5â1 Higashiyama, Myodaiji, Okazaki 444â8787 Japan; 46Graduate School of
Pharmaceutical Sciences, Nagoya City University, 3â1 Tanabe-dori, Mizuhoku, Nagoya 467â8603 Japan; 47Medical & Biological Laboratories
Co., Ltd, 2-22-8 Chikusa, Chikusa-ku, Nagoya 464â0858 Japan; 48National Institute for Biological Standards and Control, Blanche Lane, South
Mimms, Potters Bar, Hertfordshire EN6 3QG United Kingdom; 49Division of Biological Chemistry & Biologicals, National Institute of Health
Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158â8501 Japan; 50New England Biolabs, Inc., 240 County Road, Ipswich, Massachusetts
01938; 51New York University, 100 Washington Square East New York City, New York 10003; 52Target Discovery Institute, Nuffield Department
of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, United Kingdom; 53GlycoScience Group, The National Institute for
Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland; 54Department of Chemistry, North
Carolina State University, 2620 Yarborough Drive Raleigh, North Carolina 27695; 55Pantheon, 201 College Road East Princeton, New Jersey
08540; 56Pfizer Inc., 1 Burtt Road Andover, Massachusetts 01810; 57Proteodynamics, ZI La Varenne 20â22 rue Henri et Gilberte Goudier 63200
RIOM, France; 58ProZyme, Inc., 3832 Bay Center Place Hayward, California 94545; 59Koichi Tanaka Mass Spectrometry Research Laboratory,
Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho Nakagyo-ku, Kyoto, 604 8511 Japan; 60Childrenâs GMP LLC, St. Jude Childrenâs
Research Hospital, 262 Danny Thomas Place Memphis, Tennessee 38105; 61Sumitomo Bakelite Co., Ltd., 1â5 Muromati 1-Chome, Nishiku,
Kobe, 651â2241 Japan; 62Synthon Biopharmaceuticals, Microweg 22 P.O. Box 7071, 6503 GN Nijmegen, The Netherlands; 63Takeda
Pharmaceuticals International Co., 40 Landsdowne Street Cambridge, Massachusetts 02139; 64Department of Chemistry and Biochemistry,
Texas Tech University, 2500 Broadway, Lubbock, Texas 79409; 65Thermo Fisher Scientific, 1214 Oakmead Parkway Sunnyvale, California
94085; 66United States Pharmacopeia India Pvt. Ltd. IKP Knowledge Park, Genome Valley, Shamirpet, Turkapally Village, Medchal District,
Hyderabad 500 101 Telangana, India; 67Alberta Glycomics Centre, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 68Department
of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 69Department of Chemistry, University of California, One Shields Ave,
Davis, California 95616; 70HorvaÂŽ th Csaba Memorial Laboratory for Bioseparation Sciences, Research Center for Molecular Medicine, Doctoral
School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Egyetem ter 1, Hungary; 71Translational Glycomics
Research Group, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprem, Egyetem ut 10, Hungary;
72Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way Newark, Delaware 19711; 73Proteomics Core Facility, University
of Gothenburg, Medicinaregatan 1G SE 41390 Gothenburg, Sweden; 74Department of Medical Biochemistry and Cell Biology, University of
Gothenburg, Institute of Biomedicine, Sahlgrenska Academy, Medicinaregatan 9A, Box 440, 405 30, Gothenburg, Sweden; 75Department of
Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Bruna Straket 16, 41345 Gothenburg,
Sweden; 76Department of Chemistry, University of Hamburg, Martin Luther King Pl. 6 20146 Hamburg, Germany; 77Department of Chemistry,
University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2; 78Laboratory of Mass Spectrometry of Interactions and
Systems, University of Strasbourg, UMR Unistra-CNRS 7140, France; 79Natural and Medical Sciences Institute, University of Tuš bingen,
Markwiesenstrae 55, 72770 Reutlingen, Germany; 80Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical
Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; 81Division of Bioanalytical Chemistry, Amsterdam Institute for
Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; 82Department
of Chemistry, Waters Corporation, 34 Maple Street Milford, Massachusetts 01757; 83Zoetis, 333 Portage St. Kalamazoo, Michigan 49007
Authorâs ChoiceâFinal version open access under the terms of the Creative Commons CC-BY license.
Received July 24, 2019, and in revised form, August 26, 2019
Published, MCP Papers in Press, October 7, 2019, DOI 10.1074/mcp.RA119.001677
ER: NISTmAb Glycosylation Interlaboratory Study
12 Molecular & Cellular Proteomics 19.1
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ted a total of 103 reports on glycan distributions. The
principal objective of this study was to report and compare
results for the full range of analytical methods presently
used in the glycosylation analysis of mAbs. Therefore,
participation was unrestricted, with laboratories
choosing their own measurement techniques. Protein glycosylation
was determined in various ways, including at
the level of intact mAb, protein fragments, glycopeptides,
or released glycans, using a wide variety of methods for
derivatization, separation, identification, and quantification.
Consequently, the diversity of results was enormous,
with the number of glycan compositions identified by
each laboratory ranging from 4 to 48. In total, one hundred
sixteen glycan compositions were reported, of which 57
compositions could be assigned consensus abundance
values. These consensus medians provide communityderived
values for NISTmAb PS. Agreement with the consensus
medians did not depend on the specific method or
laboratory type. The study provides a view of the current
state-of-the-art for biologic glycosylation measurement
and suggests a clear need for harmonization of glycosylation
analysis methods. Molecular & Cellular Proteomics
19: 11â30, 2020. DOI: 10.1074/mcp.RA119.001677.L
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