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E N O A E S S S L T A E A C R C I N S M S E E H C C TI N O CA February 2009 Vol. LXXXVII, No. 6 N • AMERI

Monthly Meeting Professor Wilton L. Virgo of Wellesley College to Speak at Simmons College Tips for Job Seekers By Megan Driscoll Summer Scholar Report Identification of Genes Regulated by Transcriptional Regulator, p8 By Derek Kong This Month in Chemical History By Harold Goldwhite, California State University, Los Angeles February Historical Events in by Leopold May, The Catholic University of America, Washington, DC February 1, 1905 methods for the determination of ing and used it against pellagra and Fifty years ago, Emilio Segré shared crystal structures, was born on this pursued the idea that diseases such the Nobel Prize in Physics (1959) day. as beriberi, scurvy, rickets and pella- with Owen Chamberlain for their gra were caused by lack of vital sub- discovery of the antiproton. He co- February 16, 1955 stances in the diet. discovered with C. Per- F. P. Bundy, H. T. Hall, H. M. Strong rier in 1937, and astatine with D. R. and R. H. O. Wentoff announced the February 25, 1880 Corson and R. MacKenzie in 1940, synthesis of diamonds at General Arthur B. Lamb, who was the editor and demonstrated the existence of Electric Research Laboratories on of the Journal of the American the antiproton in 1955. He was born this date. Chemical Society (1917-1949), was born on this day. on this date. February 19, 1859 February 2, 1802 One hundred and fifty years ago, February 28, 1901 Jean Baptiste Boussingault, who Svante A. Arrhenius was born. He Linus C. Pauling, who was born on demonstrated that plants absorb devised a theory of electrolytic dis- this date, received the Nobel Prize nitrogen from soil in the form of sociation and was a researcher in for Chemistry in 1954 for his nitrates and not from air as previ- viscosity and reaction rates. In 1903 research into the nature of the chem- ously believed, was born on this day. he was awarded the Nobel Prize in ical bond and its application to the Chemistry in recognition of the elucidation of the structure of com- February 6, 1892 extraordinary services he had ren- plex substances and the Nobel Peace Seventy-five years ago, William P. dered to the advancement of chem- Prize in 1962. He did research on Murphy shared the Nobel Prize in istry by his electrolytic theory of the structure of molecules such as Physiology or Medicine (1934) with dissociation. proteins and investigated the con- George R. Minot & George H. cepts of valency and resonance. February 23, 1884 Whipple for their discoveries con- Additional historical events can be cerning liver therapy in cases of One hundred and twenty-five years ago Casimir Funk was born. He iso- found at the CSW website or Dr. anemia. He was born on this date. May’s website, faculty.cua.edu/may/ lated nicotinic acid from rice polish- N February 7, 1834 history.htm. One hundred and seventy-five years ago Dimitri I. Mendeleev was born. He discovered the Periodic Law (Table) at same time as Lothar Meyer, who published later. February 8, 1795 One hundred and seventy-five years ago Friedlieb F. Runge discovered carbolic acid (phenol) and aniline in coal tar. He also investigated dry distillation and the composition of matter and was born on this date. February 12, 1826 , who was born on this date, did research in semi-per- meable membranes, sugars, respira- tion, fermentation, oxidation, protoplasm, and muscle. February 14, 1917 Herbert A. Hauptman, who devel- oped methods for the determination of crystal structures and received the Nobel Prize in 1985 with Jerome Karle for their outstanding achieve- ments in the development of direct

2 The Nucleus February 2009 The Northeastern Section of the American Chemical Society, Inc. Contents Office: Marilou Cashman, 23 Cottage St., Natick, MA 01360. 1-800-872-2054 February Historical Events in Chemistry 2 (Voice or FAX) or 508-653-6329. ______e-mail: mcash0953(at)aol.com by Leopold May, Catholic University of America Any Section business may be conducted Notable New England 4 via the business office above. NESACS Homepage: ______http://www.NESACS.org Eben Horsford, Wolcott Gibbs, Josiah Cooke, Jr. and Thomas Hunt David Cunningham, Webmaster Monthly Meeting 5 ACS Hotline, Washington, D.C.: ______1-800-227-5558 Professor Wilton L. Virgo, Wellesley College, to Speak At Simmons College Officers 2009 Announcements 6 Chair: ______Dr. E. Joseph Billo NSYCC Event-Overcoming Barriers in Careers in Chemistry and Chemical Sci- 13 Shattuck Street ences Natick, MA 01760 Call for Nominations 6 508-653-3074, joseph.billo(at)verizon.net ______Chair-Elect: John McKew Award for Outstanding Achievement in the Teaching Of Wyeth Research Chemistry, Philip L. Levins Memorial Prize 200 Cambridge Park Drive This Month in Chemical History 7 Cambridge, MA 02140 ______Immediate Past Chair: By Harold Goldwhite, California State University, Los Angeles Marietta Schwartz Summer Scholar Report 8 Chemistry Department, UMass- Boston, MA 02125 ______617-287-6146; marietta.schwartz(at)umb.edu Identification of Genes Regulated by Transcriptional Regulator, p8 Secretary: By Derek Kong, Sandro Goruppi and John Kyriakes, Molecular Cardiology Michael Singer Research Institute, Tufts University, Medford, MA Sigma-Aldrich Tips for Job Seekers in a Contracting Environment 11 3 Strathmore Rd., Natick, MA 01360 ______508-651-8151X291; msinger(at)sial.com By Megan Driscoll, Pharmalogics Recruiting Treasurer: James Piper 2009 Chair’s Statement 11 19 Mill Rd., Harvard, MA 01451 ______978-456-3155, piper28(at)attglobal.net Correction: E. Joseph Billo’s Actual 2009 statement! Auditor: Photos from National Chemistry Week 12 Anthony Rosner ______Archivist: By Morton Z. Hoffman Myron S. Simon Cover: 20 Somerset Rd. Professor (University of Wisconsin-Madison), Newton, MA 02465; 617-332-5273 Phyllis A. Brauner Memorial Lecturer at the Boston Museum of Science during Romysimon(at)mindspring.com Trustees: National Chemistry Week (Photo by Morton Z. Hoffman) Joseph A. Lima, Esther A. H. Hopkins, Deadlines: Michael E. Strem April 2009 Issue: February 13, 2009 Councilors Alternate Councilors May 2009 Issue: March 13, 2009 Term Ends 12/31/2009 Catherine Costello Julia H.Miwa Patricia Mabrouk Alfred Viola Michaeline F. Chen Jerry P. Jasinski Dorothy J. Phillips Eva B. Binnun Amy Tapper Barney Grubbs The Nucleus is published monthly, except June and August by the Northeastern Section of the American Term Ends 12/31/2010 Chemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Text Thomas R. Gilbert Timothy B. Frigo must be received by the editor six weeks before the date of issue. Pamela Nagafuji Mark Froimowitz Robert Lichter David Cunningham Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G, Michael Singer Erik Rozners Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070 Term Ends 12/31/2011 Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273 Doris I. Lewis C. Jaworek-Lopes Sheila E Rodman, Konarka Technologies, Inc., 116 John St. Suite 12, Lowell, Mary Burgess Patrick M. Gordon MA 01852 email:srodman(at)konarka.com tel 978-569-1414 Morton Z. Hoffman Lawrence Scott Assistant Editors: Stefan G. Koenig, Mindy Levine Michael P. Filosa Donald Rickter Kathi Brown Liming Shao Board of Publications: David Cunningham (Chair), Mary Mahaney, Vivian K. Walworth Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622 All Chairs of standing Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050, Committees, the editor Tel: 781-837-0424 of THE NUCLEUS, and Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews the Trustees of Section Calendar Coordinator: Sheila Rodman, email: srodman(at)konarka.com Funds are members of the Board of Directors. Any Photographers: Morton Z. Hoffman and James Phillips Coun cilor of the American Chemical Society Proofreaders: Donald O. Rickter, Myron S. Simon, Vivian K. Walworth, E. Joseph Billo, residing within the section area is an ex officio Webmaster: David Cunningham, webmaster(at)nesacs.org member of the Board of Directors. Copyright 2008, Northeastern Section of the American Chemical Society, Inc. The Nucleus February 2009 3 American Academy of Arts and Sci- Notable New ences. He was deeply interested in the Corporate Patrons ($2000+) chemistry of foods, an interest shown Abbott Bioresearch by many articles, his book on “Theory Genzyme England Lyophilization Service of New England and Art of Breadmaking” (1861), and Merck the development of processes for man- National ACS Chemists ufacturing condensed milk and baking Novartis powder. Pfizer From Myron S. Simon Schering Corporation Here we continue with the short biog- Wolcott Gibbs Sepracor raphies by Lyman C. Newell and Ten- 1822-1908 Serono Reproductive Institute ney L. Davis of Noted New England Wolcott Gibbs was the son of an enthu- Vertex Pharmaceuticals chemists of bygone days. siastic mineralogist. He was born in Wyeth Pharmaceuticals and received the Bach- Eben Norton Horsford Patrons ($1000-$1999) elor’s degree from Columbia Univer- Aptuit 1818-1893 sity in 1841. He then served for a time Astra-Zeneca R&D Boston Eben Norton Horsford was born in as an assistant to Robert Hare in Broad Institute Moscow, NY. He graduated from the . In 1845 he was awarded Creagen Biosciences Rensselaer Polytechnic Institute as a the degree of Doctor of Medicine by Estate of Wallace Gleekman civil engineer in 1838. After working a the College of Physicians and Sur- Irix Pharmaceuticals year or so on the geological survey of geons in New York, but never engaged Millennium Pharmaceuticals New York, he was appointed (1840) in the practice of medicine. He studied PCI Synthesis Professor of Mathematics and Natural chemistry further with Rammelsburg Shasun USA Sciences in the Albany, N.Y., Female in , with Heinrich Rose for a Sirtris Pharmaceuticals Academy. Here he remained four year, and with Liebig at Giessen for Strem Chemicals years, also delivering annually a course one semester. In Paris he attended the ZINK Imaging of lectures on chemistry in a neighbor- lectures of Laurent, Dumas and Reg- Ziopharm Oncology, Inc. ing state. nault. He returned home in 1848, and Donors ($300-$999) In 1844 he went to and in 1849 became Professor of Chem- Cambridge-Major Laboratories spent two years in Liebig’s laboratory istry at the College of the City of New Medicilon Inc at Giessen. On his return early in 1847 York, in which position he remained Occidental he was appointed Rumford Professor for fourteen years. Organix of the Application of Science to the In 1863 he became Rumford Pro- Peptech Corp Useful Arts in . fessor at Harvard University. Here he Royal Society of Chemistry Stirred by his experiences in Liebig’s continued and expanded the work of SAFC Pharma laboratory, Horsford prepared a plan Horsford, his predecessor, though for SAPA-NE for a department of analytical and his main work he had charge of the applied chemistry, which led to the laboratory of the Lawrence Scientific establishment of the Lawrence Scien- School, remaining for eight years until analytical methods and laboratory tific School. The laboratory of the the laboratory was consolidated with techniques. School was one of the first in which that of the College. After that he main- analytical chemistry was taught sys- tained a private laboratory. He was Josiah Parsons Cooke, Jr. tematically to individual students. The one of the founders of the National 1827-1894 work and workers exerted a profound Academy of Sciences and at one time Josiah Parsons Cooke, Jr. was born in influence on the development of chem- its president. His first paper, published Boston, MA. When a mere lad his istry in America. while he was a junior at Columbia, interest in chemistry was aroused by a In 1862 Horsford resigned to described, probably for the first time, a course of lectures, illustrated by exper- engage in industrial chemistry, a field battery in which the inactive electrode iments, delivered by Benjamin Silli- which always fascinated him. Up to was a plate of carbon. He is best man at the Lowell Institute. He bought this time he had published over thirty known for his researches on the cobalt chemicals and performed many of the original articles, starting with four in ammonia complex salts, on com- experiments in Turner’s Chemistry. 1846 in Liebig’s Annalen, and continu- pounds of iridium and osmium, on the Entering in 1844 he ing with a dozen or so in Silliman’s phospho-tungstates and phospho- pursued the regular course and contin- American Journal of Science and an molybdates, and on similar compounds ued to study chemistry by himself. equal number in the Proceedings of the of arsenic, antimony, tin, selenium, tel- While at Harvard he attended only American Association for the Advance- lurium, vanadium, cerium, and ura- a few, more or less, spectacular lec- ment of Science and the Memoirs of the nium, and for the development of new continued on page 10

4 The Nucleus February 2009 Monthly Meeting Biography Dr. Wilton L. Virgo earned his first The 894th Meeting of the Northeastern Section of the American degree in chemistry in 2000, complet- Chemical Society ing the rigorous science curriculum at Princeton University. As a Princeton Thursday – February 12, 2009 undergraduate, he was accepted into Simmons College the Summer Scholars Institute, was Paresky Center, Main Campus Building chosen by the Department of Chem- 300 The Fenway, Boston, MA 02115 istry to be a tutor for the general chem- 4:30 pm Board Meeting istry course, selected for the Leadership Alliance Early Identification Program, 5:30 pm Social Hour and received a certificate for the 6:30 pm Dinner Chemistry Outreach Program. For his senior thesis research, he constructed 7:45 pm Evening Lecture, NESACS Chair, E. Joseph Billo, presiding an infrared spectrometer designed for Speaker: Wilton L. Virgo, Diana Chapman Walsh Assistant Profes- measurement of trace gases and detec- sor of Chemistry, Wellesley College. Title: Tracking Energy in tion of peptic ulcers. Chemical Dynamics from MIT to Wellesley: What are the Path- As a Professional Associate at ways for Electronic Energy Flow and Photochemistry? Brookhaven National Laboratory, Dr. Dinner reservations should be made no later than noon, Thursday, February 5, Virgo built a tunable diode laser spec- 2009. Please call or fax Marilou Cashman at 800-872-2054 or e-mail at trometer for production and analysis of Mcash0953(at)aol.com. Please specify vegetarian. Reservations not cancelled at transient molecules that are important least 24 hours in advance must be paid. Members, $30; Non-members, $35; in combustion reactions. He then spent Retirees, $18; Students, $10. an exciting four years at Arizona State University. His graduate research at THE PUBLIC IS INVITED ASU involved investigating the PUBLIC TRANSPORTATION: Take MBTA green line E train (Heath Street) to response of diatomic chemical interme- Museum stop. Turn right onto Louis Prang Street. From here you can see Sim- diates to electric and magnetic fields. mons’ green cupola. Walk past the Isabella Stewart Gardner Museum on left. His collaboration with Professor John Simmons College, 300 The Fenway, will be on left. Brown of Oxford University on the Anyone who needs special services or transportation, please call Marilou Cash- N theory of molecules in external fields man a few days in advance so that suitable arrangements can be made. was in the best tradition of scientific continued on page 13

At MIT our research is focused on reactions proceed through multiple ABSTRACT inventing new models to describe the channels involving photodissociation. mechanism of intramolecular chemical Photochemistry provides the driving Tracking Energy in Chemical energy flow in highly energized, pro- force behind the chemical reactions Dynamics from MIT to foundly distorted forms of organic that mediate the production and Wellesley: What are the molecules. Our work provides strong removal of ozone in the atmosphere. Pathways for Electronic support for a new deterministic door- We are designing and building a veloc- way mechanism for chemical energy ity map imaging apparatus in order to Energy Flow and flow in molecules, rather than the more elucidate the major photochemical Photochemistry ? traditional, purely statistical decay mechanisms and processes that initiate One of the major goals in the field of mechanism. Using a simple experimen- and drive atmospheric chemical reac- physical chemistry is to elucidate the tal method to observe the time-evolu- tions related to ozone production and mechanism of energy flow during a tion of a spectrum, we can obtain all removal. The experiment provides chemical reaction. Since the 1960s the necessary information in order to deep insight into the ways that energy there has been a great deal of scientific use a deconvolution procedure that is funneled through different photodis- research focused on understanding the extracts the energy of the doorway state sociation channels. The goal is to detailed mechanism of energy flow and relevant coupling matrix elements understand the fundamental chemistry involving Inter-System Crossing by that describe the decay mechanism. of the key molecular protagonists that analyzing molecular spectra. However, At Wellesley College the main mediate atmospheric reactions. With there has never been sufficient informa- research problem to be addressed is the fundamental understanding of tion in traditional spectra to determine how photochemical energy is parti- atmospheric chemistry derived from the important mechanistic details. tioned and transformed as atmospheric continued on page 12 The Nucleus February 2009 5 NSYCC Call for Call for Event Nominations Nominations

Overcoming Barriers in The 2009 James Flack Norris Philip L. Levins Memorial Prize Careers in Chemistry and Award for Outstanding Nominations for the Philip L. Levins Chemical Sciences Achievement in the Teaching of Memorial Prize for outstanding per- Chemistry formance by a graduate student on the 5:00-6:30 pm way to a career in chemical science Deadline: April 15, 2009 February 27, 2009 should be sent to the Administrative Nominations are invited for the 2009 Secretary of NESACS, 23 Cottage St., Location TBA James Flack Norris Award, which con- Natick, MA 01760 by March 1, 2009. Hosted by the Northeastern Section sists of a certificate and an honorarium The graduate student’s research Younger ’s Committee of $3,000, and is given annually by the should be in the area of organic analyt- (NSYCC) Northeastern Section (NESACS). The ical chemistry and may include other presentation will take place at a cere- The NSYCC (www.nsycc.org) would areas of organic analytical chemistry mony and dinner in November 2009, such as environmental analysis, bio- like to announce that registration is and will include a formal address by chemical analysis, or polymer analysis. under way for our upcoming panel dis- the awardee. The Award was estab- Nominations may be made by a cussion entitled, “Overcoming Barriers lished in 1950 by NESACS to honor faculty member, or the student may in Careers in Chemistry and Chemical the memory of James Flack Norris submit an application. A biographical Sciences.” The discussion will be held (1871-1940), a professor of chemistry sketch, transcripts of graduate and February 27th from 5 pm to 6:30 pm at at Simmons College and M.I.T., chair undergraduate grades, a description of the a location to be announced. Dan of NESACS in 1904, and ACS Presi- present research activity, and three ref- Eustace, moderator of the discussion, dent in 1925-26. erences must be included. The nomina- encourages all interested chemists to Nominees should have served tion should be specific concerning the register with NSYCC Publicity Chair with special distinction as teachers of contribution the student has made to Kathryn Bewley (kathryn.bewley(at) nsycc.org). Get directions and the lat- chemistry at any level: secondary the research and publications (if any) est details at www.nesacs.org or www. school, college, and/or graduate with multiple authors. nsycc.org school. With the presentation of the The award will be presented at the N The meeting will serve as a forum first Award in 1951, awardees have May 2009 Section Meeting. for younger chemists to ask questions included many eminent teachers at all and receive advice on meeting chal- levels whose efforts have had a wide- professional activity at the local, lenges on the path toward a successful ranging effect on chemical education. national, and international levels. career in chemistry. Questions can be The recipient will be selected from an The nomination materials should submitted anonymously (3x5 card) or international list of nominees who consist of the primary nomination let- the panelists can be queried directly have served with special distinction as ter, supporting letters, and the candi- during the event. teachers of chemistry with significant achievements. date’s curriculum vitae. Reprints or Members of the panel will include: A nomination in the form of a let- other publications should NOT be • Professor Wilton Virgo, Assistant ter should focus on the candidate’s included. The material should not Professor of Chemistry, Wellesley contributions to and effectiveness in exceed thirty (30) pages, and should be College teaching chemistry. The nominee’s submitted electronically in Adobe PDF • Professor Valerie Petit Wilson, curriculum vitae should be included format through April 15, 2009 to Ms. Executive Director, Leadership and, where appropriate, a list of hon- Marilou Cashman, NESACS Adminis- Alliance and Clinical Professor of ors, awards, and publications related to trative Secretary . sity may also be included; these should For more information about the Award, see . tor of Strategic Marketing, Waters teaching for inspiring colleagues and Questions about the Award or the Corporation students toward an active life in the chemical sciences and attest to the nomination process should be directed Refreshments will be served. Space N influence of the nominee’s other activi- to the Chair of the Norris Award Com- is limited, so register now! mittee, Prof. Morton Hoffman, Boston ties in chemical education, such as N textbooks, journal articles, or other University ..

6 The Nucleus February 2009 This Month in Chemical History

Harold Goldwhite, California State University, Los Angeles [email protected] Part I. among different experimental studies, from the general question of publish- To quote verbatim from an earlier perhaps attributable to different levels ing carefully worked out installments essay: “The idea of critically reviewing of adsorption of carbon dioxide by dif- of a large research, the scramble for substantial areas of chemistry and pro- ferently sized particles. E.C. Franklin priority, happily not common in this ducing a periodic report of progress has been studying conductivities of country[!], is often responsible for the originated with the great Swedish electrolyte solutions in liquid ammo- appearance of immature work.” chemist of the early nineteenth century, nia; he had done many pioneering Sir William Ramsay has been Jons Jacob Berzelius (1779-1848). The studies of this remarkable solvent. unable to detect helium in the radioac- original series of Jahresberichte, Ostwald’s dilution law relating concen- tive breakdown of thorium. There has Berzelius’ brain child and the first of tration and degree of ionization, has been much discussion of Prout’s the Annual Reports, did not survive its been investigated for a wide range of hypothesis, that all atomic masses originator. But there are other long- carboxylic acids. should be integral on the scale of H = lived series of such reports.” In reviewing inorganic chemistry, 1, but since 1909 was before the fuller This essay will focus on Volume H. B. Baker (whose work on intensive understanding of isotopes the argu- VI of the Annual Reports on the drying I wrote on some years ago in ments descended into numerology Progress of Chemistry issued by the the Journal of Chemical Education) rather than verifiable science. Mean- Chemical Society (of London), which writes: “it is difficult to give a general while, new determinations of atomic has now metamorphosed into the idea of a year’s work” – presumably in weights have improved values for, Royal Society of Chemistry. This the 22 pages or so allocated to him. He among others, chlorine, nitrogen, and ambitious attempt to encapsulate the makes some interesting remarks which carbon. total of the significant work in chem- could well apply to work done a cen- Silane and disilane have been istry for a whole year covers 1909 in a tury later! “In an ideal chemical world, obtained as pure compounds, and vari- mere 270 pages. It was, relatively, a nothing would be published until a ous chlorosilanes probably containing peaceful year in world history; 5 years complete account of the subject of chains of four and six silicon atoms before World War I. Tensions were research could be presented. But apart continued on page 10 building in Europe but had not yet reached a boiling point. Reviewing general and physical chemistry, T. M. Lowry, of Bronsted- Lowry fame, looks first at pressure effects on physical and chemical prop- erties. R.Threlfall has found no con- version of graphite to diamond at pressures up to 10,000 atmospheres and “temperatures up to the melting point of magnesia” – about 3100K. A new form of ice (shades of Vonnegut?), Ice III, has been observed at 3000kg/square cm. P.W. Bridgman, the high-pressure guru, has described two new high-pressure gauges based on a direct measurement of gas volume and on the resistance of a mercury column. New precision has been achieved in measuring osmotic pressure, including investigations by the Earl of Berkeley and his colleagues; so much for the stereotype of the indolent nobility. Detailed studies of the thermal dissoci- ation of calcium carbonate by Le Chatelier show marked deviations

The Nucleus February 2009 7 Summer Scholar Report Identification of Genes Regulated by Transcriptional Regulator, p8 Derek Kong, Sandro Goruppi, John Kyriakis, Molecular Cardiology Research Institute, Tufts University, Medford, MA Background human gene coding for a protein. The array was screened Approximately five million people in the for genes that were either upregulated or downregulated by have heart failure. It is a disease that contributes to 300,000 the presence and absence of p8. A list of the 30 genes that deaths every year. Heart failure is a progressive disorder that were most affected by the presence of p8 was obtained and a is caused by the weakening of cardiovascular tissue due to thorough screening at the RNA level was performed. stress, injury, or adverse reactions that other body systems RNA was purified using the method of phe- have in response to heart impairment. Initially, the heart nol/chloroform extractions from several cell lines including responds to harmful stimuli by attempting to compensate. U2OS (osteosarcoma) and HAE (human aortic endothelial) This is known as a compensatory response. However, if the cells that had been previously treated with siRNA specific stressors are not relieved, cardiac hypertrophy occurs and a for the p8 mRNA (sip8) or a control siRNA (siCTRL). In pathologic response results. Hypertension and ischemia are addition, the cells were activated with +/- TNFα. among the large number of stressors that cause hypertrophy, Reverse Transcription Polymerase Chain Reactions cardiomyocyte death, ventricular remodeling, and ventricu- (RT-PCR) were used to analyze the regulation of specific lar decomposition. These pathways ultimately lead to heart genes by p8. Reverse transcription was performed for one failure. hour, and the cDNA was amplified. PCR products were run Whether the heart responds to stressors by a compensa- on 1.8% agarose gels. tory or pathologic response is determined by various cellular Results signal transduction pathways. Via these pathways, cells RNA levels of genes treated with sip8 – The results of recruit proteins to specific segments of DNA for transcrip- the oligonucleotide array indicated that a large number of tion. On such protein is p8, a small, high-turnover, stress- genes are regulated by p8. Therefore, it was hypothesized induced helix-loop-helix protein that acts as a transcriptional that p8 may be a general transcription factor involved in regulator in the nucleus and associates with cytoplasmic proteins.1 p8 is required to activate compensatory heart responses, such as cardiac hypertrophy, when the heart is subjected to environmental stressors. After myocardial infarction, inflammatory cytokines, including TNFα, trigger the production of matrix metalloprotease 9 (mmp9) in car- diac fibroblasts at the site of the infarct.1 Secreted mmp9 digests and remodels the extracellular matrix to allow fibrous tissue to replace dead myocytes. We have previously shown that p8 is required for the induction of mmp9 by TNFα.2 Here we identify several novel genes as transcriptional targets of p8 and show that p8 is required for upregulation of transcription of these genes. In addition, we show that p8 activity is specific, and that it is not a general transcription factor for inflammatory genes in stress-induced pathways.

Figure 1: A scheme of the human p8 protein containing P: proline, E: glutamic acid, S: serine. T: threonine sequence contributing to short half-life and high turnover rate of p8. B: basic, H: helix, L: loop (bHLH) sequence. N: nuclear, L: localization, S: signal. Figure 2: A) Human aortic endothelial cells treated with +/- sip8, Materials and Methods +/- TNFα for 8 hours and serum starved. p8 silencing was con- firmed using RT-PCR and p8 regulation of known inflammatory Human tumor cells were infected with GFPp8, an markers were checked. Actin levels shown to indicate consistent unusually stable form of p8, so that the protein could be loading and successful RT-PCR reactions. B) RNA from human aor- expressed at higher than normal levels. The cell cultures tic endothelial cells was used to screen genes A, C, and E, which were expanded and the RNA was isolated. This RNA was seemed to be regulated by p8 in other cell lines. C) Regulation of applied to a HEEBO oligonucleotide array containing 48,958 inflammatory genes by p8 checked in U2OS tumor cells that were 70-mer oligonucleotide sequences, each corresponding to a serum starved prior to lysis.

8 The Nucleus February 2009 stress pathways. Because TNFα is a major inflammatory relation between the presence of p8 and gene transcription. cytokine and p8 is required for TNFα-mediated induction of Genes D and F-M showed no visible regulation by p8. mmp9, a screening of inflammatory markers was per- Discussion formed. The markers included E-selectin, Icam, Vcam, and This preliminary gene screening yielded significant Interleukin-8. RT-PCRs using RNA isolated from HAECs results in expanding our knowledge of the genes and pro- showed that TNFα-activated HAECs express an increased teins that are affected by p8. Among the most interesting quantity of these genetic markers; however, the basal and genes regulated by p8 were genes A and B. They code for activated levels of these genetic markers are unaffected by proteins that have not yet been characterized in the cardio- p8 presence in the cells. This finding was confirmed in both vascular system; however, these proteins may be interesting HAECs and U2OS cells. to study as downstream targets of p8 and may play a role in We have shown that several novel genes are transcrip- heart disease pathology. In this study, we have shown that tional targets of p8. Transcription of these genes is turned on the silencing of p8 almost completely shuts off production when p8 is present in the cells, but turned off when p8, is of mRNA transcripts that correspond to these genes. In addi- silenced using RNAi specific for p8. Genes A, B, C, and E tion, because we observed a transcriptional response within were most actively downregulated in the absence of p8 as * 4-8 hours, we infer that genes A, B, C, and E are most likely shown in figure 2, panels C, D, and E. The RT-PCRs indi- direct targets of p8 regulation. If these genes were further cate that under several different conditions (serum starvation downstream, we would have expected a longer period of and absence of growth factors or in the presence of 10% time between the time of p8 silencing and the time when fetal bovine serum) and in different cell lines (endothelial gene A, B, C, or E mRNA was completely degraded. cells and tumor cells) the mRNA transcripts of these genes Our lab has previously shown that p8 and TNFα are consistently higher in the presence of p8 and lower after directly interact during the process of ventricular remodel- p8 is silenced. ing that follows heart failure. Based on this study, however, Figure 3, panels D and E show the RT-PCR results of we conclude that p8 does not play a role in other general specific genes. Genes A, B, C, and E showed a positive cor- inflammatory pathways in which TNFα and TGFβ are pres- ent in high quantities. Apparently, p8 acts only in the con- text of stress-related heart disease, not general inflammation. Additional data is required for a thorough understanding of this p8 specificity. Future Directions We are currently studying one of the genes that we identified from the oligonucleotide array as being regulated by p8. Preliminary data indicates that gene A codes for a protein whose cellular presence is directly proportional to the presence p8, and is highly expressed in stem cells before differentiation. We are currently working in several different cell lines including human and mouse cardiac fibroblasts, human aortic endothelial cells, and human glioblastoma cells to confirm that a functional protein is indeed tran- scribed from the mRNA transcripts that were amplified in our RT-PCRs. One important aspect of our research is to determine whether gene A independently promotes the pro- duction of mmp9. If protein A is expressed in the cardiovas- cular system, it may have an important role in the progression of heart failure and heart disease. It is our goal to characterize these proteins and further our understanding of their specific activity in the cardiovascular system. Acknowledgements Derek Kong was supported by the Norris/Richards Summer Research Grant and by the Molecular Cardiology Research Institute. Figure 3: D) U2OS cells treated with +/- sip8, +/- TNFα, +/- References TGFβ, and serum starved. p8 silencing was confirmed using RT- 1) Goruppi, S., Richard Patten, Thomas Force, John Kyriakis. PCR and p8 regulation of specific genes were checked. βActin lev- 2006. HLH protein p8: a Transcriptional Regulator Required els shown to indicate consistent loading and successful RT-PCR continued on page 10 reactions. E) U2OS cells treated with +/- sip8, +/- TNFα, and left * N.B. – Gene A is a transcription factor. Gene B is a growth in 10% fetal bovine serum. factor. Genes C and E are protein kinases. The Nucleus February 2009 9 Chemical History Notable NE Chemists Summer Scholar

Continued from page 7 Continued from page 4 Continued from page 9 have been characterized. Raschig has tures given by Professor John W. Web- for Cardiomyocyte Hypertrophy and isolated chloramine for the first time, ster at the Medical School. He “picked Cardiac Fibroblast MMP Induction. and the dangerous nitrogen trichloride up” some chemistry in Europe during a Mol. Cell. Biol. 10.1128/MCB. 00996- has also been prepared in pure form. A year’s study, and entered upon his life 06. new electrolytic ozonizer produces as work in 1849 - “a self-made chemist,” 2) Goruppi, S., and John Kyriakis. 2004. much as 23% of ozone in oxygen. The as he often said. In 1850 Cooke was The Pro-hypertrophic Basic Helix- Loop-Helix Protein p8 is Degraded by disputed existence of sulfur dichloride elected Erving Professor of Chemistry the Ubiquitin/Proteasome System in a has now been confirmed. and Mineralogy. Within a decade he Protein Kinase B/Akt- and Glycogen pushed chemistry into Harvard Col- Part II. Synthase Kinase-3-dependent Manner, lege, built up several courses, raised whereas Endothelin Induction of p8 In continuing to review some signifi- money for a chemistry building (Boyl- mRNA and Renal Mesangial Cell cant developments in chemistry as Hypertrophy Require NFAT4. J. Biol. ston Hall), and supervised its erection N reported in “Annual Reports of the and equipment. Moreover, he inter- Chem. 279, 20 20950-20958. Progress of Chemistry for 1909”, pub- ested students in a subject new to Har- lished by The Chemical Society in vard, secured the academic respect of Laurent and Gerhardt on atoms and 1910, I turn my attention first to the his classical colleagues, and won the molecules, and between 1850 and 1860 section on organic chemistry written confidence of the university adminis- he presented his own views on theoret- by Cecil H. Desch and Arthur Lap- tration. As soon as Boylston Hall was ical chemistry — especially the water worth. The latter was a significant pio- completed, the little private laboratory type. In the latter field he anticipated neer in physical organic chemistry. To where a few choice students were the views of such noted chemists as put the period in perspective (recall taught was replaced by commodious Williamson and Wurtz. Indeed, Hunt that Bohr’s theory of the hydrogen quarters and research begun. was usually on the skirmish line. For atom is still in the future) let me quote: Cooke’s original papers on chemi- example, he anticipated Schonbein in “The chemical importance of certain cal topics number about seventy, the the interpretation of the origin of physical properties, notably colour and noteworthy ones being devoted to nitrites and nitrates in nature, and fluorescence, in their relation to struc- atomic weights. His books, especially Dumas in researches on the equivalent ture, has been dealt with in several pre- “Principles of Chemical Philosophy” volumes of liquids and solids. Again in vious Annual Reports ….we are still (1868) and “The New Chemistry” his “Introduction to Organic Chem- far from possessing a complete theory (1874), exerted a profound influence istry,” published in 1852 (with Silli- of the phenomena. …The formulation on the progress of chemistry. man’s “First Principles of Chemistry”) of ideas of structure in terms of the he was one of the first chemists — per- electron theory has so far made little haps the first American chemist — to progress in organic chemistry, the con- 1826-1892 define organic chemistry as “the chem- ception being still too indefinite for Thomas Sterry Hunt was born in Nor- istry of carbon and its compounds.” immediate application to so complex a wich, Conn. He attended Yale College In 1872 Hunt was appointed Pro- problem.” and studied chemistry under Benjamin fessor of in the Massachusetts A later paragraph goes on to say: Silliman. Being broad-minded, he Institute of Technology, resigning, “The influence of unsaturated or dou- chose several fields of labor and however, in 1878 to devote his entire ble linkings on the properties of a com- throughout his life excelled in two, time to expert work and literary pur- pound …and the nature of so-called chemical geology and chemical theory. suits. Hunt published about one hun- “partial valencies” are questions which In 1847 he was appointed chemist and dred and sixty articles — chiefly in the recur...” We tend to think of Alfred mineralogist of the Geological Survey American Journal of Science. His best Werner in connection with his insight- of Canada. During the twenty-five known books are “Chemical and Geo- ful investigations into coordination years he held this joint position he logical Essays” (1874) and “A New compounds, but he came to that area made many long reports of fundamen- Basis for Chemistry” (1887), later via chemical and stereochemical stud- tal importance. Within the same period, translated into French and Russian. He ies of oximes with Hantzsch, and the particularly about 1850, he expounded was president of the American Chemi- N 1909 Report goes into considerable by lectures and papers the views of cal Society in 1880 and 1888. detail on Werner’s ideas on how “ele- ments of decidedly electropositive or The NESACS website negative character” will exert their Updated frequently • Late-breaking news • position postings polar character on reactions of unsatu- Back issues of the Nucleus archived • Career-related Links • Awards and Scholarships rated compounds containing them in WWW.NESACS.org continued on page 12

10 The Nucleus February 2009 Tips for Job Correction: Seekers in a Message from the Chair - 2009 Note from editor: In a mix-up in the January issue the statement of last year’s Contracting chair, Marietta Schwartz, was substituted for the statement from this year’s chair, Joe Billo. Here is Joe’s statement. Environment Welcome to NESACS 2009! tion’s problem, as I see it, is that the During my term as chair of the section, same few dedicated people fill the Megan Driscoll, President, Pharma- I hope that I can make this the Year of elected and non-elected positions year Logics Recruiting, Greater Membership Involvement. I after year. So I encourage you to look www.pharmalogicsrecruiting.com have three suggestions. at the list of committee chairs that can be found elsewhere in this issue, and In these uncertain times, it is very easy First, I urge you to attend our see if there is a committee that you to get worried about your future. monthly meetings. As well as enjoy- would like to join. I know that the Maybe you have lost your job already, ing a delicious meal and a stimulating committee chairs listed there would all or you are facing an upcoming layoff talk, you will be able to mingle and welcome additional volunteers; you at your company. Even if you are still network with chemists of all kinds, can contact them via e-mail. happily employed, the economic from students to Nobel laureates. Third, I hope during 2009 to downturn is enough to make anyone a Second, I want to encourage you encourage the formation of some addi- little nervous. However, it is not a to become involved in the operations tional “interest groups” within time to panic. Thankfully, Bio-Pharma of the Northeastern Section. But first, NESACS. Currently we have a very is usually the last industry to be let me tell you a little story. In January active and successful Medicinal Chem- affected by a recession and the first to of 2008, as chair-elect of our section, I istry group with a large membership. recover from it. Our firm is actually attended the ACS Leadership Institute The MedChem group has a separate quite busy with new positions coming for newly elected chairs of all 189 sec- executive, a separate budget, and holds into our office every day, so don’t lose tions. There I had the opportunity to separate meetings, as well as providing hope. For candidates who are looking, speak with chairs-elect of small sec- speakers for some of our regular it is important to remember a few spe- tions, some with only 150 members. monthly meetings. I believe that other cific things: These chairs-elect were often strug- gling with the logistics of scheduling a interest groups, such as a consultants • Make sure you have a great resumé group or retired chemists group, or an to present. Share it with peers for monthly meeting or hoping to be able to put out an occasional newsletter. In interest group focused on analytical feedback to ensure it is as good as it chemistry, inorganic chemistry, educa- can be. contrast, our section, with over 6500 members, is a large, well-run opera- tion, or informatics, could be a valu- • Research companies that have prod- tion. We have regular monthly meet- able addition to our section. If you’d ucts similar to the ones you have like to work with me to establish such ings and the Nucleus is one of the best N worked on in the past, and approach local section publications. Our sec- a group, please contact me. them with your qualifications. • Re-invent yourself. Be looking for positions that would be slightly out- side your current scope of experi- interests for the future. Often, What’s Yours? ence and think of creative ways to recruiters know about jobs before DMPK Scientist, present your background to them. they even open up. LC/MS Product Specialist, • Don’t submit yourself to a position • Be patient, your job search is going Mass Spec Operator, on line unless you absolutely have to. to take longer. Three months would Staff Investigator, Use your network and the respected be the average last year, but it could Process Chemist, recruiters you know to get in first. take up to six months this year. QA Manager, In this economic environment, the • Use your network. Be assertive in Synthetic Chemist, databases are overflowing with contacting and presenting your qual- Lab Instructor ifications to current and former col- resumes and it is hard for companies to filter through. Many local employers post positions leagues. No one can sell you like on the NESACS job board. you, so don’t hesitate to pick up the If you have additional questions about phone. your job search, please e-mail Megan Find yours at at: mdriscoll(at)pharmalogicsrecruiting www.nesacs.org/jobs • Contact recruiters you trust to let N them know of your background and .com The Nucleus February 2009 11 National Chemical History Abstract Continued from page 10 Continued from page 5 Chemistry contrast to the relatively non-polar car- these chemical dynamics experiments, bon and hydrogen. one can begin to accurately model and Perhaps reflecting Lapworth’s predict the chemical response of the Week 2008 interests, there is an extended section global atmosphere to both natural and on “Mechanism of Chemical Change” anthropogenic perturbations. Since (Photos by Mort Hoffman) of organic systems, including interpre- atmospheric chemistry is governed by tation of the effects of acid catalysts in the photodissociation of molecules by reactions of carbonyl compounds; sunlight and the internal energy of kinetic studies of the rate of formation vibrating molecules, the proposed of urea from ammonium ions and experiment will yield deep insight into cyanate ions (Woehler’s famous syn- the chemistry of global climate change. N thesis); the Walden inversion; and iso- meric changes such as the Hofmann and Beckmann reactions. The new cat- alytic reactions of Sabatier and coiner of the term isotope, and Nobel Senderens include reductions with Laureate for chemistry in 1921. The Professor Bassam Shakhashiri (University of hydrogen over metal catalysts; and report starts with a metaphorical bang. Wisconsin-Madison) during the Phyllis A. hydration, dehydration, oxidation, and Alpha radiation has been conclusively Brauner Memorial Lecture elimination of hydrogen halide – ver- proved to be doubly charged helium satile systems, indeed. E. Fischer’s syn- atoms. The emanation from 140 mg of theses of polypeptides and of amino- radium was collected and its emission acids are reported. spectrum confirmed that helium was A section on stereochemistry by produced by radium decay. You’ll H. O. Jones features prominently the recall that this work is prior to Ruther- first resolutions of organic compounds ford’s proposal of the nuclear atom, that have “enantiomorphism of the and the next reports foreshadow that molecule without being assignable to a work. Two methods: zinc sulfide scin- single asymmetric atom…” Perkin, tillations, and the Geiger counter Pope, and Wallach resolved 1-methyl- announced by Rutherford and Geiger, (L-R) Professor Shakhashiri, Susan Brauner, cyclohexylidene-4-acetic acid, and can count individual alpha particles. daughter of Phyllis Brauner, and Doris Lewis Mills and Miss Bain (!), 4-oximinocy- The ratio e/m for beta particles has (Suffolk University), Chair of the Brauner experimentally been determined to Memorial Lecture Committee clohexanecarboxylic acid. Each of these molecules is devoid of a plane of decrease as the velocity of the particles symmetry but contains no individual (electrons) approaches that of light. “asymmetric” atom. Optically active The results are in complete accord with compounds with an “asymmetric” sili- the Lorentz equation and this “experi- con atom have been resolved. Pasteur’s mental proof appears also to have biochemical method has been used to important metaphysical [!] conse- partially resolve benzaldehyde quences in establishing the Lorentz- cyanohydrin; emulsin catalyses the Einstein principle of relativity.” A young chemist hydrolysis of the d-enantiomer more Gamma rays are still, in 1909, (Olivia F.) doing rapidly than that of the l-enantiomer. In regarded as particulate, and the con- an NCW experi- addition, a number of amino acids temporary theory, known as the neu- ment. have been resolved by the action of tral-pair theory, holds that a gamma ray yeast in the presence of sugar, includ- consists of an electrically neutral pair ing d-phenylalanine and d-serine. Fur- of a negative and a positive electron.` ther examples of optically active I cannot claim to have read care- nitrogen compounds have been stud- fully every word of Soddy’s review, ied, including the quite simple N- but I think I am correct in claiming that methyl-N-ethylaniline oxide, resolved he never uses the word transmutation via its d-bromocamphorsulfonate salt. in describing radioactive change – an I conclude with the report on interesting reflection on the disrepute in which this alchemical term was held radioactivity by none other than Fred- N Kyle G. at an NCW activity. erick Soddy, Rutherford’s collaborator, at that period.

12 The Nucleus February 2009 BUSINESS DIRECTORY SERVICES SERVICES SERVICES

Biography

Continued from page 5 teamwork. At ASU Dr. Virgo was the recipient of numerous honors and awards, including being a More Gradu- ate Education at Mountain States Alliance Scholar from 2002-2005, the Rao Prize for the most outstanding stu- dent talk at the 2002 Ohio State Uni- versity International Symposium on Molecular Spectroscopy, the 2003 ASU Department of Chemistry and Biochemistry Outstanding Graduate Research Assistant Award, and the 2005 Eastman Kodak - Dr. Theophilus Sorrell Graduate Fellowship Award. His research at ASU resulted in eleven publications, two as first author, lead- ing to the doctorate in chemistry. Dr. Virgo arrived at the Massachusetts Institute of Technology in January 2006 as a Postdoctoral Associate in Professor Robert Field’s group in the Department of Chemistry. Later, he was honored to become a Postdoctoral Fellow and MLK Scholar. Dr. Virgo led a team of three graduate students continued on page 16

The Nucleus February 2009 13 BUSINESS DIRECTORY SERVICES SERVICES SERVICES

14 The Nucleus February 2009 BUSINESS DIRECTORY SERVICES SERVICES CAREER SERVICES

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The Nucleus February 2009 15 Harvard, MA 01451 19 Mill Road Calendar Check the NESACS Homepage Feb 11 for late additions: Etsuko Fujita (Brookhaven National Lab) http://www.NESACS.org “Photochemical CO2 Reduction: A Daunting Note also the Chemistry Department web Challenge” pages for travel directions and updates. Harvard, Pfizer Lecture Hall These include: 4:00 pm http://chemserv.bc.edu/seminar.html Feb 12 http://www.bu.edu/chemistry/events/ Arieh Warshel (University of Southern http://www.chem.brandeis.edu/colloquium.shtml California) http://www-chem.harvard.edu/events/ TBA http://web.mit.edu/chemistry/ Harvard, Pfizer Lecture Hall www.chem.neu.edu/web/calendar/index.html 4:00 pm http://chem.tufts.edu/seminars.html [CHEM.] Feb. 17 http://ase.tufts.edu/chemical/seminar.htm [CHEM. ENGG.] Bjorn Soderberg (West Virginia Univ.) http://www.chem.umb.edu/ UNH, Iddles Auditorium, Room L103 www.umassd.edu/cas/chemistry/seminars.cfm 11:10 am www.uml.edu/Dept/Chemistry/speakers.html Feb 17-18 http://www.unh.edu/chemistry/seminars.html AMERICAN CHEMICAL TY Shen Lecture U.S. POSTAGE PAID Feb 05 NONPROFIT ORG. NORTHEASTERN Vern L. Schramm (Albert Einstein College of SOCIETY SECTION Bristol Myers Squibb Lectures Medicine) Guy Lloyd-Jones (Univ. Bristol) Contact Betty Lou McClanahan TBA [[email protected]] and Prashant Deshpande (Bristol Myers MIT location TBA Squibb) 4:00 pm TBA Feb 26 MIT 6-120 4:00 pm Gabor Somorjai (U. C., Berkeley) Trevor Douglas (Univ. Montana) TBA Biography TBA Harvard, Pfizer Lecture Hall Harvard, Pfizer Lecture Hall 4:00 pm Continued from page 13 4:00 pm Gregory Tew (Univ. Massachusetts, Amherst) Feb 09 TBA and two undergraduate researchers at UNH, Iddles Auditorium, Room L103 MIT. Dr. Virgo’s research at MIT has Prof. Timothy Swager (MIT) 11:10 am established a new class of molecular “Polymer Electronics for Ultra-Sensitive Feb 27 beam spectroscopy. The goal of his Chemical Sensors” Brandeis Univ, Gerstenzang 122 C. Dale Poulter (Univ. Utah) research is to characterize well known 3:45 pm TBA unsaturated organic molecules in pro- Daniel Nocera (MIT) MIT 6-120 foundly distorted and highly excited TBA 4:00 pm forms using sophisticated laser tech- Harvard, Pfizer Lecture Hall niques and detection on metal surfaces. 12:00 pm Notices for The Nucleus The results of Dr. Virgo’s research at Feb. 10 Calendar of Seminars MIT have been published in the Jour- Han Wang (UNH) should be sent to: nal of Physical Chemistry. He has pre- “Explorations of Gold Complexes with Sheila E Rodman sented his MIT research at international Luminescence Properties” Konarka Technologies, Inc. UNH, Iddles Auditorium, Room L103 symposia, including the 3rd US- 11:10 am 116 John St. Suite 12 African Advanced Institute in Cairo, Lowell, MA 01852 N Prof. Krishna Kumar (Tufts University) email: srodman(at)konarka.com Egypt 2008, the Gordon Conference TBD for Electronic Spectroscopy and Boston College, Merkert 130 Dynamics in 2006 in Les Diablerets, 4:00 pm Switzerland, The Ohio State University International Symposium on Molecular Spectroscopy 2006-2007, and the 234th American Chemical Society National Meeting in Boston 2007. Dr. Virgo’s reputation and research at MIT July 2008 Dr. Virgo started his new Looking for seminars have garnered invitations to give a faculty position as the Diana Chapman in the Boston area? Modern Optics and Spectroscopy Sem- Walsh Assistant Professor of Chem- inar at MIT, two seminars at Princeton istry at Wellesley College. He is cur- Check out the University, a seminar at Wesleyan Uni- rently building a new laboratory at NESACS Calendar versity, and three seminars at Wellesley Wellesley to study atmospheric photo- College. Dr. Virgo has developed inter- chemical dynamics using innovative www.nesacs.org/seminars national collaborations with scientists laser techniques and creative molecular N in Switzerland, Japan, and Taiwan. In theory.