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PubMed2002

[The French project ETOILE: review of clinical data for light ion hadrontherapy].

The Lawrence Berkeley Laboratory was the pioneer in light ions hadrontherapy with almost 2500 patients treated between 1957 and 1993 with Helium and Neon. The NIRS (National Institute For Radiological Science, Chiba, Japan) was the first dedicated medical centre for cancer with more than 1200 patients exclusively treated with carbon ion from 1994. A three-year 70 to 100% local control was reported for radio-resistant cancers, supporting the use of high LET particles. Hypo-fractionation was particularly explored for lung cancers and hepatocarcinoma (4 sessions only). Dose escalation studies demonstrated a tumour dose-effect and permitted to precise dose constraints for healthy tissues especially for the rectum. More than 140 patients were treated with carbon ion exclusively or associated with photons since 1997 in the GSI laboratory Gesellschaft Für Schwerionenforschung, Darmstadt, Germany). A very high local control was also obtained for radioresistant cancer of the base of the skull. Preliminary clinical data seem to confirm the expected therapeutic gain with light ions, due to their ballistic and radio-biological properties, and justify the European projects for the construction of dedicated medical facilities for cancers. The French "Etoile" project will be integrated in the European hadrontherapy network "Enlight", with the objectives to coordinate technologic, medical and economic features.

Carbon↗
PubMed2003

Biological sample collection and processing for molecular epidemiological studies.

Molecular epidemiology uses biomarkers and advanced technology to refine the investigation of the relationship between environmental exposures and diseases in humans. It requires careful handling and storage of precious biological samples with the goals of obtaining a large amount of information from limited samples, and minimizing future research costs by use of banked samples. Many factors, such as tissue type, time of collection, containers used, preservatives and other additives, transport means and length of transit time, affect the quality of the samples and the stability of biomarkers and must be considered at the initial collection stage. An efficient study design includes provisions for further processing of the original samples, such as cryopreservation of isolated cells, purification of DNA and RNA, and preparation of specimens for cytogenetic, immunological and biochemical analyses. Given the multiple uses of the samples in molecular epidemiology studies, appropriate informed consent must be obtained from the study subjects prior to sample collection. Use of barcoding and electronic databases allow more efficient management of large sample banks. Development of standard operating procedures and quality control plans is a safeguard of the samples' quality and of the validity of the analyses results. Finally, specific state, federal and international regulations are in place regarding research with human samples, governing areas including custody, safety of handling, and transport of human samples, as well as communication of study results.Here, we focus on the factors affecting the quality and the potential future use of biological samples and some of the provisions that must be made during collection, processing, and storage of samples, based on our experience in the Superfund Basic Research Program and Children's Environmental Health Center, at the University of California, Berkeley.

Humans↗
PubMed2003

Open Source software in medical informatics--why, how and what.

'Open Source' is a 20-40 year old approach to licensing and distributing software that has recently burst into public view. Against conventional wisdom this approach has been wildly successful in the general software market--probably because the openness lets programmers the world over obtain, critique, use, and build upon the source code without licensing fees. Linux, a UNIX-like operating system, is the best known success. But computer scientists at the University of California, Berkeley began the tradition of software sharing in the mid 1970s with BSD UNIX and distributed the major internet network protocols as source code without a fee. Medical informatics has its own history of Open Source distribution: Massachusetts General's COSTAR and the Veterans Administration's VISTA software have been distributed as source code at no cost for decades. Bioinformatics, our sister field, has embraced the Open Source movement and developed rich libraries of open-source software. Open Source has now gained a tiny foothold in health care (OSCAR GEHR, OpenEMed). Medical informatics researchers and funding agencies should support and nurture this movement. In a world where open-source modules were integrated into operational health care systems, informatics researchers would have real world niches into which they could engraft and test their software inventions. This could produce a burst of innovation that would help solve the many problems of the health care system. We at the Regenstrief Institute are doing our part by moving all of our development to the open-source model.

Database Management Systems↗
PubMedDate not supplied

Visual clues to emotional states: Rodin's "Burghers of Calais".

In the well-known, recorded Gsell-Rodin conversations of 1911, Gsell summarized Rodin's theory of the expressiveness of the human image: "Generally the face alone is considered to be the mirror of the soul: the mobility of the features of the face seems to us the unique exteriorization of the spiritual life. In reality, there is not one muscle of the body that does not express variations within. Each speaks of joy or sadness, enthusiasm or despair, calm or rage. Out-stretched arms, an unrestrained torso can smile with as much sweetness as eyes or lips. But in order to be able to interpret all aspects of the flesh, one must be trained patiently in the spelling and reading of the pages of this beautiful book" (Art: Conversations With Paul Gsell. Translated by deCaso J, Sanders PB. Berkeley, CA, University of California Press, 1984, p 10). The question thus arises, how can we as students of the human condition undertake this necessary training? How might we develop the aesthetic senses to appreciate the legibility of the human face and form more fully? For assistance in this undertaking we naturally turn to the artist. For the artist "sees" the world through eyes trained to acutely appreciate color, light and shadow, surface and volume, and inner truth. In particular, the education and training of Rodin, and the development of his artistic technique and insight, offer the health care professional rich intellectual material for this study. A closer look at the conception and evolution of Rodin's masterpiece, "The Burghers of Calais," amply illustrates this vision.

Altruism↗
PubMed2006

Divide and conquer: investigating the mechanisms behind mitosis.

Soon after a sperm meets an egg, the single fertilized cell splits into two cells, then four, and then eight. Cell division is responsible for producing each of the trillions of cells present in every human body. During adulthood, division supplies replacements for cells lost to age, injury, and disease, but it can also form the basis for illnesses such as cancer. Despite the importance of mitosis in development and medicine, researchers have much to learn about the molecular mechanisms that regulate it. Cell biologist Rebecca Heald of the University of California, Berkeley, is striving to iron out these details. Heald's work concentrates on the mitotic spindle, a structure that is essential for correctly distributing copied chromosomes to daughter cells. Using techniques that blend biology and chemistry, she and her colleagues are identifying molecules and proteins that play major roles in directing this dynamic cell process.

Animals↗
PubMed2001

Biomass byproducts for the remediation of wastewaters contaminated with toxic metals.

Pollution of the environment with toxic metals is widespread and often involves large volumes of wastewater. Remediation strategies must be designed to support high throughput while keeping costs to a minimum. Biosorption is presented as an alternative to traditional physicochemical means for removing toxic metals from wastewater. We have investigated the metal binding qualities of two biomass byproducts that are commercially available in quantity and at low cost, namely "spillage", a dried yeast and plant mixture from the production of ethanol from corn, and ground corn cobs used in animal feeds. The biomass materials effectively removed toxic metals, such as Cu, Cs, Mo, Ni, Pb, and Zn, even in the presence of competing metals likely to be found in sulfide mine tailing ponds. The effectiveness of these biosorbents was demonstrated using samples from the Berkeley Pit in Montana. Investigations included column chromatography and slurry systems, and linear distribution coefficients are presented. X-ray spectroscopy was used to identify the binding sites for metals adsorbed to the spillage material. The results of our experiments demonstrate that the biosorption of metals from wastewaters using biomass byproducts is a viable and cost-effective technology that should be included in process evaluations.

Adsorption↗
PubMed2005

Assessing the influence of climate variability on atmospheric concentrations of polychlorinated biphenyls using a global-scale mass balance model (BETR-global).

We introduce a new global-scale multimedia contaminant fate model (the Berkeley-Trent Global Model; BETR-Global) that integrates global climate data from the National Centers for Environmental Prediction (NCEP). BETR-Global represents the global environment as a connected set of 288 multimedia regions on a 15 degrees grid. We evaluate the model by simulating the global fate and transport of seven PCB congeners over a 70 year period and find satisfactory agreement between model output and observations of atmospheric PCB concentrations at 11 long-term monitoring stations in the Northern Hemisphere. We demonstrate the use of the model as a tool for understanding global pollutant dynamics by examining the hypothesis that variability in global-scale climate conditions, as reflected bythe North Atlantic Oscillation (NAO), influences atmospheric PCB concentrations in the Northern Hemisphere. We estimate that the maximum variability in atmospheric PCB concentrations attributable to NAO variability is approximately a factor of 2. The influence of variability in the NAO on PCB concentrations in air is most likely to be observed in the winter and spring at monitoring sites in Northern Europe and the Arctic. Analysis of long-term monitoring data from 11 sites shows some statistically significant relationships between NAO indices and atmospheric PCB concentrations during the winter and spring. Giving consideration to competing factors that influence atmospheric PCB concentrations, longer time series of monitoring data are required to fully evaluate the modeling results and to improve our understanding of the role of climate variability on the long-term fate of persistent semivolatile pollutants.

Arctic Regions↗
PubMed2006

Energy-resolved photoionization of alkylperoxy radicals and the stability of their cations.

The photoionization of alkylperoxy radicals has been investigated using a newly developed experimental apparatus that combines the tunability of the vacuum ultraviolet radiation of the Advanced Light Source at Lawrence Berkeley National Laboratory with time-resolved mass spectrometry. Methylperoxy (CH(3)OO) and ethylperoxy (C(2)H(5)OO) radicals are produced by the reaction of pulsed, photolytically produced alkyl radicals with molecular oxygen, and the mass spectrum of the reacting mixture is monitored in time by using synchrotron-photoionization with a double-focusing mass spectrometer. The kinetics of product formation is used to confirm the origins and assignments of ionized species. The photoionization efficiency curve for CH(3)OO has been measured, and an adiabatic ionization energy of (10.33 +/- 0.05) eV was determined with the aid of Franck-Condon spectral simulations, including ionization to the lowest triplet and singlet cation states. Using the appearance energy of CH(3)(+) from CH(3)OO, an enthalpy of formation for CH(3)OO of Delta(f) (CH(3)OO) = (22.4 +/- 5) kJ mol(-1) is derived. The enthalpy of formation of CH(3)OO(+) is derived as Delta(f) = (1019 +/- 7) kJ mol(-1) and the CH(3)(+)-OO bond energy as (CH(3)(+) - O(2)) = (80 +/- 7) kJ mol(-1). The C(2)H(5)OO(+) signal is not detectable; however, the time profile of the ethyl cation signal suggests its formation from dissociative ionization of C(2)H(5)OO. Electronic structure calculations suggest that hyperconjugation reduces the stability of the ethylperoxy cation, making the C(2)H(5)OO(+) ground state only slightly bound with respect to the ground-state products, C(2)H(5)(+) and O(2). The value of the measured appearance energy of C(2)H(5)(+) is consistent with dissociative ionization of C(2)H(5)OO via the Franck-Condon favored ionization to the ã (1)A' state of C(2)H(5)OO(+).

Journal Article↗
PubMed2006

Berkelic acid, a novel spiroketal with selective anticancer activity from an acid mine waste fungal extremophile.

Berkeley Pit Lake is an abandoned open-pit copper mine filled with 30 billion gallons of acidic, metal-contaminated water. This harsh environment is proving to be a source of unusual microorganisms that produce novel bioactive metabolites. Bioassay-guided fractionation using signal transduction enzyme assays led to the isolation of the novel spiroketal, berkelic acid 1, and of the known gamma-pyrone, spiciferone A 4. Berkelic acid has shown selective, nanomolar activity against OVCAR-3, an ovarian cancer cell line in the National Cancer Institute cell line screen. The isolation and characterization of these compounds are reported here.

Antineoplastic Agents↗
PubMed2005

Light scattering of ultrafine silica particles by VUV synchrotron radiation.

Vacuum ultraviolet (VUV) light scattering from ultrafine silica particles is studied with an aerosol instrument recently established at the Advanced Light Source (ALS) in Berkeley. Silica particles, size-selected by a differential mobility analyzer, are introduced into vacuum through a set of aerodynamic lenses to form a particle beam. The scattered photons from the crossing area of the VUV synchrotron beam and particle beam are detected with a rotatable VUV photon detector. The angular distributions of scattered photons (ADSP) originating from 70, 100, 200 nm diameter silica particles are measured with 145.9 and 118.1 nm synchrotron radiation. These angular distributions show strong forward scattering. The measured ADSPs are consistent with simulation of Mie scattering. The refractive indices of silica particles, 2.6 + 1.1i and 1.6 + 0.0001i for 118.1 and 145.9 nm, respectively, are obtained by fitting the measured ADSPs; the least average percentage deviations are 18% and 6%, respectively. The scattered fluxes at widely different wavelengths (visible versus VUV) also exhibit clear size sensitivity. Under comparable experimental conditions of photon fluxes and detection efficiencies, limits of particle size detection of 70 and 250 nm are obtained, respectively, when using 118.1 and 532 nm illumination. As anticipated, VUV scattering is a more sensitive probe for ultrafine particles, which will find application in detection of these ubiquitous species beyond the confines of a laboratory.

Light↗
PubMed2003

A novel 5-HT receptor ligand and related cytotoxic compounds from an acid mine waste extremophile.

Berkeley Pit Lake in Butte, Montana, is an acid mine waste reservoir rich in toxic metals. A Pithomycessp. isolated from the Pit Lake yielded three tyrosine derivatives (1-3), one of which acts as a 5-HT((2a)) receptor ligand. This type of activity has been associated with migraine preventative and antihypertensive drugs. The isolation and characterization of compounds 1-3 and three sesquiterpenes (5-7) that have been isolated previously from higher plants are reported here.

Animals↗
PubMed2004

Novel sesquiterpenoid matrix metalloproteinase-3 inhibitors from an acid mine waste extremophile.

Berkeley Pit Lake is a 1500 ft deep abandoned open-pit copper mine filled with 30 billion gallons of acidic, metal-contaminated water. This harsh environment is proving to be a source of unusual, biologically active microorganisms. Bioassay-guided fractionation using signal transduction enzyme assays led to the isolation of three novel bisabolane sesquiterpenes and a novel coumarin. The isolation and characterization of these compounds are reported here.

Acetylation↗
PubMed2004

Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism.

[structure: see text] Two novel hybrid polyketide-terpenoid metabolites were isolated from a Penicillium sp. growing in the Berkeley Pit Lake of Butte, Montana. Their structures were deduced by spectroscopic analysis and confirmed by single-crystal X-ray analysis on berkeleydione (1). Both compounds inhibited matrix metalloproteinase-3 and caspase-1, and berkeleydione showed activity toward non-small-cell lung cancer in NCI's human cell line antitumor screen.

Acids↗
PubMed2002

Following the path of carbon in photosynthesis: a personal story.

Chronological recognition of the intermediates and mechanisms involved in photosynthetic carbon dioxide fixation is delineated. Sam Ruben and Martin Kamen's development of application of radioactive carbon for the study of carbon dioxide fixation provided impetus and techniques for following the path of carbon in photosynthesis. Discovery The identity of the primary carboxylation enzyme and its identity with the major protein of photosynthetic tissues ('Fraction 1' protein of Sam Wildman) is reviewed. Memories are dimmed by sixty years of exciting discoveries exploration in newer fields [see Benson 2002 (Annu Rev Plant Biol 53: 1-25), for research and perspectives beyond the early Berkeley days].

Journal Article↗
PubMed2003

Advances in biotreatment of acid mine drainage and biorecovery of metals: 2. Membrane bioreactor system for sulfate reduction.

Several biotreatmemt techniques for sulfate conversion by the sulfate reducing bacteria (SRB) have been proposed in the past, however few of them have been practically applied to treat sulfate containing acid mine drainage (AMD). This research deals with development of an innovative polypropylene hollow fiber membrane bioreactor system for the treatment of acid mine water from the Berkeley Pit, Butte, MT, using hydrogen consuming SRB biofilms. The advantages of using the membrane bioreactor over the conventional tall liquid phase sparged gas bioreactor systems are: large microporous membrane surface to the liquid phase; formation of hydrogen sulfide outside the membrane, preventing the mixing with the pressurized hydrogen gas inside the membrane; no requirement of gas recycle compressor; membrane surface is suitable for immobilization of active SRB, resulting in the formation of biofilms, thus preventing washout problems associated with suspended culture reactors; and lower operating costs in membrane bioreactors, eliminating gas recompression and gas recycle costs. Information is provided on sulfate reduction rate studies and on biokinetic tests with suspended SRB in anaerobic digester sludge and sediment master culture reactors and with SRB biofilms in bench-scale SRB membrane bioreactors. Biokinetic parameters have been determined using biokinetic models for the master culture and membrane bioreactor systems. Data are presented on the effect of acid mine water sulfate loading at 25, 50, 75 and 100 ml/min in scale-up SRB membrane units, under varied temperatures (25, 35 and 40 degrees C) to determine and optimize sulfate conversions for an effective AMD biotreatment. Pilot-scale studies have generated data on the effect of flow rates of acid mine water (MGD) and varied inlet sulfate concentrations in the influents on the resultant outlet sulfate concentration in the effluents and on the number of SRB membrane modules needed for the desired sulfate conversion in those systems. The pilot-scale data indicate that the SRB membrane bioreactors systems can be applied toward field-scale biotreatment of AMD and for recovery of high purity metals and an agriculturally usable water.

Acids↗
PubMed2004

An automated small-scale protein expression and purification screening provides beneficial information for protein production.

One of the first key steps in structural genomics is high-throughput expression and rapid screening to select highly soluble proteins, the preferred candidates for crystal production. Here we describe the methodology used at the Berkeley Structural Genomics Center (BSGC) for automated parallel expression and small-scale purification of fusion proteins using a 96-well format. Our robotic method includes cell lysis, soluble fraction separation and purification with affinity resins. For detection of His-tagged proteins in the soluble fractions and after affinity resin elution, a dot-blot procedure with an anti-His-antibody is used. The expression level and molecular mass of recombinant proteins are checked by SDS-PAGE. With this approach, we are able to obtain beneficial information to be used for large-scale protein expression and purification.

Automation↗
PubMed1992

Tolman and Tryon. Early research on the inheritance of the ability to learn.

Few psychologists today are aware of the seminal role played by learning theorist Edward C. Tolman in the early development of the field of behavior genetics. Tolman was the first to publish a study of selective breeding for maze-learning ability in rats. He continued to foster research in this field by supporting the work of his students, particularly Robert C. Tryon. Tryon carried out the first major long-term study of maze-bright and maze-dull rats. This article focuses on Tolman's early years at Berkeley and the events culminating in the inheritance project, as well as on the evolution of this research under Tryon's direction.

Animals↗
PubMed1982

Personality correlates of sense of direction and geographical orientation.

Personality measures were related to several dimensions of geographical orientation ability. Participants completed a questionnaire about their sense of direction and pointed to unseen locations on or near the Berkeley campus of the University of California. In addition, participants completed the Mental Rotations Test and the California Psychological Inventory (CPI). The CPI scales assessing interpersonal dimensions related both to pointing performance and to worrying about becoming lost but not to self-reports of sense of direction. In multiple regression analyses, personality scores on Capacity for Status, Sociability, and Self-Acceptance were found to account for a significant additional portion of the variance in pointing error even after various possible mediating variables (e.g., exploration, familiarity, spatial visualization) were taken into account. It is suggested that plans of action and attitudes toward the environment engage individuals differentially in building accurate real world representations.

Adult↗