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Life Sciences Division Newsletter
February 2013
In this issue:
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Scientific News »
- How Cilia — Organelles Key to Good Health — Get Organized »
- New Clue to Clinical Trial Failures of MMP Cancer Therapies »
- Computational Pipeline Analyzes Tumor Images to Help Predict Cancer Therapy Response »
- Lab Scientists Help Map Molecular Architecture of Organelle Critical to Hearing »
- New Key to Organism Complexity Identified »
- To Revert Breast Cancer Cells, Give Them the Squeeze »
- Art from Auer Group on Environmental Microbiology Reports Cover »
- LaBarge Presents Future Leaders, New Directions in Aging Research Talk »
- In the News »
- Recent Publications »
- Jagust Awarded Potamkin Prize for Alzheimer’s Research »
- Work of LaBarge and Colleagues Selected ASCB “Novel & Newsworthy” Top Pick »
- Welcome to New Hires Adabi and Parplys »
- Welcome to Baby Ollin César »
- Costes and Study Partner Wong Graduate from Emerging Leader Program 2012 »
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Scientific News
How Cilia — Organelles Key to Good Health — Get Organized
Ken Downing and Puey Ounjai of the Life Sciences Division used electron microscopy to identify a key component of cilia, microscopic organelles that are critical to good health. The newly discovered structure, called the “ciliary partitioning system,” appears to have all the features required for cilium partitioning and compartmentalization, which is critical to proper cilia functioning. This CPS might one day provide a prime target for pharmaceutical ciliopathic therapies. Downing, Ounjai, and colleagues have published a paper on this research in the journal Current Biology titled “Architectural Insights into a Ciliary Partition.” Co-authors were Keunhwan Kim, Haichuan Liu, Ming Dong, Andrew Tauscher and Ewa Witkowska. More »
Their research paper was also selected for the cover of the journal’s February 18 issue. The cover image is a representation of a barrier between the cytoplasm of a Tetrahymena cell and its cilia, which appears to be part of the mechanism that regulates the passage of material into and out of the cilia. The barrier contains nine pores through which pass microtubule doublets that continue out into the axoneme of the cilia. The size of the outer region of the pore is appropriate for passage of complexes, called “intraflagellar transport particles,” which travel along the microtubules and carry components for assembly of the cilia. Proper control of the flow of this material is essential for formation of fully functional cilia. The image, "Structure of the Ciliary Barrier," was prepared by Puey Ounjai.
Adapted from Today at Berkeley Lab, February 19, 2013
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New Clue to Clinical Trial Failures of MMP Cancer Therapies
Proposed cancer therapeutic drugs based on blocking the catalytic activities of matrix metalloproteinases (MMPs), which profoundly remodel the environment surrounding a breast cell, have performed poorly in clinical trials. In mouse studies of MMP14, an enzyme that is often highly expressed in breast cancer, Berkeley Lab life scientists Mina Bissell and Hidetoshi Mori have found a possible clue as to why. If confirmed for other MMPs, the finding could point the way to new strategies for future MMP-based cancer therapies. More »
Today at Berkeley Lab, February 14, 2013
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Computational Pipeline Analyzes Tumor Images to Help Predict Cancer Therapy Response
Berkeley Lab scientists led the development of an algorithm and a computational pipeline that analyzes large sets of tumor images. Their work will help scientists learn more about the genetic and molecular mechanisms that control tumor signatures. It will also shed light on whether tumor subtype can predict the effectiveness of therapies. The research was led by Hang Chang, Ju Han, Leandro Loss, and Bahram Parvin of the Life Sciences Division, as well as scientists from several other institutions. The scientists validated their pipeline by applying it to 377 whole-slide images from patients who have an aggressive brain cancer. More »
Today at Berkeley Lab, January 31, 2013
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Lab Scientists Help Map Molecular Architecture of Organelle Critical to Hearing
A team that includes Berkeley Lab scientists has identified and mapped the locations of many of the proteins that compose a hair bundle, which is an organelle that sprouts from hair cells in the inner ear. As recently published online in Nature Neuroscience, Manfred Auer and other scientists from the Life Sciences Division used three-dimensional electron tomography to image stereocilia, which make up hair bundles. Their work complements mass spectrometry data collected by Oregon Health & Science University scientists. Other Lab scientists involved in the research include Ahmed Hassan, Zoltan Metlagel, and Andrew Tauscher. More »
Today at Berkeley Lab, January 30, 2013
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New Key to Organism Complexity Identified
Eva Nogales of the Life Sciences Division, working with Michael Cianfrocco, led the discovery that TFIID transcription factor protein co-exists in two states — canonical and arranged. Furthermore, they found it is only in the arranged state that TFIID can bind to DNA and start the process by which genetic information gets copied into RNA for the production of proteins. Also working on this study were George Kassavetis, Patricia Grob, Jie Fang, Tamar Juven-Gershon and James Kadonaga. More »
Today at Berkeley Lab, January 17, 2013
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To Revert Breast Cancer Cells, Give Them the Squeeze
UC Berkeley and Berkeley Lab researchers have put the squeeze — literally — on malignant mammary cells to guide them back into a normal growth pattern. The findings show that mechanical forces alone can revert and stop the growth of cancer cells. This change happens even though the genetic mutations responsible for malignancy remain. “We are showing that tissue organization is sensitive to mechanical inputs from the environment at the beginning stages of growth and development,” said Lab physical bioscientist Daniel Fletcher. “An early signal, in the form of compression, appears to get these malignant cells back on the right track.” More »
Today at Berkeley Lab, January 3, 2013
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Art from Auer Group on Environmental Microbiology Reports Cover
Data/artwork of Manfred Auer’s group was selected for the February 2013 cover of Environmental Microbiology Reports, the journal’s thematic issue on Environmental Ecology of Pathogens and Resistances. The journal is an, online only, sister journal of Environmental Microbiology, that publishes papers reporting significant advances which can be documented concisely though a limited amount of text and a small number of displays. It is published on behalf of Society for Applied Microbiology.
The cover image depicts a small region of the lignocellulose degrading termite hindgut microbial community with a 3D rendering of bacteria in a small cuboid volume being overlaid onto a slice of the raw 3D focused ion beam scanning electron microscopy data. It illustrates an exciting new development in microbial ecology, namely the ability of imaging large volumes of microbial communities at high resolution, allowing the visualization and quantitative analysis at the level of macromolecular complexes, of cells as well as of community organization.
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LaBarge Presents Future Leaders, New Directions in Aging Research Talk
Mark LaBarge presented his work on “Aging Makes Human Mammary Gland More Vulnerable to Cancer” in the Future Leaders, New Directions in Aging Research Symposium of the 2012 Gerontological Society of America (GSA) 65th Annual Scientific Meeting, Charting New Frontiers in Aging, November 14-18, 2012, in San Diego. He presented his work alongside two other selected leaders, speaking on understanding aging under the chairmanship of David Sinclair and Terrie Vasilopoulos, according to the meeting’s program book.
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In the News
A review of Life Sciences researchers, staff, and students who have appeared in the news media. This is but a sampling of our coverage. Please note that some links may expire after time.
A Jan. 31 MedGadget story highlighted efforts by the Lab’s Bahram Parvin to use computers to help identify tumors and predict outcomes in cancer patients.
http://www.medgadget.com/2013/01/computer-vision-system-identifies-tumor-helps-predict-patient-outcomes.html
A Jan. 30 Scientific American story on aging included a Q&A with the Lab’s Judith Campisi.
http://www.scientificamerican.com/article.cfm?id=aging-ask-the-experts-can-aging-be-controlled
A Jan. 17 SciCasts.com story featured work led by the Lab’s Eva Nogales showing new complexity in organisms.
http://scicasts.com/gene/5260-team-identifies-new-key-to-organism-complexity
A Jan. 3 Cancer Discovery story featured a Q&A with Mina Bissell on tumors as organs.
http://cancerdiscovery.aacrjournals.org/content/early/2013/01/01/2159-8290.CD-ND2013-001.full
A Dec. 24 Daily Cal story featured breast cancer research by the Lab’s Daniel Fletcher and Mina Bissell.
http://www.dailycal.org/2012/12/24/researchers-find-that-exerting-pressure-on-breasts-can-suppress-cancer-cell-growth/
A Dec. 17 R&D magazine story featured work led by the Lab’s Andy Wyrobek to develop a quick way to identify people exposed to ionizing radiation.
http://www.rdmag.com/news/2012/12/scientists-develop-quick-way-identify-people-exposed-ionizing-radiation
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Recent Publications
What follows is a review of Life Sciences recent publications. It is not a complete list, but only a sampling.
Rao X, Evans J, Chae H, Pilrose J, Kim S, Yan P, Huang RL, Lai HC, Lin H, Liu Y, Miller D, Rhee JK, Huang YW, Gu F, Gray JW, Huang TM, Nephew KP. CpG island shore methylation regulates caveolin-1 expression in breast cancer. Oncogene. 2012 Nov 5. [Epub ahead of print] PMID: 23128390 Abstract »
Alkalay A, Rabinovici GD, Zimmerman G, Agarwal N, Kaufer D, Miller BL, Jagust WJ, Soreq H. Plasma acetylcholinesterase activity correlates with intracerebral ß-amyloid load. Current Alzheimer Research. 2012 Nov 5. [Epub ahead of print] PMID: 23157337 Abstract »
Srinivasan K, Leone DP, Bateson RK, Dobreva G, Kohwi Y, Kohwi-Shigematsu T, Grosschedl R, McConnell SK. A network of genetic repression and derepression specifies projection fates in the developing neocortex. Proceedings of the National Academy of Sciences U S A. 2012 Nov 20;109(47):19071-8. Epub 2012 Nov 9. PMID: 23144223 Abstract »
Liu Y, Ren S, Castellanos-Martin A, Perez-Losada J, Kwon YW, Huang Y, Wang Z, Abad M, Cruz-Hernandez JJ, Rodriguez CA, Sun Y, Mao JH. Multiple novel alternative splicing forms of FBXW7a have a translational modulatory function and show specific alteration in human cancer. PLoS One. 2012;7(11):e49453. Epub 2012 Nov 14. PMID: 23166673 Abstract »
Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, Mintun MA; for the Alzheimer’s Disease Neuroimaging Initiative. Amyloid-ß Imaging with Pittsburgh Compound B and Florbetapir: comparing radiotracers and quantification methods. Journal of Nuclear Medicine. 2012 Nov 19. [Epub ahead of print] PMID: 23166389 Abstract »
Dang LC, O’Neil JP, Jagust WJ. Genetic effects on behavior are mediated by neurotransmitters and large-scale neural networks. Neuroimage,66:203–214, February 1, 2013. [on-line ahead of print] Abstract »
Derenzo SE, Bourret-Courchesne E, Yan Z, Bizarri G, Canning A, Zhang G. Experimental and theoretical studies of donor-acceptor scintillation from PbI2. Journal of Luminescence, 134:28–34, February 2013. [on-line ahead of print] Abstract »
Berleman J, Auer M. The role of bacterial outer membrane vesicles for intra- and interspecies delivery.Environmental Microbiology. 2012 Nov 21. [Epub ahead of print] PMID: 23227894 Abstract »
Petersen PD, Lau J, Ebert B, Yang F, Verhertbruggen Y, Kim JS, Varanasi P, Suttangkakul A, Auer M, Loqué D, Scheller HV. Engineering of plants with improved properties as biofuels feedstocks by vessel-specific complementation of xylan biosynthesis mutants. Biotechnology of Biofuels. 2012 Nov 26;5(1):84. [Epub ahead of print] PMID: 23181474 Abstract »
Chen X, Vega-Sánchez ME, Verhertbruggen Y, Chiniquy D, Canlas PE, Fagerström A, Prak L, Christensen U, Oikawa A, Chern M, Zuo S, Fan L, Auer M, Willats WG, Bartley L, Harholt J, Scheller HV, Ronald PC. Inactivation of OsIRX10 leads to decreased xylan content in ricestem cell walls and improved biomass saccharification. Molecular Plant. 2012 Nov 23. [Epub ahead of print] PMID: 23180670
Yang F, Mitra P, Zhang L, Prak L, Verhertbruggen Y, Kim JS, Sun L, Zheng K, Tang K, Auer M, Scheller HV, Loqué D. Engineering secondary cell wall deposition in plants. Plant Biotechnology Jounal. 2012 Nov 12. [Epub ahead of print] PMID: 23140549 Abstract »
Di Modugno F, Iapicca P, Boudreau A, Mottolese M, Terrenato I, Perracchio L, Carstens RP, Santoni A, Bissell MJ, Nisticò P. Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors. Proceedings of the National Academy of Sciences U S A. 2012 Nov 20;109(47):19280-5. Epub 2012 Nov 5. PMID: 23129656 [PubMed - in process] Abstract »
O'Brien B, Zeng H, Polyzos AA, Lemke KH, Weier JF, Wang M, Zitzelsberger HF, Weier HU. Bioinformatics tools allow targeted selection of chromosome enumeration probes and aneuploidy Detection.Journal of Histochemistry and Cytochemistry. 2012 Nov 29. [Epub ahead of print] PMID: 23204113
Chang H, Han J, Borowsky A, Loss L, Gray J, Spellman P, Parvin B. Invariant delineation of nuclear architecture in glioblastoma multiforme from The Cancer Genome Atlas Cohort. IEEE Transactions on Medical Imaging. 2012 Dec 4. [Epub ahead of print] PMID: 23221815 Abstract »
Wang M, Saha J, Hada M, Anderson JA, Pluth JM, O'Neill P, Cucinotta FA. Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFß and ATM pathways. Nucleic Acids Research. 2012 Dec 5. [Epub ahead of print] PMID: 23221633 Abstract »
Kang HC, Wakabayashi Y, Jen KY, Mao JH, Zoumpourlis V, Del Rosario R, Balmain A. Ptch1 overexpression drives skin carcinogenesis and developmental defects in K14Ptch(FVB) mice. Journal of Investigative Dermatology. 2012 Dec 6. [Epub ahead of print] PMID: 23223138 Abstract »
Ordinario E, Han HJ, Furuta S, Heiser LM, Jakkula LR, Rodier F, Spellman PT, Campisi J, Gray JW, Bissell MJ, Kohwi Y, Kohwi-Shigematsu T. ATM suppresses SATB1-induced malignant progression in breast epithelial cells. PLoS One. 2012;7(12):e51786. Epub 2012 Dec 10. PMID: 23251624 Abstract »
Fisher WW, Li JJ, Hammonds AS, Brown JB, Pfeiffer BD, Weiszmann R, Macarthur S, Thomas S, Stamatoyannopoulos JA, Eisen MB, Bickel PJ, Biggin MD, Celniker SE. DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. Proceedings of the National Academy of Science U S A. 2012 Dec 10. [Epub ahead of print] PMID: 23236164 Abstract »
Dalhus B, Nilsen L, Korvald H, Huffman J, Forstrøm RJ, McMurray CT, Alseth I, Tainer JA, Bjørås M. Sculpting of DNA at Abasic sites by DNA Glycosylase Homolog Mag2. Structure. 2012 Dec 11. pii: S0969-2126(12)00419-4. [Epub ahead of print] PMID: 23245849 Abstract »
Diao J, Grob P, Cipriano DJ, Kyoung M, Zhang Y, Shah S, Nguyen A, Padolina M, Srivastava A, Vrljic M, Shah A, Nogales E, Chu S, Brunger AT. Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion. eLife. 2012;1:e00109 Epub 2012 Dec 13. PMID: 23240085 Abstract »
Mao P, Gomez-Sjoberg R, Wang D. Multinozzle emitter array chips for small-volume proteomics. Analytical Chemistry. 2012 Dec 19. [Epub ahead of print] PMID: 23252432 Abstract »
Yakovlev S, Downing KH. Visualization of clusters in polymer electrolyte membranes by electron microscopy. Physical Chemistry Chemical Physics. 2012 Dec 19;15(4):1052-64.. PMID: 23165242 Abstract »
Jagust WJ, Landau SM. Apolipoprotein E, Not Fibrillar ß-Amyloid, reduces cerebral glucose metabolism in normal aging. For the Alzheimer's Disease Neuroimaging Initiative. Journal of Neuroscience. 2012 Dec 12;32(50):18227-18233. PMID: 23238736 Abstract »
Mori H, Lo AT, Inman JL, Alcaraz J, Ghajar CM, Mott JD, Nelson CM, Chen CS, Zhang H, Bascom JL, Seiki M, Bissell MJ. Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin ß1. Development. 2013 Jan;140(2):343-52. PMID: 23250208 Abstract »
Downing KH. Future developments in instrumentation for electron crystallography. Methods in Molecular Biology. 2013;955:353-79. PMID: 23132071 Abstract »
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Awards Highlights
Jagust Awarded Potamkin Prize for Alzheimer’s Research
William Jagust
William Jagust, a faculty senior scientist in the Life Sciences Division who also has appointments at UC Berkeley’s School of Public Health and the Helen Wills Neuroscience Institute, has been awarded the 2013 Potamkin Prize by the American Academy of Neurology. The Potamkin Prize honors researchers for their work in helping to advance the understanding of Pick’s disease, Alzheimer’s disease and related disorders. Jagust is receiving the award his research about beta-amyloid, or plaques in the brain, which are a possible cause of Alzheimer’s disease. He uses imaging techniques to help outline amyloid protein and its effects on the brain. Two other neurologists also received the award. More »
Today at Berkeley Lab, January 28, 2013
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Work of LaBarge and Colleagues Selected ASCB “Novel & Newsworthy” Top Pick
The American Society for Cell Biology (ASCB) selected the work on aging of Mark LaBarge and colleagues among their "Novel & Newsworthy" Top Picks of the 52nd the Annual ASCB Meeting in San Francisco, December 15–19, 2012. The abstract, "Recalculating the Age and Breast Cancer Equation," was included in Cell Biology 2012, the press guide from ASCB’s Public Information Committee (PIC), featuring the "Novel & Newsworthy" Top Picks. In two complete rounds, the scientist–members of PIC peer-screened 984 abstracts submitted for live presentation, to come up with their 11 Top Picks.
LaBarge presented in the Tumor Microenvironment Session on December 17 and was recorded in a Top Picks video (2.29 min.) discussing his work: “Breast cancer in older women is not just a matter of accumulated mutations but also the different population mix of mammary cell types and progenitors.”
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Employee News
Welcome to New Hires Adabi and Parplys
Kian Adabi
Kian Adabi, research assistant in the Pluth lab per December 5, 2012, primarily works on a NASA funded project focused on understanding the impact of age, genetic susceptibility and radiation quality on the carcinogenic potential of different radiation qualities using normal early passage breast epithelial cells.
Ann Parplys
Ann Parplys from Hamburg, Germany, postdoctoral fellow in the Wiese lab per January 11, 2013, will establish the DNA Fiber Assay in the lab, a special method to analyze replication processes in cell lines.
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Welcome to Baby Ollin César
Baby Ollin César
Welcome to baby boy Ollin César, daughter of Lorena Eva Mora Blanco (LaBarge lab) and Niels Klitgord (formerly of the Northen lab), brother of Maristela. Ollin was born on December 30, 2012, weighted in at 10lbs 2oz and measured 21.5 inches long.
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Costes and Study Partner Wong Graduate from Emerging Leader Program 2012
In November, Life Sciences Sylvain Costes and Michelle Wong of the Tech Transfer Department graduated from the Emerging Leader Program, a Berkeley Lab-sponsored leadership development program designed to build and improve the readiness of scientist and non-scientist managers to be successful in a leadership role at Berkeley Lab. The year-long program was developed and delivered by Berkeley Lab Learning Institute (BLI) in partnership with UCB Haas School of Business. The objective of the program is to help strengthen leadership acumen and skills, and broaden peer and management relationships that are critical to achieving the Berkeley Lab’s mission. Here Costes and Wong tell their story:
- Can you tell me more about the Emerging Leader Program and who participated?
Costes: “About 30 people across the Lab participated, including both scientists and administrators.”
Wong chimes in: “The program gave us the opportunity to get to know many individuals from various divisions across the Lab. It was an honor to be a part of a cohort of emerging leaders here at LBNL.”
About the program Costes says it “was split into three sessions. A three-day session in May introduced us to management skills, including time-organization, listening/communication, and strategy. We were left over the summer to start defining a project -using those skills- that would advance our career while benefiting the Lab. This was a time when we gathered and exchanged our ideas among selected partners. Michelle ended up being a close partner for my project as I had decided to investigate the possibility of hosting life sciences startups within LBNL, a topic of interest for Tech Transfer. We also had a special treat over the summer as the program included a 360 review for each trainee. A 360 review consists of collecting feedback from colleagues, mentors, and people we supervise. This anonymous feedback was extremely valuable at understanding our impact on others and at identifying areas we needed to improve. We resumed our training in October for another three-day session focusing on more strategic approaches, public speaking techniques and going over our 360 review. This was also the time to practice a 15 min. pitch aimed at various division directors of the Lab that was going to take place in November. We finalized our project and gathered among our partners a few more times between session two and the last one-day session, ‘our graduation day,’ in November.”
Sylvain Costes (front, middle) and Michelle Wong (front, third from right) in Emerging Leader Program 2012 group photo
- Did the program meet your expectations?
Costes and Wong agree that “the training surpassed both of our expectations.” Costes adds: “This kind of training was an eye opener encouraging us to tap into resources previously unknown to us, helping us know how to prioritize our time and giving us a better sense of what we can accomplish using long term strategies.”
- Your final assignments, can you say more about those?
Costes: “I briefly mentioned it already: My final pitch regarded the new Richmond Bay Campus and promoting the idea of integrating both early-stage startup and established biotechs as direct partners of the Life Sciences Division in this future campus. The concept could be called a "scientific hub," where discoveries made at the Lab find a rapid way to commercialization by either establishing startups focused on this technology or by transferring this technology to local biotech partners. Another idea proposed was to create a commercial entity located in the new Bay campus that would specialize in commercializing these discoveries. There is currently no system in place to allow startups born from LBNL research to grow within LBNL. This reduces the chance for LBNL technologies to be licensed or be used commercially. The mission of the Lab is not only to study basic science but as a National Lab, we also have the responsibility to bring solutions to our primary stakeholders: our citizens. The establishment of a "scientific hub" will help achieve this goal. In addition, as funding is getting more difficult due to governmental cuts, such approach would also open the door to new ways of funding research. It is therefore a win-win situation.”
Wong: “My proposal dovetailed with Sylvain’s and focused in on the need to build a culture here at the Lab that truly supports innovation and commercialization. I think we fall short of fully accomplishing our mission of "Bringing Science Solutions to the World" Our mission is to not only generate knowledge and basic research, but to bring science solutions to the world.
Bringing science solutions to the world involves engaging with industry partners to ensure that our inventions and discoveries are actually used by the public. Transferring technology and technology commercialization are often the only mechanisms by which our research and inventions can make their way out to the world. There are definite gaps in the road to commercialization of any invention Sylvain's proposal addresses one way to bridge that gap. But overall, there is also a gap in awareness and appreciation for how technology transfer and commercialization contribute to bringing science solutions to the world.
We need to increase awareness of technology transfer and commercialization and we need to expand our Lab values to include continuing research & development of real-world solutions and the entrepreneurs and innovators who bring those solutions out to the world. Our Lab management, Area leaders and division directors can do a lot to promote and influence the culture but so can LBNL researchers and investigators by considering their individual and collective technology transfer goals, engaging with industry and finding innovative ways to ensure that they are bringing science solutions to the world.”
- What did you take with you from this program and how will you apply what you have learned?
Costes: “I am coming out of this program with new ambitions and I have been redirecting my research towards more applied goals. I have come to realize we need to step out of our narrow focused research topics to see how we fit within the lab and how we can build bigger teams to answer bigger questions together.”
Wong: “Through this program I learned a lot about my own strengths and weaknesses as a leader and what I need to improve upon to be a more effective leader. The different sections also helped deepen my understanding of strategy in an organization and how effective leadership is needed to implement any strategy in an organization like LBNL.”
- Next steps?
Costes: “I will work with Michelle at Tech Transfer, Helen Cademartori and Gary Karpen in the Life Sciences Division and Mary Maxon, Biosciences head of strategic planning and development, to make the "scientific hub" a reality. As a first step, with the help of Tech Transfer we will try to find creative solutions to allow startups to grow within LBNL. As a step two, with the help of Mary Maxon, I would like to see how we could start integrating already existing biotech in the new campus and start building this new "scientific hub.”
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