Radiation and Nitric Oxide Formation in Turbulent Non-Premixed Jet Flames

DTIC Science & Technology

2000-08-04

axial coordinate was nor- malized by the stoichiometric flame length . of possible soot-NO interactions and reduces inter- ference with the laser...through the top of the cylinder was small if the height of the axial traverse was 3 to 4 times the stoi- chiometric flame length . The calibration of the...jet Reynolds numbers, Re, stoichiometric flame length , Lstoich, and convective residence times, s. The convective residence time was determined by s

DMPL: Programming and Verifying Distributed Mixed Synchrony and Mixed Critical Software

DTIC Science & Technology

2016-06-16

ference on Intelligent Robots and Systems, pages 1495–1502, Chicago, IL, September 2014. IEEE Computer Society. [21] MADARA website . http://sourceforge.net...4.6 DMPL program for 5- robot reconnaissance example 19 Figure 5.1 Generated C++ code for example DMPL program. In practice, local vari- ables (lines...examples of collision avoidance in multi- robot systems. CMU/SEI-2016-TR-005 | SOFTWARE ENGINEERING INSTITUTE | Carnegie Mellon University vii

Gender, Equity, and Job Satisfaction

DTIC Science & Technology

1992-02-01

Kahn, Nelson, and Gaeddert ers. Among married personnel, breadwinner (1980, p. 748) argued that "much of the research status (i.e., whether or not the...a lack of clarity on this issue and that not ners. Non- breadwinners , on whose income the all relevant variables have been identified. As family does...Sauser, W. I., & York, M. (1978). Sex dif- and female means to a just end. Basic and ferences in job satisfaction: A re-examination. Applied Social

An HLA-Based Approach to Quantify Achievable Performance for Tactical Edge Applications

DTIC Science & Technology

2011-05-01

in: Proceedings of the 2002 Fall Simulation Interoperability Workshop, 02F- SIW -068, Nov 2002. [16] P. Knight, et al. ―WBT RTI Independent...Benchmark Tests: Design, Implementation, and Updated Results‖, in: Proceedings of the 2002 Spring Simulation Interoperability Workshop, 02S- SIW -081, March...Interoperability Workshop, 98F- SIW -085, Nov 1998. [18] S. Ferenci and R. Fujimoto. ―RTI Performance on Shared Memory and Message Passing Architectures‖, in

The Effects of Material and Task Variations on a Brief Cognitive Learning Strategies Training Program

DTIC Science & Technology

1980-08-01

EFFECTS OF MATERIAL AND TASK VARIATIONS ON A BRIEF COGNITIVE LEARNING STRATEGIES TRAINING PROGRAM Introduction As scholastic achievement scores continue to...variance of the test scores revealed no significant dif- ferences among the three treatment conditions on any of the tests. Although these results...tentative because of the group performance patterns. On the first (easier) passage, group means indicated nearly perfect scores for all three of the

Integrated Geophysical Survey on Deák Ferenc Sluice in Hungary

NASA Astrophysics Data System (ADS)

Kanli, A. I.

2015-12-01

ALI ISMET KANLI1*, G. TALLER2, Z. PRONAY2, P. TILDY2, P. NAGY3, E. TOROS2 *1Istanbul University, Turkey, kanli@istanbul.edu.tr, 2Geological and Geophysical Institute of Hungary,3MinGeo, Hungary The Ferenc Channel is one of the main irrigation and ship channel in south of Hungary, existing from 1801. The water level is controlled by the Deák Ferenc Sluice in the channel which was constructed in 1875. At that time, the sluice was unique in Europe with its two channels and brick-walls. The west channel was used for controlling the amount of water and the east channel was used for shipping. In the study, before starting to the restoration and reinforcement plannings at the sluice, non-destructive geophysical investigations were executed. In the first stage, ultra-high frequency seismic (80 kHz) and acoustic (5 kHz) investigations of the floor slab were carried out from a boat on the water level. Due to the water level was approximately 2 m, we could use the advantage of the water ensuring very good coupling with seismic sensors for high frequency seismic and acoustic measurements. In the second stage, resistivity measurements were carried out in the eastern part of the sluice which was used as the shipping channel. Three profiles were measured to map the resistivity distribution of the slab. In the third stage, for better understanding the stability conditions of the walls and easy to compare with the data of GPR measurements, the wall of the sluice were investigated by a simple seismic direct wave method using seismic P-waves for mapping seismic velocities. The last stage of the survey was the GPR measurements that were carried out both on the walls and on the slab of the sluice. During the investigation, the channels were empty and without water. The integrated survey and the interpretation of the results showed us that there were some faults, cracks and voids in the slab existed in the whole grossness of the slab and the brick walls were builded from inhomogenous construction material. Integrated geophysical surveys provided optimum solutions for planning restoration and reinforcement work on this ancient and very old building structure. Acknowledgment: Ali Ismet Kanli was supported by The Division of Scientific Research Projects of Istanbul University, International Research Projects, Project number: IRP-50242.

Thermonuclear Propaganda: Presentations of Nuclear Strategy in the Early Atomic Age

DTIC Science & Technology

2014-06-01

comics .17 One scholar of atomic culture noted the ambiguity of the duality of the atomic age as a central tenant to building the “most powerful of all...2004). 18 Ferenc Morton Szasz, Atomic Comics : Cartoonists Confront the Nuclear World (Reno, NV: University of Nevada Press, 2012), 135. 19 Ibid...research.archives.gov/description/36952. 28 Osgood, Total Cold War; Szasz, Atomic Comics ; Zeman and Amundson, Atomic Culture, 3-4. 10 the most modern

Demonstration of Hybrid DSMC-CFD Capability for Nonequilibrium Reacting Flow

DTIC Science & Technology

2018-02-09

Lens-XX facility. This flow was chosen since a recent blind-code validation exercise revealed differences in CFD predictions and experimental data... experimental data that could be due to rarefied flow effects. The CFD solutions (using the US3D code) were run with no-slip boundary conditions and with...excellent agreement with that predicted by CFD. This implies that the dif- ference between CFD predictions and experimental data is not due to rarefied

Journal of Special Operations Medicine. Volume 2, Edition 4, Fall 2002

DTIC Science & Technology

2002-01-01

Blessing Journal of Special Operations Medicine6 GENERAL RULES FOR SUBMISSIONS 1. Use the active voice when possible. 2. Secure permission before...Afghanistan to the Philippines . I am currently writ- ing this at the "Advanced Technology Applications for Combat Casualty Care" (ATACCC) meeting...ference some of the time. 91W Transition- All active component SOF units with medics that are not 18D are 91Ws as 91W_W1 Special Operations Combat

Strategic Forum. Number 274. January 2012. Raising Our Sights: Russian-American Strategic Restraint in an Age of Vulnerability

DTIC Science & Technology

2012-01-01

leader. Although Russians remain wary of the United States, perpetuating and accenting American- Russian dif- ferences is no longer the formula for...truly seek a nonadversarial relationship, each can agree not to be the Raising Our Sights: Russian - American Strategic Restraint in an Age of...Raising Our Sights: Russian -American Strategic Restraint in an Age of Vulnerability 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Environmental Impact Research Program. Yellow Sweetclover (Melilotus officinalis) Section 7.3.4, U.S. Army Corps of Engineers Wildlife Resources Management Manual.

DTIC Science & Technology

1986-07-01

Gambel’s quail (Callipepla gconbelii), and California quail (C. californica). Muskrats (Ondatra zibethicus) and cottontails (Sylvi- 7agus spp.) eat the...sodbound grass stands that need renovation can benefit from sweetclover seedings. In these areas sweetclover can be used as green manure; a cover crop...prevent inter- ference with carbohydrate storage and rootcrown bud development. Second-year production of sweetclover is closely correlated with the

Translations on South and East Asia, Numbe r731, Laos Is Marching Forward Along the Glorious Path of the Era.

DTIC Science & Technology

1977-08-09

independence and national concord of the people in the two capi- tal cities and throughout the country. This showed the strong desire for free ...included varying periods of highs and lows and our people took very seriously their role of keeping their country free in the face of the danger of...August 1950, the first great con- ference of free representatives from all over the country was assembled. The conference unanimously passed the

Sources & Transport Mechanisms of Sediments in the Oceans.

DTIC Science & Technology

1982-03-31

estuaries 03si e m arh ket. The. peristaltic action, dugt is. pro ~gre- and oceans. The concentration of doe suspended sample was testig were obtained by...waters: Clays Clay Minerals, Seventh National Con - weer: Progress in water technology. v. 7, p. 207-216. ference, p. 1-79. Guess, R. J. (1977), Clay...the (10) ZAbawa, C. Science (Wahigton, D.C) 1978,202,49.4 dlyt Of the GMo wer 45 jum wit a meal portion (11) G b.I J.; Kenwar, L Environ. Sci. Technol

Feasibility Study of Quantitative Erosion Models for Use by the Federal Emergency Management Agency in the Prediction of Coastal Flooding.

DTIC Science & Technology

1987-06-01

Terrebonne Parish, La. Erosional 4 II Terrebonne-Jefferson Parishes, La. Erosional 5 111 Mississippi river delta front, La. Marsh/mud coast 6 I Chandeleur ...response along the transgressive Chandeleur barrier island arc southeast of the Mississippi Delta plain is variable because of local dif- ferences in...storms are the primary agents causing erosion and migration of this barrier arc. Frederic’s greatest impact was in the duneless southern Chandeleurs

Relative Radiation Density and Temperature Distribution of Rocket Flames

DTIC Science & Technology

1951-07-10

traversed along the axis of the flame image to determine the flame length and the position of the Mach nodes. Other traverses were made across the...variation is due to different stages of flame growth. Other variations especially those of 2 6• flame length , can be accounted for by dif- U L L ference...The temperature gradient is considerably less at the tip of the flame and by similar reasoning would give greater variation in flame length . The problem

North Atlantic Regional Water Resources Study. Appendix O. Fish and Wildlife.

DTIC Science & Technology

1972-05-01

somewhat drier climate. They enjoy a varied diet , preferring annual plants , grasses , and legumes. Cereal grains are not a requirement , though they are...dators , and access to t ood~ consisting of annual plants and their ‘,ee j.4 cereal grains , and legume s . They cannot survive severe ‘riers...variation in pre- ference . Walleye and smalimouth bass , for example , favor the lower part of the range (70 0 to 80°) and do well even in waters with maxi

Three Dimensional Reconstruction Algorithm for Imaging Pathophysiological Signals Within Breast Tissue Using Near Infrared Light

DTIC Science & Technology

2006-07-01

months.31 A heated mixture of water, gelatin (G2625, Sigma Inc.), India ink (for absorption), and titanium dioxide powder (for scatter) (TiO2, Sigma Inc...for absorption, and titanium dioxide powder for scat- ter TiO2, Sigma Inc. that are solidified by cooling to room temperature. Optically...2713-2727. 8. Bolin, F.P., Preuss, L. E., Taylor, R. C., Ference, R. J, Refractive index of some mammalian tissue using a fiber optic cladding method

Three Dimensional Reconstruction Algorithm for Imaging Pathophysiological Signals Within Breast Tissue Using Near Infrared Light

DTIC Science & Technology

2006-07-01

of water, gelatin (G2625, Sigma Inc.), India ink (for absorption), and titanium dioxide powder (for scatter) (TiO2, Sigma Inc.) is poured into a mold...R. C., Ference, R. J, Refractive index of some mammalian tissue using a fiber optic cladding method. Applied Optics, 1989. 28(12): p. 2297-2303. 3...scans. The NIR system utilizes six optical wavelengths from 660 to 850 nm using intensity modulated diode lasers nominally working at 100 MHz

Task Analysis Schema Based on Cognitive Style and Supplantational Instructional Design with Application to an Air Force Training Course.

DTIC Science & Technology

1980-02-01

ADOAA82 342 OKLAHOMA UNIV NORMAN COLL OF EDUCATION F/B 5/9 TASK ANALYSIS SCHEMA BASED ON COGNITIVE STYLE AND SUPPLANFATION--ETC(U) FEB GO F B AUSBURN...separately- perceived fragments) 6. Tasks requiring use of a. Visual/haptic (pre- kinesthetic or tactile ference for kinesthetic stimuli stimuli; ability...to transform kinesthetic stimuli into visual images; ability to learn directly from tactile or kinesthet - ic impressions) b. Field independence/de

Physical and Mechanical Characterization of a Nano Carbon Infused Aluminum-Matrix Composite

DTIC Science & Technology

2011-10-01

n (EBSD) a results are s f hardness correlation Vickers ha condition, opy and Im clusions in son 6061 ma num specim s and appe , which are... extrusi perties to po inum in the ference poin wever no s view of a ha ly a carbon image in ations of am rticular hea Electron B and covetic unted...as a n the were point ased veals rbon No atter ere metallogr significan grains in having g distributi area cov grains un

Small Caliber Lethality: 5.56mm Performance in Close Quarters Battle. WSTIAC Quarterly, Volume 8, Number 1

DTIC Science & Technology

2008-01-01

occurs to the target. In the end, “foot- pounds of energy” is misleading, “stopping power” is a myth, and the “ oneshot drop” is a rare possibility...Crane, IN, (NSWC- Crane) and the Army’s Armaments Research , Development, and Engineering Center (ARDEC) at Picatinny Arsenal, NJ, pro- duced...still had differences that could not initially be explained. The IPT was ultimately able to determine a reason for the dif- ferences. The Army Research

Dual Cylindrical Wave Laser-Doppler Method for Measurement of Skin Friction in Fluid Flow.

DTIC Science & Technology

1987-01-01

instrument to the flow channel. The individual modules must not be dis-assembled and handled with care in order to prevent acci- dental misalignment...of light as a wave, according to which each point on a primary wavefront may be considered as a source of a secondary wavelet . Inter- ference between...secondary wavelets produces various patterns of inten- sity in the case of diffraction from an aperture. An envelope of the secondary wavelets may be

Advanced Electron Optics for Vibrational Spectroscopy.

DTIC Science & Technology

1987-10-02

observations of vibrational losses measured 0 2z b n t l o a i r u e h s i by inelastic elctron scattering from surfaces. The basic dif- ference...AFOSR-86-6291 UNCLASSIFIED F/Ci 26/14 U EhEilEEEEEBI / E /EEiEEElh E /EEEE~h R-~ ~ 3 -00 0 0 S *...S :04 *.: UNA A ASSIFIED 469 RT CLASSIFICATION OF THIS...Surfaces", J.L. Erskine, American Vacuum Society Lecture, Texas A&M Unversity, College Station, Texas, April 24,1984. e "Electron Energy Loss Studies of

A Statistical Analysis Plan to Support the Joint Forward Area Air Defense Test.

DTIC Science & Technology

1984-08-02

hy estahlishing a specific significance level prior to performing the statistical test (traditionally a levels are set at .01 or .05). What is often...undesirable increase in 8. For constant a levels , the power (I - 8) of a statistical test can he increased by Increasing the sample size of the test. fRef...ANOVA Iparison Test on MOP I=--ferences Exist AmongF "Upon MOP "A" Factor I "A" Factor I 1MOP " A " Levels ? I . I I I _ _ ________ IPerform k-Sample Com- I

High Voltage Design Guide for Airborne Equipment

DTIC Science & Technology

1976-06-01

Capacitance (Capacity). That property of a system of conductors and dielec- trics which permits the storage of electricity when potential dii’ference exists...rjldtlve low prr•strPs ani’d t (.::;•t.rd t LJr e S Pol yI, rene. A thc r:".li1 ti c p!c.,duu.•’d by th [ olyref r i i it on of st yreute (vi nyl Poly i...by cutting continuous filaments, to short lengtn~s. Storage Life. The period nf time during .inich ,liquid re-i: or adi* dye ca3r. be sored anu remain

[History of Smallpox Vaccination and of the Vaccine Supply in Hungary, up to 1890].

PubMed

Kiss, László

2015-01-01

One of the preconditions for the spread of vaccination against pox diseases was making vaccination available. The first vaccinations were carried out using original cowpox lymph sent by Jenner. For further vaccinations the vaccine was extracted from the blisters of those who had been successfully inoculated. In order to provide vaccine continuously six vaccine centres were set up in 1804 in the following cities: Pest, Buda, Kassa, Gyula, Pozsony and Zágráb (Croatia). Detailed information is available only about the centre in Pest which operated in Rókus Hospital under the leadership of the hospital director András Bossányi. Besides regular vaccination they also provided vaccine for the countryside. From 1824 the vaccine was relocated to the medical faculty of the university in Pest and Ferenc Gebhardt, an instructor of surgeons, became its head. The centre operated in the building of the medical faculty and vaccinations were given on Thursdays and Sundays. After the retirement of Gebhardt in 1860, the centre was taken over by the dermatologist Ferenc Poor for a short time, then by Ignác Semmelweis. From 1863 Gergely Patrubány was responsible for managing the centre. In 1874 the central vaccine institution moved to the Hospital for Poor Children in Pest where it was led first by Lázár Wittman, then by Géza Hainiss. In the 1880s private institutions appeared, the best known were Dani Pécsi's centre in Pest and Béla Intze's one in Tirgu Lapus (Romania). Between 1873 an 1889 András Kreichel ran a vaccine centre in Nálepkovo (Slovakia).

"Where could paul street boys play?" child psychotherapy as co-construction of a playground.

PubMed

Gonella, Vittorio

2014-03-01

In this clinical paper, I present the development of the foundation of a child psychoanalytic treatment to explain in clinical terms what it means to build a "playground," a place where a child could go to play. The aim of the paper, with references to Paul Street Boys, a famous novel by Ferenc Molnár, a Hungarian contemporary of Sándor Ferenczi, is to use the metaphor of the "playground" for describing how, thanks to his personal use of the setting, and thanks to the development of the relationship with the therapist, a traumatized child could gradually begin to build, together with the therapist, a place unknown in his past.

RF Communication Subsystem Integration Research

DTIC Science & Technology

2010-10-15

are filte s) and then  verter (ADC ide, baseban  envelope p followed by  does not r ference  inco . Although t ect sequenc  switch will plified µNod...is to  inco receivers Identifica area and infrastru research  included  operatio WIRELES Figure 40 mechani system o antenna  antenna  switch an...matched  at 5.8 GHz.  ENTAL  RES rograph for  Figure 49. T switch exclu OS  process dance of the   switch is tu of the wirele hart (X2) at  ad band re

The description of all four cardinal signs of Parkinson's disease in a Hungarian medical text published in 1690.

PubMed

Bereczki, Dániel

2010-05-01

One of the most prevalent neurological disorders is Parkinson's disease (PD), characterized by four cardinal signs: tremor, bradykinesia, rigor and postural instability. Although individual signs of Parkinson's disease - most frequently tremor - have been described since ancient times, the first systematic description of the disease is attributed to James Parkinson in 1817. Here we present evidence that not only individual signs, but the disease itself with all four cardinal signs were described in 1690 by Ferenc Pápai Páriz, in a Hungarian medical text over 120 years before the classical description of James Parkinson. In this article I draw the reader's attention to the descriptive chapter in Pápai's book that was published in Hungarian, which because it is understood by so few people, has resulted in this description of PD being ignored in the medical literature. Copyright 2009 Elsevier Ltd. All rights reserved.

The fate of Hungarian Jewish dermatologists during the Holocaust: Part 2: Under Nazi rule.

PubMed

Bock, Julia; Burgdorf, Walter H C; Hoenig, Leonard J; Parish, Lawrence Charles

At least 564,500 Hungarian Jews perished during the Holocaust, including many physicians. Exactly how many Jewish dermatologists were killed is not known. We have identified 62 Hungarian Jewish dermatologists from this period: 19 of these dermatologists died in concentration camps or were shot in Hungary, 3 committed suicide, and 1 died shortly after the Holocaust, exhausted by the War. Fortunately, many Hungarian Jewish dermatologists survived the Holocaust. Some had fled Europe before the Nazi takeover, as was described in Part 1 of this contribution. Two Holocaust survivors, Ferenc Földvári and Ödön Rajka, became presidents of the Hungarian Dermatologic Society and helped rebuild the profession of dermatology in Hungary after the War. This contribution provides one of the first accounts of the fate of Hungarian Jewish dermatologists during the Holocaust and serves as a remembrance of their suffering and ordeal. Copyright © 2016. Published by Elsevier Inc.

Nasa university program review conference. summary report, mar. 1 - 3, 1965

NASA Technical Reports Server (NTRS)

Montgomery, D. J.

1965-01-01

The purpose of the NASA University Program Review Conference was to describe the nature of the Program, the manner in which it is being conducted, the results that it is producing, and the impact it may be having. The presentations, except for some expository papers by NASA offi- cials, were made by members of the university and nonprofit community. ference message as it has come to me, a university professor spending a year in making a study of NASA-University relations under a NASA contract with my institution. In preparing the report, my guiding principle has been to try to maximize its usefulness by making it accurate, brief, and prompt. These qualities are largely incompatible, and I am sure that the result of my search for an optimum compromise will please no one. Open editorializing is mainly confined to a brief section constituting my Evaluation of Program. The complete transcript will shortly be available, to stand as the authoritative source for statements that anyone may wish to attribute to the speakers.

The relationship between human field motion and preferred visible wavelengths.

PubMed

Benedict, S C; Burge, J M

1990-01-01

The purpose of this study was to investigate the relationship between human field motion and preferred visible wavelengths. The study was based on the principle of resonancy from Rogers' science of unitary human beings; 201 subjects were tested using a modified version of Ference's human field motion test (HFMT). Two matrices of color were projected to provide an environment for the measurement of preferred visible wavelengths. There was no statistically significant relationship (r = 0.0387, p = 0.293) between scores on the human field motion test and preferred visible wavelengths as measured in nanometers. The Rogerian concept of accelerated human field rhythms being coordinate with higher frequency environment patterns was not supported in this study. Questions concerning the validity of the HFMT were expressed and were based upon the ambiguity of the terminology of the instrument and the lack of understanding of the concepts used to describe human field motion. Recommendations include the use of other methods to study Rogers' framework, and the development of other instrumentation to measure human field motion.

[Once upon a time there was a medical faculty--a brief history of the Medical Faculty of the Erzsébet University in Pressburg (1914-1919)].

PubMed

Kiss, László

2010-01-01

Despite the fact that the idea of expanding the medical faculties of Budapest and Kolozsvár was formed in the 1870s, it only came true in the 1910s. The XXXVI. Law of 1912 ensured establishing new faculties in Pozsony and Debrecen. The medical faculty of Erzsébet University in Pozsony opened in 1914. The first three professors, i.e. Lajos Bakay, Ferenc Herzog and Dezső Velits, who formerly worked as head physicians for the State Hospital in Pozsony and the Institute for Midwives, were appointed then. The appointment of further professors and launching the 3rd, 4th and 5th forms were delayed by the outbreak of the war until 1918. After the collapse of the Austro-Hungarian Monarchy the newly formed Czechoslovakia dissolved the Hungarian university in 1919. The clinics and institutes of the medical faculty were passed to Czechoslovak ownership, the Hungarian lecturers were dismissed. It is worth mentioning though that Albert Szent-Györgyi and Carl Ferdinand Cori (both Nobel Prize winners) started their scientific career in Pozsony.

1939 versus 1989—A Missed Opportunity to Create a European Lieu de Mémoire?

PubMed Central

Sierp, Aline

2017-01-01

This article is part of the special section titled The Genealogies of Memory, guest edited by Ferenc Laczó and Joanna Wawrzyniak This article analyses the wider context of policy conflict concerning public memory of the 1989 events. It uses Pierre Nora’s concept of lieux de mémoire in trying to explain why 23 August 1939 has been turned into a European Remembrance Day whereas 9 November 1989 has not. By investigating closely the role that various memory actors played during debates at the European level, it advances the idea that the anniversary of the Molotov–Ribbentrop Pact has been more successful in establishing itself within the European remembrance landscape because it has allowed for the promotion of a unifying narrative of the European past. In doing so, the article questions the frequently advanced idea that memory clashes in the EU form around an East–West divide that in some cases overlaps with a Right–Left divide. The analysis digs deep into the complex dynamics lying at the heart of memory contests concerning the end of the Cold War within the EU and provides a more differentiated view of discussions preceding EU decisions on policies of memory. PMID:29081594

SBIR Grant:No-Vibration Agile Cryogenic Optical Refrigerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epstein, Richard

2013-04-09

Optical refrigeration is currently the only all-solid-state cryocooling technology that has been demonstrated. Optical cryocoolers are devices that use laser light to cool small crystal or glass cooling elements. The cooling element absorbs the laser light and reradiates it at higher energy, an example of anti-Stokes fluorescence. The dif-ference between the energy of the outgoing and incoming light comes from the thermal energy of the cooling element, which in turn becomes colder. Entitled No-Vibration Agile Cryocoolers using Optical Refrigeration, this Phase I proposal directly addressed the continued development of the optical refrigerator components necessary to transition this scientific breakthrough intomore » National Nu-clear Security Administration (NNSA) sensor applications in line with the objectives of topic 50b. ThermoDynamic Films LLC (TDF), in collaboration with the University of New Mexico (UNM), cooled an optical-refrigerator cooling element comprised of an ytterbium-doped yttrium lithium fluoride (Yb:YLF) crystal from room tempera-ture to 123 K with about 2% efficiency. This is the world record in optical refrigera-tion and an important step toward revolutionizing cryogenic systems for sensor ap-plications. During this period, they also designed and analyzed the crucial elements of a prototype optical refrigerator including the thermal link that connects the cool-ing element with the load.« less

Survival of Columbian white-tailed deer in western Oregon

USGS Publications Warehouse

Ricca, Mark A.; Anthony, Robert G.; Jackson, Dewaine H.; Wolfe, Scott A.

2002-01-01

Columbian white-tailed deer (Odocoileus virginianus leucurus; CWTD) are an endangered subspecies on which little demographic information exists. We determined survival rates and causes of mortality for 64 radiocol- lared adults from 1996 to 1998, and for 63 radiocollared neonatal fawns during the summer and fall months of 1996-2001 in Douglas County, Oregon, USA. Annual adult survival rates averaged 0.74 over 3 years, and most mor- tality (73%) occurred between fall and winter. Seasonal survival was lowest (0.75) for the fall-winter 1997-1998, and was 20.90 during all spring-summer periods. Annual and seasonal survival rates did not differ by gender. Average annual survival was 0.77 for deer in wildland areas compared with 0.66 for deer in suburban areas, but these dif- ferences were not consistent between years and seasons. Survival over the entire 3-year study was low (0.38). Eight deer died from a combination of emaciation and disease, and almost all (92%) necropsied deer were in poor body condition. Fawn survival to 7 months was low (0.14, 95% CI = 0.02-0.26) and declined most rapidly during the first 1.5 months of life. Predation (n = 21) and abandonment (n = 6) were the most frequent known causes of death for fawns. Our results suggest that CWTD may have responded to density-dependent factors during this short-term study, although the effects of other environmental or intrinsic factors cannot be ignored. Fawn survival may be insufficient to produce enough recruits for population growth and eventual range expansion.

Overview of Atmospheric Ionizing Radiation (AIR)

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Maiden, D. L.; Goldhagen, P.; Tai, H.; Shinn, J. L.

2003-01-01

The SuperSonic Transport (SST) development program within the US was based at the Langley Research Center as was the Apollo radiation testing facility (Space Radiation Effects Laboratory) with associated radiation research groups. It was natural for the issues of the SST to be first recognized by this unique combination of research programs. With a re-examination of the technologies for commercial supersonic flight and the possible development of a High Speed Civil Transport (HSCT), the remaining issues of the SST required resolution. It was the progress of SST radiation exposure research program founded by T. Foelsche at the Langley Research Center and the identified remaining issues after that project over twenty-five years ago which became the launch point of the current atmospheric ionizing radiation (AIR) research project. Added emphasis to the need for reassessment of atmospheric radiation resulted from the major lowering of the recommended occupational exposure limits, the inclusion of aircrew as radiation workers, and the recognition of civil aircrew as a major source of occupational exposures. Furthermore, the work of Ferenc Hajnal of the Environmental Measurements Laboratory brought greater focus to the uncertainties in the neutron flux at high altitudes. A re-examination of the issues involved was committed at the Langley Research Center and by the National Council on Radiation Protection (NCRP). As a result of the NCRP review, a new flight package was assembled and flown during solar minimum at which time the galactic cosmic radiation is at a maximum (June 1997). The present workshop is the initial analysis of the new data from that flight. The present paper is an overview of the status of knowledge of atmospheric ionizing radiations. We will re-examine the exposures of the world population and examine the context of aircrew exposures with implications for the results of the present research. A condensed version of this report was given at the 1998 Annual Meeting of the NCRP with proceedings published in the journal of Health Physics.

Study of mouse behavioural response in microgravity: ethogram and neurobiological related

NASA Astrophysics Data System (ADS)

Santucci, Daniela; Francia, Nadia; Schwartz, Silvia; Biticchi, Roberta; Liu, Yi; Cancedda, Ranieri; Aloe, Luigi

The conquest of space, which started with the dog Laika in 1966 to be followed few years later by Yuri Gagarin, has witnessed an increasing numbers of both vertebrates (tadpoles, frogs, rats mice etc.) and invertebrates (flies, scorpions, protozoa) species exposed to zero gravity levels. Animals are sent into orbit to proactively foresee possible health problems in humans. The issue of animal exposure to un-physiological gravity is of primary importance to i) understand behavioural and physiological adaptations in such environment as well as ii) develop coun-termeasures to improve 0-g life conditions and reduce possible animal suffering. The Mouse Drawer System (MDS), an Italian facility, has been transferred to the International Space Sta-tion with a first experiment investigating mechanisms underlying bone mass loss in microgravity in mice. Preliminary and ground-based control experiments have been conducted with six mice housed individually inside the MDS facility for 20 and 100 days. The behavioural repertoire of wild-type and transgenic mice housed in the MDS has been videorecorded with the observation subsystem, which allows to monitor animal's behavior through the use of 6 video cameras. The behavioural patterns characterizing mice in the MDS system have been finely analysed at several time points during the the experiment. Moreover, neurobiological parameters, known to be involved in the response to stress, have been evaluated. In particular, NGF and BDNF levels have been measured in the central nervous system (hippocampus, striatum, and cortex), adrenal gland and limbs. Preliminary data from ground based experiment revealed Several dif-ferences in behavioural profile between wt and tg mice, with transgenic ones apparently more active than wild type controls. Moreover a clear difference in time spent in different areas of the MDS cage was observed. Finally changes in neurotrophins levels were observed in relation to both genotype and environmental conditions. Data so far collected will be used as baseline and will compared with those obtained during spaceflight exposure currently under analysis and a fine characterization of the behavioral repertoire (ethogram) of the mice exposed to space environment will be reported.

EDITORIAL: Computational materials science Computational materials science

NASA Astrophysics Data System (ADS)

Kahl, Gerhard; Kresse, Georg

2011-10-01

Special issue in honour of Jürgen Hafner On 30 September 2010, Jürgen Hafner, one of the most prominent and influential members within the solid state community, retired. His remarkably broad scientific oeuvre has made him one of the founding fathers of modern computational materials science: more than 600 scientific publications, numerous contributions to books, and a highly cited monograph, which has become a standard reference in the theory of metals, witness not only the remarkable productivity of Jürgen Hafner but also his impact in theoretical solid state physics. In an effort to duly acknowledge Jürgen Hafner's lasting impact in this field, a Festsymposium was held on 27-29 September 2010 at the Universität Wien. The organizers of this symposium (and authors of this editorial) are proud to say that a large number of highly renowned scientists in theoretical condensed matter theory—co-workers, friends and students—accepted the invitation to this celebration of Hafner's jubilee. Some of these speakers also followed our invitation to submit their contribution to this Festschrift, published in Journal of Physics: Condensed Matter, a journal which Jürgen Hafner served in 2000-2003 and 2003-2006 as a member of the Advisory Editorial Board and member of the Executive Board, respectively. In the subsequent article, Volker Heine, friend and co-worker of Jürgen Hafner over many decades, gives an account of Hafner's impact in the field of theoretical condensed matter physics. Computational materials science contents Theoretical study of structural, mechanical and spectroscopic properties of boehmite (γ-AlOOH) D Tunega, H Pašalić, M H Gerzabek and H Lischka Ethylene epoxidation catalyzed by chlorine-promoted silver oxide M O Ozbek, I Onal and R A Van Santen First-principles study of Cu2ZnSnS4 and the related band offsets for photovoltaic applicationsA Nagoya, R Asahi and G Kresse Renormalization group study of random quantum magnetsIstván A Kovács and Ferenc Iglói Ordering effects in disordered systems: the Au-Si systemN Jakse, T L T Nguyen and A Pasturel On the stability of Archimedean tilings formed by patchy particlesMoritz Antlanger, Günther Doppelbauer and Gerhard Kahl

Characterization of Different Land Classes and Disaster Monitoring Using Microwave Land Emissivity for the Indian Subcontinent

NASA Astrophysics Data System (ADS)

Saha, Korak; Raju, Suresh; Antony, Tinu; Krishna Moorthy, K.

Despite the ability of satellite borne microwave radiometers to measure the atmospheric pa-rameters, liquid water and the microphysical properties of clouds, they have serious limitations over the land owing its large and spatially heterogeneous emissivity compared to the relatively low and homogenous oceans. This calls for determination of the spatial maps of land-surface emissivity with accuracies better than ˜2%. In this study, the characterization of microwave emissivity of different land surface classes over the Indian region is carried out with the forth-coming Indo-French microwave satellite program Megha-Tropiques in focus. The land emissivity is retrieved using satellite microwave radiometer data from Special Sensor Microwave/Imager (SSM/I) and TRMM Microwave Imager (TMI) at 10, 19, 22, 37 and 85 GHz. After identify-ing the clear sky daily data, the microwave radiative transfer computation, is applied to the respective daily atmospheric profile for deducing the upwelling and downwelling atmospheric radiations. This, along with the skin temperature data, is used to retrieve land emission from satellites data. The emissivity maps of placecountry-regionIndia for three months representing winter (January) and post-monsoon (September-October) seasons of 2008 at V and H polar-izations of all the channels (except for 22 GHz) are generated. Though the land emissivity values in V-polarization vary between 0.5 and ˜1, some land surface classes such as the desert region, marshy land, fresh snow covered region and evergreen forest region, etc, show distinct emissivity characteristics. On this basis few typical classes having uniform physical properties over sufficient area are identified. Usually the Indian desert region is dry and shows low emis-sivity (˜0.88 in H-polarisation) and high polarization difference, V-H (˜0.1). Densely vegetated zones of tropical rain forests exhibit high emissivity values (˜0.95) and low polarization dif-ference (lt;0.01). The mangrove forest region and marshy areas exhibit very low emissivities (˜0.8) with very high polarization difference (˜0.2). The usefulness of microwave emissivity to identify and quantify natural disasters such as the inundated regions in the vast Ganga basin during the severe floods in 2008 over country-regionIndia and placecountry-regionBangladesh is also demonstrated as a case study Keywords: Land surface emissivity, Microwave Remote sensing, Megha-Tropiques, Disaster monitoring *corresponding author: koraksaha@gmail.com

PREFACE: 8th Edoardo Amaldi Conference on Gravitational Waves

NASA Astrophysics Data System (ADS)

Marka, Zsuzsa; Marka, Szabolcs

2010-04-01

(The attached PDF contains select pictures from the Amaldi8 Conference) At Amaldi7 in Sydney in 2007 the Gravitational Wave International Committee (GWIC), which oversees the Amaldi meetings, decided to hold the 8th Edoardo Amaldi Conference on Gravitational Waves at Columbia University in the City of New York. With this decision, Amaldi returned to North America after a decade. The previous two years have seen many advances in the field of gravitational wave detection. By the summer of 2009 the km-scale ground based interferometric detectors in the US and Europe were preparing for a second long-term scientific run as a worldwide detector network. The advanced or second generation detectors had well-developed plans and were ready for the production phase or started construction. The European-American space mission, LISA Pathfinder, was progressing towards deployment in the foreseeable future and it is expected to pave the ground towards gravitational wave detection in the milliHertz regime with LISA. Plans were developed for an additional gravitational wave detector in Australia and in Japan (in this case underground) to extend the worldwide network of detectors for the advanced detector era. Japanese colleagues also presented plans for a space mission, DECIGO, that would bridge the gap between the LISA and ground-based interferometer frequency range. Compared to previous Amaldi meetings, Amaldi8 had new elements representing emerging trends in the field. For example, with the inclusion of pulsar timing collaborations to the GWIC, gravitational wave detection using pulsar timing arrays was recognized as one of the prominent directions in the field and was represented at Amaldi8 as a separate session. By 2009, searches for gravitational waves based on external triggers received from electromagnetic observations were already producing significant scientific results and plans existed for pointing telescopes by utilizing gravitational wave trigger events. Such multimessenger approaches to gravitational wave detection also received special attention at the meeting. For the first time in the history of Amaldi conferences, plenary and contributed sessions were held to transfer ideas and experience gained with gravitational wave science inspired education and outreach projects. Additionally, Columbia University faculties working in frontier fields, which currently may not have direct connection to the field of gravitational wave science, gave enthralling presentations in the form of a 'wake-up' lecture series. The meeting also facilitated the exchange of scientific results and new ideas among all members of gravitational wave experiment collaborations and the gravitational wave theory community. Additionally, future directions in gravitational wave detection were discussed in a special session dedicated to the Gravitational Wave International Committee Roadmap. A highly entertaining and inspiring public talk titled "Songs from Space: Black Holes and the Big Bang in Audio" was given by Janna Levin and it attracted over 300 young and old science enthusiasts from and around New York City. This special issue of Classical and Quantum Gravity (Volume 27, Number 8, 2010) is published as the proceedings of Amaldi8. It contains the overview articles by invited plenary speakers, and some of the highlights of the meeting as selected by session chairs and organizers. Other Amaldi8 talks and posters appear in the refereed issue of the electronic Journal of Physics: Conference Series. This issue of CQG and the JPCS issue are electronically linked. The conference organizers gratefully acknowledge the financial support of Columbia University in the City of New York, the International Union of Pure and Applied Physics and the United States National Science Foundation. We would like to thank the Gravitational Wave International Committee for the scientific oversight, the Local Organizing Committee for the program selection, and the session chairs for the thoughtful delivery of conference goals and enabling many lively discussions that are much needed for the development of our frontier field. We would also like to thank the hard work of Columbia University Physics Department administrators for handling some of the practical aspects of the organization. Finally, a team of students (Jonathan Berliner, Rutu Das, David Fierroz, Alyssa Miller, David Murphy and Keith Redwine) provided assistance behind the scene. Their hard work, practical ideas, and dedication are greatly appreciated. We are also grateful for Keith Redwine for his help in organizing the JPCS proceedings articles. Finally, we would like to thank the over 310 participants for their interesting and lively contributions that ultimately made the conference a success. Zsuzsa Marka Local Organizing Committee Szabolcs Marka Chair, Local Organizing Committee Columbia Astrophysics Laboratory and Physics Department, Columbia University Guest Editors AMALDI picture

Application of blind source separation to gamma ray spectra acquired by GRaND around Vesta

NASA Astrophysics Data System (ADS)

Mizzon, H.; Toplis, M. J.; Forni, O.; Prettyman, T. H.; Raymond, C. A.; Russell, C. T.

2012-12-01

The bismuth germinate (BGO) scintillator is one of the sensors of the gamma ray and neutron detector (GRaND)1 on board the Dawn spacecraft, that has spent just over one year in orbit around the asteroid 4-Vesta. The BGO detector is excited by energetic gamma-rays produced by galactic cosmic rays (GCR) or energetic solar particles interacting either with Vesta and/or the Dawn spacecraft. In detail, during periods of quiet solar activity, gamma ray spectra produced by the scintillator can be considered as consisting of three signals: i) a contribution of gamma-rays from Vesta produced by GCR interactions at the asteroid's surface, ii) a contribution from the spacecraft excited by neutrons coming from Vesta, and iii) a contribution of the spacecraft excited by local interaction with galactic cosmic rays. While the first two contributions should be positive functions of the solid angle of Vesta in the field of view during acquisition, the last one should have a negative dependence because Vesta partly shields the spacecraft from GCR. This theoretical mix can be written formally as: S=aΩSV+bΩSSCNV+c(4π-Ω)SSCGCR (1) where S is the series of recorded spectra, Ω is the solid angle, SV is the contribution of gamma rays coming from Vesta, SSCNV is the contribution of gamma rays coming from the spacecraft excited by the neutron coming from Vesta and SSCGCR is the contribution of gamma rays coming from the spacecraft excited by GCR. A blind source separation method called independent component analysis enables separating additive subcomponents supposing the mutual statistical independence of the non-Gaussian source signals2. Applying this method to BGO spectra acquired during the first three months of the low-altitude measurement orbit (LAMO) reveals two main independent components. The first one is dominated by the positron electron annihilation peak and is positively correlated to the solid angle. The second is negatively correlated to the solid angle and displays peaks of elements present in the spacecraft, of energy in the range 1 to 3.5 MeV. At energy >3.5 MeV, the dominant independent component highlighted by this method has no significant peaks, suggesting that it is not influenced by Vesta itself which is known to have a strong signal associated with iron at 7.6 MeV. Our method therefore represents a first step in retrieving the contribution of the spacecraft that could be used in conjunction with the mixing equation (1) to determine the contribution from the planet itself. 1 : Prettyman, T. H., Mcsween, Jr., H. Y., Feldman, W. C., JUN 2010. Dawn's GRaND to map the chemical composition of asteroids Vesta and Ceres. Geochimica and Cosmochimica Acta 74 (12, 1), A832, Con- ference on Goldschmidt 2010 - Earth, Energy, and the Environment, Knoxville, TN, JUN 13-18, 2010. 2 : Hyvarinen, A., Oja, E., May-Jun 2000. Independent component analysis: algorithms and applications. Neural Networks 13 (4-5), 411-430.

Characterization of salinity and selenium loading and land-use change in Montrose Arroyo, western Colorado, from 1992 to 2010

USGS Publications Warehouse

Moore, Jennifer L.

2011-01-01

Salinity and selenium are naturally occurring and perva-sive in the lower Gunnison River Basin of Colorado, includ-ing the watershed of Montrose Arroyo. Although some of the salinity and selenium loading in the Montrose Arroyo study area is from natural sources, additional loading has resulted from the introduction of intensive irrigation in the water-shed. With increasing land-use change and the conversion from irrigated agricultural to urban land, land managers and stakeholders need information about the long-term effects of land-use change on salinity and selenium loading. In response to the need to advance salinity and selenium science, the U.S. Geological Survey, in cooperation with the Bureau of Reclamation, Colorado River Basin Salinity Control Forum, and Colorado River Water Conservation District, developed a study to characterize salinity and selenium loading and how salinity and selenium sources may relate to land-use change in Montrose Arroyo. This report characterizes changes in salinity and selenium loading to Montrose Arroyo from March 1992 to February 2010 and the magnitude of land-use change between unirrigated desert, irrigated agricultural, and urban land-use/land-cover types, and discusses how the respective loads may relate to land-use change. Montrose Arroyo is an approximately 8-square-mile watershed in Montrose County in western Colorado. Salinity and selenium were studied in Montrose Arroyo in a 2001 study as part of a salinity- and selenium-control lateral project. The robust nature of the historical dataset indicated that Montrose Arroyo was a prime watershed for a follow-up study. Two sites from the 2001 study were used to monitor salinity and selenium loads in Montrose Arroyo in the follow-up study. Over the period of 2 water years and respective irrigation seasons (2008-2010), 27 water-quality samples were collected and streamflow measurements were made at the historical sites MA2 and MA4. Salinity and selenium concen-trations, loads, and streamflow were compared between the pre-lateral-project and post-growth periods and between the post-lateral-project and post-growth periods. No significant differences in streamflow, salinity (concen-tration and load), or selenium (concentration and load) were found at MA4 between the pre-lateral project and post-growth periods or between the post-lateral-project and post-growth periods. The statistical analysis indicated no significant dif-ferences in streamflow or salinity (both concentration and load) between the pre-lateral-project and post-growth periods or between the post-lateral-project and post-growth periods at MA2; however, selenium concentrations and loads were significantly greater between the pre-lateral-project and post-growth periods and between the post-lateral-project and post-growth periods at MA2. Land-use change between MA4 and MA2 may have contributed to the determined differences in selenium values, but the specific mechanisms causing the increases between periods are unknown. The size of the urbanized area in Montrose Arroyo was quantified for 1993, 2002, and 2009 by using a geographic information system (GIS) with imagery from the specified years. The greatest change in land use from 1993 to 2009 was the increase of urban land due to conversion from irrigated agricultural land. The conversion of previously unirrigated desert to urban land or irrigated agriculture could become more common if urbanization and development expands into the eastern part of the watershed because a majority of the un-urbanized land in eastern Montrose Arroyo is unirrigated desert. By applying GIS to the City of Montrose 2008 com-prehensive growth plan, it was estimated that approximately 786 acres of previously irrigated agricultural land will be converted to urban land and 689 acres of unirrigated desert will be converted to urban land under the plan scenario. New development on previously unirrigated land in shale areas would likely increase the potential for mobilization of sele-nium and salinity from new sources to Montrose Arroyo and the Lower Gunnison River Basin.

Poster Session B

PubMed Central

2014-01-01

B.1 Development of a Proximity Labeling Method to Identify the Protein Targets of Bioactive Small Molecules Zachary Hill, Min Zhuang, James Wells University of California, San Francisco, CA, USA Identifying the direct protein targets of a bioactive small molecule gives insight into the compound's mechanism of action, its efficacy, and possible toxicity. Target identification is becoming an increasingly important part of the drug- development process. However, given the transient and heterogeneous nature of interactions between small molecules and proteins, this step is often difficult, greatly slowing the development of new therapeutics. For this reason, new methods to rapidly identify the direct protein targets of bioactive small molecules are of great importance. Enrichment strategies coupled with quantitative mass spectrometry have shown great promise in target identification. Here we will present our progress toward developing an engineered enzymatic tagging method that enables specific labeling and enrichment of protein targets from complex lysates. This method couples the binding of a small molecule to a proximity-based labeling event. Labeled target proteins are enriched and subsequently identified using quantitative LC-MS/MS. We will discuss several variations of this method, and highlight our progress towards applying proximity labeling to small-molecule target identification and validation. B.2 Modelling Atherosclerosis: Molecular Changes in the Ascending Aorta of Cholesterol-fed Rabbits Jingshu Xu1,2, Mia Jüllig1,2, Martin J. Middleditch1,2, Garth J.S. Cooper1,2,3,4 1School of Biological Sciences, University of Auckland, New Zealand; 2Maurice Wilkins Centre for Molecular Biodiscovery, Faculty of Science, University of Auckland, New Zealand; 3Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford, UK; 4Centre for Advanced Discovery and Experimental Therapeutics, NIHR Manchester Biomedical Research Centre, the University of Manchester, Manchester, UK The cholesterol-fed rabbit is commonly used to study the effect of hypercholesterolaemia and the associated atherosclerotic lesions. Here we maintained New Zealand White rabbits on a diet containing 2% (w/w) cholesterol (HC diet) for 12 weeks, after which their ascending aortas were excised and subjected to proteomic analysis. Extracts from ten individually obtained ascending aorta samples were labelled with isobaric (iTRAQ) tags and analyzed by LC-MS/MS to profile the proteomic changes in response to the HC diet (n=5) in comparison with non-HC, standard diet (n=5). ProteinPilot was used to search the LC-MS/MS output against the NCBI rabbit protein sequence database, leading to identification of 453 unique proteins. Of these, 74 showed significant differences in relative abundance (p<0.05), with 69 proteins higher and five lower in ascending aorta from HC diet-fed rabbits compared to controls. Many of the observed protein changes are consistent with molecular perturbations within the ascending aorta in response to the HC diet in rabbits, e.g. elevation of apolipoproteins, extracellular matrix adhesion proteins, collagens, glycolytic enzymes, heat shock proteins, proteins involved in immune defence, and proteins regulating the polymeric state of actin. We also made a number of novel observations, including an extreme (16-fold) elevation of a protein previously linked to angiogenesis but not atherosclerosis. Numerous other proteins not previously associated with atherosclerosis were also increased in ascending aorta from HC-fed rabbits. These novel observations merit further investigation as these perturbations may play important and yet undiscovered roles in the pathogenesis of atherosclerosis. B.3 Post-translational Modification Networks Vera van Noort Katholieke Universiteit Leuven, Leuven, Belgium Protein post-translational modifications (PTMs) allow the cell to regulate protein activity and play a crucial role in the response to changes in external conditions or internal states. Advances in mass spectrometry now enable proteome wide characterization of PTMs and have revealed a broad functional role for a range of different types of modifications (1). We have systematically investigated the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae (2). Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein-specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes. Reciprocally, deletion of the two putative N-acetyltransferases affects protein phosphorylation, confirming cross-talk between the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome revealed that both PTMs are very common, that (as in Eukaryotes) they often co-occur within the same protein and that they are frequently observed at interaction interfaces and in proteins that can be part of multiple protein complexes (3). The results imply previously unreported hidden layers of post-transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell. Aiming at a more global view of the interplay between PTM types, we collected modifications for 13 frequent PTM types in 8 eukaryotes, compared their speed of evolution and developed a method for measuring PTM co-evolution within proteins based on the co-occurrence of sites across eukaryotes (4). We found that PTM types are vastly interconnected, forming a global network that comprise in human alone >50,000 residues in about 6000 proteins. 1. Beltrao P, Bork P, Krogan NJ, van Noort V. Evolution and functional cross-talk of protein post-translational modifications. Mol Syst Biol 9, 714. (2013) 2. van Noort V, Seebacher J, Bader S, Mohammed S, Vonkova I, Betts MJ, Kühner S, Kumar R, Maier T, et al. Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium. Mol Syst Biol 8, 571. (2012) 3. Kühner S*, van Noort V*, etal. Proteome organization in a genome-reduced bacterium Science 326, 1235–1240. (2009) 4. Minguez P, Parca L, etal. Deciphering a global network of functionally associated post-translational modifications. Mol Syst Biol 8, 599. (2012) B.4 Extracellular Phosphorylation in the Murine Synaptosome Jonathan C Trinidad1, Ralf Schoepfer2, Alma L Burlingame3, Katalin F Medzihradszky3* 1Department of Chemistry, Indiana University, Bloomington, IN, USA; 2Department of Pharmacology, University College London, England, UK; 3Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, CA, USA Post-translational modifications (PTMs) play key regulatory roles in cellular localization and/or biological function of proteins. The site of modification within a protein; their fixed or transient nature; the stoichiometry and potential crosstalk between modifications have been the focus of numerous large-scale studies. Most of this research is focused on PTMs involved in intracellular processes, such as phosphorylation, methylation, GlcNAcylation, acetylation, and ubiquitination. Of these, phosphorylation is the most studied due to the biological importance of this modification as well as the availability of tools for such studies. While the majority of protein phosphorylation occurs on intracellular proteins, phosphorylation of secreted proteins is well established. Well-characterized examples include the secreted milk protein, beta-casein, and the serum protein fetuin. Our current understanding of the biological role of extracellular phosphorylation, as well as knowledge regarding the process by which they are modified, is incomplete. A kinase known as FAM20 has been identified and is localized to the Golgi as well as secreted. It has been shown to phosphorylate extracellular proteins with a SXE motif. We recently conducted extensive studies on the interplay between intracellular phosphorylation and GlcNAcylation on proteins isolated from murine synaptosomes. This data also allowed us to identify specific glycan structures on more than 500 secreted or transmembrane proteins. We have subsequently examined the extent to which phosphorylation was present in our sample on secreted proteins or extracellular regions of transmembrane proteins. Our goal was to determine the extent to which such phosphorylation can be explained by the known motif of Golgi-resident kinases. We analyzed the sequences around the extracellular phosphorylation sites, and the spatial relationship on the linear amino acid sequence between glycosylated and phosphorylated residues. This work was supported by NIH grant NIGMS 8P41GM103481, and by the Howard Hughes Medical Institute. B.5 Using Selective Reaction Monitoring (SRM) Mass Spectrometry To Unmask Regulatory Feedback Loops Controlling Adipogenesis Robert Ahrends1,2, Asuka Ota2, Kyle M. Kovary2, Takamasa Kudo2, Byung Ouk Park2, Mary N. Teruel2 1ISAS, Dortmund, Germany; 2Clinical and Systems Biology, Stanford University, Stanford, CA, USA Background: Due to modern lifestyle changes, obesity has a worldwide impact on human health. The obesity epidemic is now recognized as one of the most important public health problems facing the world today. Understanding adipogenesis is crucial to understanding obesity; failure of adipogenesis was shown to be a key factor in the development of diabetes. In earlier work using single-cell imaging, we demonstrated that there is a distinct decision made during the time course of adipogenesis. Thereby positive feedback loops between PPARg and other transcription factors (TFs) in the differentiation network are regulating this decision. We identified a positive feedback loop between PPARg and C/EBPb that plays a critical role in regulating adipogenesis. Since multiple feedback loops with different timing and strengths can sharpen the decision process and control the number of cells which are differentiating, we wanted to gain a better understanding of how many other proteins could be involved in the decision process. Objective: The objective of this work is to search for feedback loops that could play a key role in the commitment decision. Methods: Using Selected Reaction Monitoring (SRM) mass spectrometry combined with perturbations, we analyzed OP9 cells to detect peptides of TFs which can serve as probes. We validated these probes with isotopically coded internal peptide standards and established a SRM library of transcriptional key regulators. These probes were subsequently used to quantitatively profile different stages of adipogenesis to obtain time courses of different TFs. To achieve our major goal to elucidate the TF control network in more detail, we furthermore searched for hidden feedback loops in this differentiation system. To do so we chemically manipulated the activity level of PPARg and its potential feedback partners individually. If a protein was a component of one or several feedback loops and was experimentally manipulated, all the other components of feedback loops associated with this protein should display a relative change in abundance and vice versa. Results: We developed a SRM methodology to monitor the concentration changes of TFs during adipogenesis. Using this SRM methodology together the perturbation of PPARg, and single cell analysis we were able to validate known feedback loops (C/EBPa, C/EBPb) and to identify several new feedback Loops. Conclusions: PPARg is the master regulator of adipogenesis. To successfully differentiate preadipocytes into adipocytes, its activity needs to be tightly regulated by a network of feedback loops. Overall, the study provides a new SRM MS-based method to uncover novel feedback loops regulating TFs. Based on this method; we have identified 7 new proteins which are fundamental regulators of PPARg and the fat cell commitment decision. B.6 Application of Quantitative and Functional Phosphoproteomics In Study of Ethylene Signaling Ning Li 1 1The Hong Kong University of Science and Technology, Hong Kong, China Ethylene is a major plant hormone that regulates a diverse aspect of plant growth and development. The regulatory roles of ethylene in plants include promotion of leaf and flower petal senescence, yellowing and abscission, as well as promotion of fruit abscission and ripening. This key hormone is also involved in regulation of a number of plant biotic and abiotic stress responses. A dramatic effect of ethylene on tropic response is the dual-and-opposing effect of ethylene on stem negative gravitropic response, in which short-term ethylene treatment (0.5 hour) appears to inhibit stem bending up following re-orientation of inflorescence of Arabidopsis. In contrast, a long-term treatment (12 hours) stimulates gravitropic response and promote stem curve up faster. This time-dependent and dose- independent dual-and-opposing effect of ethylene on stem gravitropism may involve multiple signaling pathways. Stable isotope metabolic labeling-based quantitative phosphoproteomics performed on ein2–5, ctr1–1 and rcn1–1 ethylene signaling mutants indeed confirmed the time-dependent protein phosphorylation changes and some of phosphorylation events are independent to ein2 loss-of- function gene in response to ethylene treatment. Functional studies on the phosphorylated transcription factor ERF110 isoform suggest that it is required for the control of flowering time via multiple ethylene signaling pathways. B.7 Intact N- and O-linked Glycopeptide Identification from HCD Data Using Byonic Katalin F. Medzihradszky1, Jason Maynard1, Krista Kaasik1, Marshall Bern2 1University of California, San Francisco, CA, USA; 2Protein Metrics, San Carlos, CA, USA The importance of high quality analysis of glycosylated proteins is steadily increasing. Both the regulatory and signaling functions of the intracellular GlcNAc modification are widely documented, and different enrichment strategies for GlcNAcylated peptides have been developed. Extracellular glycosylation has been linked to a wide variety of diseases and both N- and O-glycosylation play important roles in providing the structural integrity of certain proteins, controlling protein clearance, protein-protein interaction, and enzymatic processing. Furthermore, most protein pharmaceuticals are glycosylated, and thus, batch to batch characterization of these drugs also involves glycosylation analysis. Towards the end of the last century mass spectrometry has become the method of choice for the analysis of post-translational modifications, and high throughput workflows have been developed for a number of different PTMs. Though mass spectrometry has been used for the characterization of N- and O-glycosylation of single proteins, its high-throughput application was prevented by a number of issues. These issues include the non-pattern based complex oligosaccharide structures, the isomeric building blocks, as well as the extensive carbohydrate fragmentation upon collisional activation. In-depth carbohydrate analysis still requires different tools: the released glycan pools are studied derivatized or unmodified using a wide variety of analytical methods, such as capillary electrophoresis, chromatography, exoglycosidase cocktails, and NMR. While such techniques will provide information on the identity of the sugar units and their linkages, the information on the localization of glycans within the protein sequence and of their site-specific heterogeneity is lost. Electron-transfer dissociation, which preserves peptide side-chain modifications, has enabled the MS/MS analysis of intact glycopeptides, and led to the successful assignment of thousands of GlcNAcylated sequences and Golgi-derived glycopeptides. This gave a boost to intact glycopeptide analysis, and search engines such as Protein Prospector and Byonic can handle even complex glycan mixtures. The most recommended acquisition workflow uses the diagnostic HexNAc oxonium ion produced by HCD analysis to trigger ETD analysis. Unfortunately, because extracellular glycosylation increases the peptide mass significantly without additional charge added, glycopeptides frequently produce low charge-density precursor ions that will yield only charge-reduced molecules upon ETD activation. However, properly acquired HCD data may contain sufficient information for glycopeptide identification. Byonic has been adjusted for the interpretation of such spectra. We will present the results from a complex N- and O-linked glycopeptide-containing mixture isolated from mouse brain synaptosome using WGA lectin weak affinity chromatography, highlighting the advantages and limitations of this approach. This work was supported by NIH grant NIGMS 8P41GM103481, and by the Howard Hughes Medical Institute (to the Bio-Organic Biomedical Mass Spectrometry Resource at UCSF, Director: A.L. Burlingame). B.8 Factors that Contribute to the Complexity of Glycopeptide Analysis – Besides Site-specific Heterogeneity Katalin F. Medzihradszky1, Zsuzsa Darula 1University of California, San Francisco, CA, USA; 2Laboratory of Proteomics Research, Biological Research Centre, Szeged, Hungary Data about the biological significance of extracellular glycosylation are compiling. Aberrant glycosylation has been implicated in diseases. Extracellular glycan remodeling has been linked to intracellular signaling. At the same time high-throughput intact glycopeptide analysis still is in its infancy. Glycosylation is a ‘special’ PTM. It includes a wide variety of structures formed by different biological pathways, performing very different biological functions. It is also unique in that aspect that the different MS/MS activation techniques provide different clues to solve the glycopeptide ‘puzzle’, but none delivers all the necessary information. Ion trap CID provides information about the glycan structure and usually reveals the mass of the peptide modified. Beam-type CID (HCD) frequently provides sufficient fragmentation information to assign the sequence modified. However, site assignment for O-glycopeptides is rarely possible. ETD identifies the sequence and site(s) modified, but one has to know the glycans present. Thus, using all these data together would offer the best solution. However, even the search engines aimed at glycopeptide identification cannot utilize all information available. We analyzed large and complex intact glycopeptide datasets, generated by LC/MS analysis of lectin-affinity-enriched mouse synaptosome and bovine or human serum samples. We will show that ETD data alone with faulty monoisotopic precursor peak-assignment, non-specific proteolytic digestion or covalent peptide modification will ‘assign’ an incorrect glycan structure. We will also present that a common buffer ingredient, Tris – widely used, even recommended for lectin-affinity chromatography- modifies sialic acid, altering not only its mass but also the chromatographic behavior of the glycopeptides. HCD analysis was instrumental in deciphering this unexpected side reaction. Acknowledgments – KFM was supported by NIH grant NIGMS 8P41GM103481, and by the Howard Hughes Medical Institute (to the Bio-Organic Biomedical Mass Spectrometry Resource at UCSF, Director: A.L. Burlingame) and by the following grants: OTKA 105611 (to Z. Darula), and BAROSS-DA07-DA-ESZK-07–2008-0036 (to the Biological Research Centre, HAS, director: P. Ormos). Z. Darula was supported by the Janos Bolyai Fellowship of the HAS. B.9 Characterizing Qualitative and Quantitative Global Changes in the Aging Heart Using pSMART, a Novel Acquisition Method Maryann S. Vogelsang, Amol Prakas, David Sarracino, Gouri Vadali, Scott Peterman Thermo Fisher Scientific, BRIMS Center, Cambridge, MA, USA The cardiovascular system has been shown to undergo significant changes as it ages. These changes range from genomic to structural. We have completed a label-free quantitative global profiling and targeted analysis of the cardiac proteome in aging mice using a novel data acquisition method, pSMART. Heart tissue was isolated and homogenized from both young (2 months old) and old (2 years old) mice. Solubilized and digested protein samples were spiked with the PRTC peptide retention time trainer kit and analyzed using unbiased data-dependent acquisition (DDA) method. Initial characterization experiments using unbiased DDA facilitated the building of detailed murine cardiac tissue spectral library. The spectral library records contain the relative retention time information based on the standard peptides as well as highly confident endogenous peptides, precursor and product ion information such as measured mass values and relative abundance used to create a consensus product ion spectrum. The spectral library information was used to create reference information to perform qual/quan determination in real-time. The pSMART method was used to acquire qualitative/ quantitative data analysis using one HR/AM MS and a series of narrow DIA mass windows. Our pSMART strategy resulted in 30% more peptide identifications per run than a standard DDA run. Additionally, using pSMART, we were able to confirm MS1 quantitation at low abundance levels with MS/MS for each peptide. This novel acquisition enabled quantitation of previously identified peptides as well as novel putative targets of aging. By identifying and quantifying more targets, we were able to better characterize the dynamic proteomic changes of cardio-dysfunction in aging mice. B.10 Quantitative Site-Specific Profiling S-glutathionylation in Macrophages in Response to Engineered Nanomaterial-induced Oxidative Stress Jicheng Duan, Vamsi K. Kodali, Matthew J. Gaffrey, Jia Guo, Rosalie K. Chu, David G. Camp, Richard D. Smith, Brian Thrall, Wei-Jun Qian Pacific Northwest National Laboratory, Richland, WA, USA Engineered nanoparticles are emerging functional materials with unique physicochemical properties, which make them desirable for commercial and medical applications. It is important to assess the toxicity of nanomaterials and recognize the underlying mechanisms of their toxicity. Oxidative stress is known to play important roles in nanomaterial-induced cellular toxicity, which leads to the generation of reactive oxygen species and alteration of protein activities and functions in cells. However, the knowledge about proteins and signaling pathways associated with nanomaterial-induced oxidative stress and nanotoxicity is still limited. Reversible cysteine-based protein modifications, such as S-glutathionylation (SSG) and S-nitrosylation (SNO), represent an important mechanism that modulates diverse cellular pathways in response to the disturbance of redox balance in cells. These redox modifications would be a potential regulatory mechanism in response to nanomaterials-induced oxidative stress and nanotoxicity. Recently, we have developed an effective proteomic approach for site-specific identification and quantification of different cysteine-based redox modifications by integrating selective reduction of oxidized cysteines, resin-assisted enrichment of thiol-containing proteins, and isobaric labeling to enable LC-MS/MS-based quantification. Herein, we present the preliminary results about the alteration of protein SSG modifications in mouse macrophages after exposure to different nanoparticles (CoO, Fe3O4 and SiO2 nanoparticles) by quantitative site-specific profiling. We observed that among these nanoparticles, CoO nanoparticles led to the most significant dose-dependent cytotoxicity and increase of protein SSG modifications in macrophages. Our site-specific SSG data highlighted redox sensitive proteins and their specific Cys residues potentially implicated in oxidative stress response. Functional analysis revealed that the most significantly enriched molecular function categories for SSG-modified proteins were free radical scavenging and cell death/survival. This preliminary result provides some insights on protein SSG modification as a potential regulatory mechanism of nanomaterial-induced oxidative stress. B.11 O-GlcNAc Regulates SOX2 Activity in Embryonic Stem Cells by Altering Protein-SOX2 Interactions Samuel Myers1, Sailaja Pedadda, Tara Freidrich, Sean Thomas, Gregor Krings, Michael Lopez, Marena Trinidad, Barbara Panning, Al Burlingame University of California, San Francisco, CA, USA SOX2 is a versatile transcription factor that maintains embryonic stem cell (ESC) pluripotency and self-renewal, and is important for proper lineage specification and adult stem cell maintenance. This versatility is likely due to post-translational modifications (PTMs) as SOX2 has been reported to be modified by numerous chemical moieties in a variety of cell types. One such PTM is O-GlcNAc, the dynamic and regulatory glycosylation of intracellular proteins. Global O-GlcNAc is essential for ESC self-renewal though the function of SOX2 O-GlcNAcylation in ESC is not understood. Here, we show that SOX2 is O-GlcNAc modified in the transactivation domain and alterations of self-renewing signals induce changes in SOX2 O-GlcNAc stoichiometry. Replacement of wild-type SOX2 with an O-GlcNAc-deficient mutant SOX2 in ESCs increases the pluripotency transcriptional network while down-regulating genes involved in differentiation. Analysis of SOX2-interacting proteins from ESCs revealed that the WT and mutant SOX2 interact with distinct subsets of transcriptional regulatory complexes. Thus, SOX2 O-GlcNAcylation modulates the transcriptional landscape of ESCs by modulating SOX2 activity and interactions with epigenetic regulatory complexes. B.12 Development of Multiplexed Assays for Oral Cancer Biomarker Verification by Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry Yung-Chin Hsiao1, Lang-Ming Chi2, Kun-Yi Chien1, Yi-Ting Chen1, Yu-Sun Chang1, Jau-Song Yu1 1Chang Gung University, Tao-Yuan, Taiwan; 2Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Oral cancer, one of the common cancers in Taiwan and other areas of Southern Asia, has become an increasing burden on the health care system in this region. Although numerous potential oral cancer biomarkers have been discovered in the past decades, very few of them have been verified and validated in parallel to compare their clinical utility. Recently, a multiplexed, targeted proteomics assay platform, termed SISCAPA-MRM-MS (stable isotope standards and capture by anti-peptide antibodies combined with multiple reaction monitoring mass spectrometry) has been shown to be a feasible approach for verifying multiple protein biomarker candidates in body fluid samples. Therefore, we sought to prioritize biomarker candidates from published literature and our in-house database and develop a high-throughput/multiplexed SISCAPA-MRM-MS assay for quantifying potential oral cancer biomarker candidates. We produced ∼400 clones of anti-peptide mAbs against 50 selected targets and effectively sieved out the high quality anti-peptide mAbs against 24 targets according to their binding affinity to peptide antigens (using peptide-immobilized SPR system) and immuno-capture capability (using SISCAPA-MS assay). These mAbs were then assembled into a 24-plex SISCAPA-MRM MS assay and applied to preliminarily evaluation of these 24 candidates in pooled saliva samples obtained from oral cancer patients and healthy controls. Eight of the 24 candidates were found to be drastically increased in pooled saliva samples from oral cancer patients as compared with healthy controls. The promise of this 24-plex SISCAPA LC-MRM MS assay allows us to systematically evaluate the abundance of targets in clinical samples for oral cancer biomarker discovery in the near future. B.13 Characterisation of Glycosylation of Paramyxovirus Surface Glycoproteins by Mass Spectrometry Cassandra L. Pegg1, C. Hoogland1, S.M. Johnson2, C.C. Gonzalez2, M.E. Peeples2, J.J. Gorman1 1QIMR Berghofer Medical Research Institute, Herston, Australia; 2Center for Vaccines & Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA The family Paramyxoviridae (paramyxovirus) contains a number of significant human and animal pathogens. Represented within this family are human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV) and Newcastle disease virus (NDV). The former two cause severe respiratory tract disease in infants, children and immunocompromised individuals. At present, safe and effective vaccines are not available for hRSV and hMPV. NDV is the causative agent of Newcastle disease (ND) afflicting a wide range of avian species. The desire to study NDV is due not only to the significant economic impact it has on the poultry industry worldwide but also its potential use as an oncolytic agent and vaccine vector for human and animal use. Additionally, findings on NDV may be translated to closely related viruses that cause disease in humans, such as parainfluenza viruses. Of great importance to paramyxoviruses are the variable attachment glycoproteins, hemagglutinin (H), hemagglutinin-neuraminidase (HN) and major surface glycoprotein (G) along with the fusion (F) glycoprotein. Glycoproteins H, HN and G are involved in viral attachment to the host cell, while F is responsible for viral entry by means of fusion with host cell membranes. Research has shown that the glycosylation sites present on these proteins can modulate the ability of the virus to infect host cells and stimulate the host immune system. Characterisation of site-specific glycan heterogeneity remains one of the few unexplored areas related to hRSV, hMPV and NDV surface glycoproteins. Previous research has been conducted to determine glycan heterogeneity, but not glycan site specificity, of NDV F. As yet, glycan site occupancy and glycan heterogeneity for glycoproteins G and F of hRSV and hMPV and HN of NDV, have not been defined at a chemical level. Revealing the glycosylation profile of these proteins may help elucidate mechanisms of viral attachment, replication and immune evasion within paramyxoviruses. Additionally, accurate identification and characterisation of protein glycosylation is required for producing glycoprotein therapeutics and for the development of targeted treatments. Liquid chromatography-MS/MS strategies utilising ETD, HCD and CID fragmentation were implemented to structurally characterise the digested glycoproteins. Initial research has revealed complex N-linked and mucin-like O-linked glycosylation of recombinant RSV G. Analysis of NDV revealed high-mannose N-linked glycans of F glycoprotein as well as high mannose and sialylated and sulphated complex N-linked glycans and a novel sialylated O-linked glycan of NDV HN. B.14 Developing A New In Vivo Cross-linking Mass Spectrometry Platform to Define Protein-Protein Interactions in Living Cells Robyn M. Kaake1, Xiaorong Wang1, Anthony Burke1, Clinton Yu1, Wynne Kandur1, Yingying Yang1, Eric J. Novtisky1, Tonya Second2, Jicheng Duan1, Athit Kao1, Shenheng Guan3, Danielle Vellucci1, Scott D. Rychnovsky1, Lan Huang1 1University of California, Irvine, CA, USA; 2Thermo Fisher Scientific, Waltham, MA, USA; 3University of California, San Francisco, CA, USA Protein-protein interactions (PPIs) are fundamental to the structure and function of protein complexes. Resolving the physical contacts between proteins as they occur in cells is critical to uncovering the molecular details underlying various cellular activities. To advance the study of PPIs in living cells, we have developed a new in vivo cross-linking mass spectrometry platform that couples a novel membrane permeable, enrichable and MS-cleavable cross-linker with multistage tandem mass spectrometry. This strategy permits the effective capture, enrichment, and identification of in vivo cross-linked products from mammalian cells, and thus enables the determination of protein interaction interfaces. The utility of the developed method has been demonstrated by profiling PPIs in mammalian cells at the proteome scale and at the targeted protein complex level. Our work represents a general approach in studying in vivo PPIs, and provides a solid foundation for future studies towards the complete mapping of PPI networks in living systems. B.15 High-resolution Orbitrap Characterization of Preferential Chain Pairing in Co-expressed Bispecific Antibody Production by MS Under Native and Acidic Conditions Luis Schachner, Jianhui Zhou, Luke McCarty, Diego Ellerman, Michael Dillon, Christoph Spiess, Jennie Lill, Paul Carter, Wendy Sandoval Departments of Protein Chemistry and Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA Bispecific antibodies possess the characteristics and binding specificity of two distinct monoclonal antibodies, and as such can bind to two targets or epitopes simultaneously. Bispecific antibodies have recently received great attention for their promising results in clinical trials or potential new modes to deliver therapeutics. Generation of a bispecific antibody by co-expression of two light and heavy chains, would result in several mispaired species. While the “knobs-into-holes” technology enables efficient hetero-dimerization of the two heavy chains, the presumed random mispairing of the light chains has not been studied in detail as technologies to readily characterize and quantify the heterodimer species were missing. Using an anti-IL-4/IL-13, a bispecific antibody, which targets the IL-4 and IL-13 cytokines involved in type 2 cytokine-induced inflammation, we describe a mass spectrometry characterization assay under native and acidic conditions for co-expressed bispecific antibodies using an Exactive Plus Extended Mass Range (EMR) Orbitrap instrument. The high mass resolving power of the EMR Orbitrap allows unambiguous identification of all light and heavy chain pairing variants in a mixture of bispecific antibodies randomly assembled in vivo upon co-expression. Using the EMR Orbitrap technology, we identify and characterize the preferential pairing of the anti-IL-13 light chain to its cognate heavy chain. This unexpected, non-random pairing may be leveraged to guide the design of a single-cell solution for the production of bispecific antibodies. B.16 Controlling Low Rates of Cell Differentiation through Noise and Ultra-high Feedback Robert Ahrends, Asuka Ota, Kyle M. Kovary, Takamasa Kudo, Byung Ouk Park, Mary N. Teruel Dept. of Chemical and Systems Biology, Stanford University, Stanford, CA, USA The tissue size of adult mammals is maintained by replacement of aging or damaged cells by slow, ongoing cell differentiation. Disruption of this rate of ongoing differentiation results in serious disease. For example, acute myeloid leukaemia (AML) is caused by a block in differentiation which results in precursor cells proliferating uncontrollably rather than differentiating into a more terminal state. Adipocytes, the key regulators of glucose and lipid metabolism, make up 10–40% of human body mass and are renewed at a rate of approximately 10% per year [1]. The adipocyte system that will be used has the unique advantage that the terminal differentiation transition is relatively short and experimentally accessible using single cell microscopy. Understanding how cells regulate such very slow differentiation rates may enable better treatments of metabolic diseases and obesity. Here we combine quantitative mass spectrometry [2–4], computational modeling, and single-cell microscopy [5] to identify the network architecture that enables pre-adipocytes to differentiate at a rate of only 0.5% every 4 days. We show that that cell-to-cell variability, or noise, in protein abundance acts within a network of more than six positive feedbacks to permit pre-adipocytes to differentiate at very low rates. This system architecture resolves two fundamental opposing requirements: to irreversibly lock cells in the differentiated state and to create large cell-to-cell signal variability to enable differentiation at very low rates. The resolution of this optimization problem by noise and ultra-high feedback connectivity provides a generalizable mechanism for mammalian tissue size control. References: 1. [1] Spalding KL et al. (2008). Dynamics of fat cell turnover in humans. Nature. Jun 5; 453(7196):783–7. 2. [2] Abell E, Ahrends R, Bandara S, Park BO, Teruel MN. (2011). Parallel adaptive feedback enhances reliability of the Ca2+ signaling system. Proc Natl Acad Sci U S A. Aug 30; 108(35):14485–90. 3. [3] Ahrends R, Ota A, Kovary KM, Kudo T, Park BO, Teruel MN. (2014). Controlling low rates of cell differentiation through noise and ultra-high feedback. Science 345, June 20. 4. [4] Ota A, Kovary KM, Shen W, Ahrends R, Kraemer FB, Teruel MN. Using selective reaction monitoring (SRM) mass spectrometry to profile nuclear protein abundance differences between adipose tissue depots of insulin-resistant mice. (submitted) 5. [5] Park BO, Ahrends R, Teruel MN. (2012). Consecutive positive feedback loops create a bistable switch that controls preadipocyte to adipocyte conversion. Cell Reports Oct 25.