bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity: A continuing source of novel drug leads
Authors: Cragg Gordon M. , Newman David J.
Published: February 2005

Nature has been a source of medicinal agents for thousands of years and continues to be an abundant source of novel chemotypes and pharmacophores. With only 5 to 15 % of the approximately 250 000 species of higher plants systematically investigated, and the potential of the marine environment barely tapped, these areas will remain a rich source of novel bioactive compounds. Less than 1 % of bacterial and 5 % of fungal species are currently known, and the potential of novel microbial sources, particularly those found in extreme environments, seems unbounded. To these natural sources can be added the potential to investigate the rational design of novel structure types within certain classes of microbial metabolites through genetic engineering. It is apparent that Nature can provide the novel chemical scaffolds for elaboration by combinatorial approaches (chemical and biochemical), thus leading to agents that have been optimized on the basis of their pharmacological activities. The proven natural product drug discovery track record, coupled with the continuing threat to biodiversity through the destruction of terrestrial and marine ecosystems and the current low number of new chemical entities in pharmaceutical industry pipelines, provides a compelling argument in favor of expanded multidisciplinary and international collaboration in the exploration of Nature as a source of novel leads for the development of drugs and other valuable bioactive agents.
Investigations toward new lead compounds from medicinally important plants
Authors: Prasad Ashok K. , Kumar Vineet , Arya Pragya , Kumar Sarvesh , Dabur Rajesh , Singh Naresh , Chhillar Anil K. , Sharma Gainda L. , Ghosh Balaram , Wengel Jesper , Olsen Carl E. , Parmar Virinder S.
Published: February 2005

Extensive phytochemical investigations on 30 Piper species growing in India and other medicinal plants have revealed the presence of a large number of novel compounds belonging to different classes. The antiviral activity of several lignans and neolignans belonging to different structural types has been evaluated against six different viral strains. Further, the effects of ethanol, chloroform, and hexane extracts of Piper longum and Piper galiatum on TNF-α induced expression of intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells have been studied, a novel aromatic ester was isolated from the most active extract of P. longum. A potential antifungal compound having implications in treating aspergillosis was isolated from an important Indian medicinal plant, Datura metel.
New anti-invasive compounds: Results from the Indo-Belgian screening program
Authors: Vanhoecke Barbara W. , Depypere Herman T. , De Beyter Anicée , Sharma Sunil K. , Parmar Virinder S. , De Keukeleire Denis , Bracke Marc E.
Published: February 2005

The development of anti-invasive and anti-metastatic drugs is a major challenge in current cancer research. A model to study invasion in vitro consisted of organotypic confronting cultures of human MCF-7/6 mammary cancer cells with embryonic chicken heart fragments. Untreated cultures show occupation and destruction of the normal heart fragments within eight days. Inhibition of invasion was observed after addition of the following alkaloids and (poly)phenolics to the culture medium: (+)-catechin, tangeretin, xanthohumol, 3,7-dimethoxyflavone, prenylated chalcones, a pyrazole derivative, an isoxazolylcoumarin, and a prenylated desoxybenzoin. The action targets have been found both in the cancer cells and the surrounding host tissue. We hope that the further characterization of these targets will eventually lead to the development of clinically applicable anti-invasive drugs.
Noniterative approach to the total asymmetric synthesis of 15-carbon polyketides and analogs with high stereodiversity
Authors: Vogel Pierre , Gerber-Lemaire Sandrine , Carmona Ana T. , Meilert Kai Torsten , Schwenter Marc-Etienne
Published: February 2005

Starting from inexpensive furan and furfuryl alcohol, a noniterative approach to the synthesis of pentadeca-1,3,5,7,9,11,13,15-octols and their derivatives has been developed. The method relies upon the double [4+3]-cycloaddition of 1,1,3-trichloro-2-oxylallyl cation with 2,2'-methylenedifuran and conversion of the adducts into meso and (±)-threo-1,1'-methylenebis (cis- and trans-4,6-dihydroxycyclohept-1-ene) derivatives. The latter undergo oxidative cleavage of their alkene moieties, generating 5-hydroxy-7-oxoaldehydes that are reduced diastereoselectively into either syn or anti-5,7-diols. Asymmetry is realized using either chiral desymmetrization with Sharpless asymmetric dihydroxylation or by kinetic resolution of polyols using lipase-catalyzed acetylations. All of the possible stereomeric pentadeca-1,3,5,7,9,11,13,15-octols and derivatives can be obtained with high stereoselectivity applying simple operations, thus demonstrating the high stereodiversity of this new, noniterative approach to the asymmetric synthesis of long-chain polyketides.
Selective transacylation reactions on 4-aryl-3,4-dihydropyrimidin-2-ones and nucleosides mediated by novel lipases
Authors: Poonam  , Prasad Ashok K. , Mukherjee Chandrani , Shakya Gaurav , Meghwanshi Gautam K. , Wengel Jesper , Saxena Rajendra K. , Parmar Virinder S.
Published: February 2005

Different (±)-4-(3/4-acetoxyaryl)-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2-ones have been synthesized and subjected to enantioselective deacetylation reactions mediated by different lipases in organic media. Novozyme 435 in tetrahydrofuran:diisopropyl ether was found to be the catalyst of choice for efficient enantioselective deacetylation of dihydropyrimidinones under study. Further, we discovered that lipase isolated from Pseudomonas aeruginosa can be used for selective acylation of secondary hydroxyl groups in nucleosides. This observation can be very useful for selective manipulation of different hydroxyl groups in nucleosides.
Electrostatic cross-modulation of the pseudoaromatic character in single-stranded RNA by nearest-neighbor interactions
Authors: Acharya Parag , Chattopadhyaya Jyoti
Published: February 2005

The generation of a single anionic or cationic center at an alkaline or acidic pH in a given molecule presents a unique opportunity to examine the electrostatic make-up of these molecules both at the neutral or ionic state. The generation of a single cationic center in the phenyl-nicotinamide system provided new straightforward evidence showing that the charge density of the electron-deficient pyridinium was actually enhanced by the donation of the charge from the electron-rich phenyl group (i.e., the pyridinyl became more basic by ca. 0.5 pK
a unit compared to an analogous system where phenyl was absent) owing to the electrostatic interactions between these two moieties. On the other hand, the generation of the 5'-guanylate ion in the hexameric single-strand (ss) RNA [5'-GAAAAC-3'], in comparison with the constituent trimeric, tetrameric, and pentameric-ssRNAs, has unequivocally shown how far the electrostatic cross-talk (as an interplay of Coulombic attractive or repulsive forces) in this electronically coupled system propagates through the intervening pAp nucleotide steps until the terminal pC-3' residue in comparison with the neutral counterpart. The footprint of the propagation of this electrostatic cross-talk among the neighboring nucleobases is evident by measurement of pK
as from the marker protons of ionization point (i.e., of G) as well as from the neighboring marker protons (i.e., of A or C) in the vicinity, as well as from the change of the chemical environment (i.e., chemical shifts) around their aromatic marker protons (δH2, δH8, δH5, and δH6) owing to a change of the stacking-destacking equilibrium as a function of pH.
A Correlation Between Dynamic Cone Penetrometer Values and Pavement Layer Moduli
Authors: Chen D-H , Lin D-F , Liau P-H , Bilyeu J
Published: February 2005

The Dynamic Cone Penetrometer (DCP) is one of the least expensive testing devices able to characterize base and subgrade properties. To fully use the DCP in pavement evaluation, an empirical relationship between DCP penetration rate and layer modulus is required. However, the literature on this correlation is limited. This study incorporates a total of 198 DCP and Falling Weight Deflectometer (FWD) tests done over 8 years on various types of highways (Interstate Highway, US, and Farm-to-Market). The computer program MODULUS was employed to backcalculate the layer moduli from the FWD results to build a correlation with DCP results. A comparison was made with the widely-used model by Powell et al. (1984). It is found that the difference between the two models decreases as the Penetration Rate (PR) increases. For a PR of less than 10 mm/blow, the difference between these two models was over 10%. The difference is only about 1.7 % when the PR is 80 mm/blow. Without knowing the true moduli, it is impossible to tell which equation is better. The correlation developed here provides another option and allows researchers to recognize the range of variability.
Flexible Crumb Tire Rubber-Filled Cement Mortars as a Protective System for Buried Infrastructure
Authors: Nehdi M , Khan A , Sumner J
Published: February 2005

Due to population growth and urban congestion, the space available for the development of public infrastructure is sharply decreasing. Engineers are therefore resorting to the efficient use of underground space, which involves the construction of tunnels and other underground structures. Many such projects will be located in rock/soil with time-dependent behavior or under high overburden pressure. Thus, under such stress conditions, there may be a need for a deformable supporting system that can serve as a buffer layer to protect tunnel linings from time-dependent deformations of the excavated rock/soil. This paper investigates the use of cement mortars containing crumb recycled tire rubber to develop a flexible interface material for such applications. The effects of the w/c ratio, rubber content, and particle size on the mechanical properties of rubber filled mortars were studied using uniaxial and triaxial compression tests. A statistical factorial experimental plan was designed to obtain response surfaces for the parameters under study. A model tunnel was made, instrumented, and tested in a specially designed pressure cell under hydrostatic pressure to investigate the effect of using flexible rubber-filled mortar layers around tunnel linings on the development of stresses. The findings of this research suggest that cement mortars containing crumb tire rubber have superior ductility and may be used to accommodate deformations around tunnel linings, pipelines, and other buried infrastructure.
Evaluation of the Effect of Crack Tip Constraint on Fatigue Crack Growth Rate in Inconel 718
Authors: Joyce JA
Published: February 2005

The objective of this work has been to characterize the fatigue crack growth rate of Inconel 718 in the elastic and elastic-plastic regimes. The major new contribution here is to develop fatigue crack growth rate data on this alloy using shallow crack specimens subjected to cyclic loadings that involve material plasticity exceeding what is allowed by the standard Linear Elastic Fracture Mechanics (LEFM) procedures of ASTM E 647.

Compact (C(T)) and three point bend (SE(B)) specimen geometries were used in this investigation. The SE(B) specimens were used to obtain shallow crack data using crack to depth ratios (a/W) as small as 0.08 in standard bend specimens with W = 50.8 mm. Compliance methods were used to estimate the crack length during the cyclic testing. The C(T) specimens were used to investigate the effect of fully reversed loading, i.e., R = −1.0. These specimens were tested only in deep crack configurations with a/W > 0.3. Both C(T) and SE(B) specimens were used to obtain high cycle fatigue crack growth data as well as some component of the low cycle fatigue crack growth rate data. The cyclic elastic stress intensity range was used to characterize the crack growth driving “force” in the high cycle regime as defined in ASTM E 647. A cyclic J integral range, as originally utilized by Dowling and Begley [1], was used in the elastic-plastic regime.

High cycle and low cycle fatigue crack growth data were successfully obtained from tests on shallow crack SE(B) specimens. High cycle fatigue crack growth was not affected by specimen geometry or by crack length ratio, even for a/W ratios as low as 0.08. The low cycle fatigue crack growth rate was similar, but not identical, to what one would get by extrapolating the high cycle fatigue crack growth rate, as proposed by Dowling and Begley [1]. Under conditions of increasing J range, the crack growth rate under elastic-plastic conditions was accelerated, while under decreasing J range conditions the crack growth rate was decelerated in comparison to the extrapolated high cycle fatigue crack growth rate measurements. The R ratio did not affect the crack growth rate for the two cases tested here, namely R = 0.1 and R = −1.0. More rapidly increasing J range conditions resulted in greater crack growth rate acceleration. In the elastic-plastic fatigue regime, shallow crack specimens demonstrated slower crack growth rates than deep crack specimens.
Evaluation of the Effect of Biaxial Loading on the To Reference Temperature Using a Cruciform Specimen Geometry
Authors: Joyce JA , Link RE , Gaies J
Published: February 2005

A series of 12 cruciform geometry fracture toughness specimens has recently been tested using A533B base plate obtained from the decommissioned Shoreham plant pressure vessel. Specimens were tested at −100°C, placing them in the lower ductile to brittle transition of this ferritic structural steel. The overall objective of this work is to compare the results of these biaxial cruciform tests to the results of standard and shallow crack fracture toughness tests to assess the effect of biaxial loading on the measured master curve and the To reference temperature as defined by ASTM E 1921. Previous work done at Oak Ridge National Laboratory (ORNL) appeared to demonstrate an increase in the To reference temperature due to the presence of the biaxial stress field established in the cruciform test geometry. Because of the cost of the ORNL tests, only a few specimens could be run, and full statistical support of the “biaxial effect” could not be demonstrated. A second goal is to demonstrate that smaller size specimens, and hence lower cost tests, can be used to evaluate the magnitude of the biaxial effect in nuclear reactor pressure vessel materials. This report presents a brief overview of the test procedure, presents the test results, and compares the results to the database available on standard and shallow crack fracture toughness results available for the Shoreham plate material.
Microstructural Influences on the Development and Growth of Small Fatigue Cracks in the Near Threshold Regime
Authors: Schneider JA , Kenik E
Published: February 2005

Orientation imaging microscopy (OIM) is being used to investigate the microstructural influence on small crack growth at the crack tip. Although grain and grain boundary orientations have been reported to influence small crack growth, the effect has been difficult to quantify. OIM uses electron backscattered diffraction (EBSD) patterns in a scanning electron microscope (SEM) to form a spatially resolved map of crystal orientation, providing information on intra- and inter-grain orientation relationships.

Mini-extended compact tension (ECT) specimens were machined from an 1100 aluminum cold rolled sheet with a 45° angle, machined notch tip. The specimens were sized to fit into a Philips XL30/FEG SEM equipped with an EDAX/TSL EBSD/OIM system. Initial images were recorded prior to cycling of the mini-ECT specimen. Fatigue testing was conducted at constant amplitude loading in the near-threshold regime where small cracks are considered to be on the order of the corresponding grain size. The constant amplitude load testing was periodically interrupted to obtain EBSD images. The ability to map an area 800 × 1300 μm in front of the machined notch tip was demonstrated. This study determined that the plastic deformation, which occurs in a zone in front of the crack tip, did not degrade the EBSD image quality. Use of this technique provides the capability to characterize local crystal orientation during deformation processes such as fatigue crack growth.
Development of a Cooling Capability Test Method for Liquid-Cooled Textile System
Authors: Cao H , Branson DH , Nam J , Peksoz S , Farr CA
Published: February 2005

A test method to evaluate the cooling capability of a 30.5 cm × 30.5 cm or smaller liquid-cooled textile system used in liquid cooling garment development has been developed. The equipment used in this method is the sweating guarded hotplate, which is used primarily to measure thermal and evaporative resistance of clothing materials in accordance with ASTM F 1868. Using the sweating guarded hotplate, a constant heat flux from the hotplate to cold liquid can be obtained. Using the conductive heat transfer equation for data analysis, this test method provides consistent and reliable evaluation of the cooling capability over a wide range of cold liquid temperatures. This method can differentiate the cooling capabilities of alternative textile systems that might vary by fabric composition, tubing material, total tubing length, and other variables of interest. Based on the zero-intercept linear regression, the thermal resistance of the textile system can be estimated, and the cold temperature requirement for a target cooling capability can be predicted.
Effects of Thermal Properties on Skin Burn Predictions in Longer Duration Protective Clothing Tests
Authors: Torvi DA
Published: February 2005

Different methods of predicting skin burns during bench top and full-scale tests of protective clothing are compared. A skin heat transfer and burn prediction model is also used to determine the effects of thermal properties of skin and blood flow rates on first, second, and third degree skin burn predictions for exposures used in longer duration tests of single and multiple-layer protective fabrics. Epidermis thickness can have a large effect on second degree burn predictions, while the dermis thickness can have a very large effect on third degree burn predictions. Subcutaneous thickness does not significantly affect burn predictions, while blood flow can affect third degree burn predictions. Results also indicate that care must be taken when analyzing burn predictions, as relatively small differences in skin temperatures can produce deceptively large differences in burn predictions when Henriques' burn integral is used.
Evaluation of Three Chemical Protective Clothing Materials for Selected Performance Properties
Authors: Stull JO , McManus RE
Published: February 2005

A study was conducted to evaluate selected properties of three different chemical protective clothing materials that are being considered for use by Dupont's DeLisle Site in Pass Christian, Mississippi for titanium chloride and related chemical service. Two of the materials represented new product offerings based on unique PTFE/fabric (HSF) laminates, while the third was a PVC/Nomex material currently used in chemical protective clothing at the Dupont DeLisle Site. The two PTFE/fabric laminates were further distinguished by the film thickness and type of surface finish. A number of tests were performed to measure permeation resistance against specific chemicals of interest: physical property testing to assess material strength and specialized tests to determine how the materials hold up to different environmental challenges (high temperature, cold temperature, and flame exposure). The study demonstrated how a series of test methods established by Committee F23 can be used to evaluate the material choices effectively for a specific set of chemical and physical exposure conditions.
The Correlation Between Microstructures and in-BWR Corrosion Behavior of Highly Irradiated Zr-based Alloys
Authors: Takagawa Y , Ishimoto S , Etoh Y , Kubo T , Ogata K , Kubota O
Published: February 2005

The microstructures of four kinds of Zircaloy-2-type materials with neutron exposure up to about 15 × 1025 n/m2 (E>1MeV) were examined to investigate the microstructural evolution and to correlate it with the in-reactor corrosion behavior at very high fluences. The materials examined in this study included two advanced Zr-based alloys with good corrosion resistance, namely High Fe Zry and High FeNi Zry, and two other kinds of Zry-2 materials with slightly different elemental compositions and fabrication processes producing differing second phase particle sizes. All alloys showed good corrosion behavior and low hydrogen pickup when irradiated up to four cycles in dummy neutron source holders located outside of channel boxes. After six irradiation cycles, all four of the alloys had an increase in the rate of uniform corrosion and hydrogen pickup. The results of the microstructure examinations after six-cycle irradiation indicated two interesting points: (1) increased insight into the dissolution process for Zr-Fe-Cr particles, and (2) a correlation between the number density of Zr-Fe-Cr particles surviving through irradiation and the corrosion behavior at high fluences. From these results, it is suggested that increasing the initial particle size and/or controlling the alloy chemistry would be beneficial to improve the uniform corrosion performance and to lower hydrogen pickup, especially at very high fluences.
Estimating Unsaturated Hydraulic Conductivity of Fine-Grained Soils Using Electrical Resistivity Measurements
Authors: Sreedeep S , Singh DN
Published: February 2005

This paper presents a methodology that can be used for easily and rapidly estimating unsaturated hydraulic conductivity of fine-grained soils. The basis of this methodology is that the flow of fluid through a porous media is analogous to the flow of a current through a medium subjected to the electrical potential. Hence, soil hydraulic conductivity can be determined by knowing the soil's electrical resistivity corresponding to different states of compaction. However, as hydraulic conductivity of the soil depends on the suction, which in turn depends on the water content and composition, electrical resistivity can be related to hydraulic conductivity. To demonstrate the usefulness of this methodology, data of two very well characterized fine-grained soils have been used.
A New Test Method for Porosity Measurements of Portland Cement Pervious Concrete
Authors: Montes F , Valavala S , Haselbach LM
Published: February 2005

Pervious concrete is emerging as an alternative material for paving to help curtail nonpoint source pollution problems. The porosity of pervious concrete is an important variable needed for pavement system design and for material comparisons. This paper researches a method for measuring the porosity of pervious concrete from field-obtained cores by applying the Archimedes principle and using standard materials laboratory equipment. The error between different operators at different testing facilities was found to be around 2.2 % porosity.
Drugs, Violence, and Moral Panic in Urban America
Authors: Singer Merrill
Published: February 2005

Beggars and Thieves: Lives of Urban Street Criminals. Mark S. Pleisher. Madison: University of Wisconsin Press, 1995. 332 pp.

Life in the Gang: Family, Friends, and Violence. Scott H. Decker and Barrik Van Winkle. Cambridge: Cambridge University Press, 1996. 303 pp.
Braving a New World: Cambodian (Khmer) Refugees in an American City
Authors: Poethig Kathryn A.
Published: February 2005

Braving. New World: Cambodian (Khmer) Refugees in an American City. MaryCarol Hopkins. Westport, CT: Bergin and Garvey, 1996. 169 pp.
Maid to Order in Hong Kong
Authors: Smart Alan
Published: February 2005

Maid to Order in Hong Kong. Nicole Constable. Ithaca, NY: Cornell University Press, 1997. 230 pp.
Natural Histories of Discourse
Authors: Brody Jill
Published: February 2005

Natural Histories of Discourse. Michael Silverstein and Greg Urban. eds. Chicago: University of Chicago Press, 1996. 352 pp.
Environmentalism and Cultural Theory: Exploring the Role of Anthropology in Environmental Discourse
Authors: Haenn Nora
Published: February 2005

Environmentalism and Cultural Theory: Eocploring the Role of Anthropology in Environmental Discourse. Kay Milton. London: Routledge Press, 1996. 266 pp.
Cracks in the Iron Closet: Travels in Gay and Lesbian Russia
Authors: Grant Bruce
Published: February 2005

Cracks in the Iron Closet: Travels in Gay and Lesbian Russia. David Tuller. Boston, MA: Faber and Faber, 1996. 313 pp.
Decolonizing Knowledge: From Development to Dialogue
Authors: Guyer Jane I.
Published: February 2005

Decolonizing Knowledge: From Development to Dialogue. Frederique Apffel‐Marglin and Stephen A. Marglin. eds. Oxford, England: Clarendon Press, 1996. 398 pp.
The Bear and His Sons: Masculinity in Spanish and Mexican Folktales
Authors: Miranda M. L.
Published: February 2005

The Bear and His Sons: Masculinity in Spanish and Mexican Folktales. James M. Taggart. Austin: University of Texas Press, 1997. 344 pp.
Anyan's Story: A New Guinea Woman in Two Worlds
Authors: Johnson Patricia Lyons
Published: February 2005

Anyan's Story:. New Guinea Woman in Two Worlds. Virginia Drew Watson. Seattle: University of Washington Press, 1997. 208 pp.
Fate and Fortune in Rural China: Social Organization and Population Behavior in Liaoning, 1774‐1873
Authors: Shu‐Min Huang
Published: February 2005

Fate and Fortune in Rural China: Social Organization and Population Beliavior in Liaoning, 1774‐1873. James Lee and Cameron Campbell. Cambridge: Cambridge University Press, 1997. 280 pp.
Synthesis and molecular structure analysis of nano‐sized methacryl‐grafted polysiloxane resin for fabrication of nano hybrid materials
Authors: Eo Young‐Joo , Lee Tae Ho , Kim Se Yun , Kang Jeung Ku , Han Young Soo , Bae Byeong‐Soo
Published: February 2005

The molecular structures of methacryl‐grafted polysiloxane resins from 3‐(trimethoxysilyl)propyl methacrylate (MPTS) and diphenylsilanediol (DPSD) were determined by theoretical computation and experimental measurement. The molecular structures obtained from theoretical computation coincided well with those from experimental measurement, and we found that the structural changes in the resins could be controlled by precursor compositions. While molecular weights and polysiloxane chain lengths of the resins increase with DPSD contents, their molecular sizes do not vary significantly. In the present study, molecular sizes and shapes of the resins with various compositions are hypothesized theoretically and proven experimentally. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 827–836, 2005
Reference points and reference directions for size-based indicators of community structure
Authors: Jennings Simon , Dulvy Nicholas K.
Published: February 2005

Size-based community and ecosystem metrics, such as mean body mass and the slopes of size spectra, have been proposed as indicators to support the Ecosystem Approach to Fisheries Management (EAFM). These metrics show relatively consistent responses to size-selective exploitation, and “unexploited” indicator reference points may be predicted with models of size-structured foodwebs. Whereas unexploited reference points provide a baseline for assessing the relative magnitude of fishing impacts, target or limit reference points are needed to guide management. Values for target or limit reference points are difficult to justify on scientific grounds. However, given that fishing impacts in most ecosystems need to be reduced to meet the objectives of the EAFM, we argue that reference directions provide alternative medium-term management targets. We show that the power of surveys to detect trends consistent with reference directions depends on the range of body size classes included in the analysis. Selection of different size ranges will weight metrics to respond to the release of small fish from predation, the depletion of larger individuals as a consequence of exploitation, or both. Such weightings may not be consistent over time, because the differential vulnerability of larger species, within-population changes, predator–prey relationships, and the effects of competition depend on contemporary rates of fishing mortality and the history of exploitation. The power of the surveys investigated is poor on time scales of less than 5–10 years. Therefore, size-based indicators provide better support for medium-term, rather than year-on-year, management decision making.
Development and Commercialization of the MiniBlock Synthesizer Family: A Historical Case Study
Authors: Weller Harold N. , Rubin A. Erik , Moshiri Ben , Ruediger Walter , Li Wen-Jeng , Allen John , Nolfo Joseph , Bertok Alexander , Rosso Victor W.
Published: February 2005

An internal development project at Bristol-Myers Squibb (BMS) led to invention of a family of organic chemistry synthesis blocks for both parallel synthesis in drug discovery and parallel reaction optimization in pharmaceutical development. The internal demand for these synthesis blocks became so great that the original development team was challenged by the burden of ongoing manufacture, support, and supply chain management. As a result, BMS entered into a unique industry partnership with Mettler-Toledo AutoChem (MT), Newark, DE, formerly Bohdan Automation, to commercialize the reactor blocks and extend the product family, now known as the MiniBlock line. This manuscript describes the initial development drivers, the overall technical design, and the ultimate successful commercialization of the MiniBlock synthesis family.
Combined Spectrophotometric— Electrochemical Impedance Imaging System for Biofilm Research
Authors: Patel Chirag , Dunn Stanley , Takhistov Paul
Published: February 2005

We propose an automatic scanning microscope that is capable of analyzing the properties of the biofilm-associated cells by using optical and impedance spectroscopy. The operating principle of the instrument is based on measuring the electrical impedance of cell culture grown on a conductive substratum that is used as one of the electrodes. At low frequencies, the impedance analysis is capable of characterizing a biofilm at the macroscale, and at high frequencies it is capable of analyzing the peculiarities of a cell layer at the level of single microorganisms. The combination of these two techniques is sufficient to give a quantitative and structural composition of a biofilm at both levels. The developed instrument can be useful in the broad range of biofilmrelated research studies, providing the data for detailed, real-time, computer-controlled, noninvasive analysis of cell-to-cell and cell-to-surface interactions.
A Stand-Alone Monitoring System for Reliable Unattended Operation of a Commercial Preparative LC/MS Purification System
Authors: Paulson James L.
Published: February 2005

Commercially available preparative liquid chromatograph/mass spectrometer (LC/MS) systems are commonly used in drug discovery research to purify large numbers of compounds made by parallel synthesis techniques. The systems in our lab are comprised of individual instruments that communicate continuously with control software in order to collect specific compounds based on mass triggering. Over time, communication errors may cause improper system operation, and excessive pressure during injection may cause system damage or a leak. The risks of sample loss and safety hazards precluded unattended overnight operation of the purification systems.

A stand-alone monitoring system was developed to ensure proper purification system operation. Custom sensors and software are used to identify failures and remotely control power to the purification system. In response to a failure, the monitoring system will either shut down the purification system or, if possible, selectively reboot an instrument to allow continued operation. With the creation of the monitoring system, the purification system can be run unattended with
Qualification of Robotic Laboratory Equipment
Authors: Caillet Christine , Pegon Yves , Neel Tanguy Le , Morin Delphine , Baudiment Cecile , Truchaud Alain
Published: February 2005

Robotic laboratory equipment malfunctions may affect the performance of integrated laboratory instruments. Thus, the qualification of robotics is necessary to ensure adequate performance of complete integrated systems. In this JALA Tutorial, we adapt the methods used in production processes to laboratory robotics and propose guidelines for performing the various steps required for qualification (i.e., installation, operational, and performance qualification), while emphasizing specific aspects of laboratory robotics. We think that the application of such guidelines will help in standardizing the acceptance of robotic equipment, facilitate their operation and performance evaluation, and improve traceability with quality assurance documentation.
Pulse Techniques in Microwave Spectroscopy
Authors: Dicke R. H. , Romer R. H.
Published: February 2005

Methods are described for exciting gases to states from which they emit coherent spontaneous radiation in the microwave frequency region. The excitation is produced by the application of short pulses of microwave power. The power subsequently radiated by the gas is calculated for several cases, and experimental methods used to detect the radiation are described. The problem of sensitivity is discussed and compared to the sensitivity obtainable in a continuous absorption experiment. The operation of a high resolution microwave spectrometer, which produces lines substantially narrower than the usual Doppler width, is described. The method used to stabilize the klystron used in these experiments, which is a modification of the Pound i.f. method, is given.
New Circuit for the Measurement of Very Short Delays
Authors: Lepri F. , Mezzetti L. , Stoppini G.
Published: February 2005

A circuit for the measurement of time intervals down to 10−10 sec is described.

The circuit works on the principle of transforming the delay τ to be measured into a flat-topped signal whose amplitude is proportional to τ, and whose length is independent of τ and controllable at will within wide limits (up to about 100 μsec). The precision and stability of the circuit are discussed.
Automatic Electrometer Scaler
Authors: Luger Paul
Published: February 2005

An automatic arrangement is described for operating an electrometer. Double parallel optical slits replace the ordinary eyepiece-reticule scale, or the scale of a mirror-scale arrangement. Photoelectric signals are produced when the real image of the electrometer needle or the light beam crosses the optical slits. These signals operate the electrometer itself and a time-interval printer. Both current and sensitivity measurements are left on a printed record. Continuous or intermittent-continuous operation make the apparatus completely automatic.
Energy Stability of the 22-Mev Betatron at the University of Illinois
Authors: Spicer B. M. , Penfold A. S.
Published: February 2005

Data are presented on the short and long term energy stability of the 22-Mev betatron at the University of Illinois. The data were taken in the course of a detailed study of the O16(γ,n)O15 yield curve. It is concluded that the machine was often stable to better than ±3 kev for periods of several hours, and that the maximum energy fluctuation which was observed over an eighteen month period was 40 kev at 17 Mev.
Jig for Aligning Specimens on Pole Figure Goniometers
Authors: Singer Joseph
Published: February 2005

An aligning jig for use with Schulz-type metal orientation goniometers is described. A procedure is given for calibrating the locating surface of the jig and using it to permit interchangeability between the Schulz head and the standard spectrometer specimen mount. The jig can be moved out of the way after aligning a sample without disturbing the sample.
Apparatus for the Simultaneous Study of Streaming Double Refraction and Viscosity
Authors: Jerrard H. G.
Published: February 2005

Many liquids, which are normally isotropic, become double refracting when subjected to shearing stresses produced by a velocity gradient established within them. A detailed description is given of a concentric cylinder apparatus in which velocity gradients of the order of 4000π sec−1 have so far been produced. Higher values are possible. The annular gap between the cylinders varies from about 0.3 mm to 0.8 mm and has an average radius of about 25 mm. The outer cylinder can rotate at speeds up to 2500 rpm or more: these are accurately determined by an electronic tachometer. The inner cylinder can be rigidly clamped or allowed to move subject to restriction by a beryllium copper torsion wire. In the latter case the viscous drag due to the moving liquid can be measured, as in a Couette viscometer, and hence values for the viscosity coefficient found simultaneously with measurements of double refraction. A cooling system, controlled by thermostats, is provided to maintain the liquid at a constant temperature; this is recorded by a thermocouple embedded in the inner cylinder. The optical system is described with brief details of the methods for the determination of the extinction directions in the liquid and the magnitude of the double refraction. The latter is measured by a sensitive quarter-wave plate compensator with a half-shadow device. The accuracy of the instrument is fully discussed.
Time of Flight Spectrometer for Fast Neutrons
Authors: Neilson G. C. , James D. B.
Published: February 2005

A fast neutron spectrometer, using the time of flight method, which may also be used to study reactions involving the simultaneous emission of neutrons and gamma rays, is described. One stilbene scintillation counter is placed close to the source, the other a suitable distance away. The two are connected to a new type of coincidence time sorter which converts delay time between associated events into a pulse amplitude distribution which may be analyzed by a kicksorter, so enabling the whole range of delay times or energies to be displayed and recorded at one time. The delay time may result from neutron flight time following scattering in the first counter, from the time of flight of a neutron from the target associated with a gamma ray entering the first counter, or from a charged particle associated with a gamma ray. Using D(d,n)He3 neutrons and a flight path of 50 cm, it has been possible to measure the energy with an accuracy of 10%. Angular correlations arising from (−,nγ) reactions may be studied with energy discrimination of the neutrons; typical results are presented for the case Be9(d,nγ)B10.
Helium-3 Filled Proportional Counter for Neutron Spectroscopy
Authors: Batchelor R. , Aves R. , Skyrme T. H. R.
Published: February 2005

The neutron transformation of helium-3 has been applied to neutron spectroscopy in the medium energy range in order to overcome the disadvantages of previous methods which have usually been based on neutron scattering. By observing the pulse-height distribution when a proportional counter filled with helium-3, krypton, and carbon dioxide is irradiated with neutrons, the spectrum can be obtained. Details of the counter construction and vacuum equipment for filling the counter are described. In the range of energy from thermal to 1 Mev the spread (relative standard deviation of a peak) is about 3% and the wall effect agrees with theoretical predictions. The pulse height varies linearly with energy and some evidence suggesting that the mean energy required to produce an ion pair in krypton for helium-3 nuclei is about 6% greater than that for protons is presented. Since the neutron reaction cross section of helium-3, as a function of energy, is required to evaluate neutron spectra from observed distributions, it has been remeasured in the range 120 kev to 1 Mev with greater accuracy than previous measurements made by J. H. Coon [Phys. Rev. 80, 448 (1950)].
Single Quartz Crystal Point Focusing X-Ray Monochromator
Authors: Berreman Dwight W.
Published: February 2005

A point focusing x-ray monochromator which uses Bragg reflection from a single lamina of quartz bent in such a way that its atomic planes are given two principal radii of curvature has been constructed for use in low-angle diffraction studies. It was found that the crystal reflects 2.78% of the incident Cu Kα1 radiation into a converging beam one meter long, with a resolution of better than half a millimeter except for a very faint halo. The instrument has been used to obtain diffraction patterns from normal and sickle-cell human hemoglobin and also from southern bean mosaic virus. The speed of the present instrument is roughly two hundred times that of an equivalent pinhole collimating system. A similar but still faster instrument is being constructed.
New Method of Flow Calorimetry
Authors: Hoxton L. G. , Weiss R. A.
Published: February 2005

A relative method has been developed whereby two conventional flow calorimeters, connected in a series combination, serve to determine the ratio of the Cp of a fluid in one state to that in another, this ratio being measured as a function of resistance ratios. Measurements of flow rate and of power input are not required, while simplifications in other respects are also to be found.

Although its determinations are not ``absolute,'' the gains in speed and simplicity, without loss of accuracy, are considered sufficient to warrant its use in exploratory work or in researches requiring the extension of known values over new temperatures and pressures, as is often the case with tables. The method is offered, therefore, as a worthwhile research tool. A brief description is given.
Apparatus for the Measurement of Extremely Small Weight, Volume, and Density Changes
Authors: Haller Wolfgang K. , Calcamuggio Glenn L.
Published: February 2005

A pressure-controlled hydraulic balance for the measurement of extremely small weight, volume, and density changes has been developed. The movement of a calibrated pressure-sensitive glass float, carrying the sample, is observed while the pressure on the float is adjusted until equilibrium of the forces is reached and movement ceases. Changes in weight or volume of the sample or in the density of the liquid result in forces compensated for by a corresponding pressure adjustment, from which the magnitude of the changes can be calculated. Applied to the study of a rate process, it has been possible to measure continuously the weight loss of silicate glasses due to corrosion in distilled water with an accuracy of 0.0003% of 3-gram total sample weight.
Cantilever Pneumograph
Authors: Whalen William J. , DeHaan Robert L.
Published: February 2005

A simple device utilizing a resistance wire strain gauge for the recording of respiratory movements is described.

Changes in chest and diaphragmatic tone may be recorded in spite of the variations in ambient temperature which markedly affect conventional bellows-type pneumographs. Greater sensitivity is obtained and leaks in the system are not a problem. The frequency response is well above the respiratory rate of panting animals. Finally, the cost is minimal.
Cathode-Ray Oscilloscope Intensity Modulator
Authors: Kemp Robert F.
Published: February 2005

An electronic system is described for modulating the beam intensity of a cathode-ray oscilloscope in such a manner as to reduce variations in trace brightness due to differences in writing speed. A voltage derived by a push-pull differentiating amplifier from the vertical deflection signal is added to the instrument's intensity-control voltage. By use of this system, improved photographs of wave forms can be obtained.
Metal Gaskets for Demountable Vacuum Systems
Authors: Van Heerden P. J.
Published: February 2005

Two different constructions were investigated of copper gasket seals for a demountable vacuum system. These were 5½ inches in diameter and with both a leak rate lower than 10−6 μl/sec could be obtained.
Integrator-Type dc Amplifier
Authors: Gardiner A. J. , Johnson H. L.
Published: February 2005

A dc amplifier that uses the condenser-charging principle of electron counting has been constructed and used for the measurement of stars as faint as magnitude 20.8 with the 82-inch and 100-inch telescope. The device is simple (15 tubes), will measure stars of any brightness permitted by the photomultiplier, and has a simple automatic recording feature using a Brown recording meter.
New Method for the Observation of Hyperfine Structure of NH3 in a ``Maser'' Oscillator
Authors: Shimoda Koichi , Wang T. C.
Published: February 2005

Weak hyperfine satellites have been observed with very large signal-to-noise ratios when microwave power at frequencies corresponding to these satellites is introduced into a ``maser'' which is oscillating at the frequency of the main inversion line of NH3. The satellite transitions are accompanied by a reduction of the amplitude of oscillation at the main-line frequency. A composite oscilloscope trace showing the structure of the weakest of the four quadrupole satellites associated with the 3–3 inversion line of N14H3 is presented.
Gas Scattering in a Strong Focusing Electron Synchrotron
Authors: Moravcsik Michael J. , Sellen J. Michael
Published: February 2005

Scattering of the electron beam by the residual gas in the vacuum chamber is calculated for the 1 Bev strong focusing Cornell Mesotron. It is shown that the elastic scattering by the nucleus and the inelastic scattering by the atomic electrons are the only important contributions to the loss due to the presence of gas. These two effects are calculated in detail. Radiation and space charge effects are not discussed. Because of the small scattering angles involved the details of the screening by the atomic electrons must be taken into account accurately. Multiple scattering is shown to be of little importance because of the damping of the beam oscillations as the energy increases. The calculations are carried out for two different injection conditions and little difference is found between them as far as the loss due to the scattering itself is concerned. The numerical results for the Cornell Mesotron show that about half of the beam gets lost at a vacuum of 5×10−6 mm Hg. The scattering losses will depend on the field lattice of the synchrotron.
Electronic Device for Measuring Reciprocal Time Intervals
Authors: MacNichol Edward F. , Jacobs Jay A. H.
Published: February 2005

A device is described which converts a train of electrical impulses into a succession of hyperbolic wave forms of amplitude proportional to the interval between successive impulses. These wave forms when applied to an oscilloscope furnish a display capable of showing rapid changes in the frequency of an electrical signal. Unlike conventional counting-rate meters response to sudden changes in frequency is immediate so that averaging over several cycles is not required. The instrument as constructed operates in the lower audio-frequency range and is being used in the study of the electrical discharge of single fibers of the optic nerve.