bluuebunny/crossref_metadata_2025 huggingface dataset:
State of the Translational Science
Authors: Zelent Arthur , Waxman Samuel , Carducci Michael , Wright John , Zweibel James , Gore Steven D.
Published: September 2005

A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.
Decreased Nucleotide Excision Repair Activity and Alterations of Topoisomerase IIα Are Associated with thein VivoResistance of a P388 Leukemia Subline to F11782, a Novel Catalytic Inhibitor of Topoisomerases I and II
Authors: Kruczynski Anna , Barret Jean-Marc , van Hille Benoît , Chansard Nathalie , Astruc Jackie , Menon Yoann , Duchier Carole , Créancier Laurent , Hill Bridget T.
Published: September 2005

Purpose: The purpose of the study was to investigate the mechanisms associated with antitumor activity and resistance to F11782, a novel dual catalytic inhibitor of topoisomerases with DNA repair-inhibitory properties.

Experimental Design: For that purpose, an F11782-resistant P388 leukemia subline (P388/F11782) has been developed in vivo and characterized.

Results: Weekly subtherapeutic doses of F11782 (10 mg/kg) induced complete resistance to F11782 after 8 weekly passages. This resistant P388/F11782 subline retained some in vivo sensitivity to several DNA-topoisomerase II and/or I complex-stabilizing poisons and showed marked collateral sensitivity to cisplatin, topotecan, colchicine, and Vinca alkaloids, while proving completely cross-resistant only to merbarone and doxorubicin. Therefore, resistance to F11782 did not appear to be associated with a classic multidrug resistance profile, as further reflected by unaltered drug uptake and no overexpression of resistance-related proteins or modification of the glutathione-mediated detoxification process. In vivo resistance to F11782 was, however, associated with a marked reduction in topoisomerase IIα protein (87%) and mRNA (50%) levels, as well as a diminution of the catalytic activity of topoisomerase IIα. In contrast, only minor reductions in topoisomerases IIβ and I levels were recorded. However, of major interest, nucleotide excision repair activity was decreased 3-fold in these P388/F11782 cells and was more specifically associated with a decreased (67%) level of XPG (human xeroderma pigmentosum group G complementing protein), an endonuclease involved in this DNA repair system.

Conclusions: These findings suggest that both topoisomerase IIα and XPG are major targets of F11782 in vivo and further demonstrate the original mechanism of action of this novel compound.
Clinical Significance of Cellular Distribution of Moesin in Patients with Oral Squamous Cell Carcinoma
Authors: Kobayashi Hiroichi , Sagara Junji , Kurita Hiroshi , Morifuji Masayo , Ohishi Masamichi , Kurashina Kenji , Taniguchi Shun’ichiro
Published: September 2005

Purpose: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC).

Experimental Design: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B).

Results: Expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor.

Conclusions: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells
Authors: Ballestrero Alberto , Nencioni Alessio , Boy Davide , Rocco Ilaria , Garuti Anna , Mela Giuseppe Sandro , Van Parijs Luk , Brossart Peter , Wesselborg Sebastian , Patrone Franco
Published: September 2005

Purpose: Overexpression of antiapoptotic Bcl-2 family members has recently been related to resistance to chemo/radiotherapy in several human malignancies, particularly lymphomas. Hence, innovative approaches bypassing this resistance mechanism are required in the therapeutic approach. This study evaluated whether chemoresistance associated with Bcl-2 and Bcl-xL overexpression would be overcome by activating the death receptor pathway by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model

Experimental Design: We made use of genetically modified Jurkat cells to evaluate the effect of Bcl-2 or Bcl-xL overexpression on the cytotoxic effect produced by the anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase activation was detected by cleavage of caspase-8 and -3. The mitochondrial transmambrane potential was assessed by staining with DiOC6 and flow cytometry. Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk.

Results: Bcl-2 and Bcl-xL overexpression but not lack of caspase-8 protects the Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-xL Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly synergistic cytotoxic effect of the combination of TRAIL with any of the antiblastic used in this study was detected in the chemoresistant cells. This effect was associated with mitochondrial disassemblage and dependent on caspase activation

Conclusions: The combination of TRAIL with conventional anticancer drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family proteins-expressing malignancies.
Correlation of Osteopontin Protein Expression and Pathological Stage across a Wide Variety of Tumor Histologies
Authors: Coppola Domenico , Szabo Marianna , Boulware David , Muraca Patrick , Alsarraj Marwan , Chambers Ann F. , Yeatman Timothy J.
Published: September 2005

Purpose: Osteopontin (OPN) is an integrin-binding protein overexpressed in various experimental models of malignancy and appears to be involved in tumorigenesis and metastasis. Although various studies have assessed OPN protein levels in several tumor types, a broad survey of OPN expression in human neoplasia under the same experimental conditions has not been carried out.

Experimental Design: We used immunohistochemistry to detect OPN in a selection of 350 human tumors and 113 normal tissues, from a variety of body sites, using stage-oriented human cancer tissue arrays. Tumors included malignancies from breast (26), ovary (22), endometrium (14), esophagus (10), stomach (11), pancreas (16), bile duct (1), liver (9), colon (20), kidney (53), bladder (33), prostate (28), head and neck (60), salivary glands (14), lung (17), skin (6), and brain (10).

Results: High cytoplasmic OPN staining was observed in 100% of gastric carcinomas, 85% of colorectal carcinomas, 82% of transitional cell carcinomas of the renal pelvis, 81% of pancreatic carcinomas, 72% of renal cell carcinomas, 71% of lung and endometrial carcinomas, 70% of esophageal carcinomas, 58% of squamous cell carcinomas of the head and neck, and 59% of ovarian carcinomas. Although OPN expression was identified in a good number of bladder, prostate, and brain tumors, the majority of 6 skin cancers, 11 of 14 salivary gland cancers, 2 thyroid carcinomas, and 23 of 26 breast cancers revealed low OPN positivity or were negative. When considering all sites, OPN expression significantly correlated with tumor stage (Spearman’s correlation coefficient, P = 0.0002). OPN score and stage were also significantly correlated for specific cancer sites including bladder (P = 0.01), colon (P = 0.004), kidney (P = 0.0001), larynx (P = 0.035), mouth (P = 0.046), and salivary gland (P = 0.011).

Conclusions: This study reports the broad distribution of OPN in human tumors from different body sites, suggesting involvement of this protein in tumor formation. The strong correlation between pathological stage and OPN across multiple tumor types suggests a role for OPN in tumor progression.
A Phase I and Pharmacokinetic Study of Irinotecan Given as a 7-Day Continuous Infusion in Metastatic Colorectal Cancer Patients Pretreated with 5-Fluorouracil or Raltitrexed
Authors: Masi Gianluca , Falcone Alfredo , Di Paolo Antonello , Allegrini Giacomo , Danesi Romano , Barbara Cecilia , Cupini Samanta , Del Tacca Mario
Published: September 2005

Purpose: The purpose is to determine the plasma pharmacokinetics, the maximum-tolerable dose and to preliminary evaluate the antitumor activity of irinotecan administered as a 7-day continuous infusion every 21 days in metastatic colorectal cancer patients pretreated with 5-fluorouracil or raltitrexed.

Experimental Design: A total of 13 patients entered the study. Three received irinotecan at 20 mg/m2/day (dose level I), 6 at 25 mg/m2/day (dose level II), and 4 at 22.5 mg/m2/day (dose level III). In 8 patients, plasma levels of irinotecan and its metabolites SN-38 and SN-38 glucuronide (SN-38glu) were measured by high-performance liquid chromatography and main pharmacokinetic parameters, including steady-state concentration, area under the time-concentration curve, and clearance, were calculated and normalized to the dose level of 22.5 mg/m2/day.

Results: Dose-limiting toxicity was grade 3–4 diarrhea, which occurred in 4 of 6 patients at dose level II and in 2 of 4 patients at dose level III. Therefore, we defined 22.5 mg/m2/day the maximum-tolerable dose and 20.0 mg/m2/day the recommended dose for Phase II studies. Hematological toxicity was rare. The pharmacokinetic data provided evidence that continuous infusion increased the metabolism of irinotecan to SN-38 with respect to standard 30/90-min administration. Indeed, the steady-state concentration of irinotecan, SN-38, and SN-38glu were 42.7 ± 25.2, 14.9 ± 1.9, and 31.7 ± 3.5 nmol/liter, respectively, and the area under the time-concentration curves of irinotecan, SN-38, and SN-38glu were 6.94 ± 0.41, 1.92 ± 0.30, and 4.23 ± 0.52 hxμmol/liter, respectively. Twelve patients were evaluable for activity, and we observed 3 (25%) partial responses, 2 (17%) minor responses, and 4 (33%) disease stabilizations.

Conclusions: The administration of irinotecan as a 7-day continuous infusion every 21 days is feasible with diarrhea being the dose-limiting toxicity; recommended dose for Phase II studies is 20.0 mg/m2/day. The comparison of the present data with those obtained after a standard 30–90 min. i.v. infusion of irinotecan demonstrates that continuous infusion improves the transformation of irinotecan to SN-38 and also results in increased glucuronidation of the active metabolite. Antitumor activity in pretreated metastatic colorectal cancer patients is encouraging.
Modular Interdependency in Complex Dynamical Systems
Authors: Watson Richard A. , Pollack Jordan B.
Published: September 2005

Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an “aggregate” manner—but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability.
State Aggregation and Population Dynamics in Linear Systems
Authors: Rowe Jonathan E. , Vose Michael D. , Wright Alden H.
Published: September 2005

We consider complex systems that are composed of many interacting elements, evolving under some dynamics. We are interested in characterizing the ways in which these elements may be grouped into higher-level, macroscopic states in a way that is compatible with those dynamics. Such groupings may then be thought of as naturally emergent properties of the system. We formalize this idea and, in the case that the dynamics are linear, prove necessary and sufficient conditions for this to happen. In cases where there is an underlying symmetry among the components of the system, group theory may be used to provide a strong sufficient condition. These observations are illustrated with some artificial life examples.
Term Limit and Political Incumbency in Africa: Implications of Staying in Power Too Long with References to the Cases of Kenya, Malawi, and Zambia
Authors: Bamfo Napoleon
Published: September 2005

African nations never seriously addressed the issue of term limits for incumbents until newly-drafted constitutions did so in the early 1990s. Since then, however, some incumbents have initiated campaigns to circumvent that measure. Some of those initiatives have been successful; others have not. Incumbents attempting to stay in office longer than what constitutions originally allowed used to be a time-honored strategy that African leaders regularly employed throughout the post-independent period until the early 1990s. The autocratic and single-party regimes that littered Africa's political landscape epitomized the extent to which political incumbents would go to keep anybody else, including members of their own party, from winning the highest political office.The response of opposition groups and the military, which assumed a guardianship role, to this wanton aggrandizement of power was a spate of military coups, counter-coups, and sabotage or destabilize those regimes. African nations paid dearly for this wave of instability to which almost all political systems became associated. This period of uncertainty and decay reminiscent of Africa's recent history is being re-invented following unsuccessful attempts of political incumbents in Kenya, Malawi, and Zambia to seek additional terms. Even as these efforts were being resisted, incumbents elsewhere were succeeding at securing additional terms. This paper examines the impact this recent trend among incumbents for term extension will have on the building of political institutions in Africa. If history were to serve as a guide, that spells an ominous foreboding.
Protest as Community Revival: Folk Religion in a Taiwanese Anti-Pollution Movement
Authors: Ho Ming-sho
Published: September 2005

By analyzing a Taiwanese anti-pollution movement, this paper tries to shed light on the elements of folk religion in collective action. The Houchin protest took place in 1987 when local people opposed to the further expansion of the China Petroleum Company (CPC). This case is an important milestone in the history of Taiwanese environmentalism and famous for its persistent protest over three years. In order to see how a local community sustains its solidarity through localistic folk religion, it is worth taking a close look at the community structure prior to the protest mobilization. The next section discusses Houchin people's reaction to the CPC's upgrading plan. Here the anti-pollution protest is viewed as an emergency occasion to revive the communal solidarity. Religion permeates the whole process of their collective action by supplying ritualized forms of contention. Religion in action is more than an instrument for mobilization, but rather substantially affects the movement goal and meaning for the participants. These highly localistic messages often escape outsiders' observation. In conclusion, the paper discusses the discovery in the light of study on Taiwanese environmental movement.
A Comparison of GOES Sounder– and Cloud Lidar- and Radar-Retrieved Cloud-Top Heights
Authors: Hawkinson James A. , Feltz Wayne , Ackerman Steven A.
Published: September 2005

An assessment of the performance of the Geostationary Operational Environmental Satellite (GOES) sounder cloud-top pressure product is presented. GOES sounder cloud-top-height data were compared with values derived from a consensus cloud boundary dataset that utilizes data from a cloud lidar and a cloud radar located at the U.S. Department of Energy’s (DOE’s) Atmospheric Radiation Measurement (ARM) Program’s Cloud and Radiation Test Bed (CART) site in Lamont, Oklahoma. Comparisons were performed from April 2000 to March 2002. A temporal filtering process was applied to the cloud lidar and cloud radar output so that a representative picture of the cloud field on the same spatial scale of the GOES sounder could be derived. Comparisons between the GOES sounder and ground-based cloud boundary measurements yielded a mean difference of 1772 m and a standard deviation of 1733 m. The difference between GOES cloud-top-height and ground-based retrievals is within ±500 m for 22% of the retrievals and within ±1500 m for 56% of the retrievals. These results are comparable to findings in similar studies that utilized the MODIS Airborne Simulator.
Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)
Authors: Lee Yun-Shien , Chen Chun-Houh , Chao Angel , Chen En-Shih , Wei Min-Li , Chen Lung-Kun , Yang Kuender D , Lin Meng-Chih , Wang Yi-Hsi , Liu Jien-Wei , Eng Hock-Liew , Chiang Ping-Cherng , Wu Ting-Shu , Tsao Kuo-Chein , Huang Chung-Guei , Tien Yin-Jing , Wang Tzu-Hao , Wang Hsing-Shih , Lee Ying-Shiung
Published: September 2005

Background

Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.

Results

Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.

Conclusion

The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.
Targeting MDM2 by the small molecule RITA: towards the development of new multi-target drugs against cancer
Authors: Espinoza-Fonseca L Michel
Published: September 2005

Background

The use of low-molecular-weight, non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Among these compounds, RITA (reactivation of p53 and induction of tumor cell apoptosis) has been shown to be effective in the selective induction of apoptosis, and this effect is due to its binding to the p53 tumor suppressor. Since biological systems are highly dynamic and MDM2 may bind to different regions of p53, new alternatives should be explored. On this basis, the computational "blind docking" approach was employed in this study to see whether RITA would bind to MDM2.

Results

It was observed that RITA binds to the MDM2 p53 transactivation domain-binding cleft. Thus, RITA can be used as a lead compound for designing improved "multi-target" drugs. This novel strategy could provide enormous benefits to enable effective anti-cancer strategies.

Conclusion

This study has demonstrated that a single molecule can target at least two different proteins related to the same disease.
Cough: are children really different to adults?
Authors: Chang Anne B
Published: September 2005

Worldwide paediatricians advocate that children should be managed differently from adults. In this article, similarities and differences between children and adults related to cough are presented. Physiologically, the cough pathway is closely linked to the control of breathing (the central respiratory pattern generator). As respiratory control and associated reflexes undergo a maturation process, it is expected that the cough would likewise undergo developmental stages as well. Clinically, the 'big three' causes of chronic cough in adults (asthma, post-nasal drip and gastroesophageal reflux) are far less common causes of chronic cough in children. This has been repeatedly shown by different groups in both clinical and epidemiological studies. Therapeutically, some medications used empirically for cough in adults have little role in paediatrics. For example, anti-histamines (in particular H1antagonists) recommended as a front-line empirical treatment of chronic cough in adults have no effect in paediatric cough. Instead it is associated with adverse reactions and toxicity. Similarly, codeine and its derivatives used widely for cough in adults are not efficacious in children and are contraindicated in young children. Corticosteroids, the other front-line empirical therapy recommended for adults, are also minimally (if at all) efficacious for treating non-specific cough in children. In summary, current data support that management guidelines for paediatric cough should be different to those in adults as the aetiological factors and treatment in children significantly differ to those in adults.
Triaxial Ultra-Small Strain Measurements Using Laser Interferometry
Authors: Heymann G , Clayton CRI , Reed GT
Published: September 2005

This paper describes a prototype device for ultra-small strain triaxial stiffness measurement, using laser-optic interferometry, and based upon the Fabry-Perot principle. The results of a test on an intact specimen of weak rock are presented, and comparisons made between measurements using this device and a submersible LVDT system. The displacement resolution of the interferometer was 0.0006 μm and the strain resolution 8 × 10−7%. It is shown that the measurement uncertainty of the instrument was low compared with the magnitude of the displacements measured and in addition it was sufficiently accurate to detect the linear stress-strain behavior of a weak rock.
Geotechnical Characterization and Sedimentation Behavior of Laterite Slurries
Authors: Azam S , Chalaturnyk RJ , Scott JD
Published: September 2005

Laterites are the main source of economic metals such as nickel and cobalt. In many parts of the globe, these metals are extracted using the pressure acid leach operation. An efficient rate of sedimentation and a high solids content of the material are two prerequisites for this process. To understand the geotechnical behavior of laterite slurries under ambient process conditions, a comprehensive laboratory characterization and sedmentation protocol was developed. Results indicate that due to changes in material characteristics, sedimentation behavior of laterite slurries is improved during the metal extraction process. The rate and concentration of sedimentation are directly related for this class of materials.
Efficiency of Seepage Consolidation for Preparation of Clay Substrate for Centrifuge Testing
Authors: Lee J , Fox PJ
Published: September 2005

Seepage consolidation under normal gravity conditions can be used to prepare clay soil substrates for subsequent testing in a geotechnical centrifuge. Currently available information provides no information regarding the general efficiency of this method, which would be expected to vary widely depending on centrifuge, test specimen, and operating conditions. A numerical investigation is presented of the efficiency of the two-stage seepage/centrifuge consolidation method for the preparation of normally consolidated clay substrates. Large strain consolidation simulations and experimental data for centrifuge and seepage/centrifuge consolidation tests conducted on reconstituted Singapore marine clay are in excellent agreement. A parametric study illustrates the effects of initial specimen void ratio, initial specimen height, surcharge stress, swelling time, and acceleration factor on the efficiency of the two-stage substrate preparation method. Efficiency of the method for Singapore marine clay ranged from 55 to essentially 100% for the simulations conducted.
Phase Composition, Structure, and Plastic Deformation Localization in Zr1%Nb alloys
Authors: Zuev LB , Zavodchikov SY , Poletika TM , Cheremnykh GS , Filippov VB , Belov VI , Arzhakova VM , Bocharov OV , Shikov AK
Published: September 2005

The feasibility of strengthening the Zrl%Nb alloy by achieving a non-uniform solid solution oxygen distribution in the α grains is considered. Technology employing Nb2O5 as an oxygen source has been developed, which permits introduction into the alloy additional oxygen up to 0.06–0.09 wt. %. Using the method of electron microscopy, the oxygen distribution of the as-produced alloy was examined. The material was found to contain Zr and Nb oxides of non-stoichiometric compositions. The regular features of plastic deformation localization were investigated. These features as revealed by the deforming material may be regarded as forerunners of necking in the course of Zr alloy tube manufacture and are indicative of probable material fracture.
Analysis of Fuels, Lubricants, and Greases Using X-ray Fluorescence Spectrometry
Authors: Wolska J , Vrebos B , Brouwer P
Published: September 2005

X-ray spectrometry (XRF) is a versatile instrumental method for elemental analysis in a wide variety of materials. The performance of three different XRF systems will be compared: a high power wavelength dispersive x-ray spectrometer (WDXRF), a low-power WDXRF, and a bench-top energy dispersive instrument (EDXRF).

The data obtained show quite clearly the large difference in sensitivities between instruments. This translates into varying lower limits of detection (LLD) or quantification and sample throughput. For quantitative analysis well above the LLD, the accuracy of the results obtained on the different instruments is similar, or — for practical purposes of quality control in many applications — the differences in accuracy between the different instruments can be considered insignificant.

Most of the applications and methods developed by a variety of laboratories and regulatory organizations are applicable to specimens of a specified nature and matrix. Some of the more versatile procedures include a method to account for differences in matrix between standard reference materials and unknowns. One of the effects that is usually neglected in this case is the wedge effect, which is caused by the fact that the volume that is excited by the beam and the volume from which characteristic radiation can be observed are not the same and vary (for a given spectrometer system) depending upon the density and the quantity of the sample. This effect will be illustrated and discussed.
Mercury Measurements in Fossil Fuels, Particularly Petrochemicals
Authors: Stockwell PB , Corns WT , ryce DW
Published: September 2005

The dangers of mercury and its derivatives, especially organomercury compounds have been well documented for almost half a century. Concerns remain regarding mercury contamination in aqueous ecosystems. Significant quantities of mercury are present in fossil fuels, particularly petrochemicals.

We still manage to pollute the atmosphere and environment by the use of coal and petrochemicals. The impact of mercury in natural gas has been such that there have been at least six experiences of plant failure which have been traced to corrosion due to mercury attacks on aluminium rotors in the plant fabric. Very little attention is being given to mercury removal strategies, and in order for these to be successful there is an urgent requirement to determine the speciation profile of the natural gas or liquid hydrocarbon condensates. Atomic fluorescence spectrometry is an ideal analytical technique to determine the levels of mercury both before and after removal systems. The authors will outline achievements of both laboratory and online measurement systems for this important area of research. These systems have been operating at the required levels of performance and in the case of some of the online systems, have been in place operating 24 hours per day 7 days per week for more than 2 years. This has encouraged other companies to install similar systems.
Informativeness of the CODIS STR Loci for Admixture Analysis
Authors: Barnholtz-Sloan JS , Pfaff CL , Chakraborty R , Long JC
Published: September 2005

Population admixture (or ancestry) is used as an approach to gene discovery in complex diseases, particularly when the disease prevalence varies widely across geographic populations. Admixture analysis could be useful for forensics because an indication of a perpetrator's ancestry would narrow the pool of suspects for a particular crime. The purpose of this study was to use Fisher's information to identify informative sets of markers for admixture analysis. Using published founding population allele frequencies we test three marker sets for efficacy for estimating admixture: the FBI CODIS Core STR loci, the HGDP-CEPH Human Genome Diversity Cell Line Panel and the set of 39 ancestry informative SNPS from the Shriver lab at Pennsylvania State University. We conclude that the FBI CODIS Core STR set is valid for admixture analysis, but not the most precise. We recommend using a combination of the most informative markers from the HGDP-CEPH and Shriver loci sets.
Searching for the IRA "Disappeared": Ground-penetrating Radar Investigation of a Churchyard Burial Site, Northern Ireland
Authors: Ruffell A
Published: September 2005

A search for the body of a victim of terrorist abduction and murder was made in a graveyard on the periphery of a major conurbation in Northern Ireland. The area is politically sensitive and the case of high profile. This required non-invasive, completely non-destructive and rapid assessment of the scene. A MALA RAMAC ground-penetrating radar system was used to achieve these objectives. Unprocessed and processed 400 MHz data show the presence of a collapse feature above and around a known 1970s burial with no similar collapse above the suspect location. In the saturated, clay-rich sediments of the site, 200 MHz data offered no advantage over 400 MHz data. Unprocessed 100 MHz data shows a series of multiples in the known burial with no similar features in the suspect location. Processed 100 MHz lines defined the shape of the collapse around the known burial to 2 m depth, together with the geometry of the platform (1 m depth) the gravedigger used in the 1970s to construct the site. In addition, processed 100 MHz data showed both the dielectric contrast in and internal reflection geometry of the soil imported above the known grave. Thus the sequence, geometry, difference in infill and infill direction of the grave was reconstructed 30 years after burial. The suspect site showed no evidence of shallow or deep inhumation. Subsequently, the missing person's body was found some distance from this site, vindicating the results and interpretation from ground-penetrating radar. The acquisition, processing, collapse feature and sequence stratigraphic interpretation of the known burial and empty (suspect) burial site may be useful proxies for other, similar investigations. GPR was used to evaluate this site within 3 h of the survey commencing, using unprocessed data. An additional day of processing established that the suspect body did not reside here, which was counter to police and community intelligence.
Fracture Pattern Interpretation in the Skull: Differentiating Blunt Force from Ballistics Trauma Using Concentric Fractures
Authors: Hart GO
Published: September 2005

There have been several anthropological studies on trauma analysis in recent literature, but few studies have focused on the differences between the three mechanisms of trauma (sharp force trauma, blunt force trauma and ballistics trauma). The hypothesis of this study is that blunt force and ballistics fracture patterns in the skull can be differentiated using concentric fractures. Two-hundred and eleven injuries from skulls exhibiting concentric fractures were examined to determine if the mechanism of trauma could be determined by beveling direction. Fractures occurring in buttressed and non-buttressed regions were examined separately. Contingency tables and Pearson's Chi-Square were used to evaluate the relationship between the two variables (the mechanism of trauma and the direction of beveling), while Pearson's r correlation was used to determine the strength of the relationship. Contingency tables and Chi-square tests among the entire sample, the buttressed areas, and the non-buttressed areas led to the null hypothesis (no relationship) to be rejected. Pearson's r correlation indicated that the relationship between the variables studied is greater than chance allocation.
Beware of the Possibility of Fingerprinting Techniques Transferring DNA
Authors: van Oorschot RAH , Treadwell S , Beaurepaire J , Holding NL , Mitchell RJ
Published: September 2005

Fingerprinting brushes have the potential to collect and transfer DNA during powdering. Squirrel-hair fingerprint brushes exposed to specific sets of saliva stains and brushes used in routine casework were tested for their ability to collect and transfer DNA containing material using standard DNA extraction procedures and AmpF/STR® Profiler Plus™ amplification and typing procedures. The tests found that the risk of transferring DNA during powdering and having a detrimental impact on the analysis increases if the examiner powders over either biological stains (such as blood or saliva) or very fresh prints and uses more sensitive PCR amplification and typing procedures. We advocate caution when powdering prints from which DNA may also be collected and provide options for consideration to limit the risk of transferred DNA contamination while fingerprinting.
The Microbial Rosetta Stone Database: A Common Structure for Microbial Biosecurity Threat Agents
Authors: Ecker DJ , Sampath R , Willett P , Samant V , Massire C , Hall TA , Hari K , McNeil JA , Büchen-Osmond C , Budowle B
Published: September 2005

Infectious microorganisms are important to multiple communities engaged in biodefense and biosecurity, including the agencies responsible for health, defense, law enforcement, agriculture, and drug and food safety. Many agencies have created lists of high priority infectious microorganisms to prioritize research efforts or to formally control the possession and distribution of specific organisms or toxins. However, the biological classification of infectious microorganisms is often complex and ambiguous, leading to uncertainty and confusion for scientists involved in biosecurity work. To address this problem, we created a database, known as the Microbial Rosetta Stone, which resolves many of these ambiguities and includes links to additional information on the microbes, such as gene sequence data and scientific literature. Here we discuss the efforts to coordinate organism names from pathogen lists from various governmental agencies according to biological relatedness and show the overlap of high-priority organisms from multiple agencies. To our knowledge, this is the first comprehensive coordination of pathogens, synonyms, and correct taxonomic names. The organized tables and visual aids are freely available at http://www.microbialrosettastone.com. This website provides a single location where access to information on a broad range of disease-causing organisms and toxins is available to members of the biosecurity community.
Stable Isotope Ratios as a Tool in Microbial Forensics—Part 3. Effect of Culturing on Agar-containing Growth Media
Authors: Kreuzer-Martin HW , Chesson LA , Lott MJ , Ehleringer JR
Published: September 2005

Stable isotope ratios of hydrogen and oxygen in microbes have been shown to be functions of the corresponding isotope ratios of the water with which the culture medium was prepared, and thus to contain a potential geographic signal. Water can evaporate from agar (solid) media during culturing, changing its isotope ratios. Here we describe the effect of drying on the isotope ratios of water extracted from agar media and the H and O stable isotope ratios ratios of Bacillus subtilis spores cultured on agar. The δ2H vs δ18O relationship of water in Petri dish agar was surprisingly constant during evaporation regardless of the ambient relative humidity, making it possible to calculate the approximate isotope ratios of the original water, even in significantly evaporated agar. The H stable isotope ratios of spores cultured on agar remained relatively unchanged as the agar dried, but the O ratio became significantly enriched.
Estimation of Sex by 3D CT Measurements of the Foramen Magnum
Authors: Uysal S , Gokharman D , Kacar M , Tuncbilek I , Kosar U
Published: September 2005

The purpose of this prospective study is to investigate the value and accuracy of the measurements of the foramen magnum (FM) by using three-dimensional computed tomography (3DCT). Cases were randomly selected among 100 patients (48 males, 52 females) who had temporal CT in the Radiology Department. Seven measurements of the foramen magnum on 3D images, modified from the nine lines previously defined by Giles and Elliot were made. Using Fisher's linear discriminant functions test, the length and width of right condyle and width of FM diameters were found to be statistically different in each sex (p < 0.001) with 81% accuracy. To our best knowledge, this is the first report studying 3DCT measurements of FM, resulting with a sex determination accuracy rate of 81%. CT/3DCT can be reliably used in further investigations to provide basis for anthropometric and forensic issues.
Identification of Anhydroecgonine Ethyl Ester in the Urine of a Drug Overdose Victim
Authors: Myers AL , Williams HE , Kraner JC , Callery PS
Published: September 2005

Toxicological evaluation of postmortem urine collected from a 41-year-old deceased white male detected anhydroecgonine ethyl ester (ethylecgonidine, AEEE), a transesterification product of smoked cocaine co-abused with ethanol. A solid phase extraction (SPE) method was used to extract cocaine, AEEE, and related metabolites from urine. SPE on a 1 mL urine sample from the decedent followed by GC-MS detected AEEE. Other metabolites identified by GC-MS included cocaine, cocaethylene, and anhydroecgonine methyl ester (AEME). To determine whether some or all of the AEEE was artifactually produced in the heated GC injector port, an alternative LC-MS method was developed. LC/MS following SPE found at least 50 ng/mL of AEEE in the extract. The mass fragmentation (MS/MS and MS3) of AEEE detected in the urine was compared to spectra of authentic, synthesized compound. AEEE is a potential additional forensic marker for the co-abuse of smoked cocaine and ethanol.
Adolescent Death: A 15-Year Retrospective Review
Authors: Batalis NL , Collins KA
Published: September 2005

Adolescents comprise an eclectic mix of people vitally important to society yet long-term comprehensive studies on the circumstances of their deaths are lacking in the pediatric forensic literature. The authors reviewed all forensic cases referred to the Medical University of South Carolina Forensic Pathology section over the fifteen years between January 1989 and December 2003. In accordance with the World Health Organization (WHO) definition of adolescents, only decedents 10-19 years of age were included. The authors examined the cause and manner of death, age, gender, and race of the victims in all cases. The toxicology results, perpetrator, death scenario and location, and victim traits were analyzed when available. For all adolescents, the most common manner of death was accident followed by homicide, suicide, natural, and undetermined. Within the adolescent population two distinct groups, 10-14 years old and 15-19 years old, were identified. Though both groups were similar in that they experienced a high number of accidental deaths, decedents of older age group suffered a higher percentage of violent deaths while decedents of the younger group were more likely to die of natural causes. Many of the accidental deaths in this review were preventable, including deaths due to motor vehicle collisions and drowning. In deaths due to homicide, the perpetrator was often known to the victim, whether as an acquaintance or family member. Toxicology testing was often positive in decedents of the older age group, while only rarely positive in decedents of the younger age group. With a solid understanding of the circumstances, it may be possible to predict, and hopefully prevent, future cases of adolescent death. The authors present their findings in this 15-year retrospective study to better aid forensic pathologists, death investigators, law enforcement, and epidemiologists.
Forensic Value of Pattern and Particle Transfers From Deployed Automotive Airbag Contact
Authors: Schubert GD
Published: September 2005

Many automobile manufacturers began installing airbags on the driver's side in the late 1980's. Passenger side airbags followed in the early 1990's. Most airbags use a solid-propellant type of material that produces a hot gas to inflate the airbags. The gas in the driver side airbag leaves the inflator at a temperature as hot as 600°C. The hot gas escapes through the vent holes after deployment, but it can also leak through the stitching seams in the front and singe a pattern on the occupant's clothing characteristic of the seam pattern. The singe patterns from the driver and passenger side airbags will be different. Cornstarch, which is used as a lubricant in some driver side airbags, can transfer to the driver's shirt. Hairs, fibers and make-up can transfer from the driver or passenger to the surface of the deployed airbags. Two cases are presented, illustrating singe patterns and particle transfers, and how they helped determine who a driver or passenger were.
The Distal Humerus-A Blind Test of Rogers' Sexing Technique Using a Documented Skeletal Collection
Authors: Falys CG , Schutkowski H , Weston DA
Published: September 2005

Continuous monitoring of existing methods of skeletal diagnosis allows improving the reliability of personal identification in forensic and archaeological contexts. This study reports on a blind test re-evaluating the sexing technique proposed by Rogers (8) involving the distal humerus. A total of 351 humeri (184 male, 167 female specimens) from the documented skeletal assemblage of St. Bride's, London, was analyzed for the following traits: trochlear constriction, trochlear symmetry, olecranon fossa shape, and angle of the medial epicondyle. Individual traits showed substantial sex-discriminatory capacity, with “olecranon fossa shape” being most consistently accurate (84.6%) in predicting sex. The combination of all four traits provided an overall accuracy of 79.1%, including those individuals assessed as “probable” male and female. This renders the technique useful for forensic applications. The distal humerus can be recommended for sex assessment in addition to more established markers, especially since this part of the skeleton is frequently well preserved.
Genetic Characteristics of Three New Y-STRs: DYS631, DYS634 and DYS635 in a Chinese Population
Authors: Zhang ZX , Gao YZ , He Y , Xia SX
Published: September 2005

EDTA anticoagulated peripheral blood or buccal swabs for this study were drawn randomly from 79 Han-ethnic male individuals representing various geographical counties in eastern China, with their consent. Ethnic origin was determined by self-declaration.
Allele Frequencies for Two STR Loci GATA31E08 and DXS6809 in Chinese Population
Authors: Bai P , Li YB , Zhou XP , Song XH , Yuan WA , Yan J , Jin B , Zhang J , Hou YP , Wu J
Published: September 2005

Blood samples were collected from unrelated individuals of Chinese Han ethnic group in Chengdu of China. DNAwas extracted using Chelex method (1). PCR amplification conditions can be accessed at http://www.legalmed.org/dna/DXS6809.htm (2). The volume of PCR reaction for each locus was 37.5 µL. The PCR products were analyzed by horizontal non-denaturing polyacrylamide gel electrophoresis with discontinuous buffer system and visualized by sliver staining (2,3). Data were analyzed using POWERSTATS program (4).
A Hemizygous Repeat Polymorphism of One STR in Four Population Groups of South India
Authors: Ahmad S , Seshadri M
Published: September 2005

DNA was extracted using rapid, non-enzymatic precipitation method (1). PCR amplification was carried out using locus specific primers
Genetic Polymorphisms of 15 STR Loci in Chinese Hui Population
Authors: Wang Z , Huang P , Chen L , Xu Y , He K , Zhu X
Published: September 2005

The blood samples were obtained from 100 unrelated individuals of Chinese Hui population living in Ningxia province with known ancestor until at least the third generations. Genomic DNA was extracted using the Chelex-100 protocol as described by Walsh et al. (1). 15 STRs loci were co-amplified by using the AmpFLSTR Identifiler kit following the amplification conditions recommended by the manufacturer. All loci were amplified in GeneAmp PCR System 9700 (PE Applied Biosystem). Detection and genotyping of all PCR products were accomplished using ABI3100 DNA Genetic Analyzer (Applied Biosystem). Allele designation was done using GeneScan3.7 and Genotyper3.7. Evaluation of Hardy–Weinberg equilibrium expectations was carried out using the exact test and further statistical parameters of forensic interest were determined by using Arlequin version1.1 (2).