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Biomedical subjects

B Ellis

Publications and source records attributed to B Ellis.

At least 19 recordsLinked to original sources

Phonons and thermodynamics of unmixed and disordered Li0.6FePO4.

The lithium-storage material Li(0.6)FePO(4) was studied by inelastic neutron scattering and differential scanning calorimetry. Li(0.6)FePO(4) undergoes a transformation from a two-phase mixture (heterosite and triphylite) to a disordered solid-solution at 200 degrees C. Phonon densities of states (DOS) obtained from the inelastic neutron scattering were similar for the two-phase sample measured at 180 degrees C and the disordered sample measured at 220 degrees C. The vibrational entropy of transformation is 1.8 +/-0.9 J/(K mol), which is smaller than the configurational entropy difference of approximately 3.1 J/(K mol). The measured enthalpy of the disordering transition was estimated as 2.5 kJ/mol. The phonon data show a small change in lattice dynamics upon disordering.

Journal Article↗

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Arabidopsis↗

Nano-network electronic conduction in iron and nickel olivine phosphates.

The provision of efficient electron and ion transport is a critical issue in an exciting new group of materials based on lithium metal phosphates that are important as cathodes for lithium-ion batteries. Much interest centres on olivine-type LiFePO(4), the most prominent member of this family. Whereas the one-dimensional lithium-ion mobility in this framework is high, the electronically insulating phosphate groups that benefit the voltage also isolate the redox centres within the lattice. The pristine compound is a very poor conductor (sigma approximately 10(-9) S cm(-1)), thus limiting its electrochemical response. One approach to overcome this is to include conductive phases, increasing its capacity to near-theoretical values. There have also been attempts to alter the inherent conductivity of the lattice by doping it with a supervalent ion. Compositions were reported to be black p-type semiconductors with conductivities of approximately 10(-2) S cm(-1) arising from minority Fe(3+) hole carriers. Our results for doped (and undoped) LiMPO(4) (M = Fe, Ni) show that a percolating nano-network of metal-rich phosphides are responsible for the enhanced conductivity. We believe our demonstration of non-carbonaceous-network grain-boundary conduction to be the first in these materials, and that it holds promise for other insulating phosphates.

Electric Conductivity↗

Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations.

PURPOSE: A prospective observational study to examine our current practice of either conscious sedation (C.S.) or general anesthetic (G.A.) for children undergoing radiation therapy (we use the term sedation to include both C.S. and G.A.). Specifically, the study examines the reasons for selection of patients, choice of drugs, safety and effectiveness of the procedure, side effects of repeated daily sedation, and compliance of the family with the regimen. METHODS AND MATERIALS: Recorded data included patient demographics, sedation technique, time for various stages of the procedure, breathing support required, sedation outcome, and complications. RESULTS: One hundred ninety-eight consecutive children underwent 4232 procedures involving either simulation or radiation treatment, an average of 21 procedures each. Seventy-four (37%) required sedation for a total of 1033 procedures, an average of 14 sedations each. For those patients who received sedation, the age ranged from 9 months to 14 years (median, 3.8) and 96% had a mold, (85% of the head and neck). The doctor's assessment of the need for sedation was correct 89% of the time. Thirty-seven percent required sedation at the start of treatment, but, even after 30 fractions, 15% still required sedation. Presedation status correlated with successful sedation and treatment (p = 0.0001). Ninety-six percent had some form of i.v. access, usually a portacath (76%); 883 sedations were performed with G.A. and 148 with C.S.; 93% of sedations were completed satisfactorily, 5% with some difficulty, and the patient was unable to be treated in 2%. With G.A., satisfactory sedation was achieved 97% of the time, whereas, with C.S., satisfactory sedation was achieved only 68% of the time. There were no complications for 97% of observations. Not one serious complication occurred. An endotracheal tube was used only twice during G.A. For C.S., the results for chloral hydrate, meperidine, and midazolam were, respectively, at least one complication, 23%, 0%, 5%; satisfactory sedation for treatment, 60%, 60%, 82%; and unable to treat 20%, 13%, 5%. For G.A., only 1 patient was unable to be treated. The median time from start of medication to the end of radiation treatment was a median of 10 min (75% complete within 15 min) for G.A., vs. 30 min (75% complete in 50 min) for C.S. On multivariate analysis, the only significant factor predicting a successful outcome was a G.A. using propofol (odds ratio, 20.6), vs. C.S. using either chloral hydrate, meperidine, or midazolam. (p = 0.0001). CONCLUSION: In this study, there were no serious complications of sedation in 1033 procedures. As a result of the study, we developed improved methods for better preparation of the patient and family to try to reduce the need for sedation, and reduce the indications for C.S., while confirming the safety and efficacy of a G.A. with propofol for children needing sedation for daily radiation therapy.

Adolescent↗

Feature extraction and normalization algorithms for high-density oligonucleotide gene expression array data.

Algorithms for performing feature extraction and normalization on high-density oligonucleotide gene expression arrays, have not been fully explored, and the impact these algorithms have on the downstream analysis is not well understood. Advances in such low-level analysis methods are essential to increase the sensitivity and specificity of detecting whether genes are present and/or differentially expressed. We have developed and implemented a number of algorithms for the analysis of expression array data in a software application, the DNA-Chip Analyzer (dChip). In this report, we describe the algorithms for feature extraction and normalization, and present validation data and comparison results with some of the algorithms currently in use.

Algorithms↗

Defects of dental appearance assessed by patient and dental student groups.

A study was carried out to establish the relative need for treatment of a range of defects of dental appearance and identify differences between individual and group assessments. Three groups (n = 42), two of patients (one referred for a defect of dental appearance and one not) and one of dental students, assessed urgency of need on a visual analogue scale (VAS), of four cases of dental defect presented as colour prints. All groups rated the need for treatment of the four cases in the same order. Data sets were non-normal with wide ranges. Patients without a defect of appearance usually assessed treatment need as significantly less urgent. Marked variation was discovered between individual assessments within otherwise similar groups. Based on group decisions, guidelines for treatment of defects of dental appearance could be established. However, so extreme are individual variations that very sympathetic application would be needed if dissatisfaction is not to result.

Adolescent↗

The effect of powder/liquid mixing ratio on the stiffness and impact strength of autopolymerising dental acrylic resins.

The stiffness of representative cured autopolymerising dental acrylic resins was determined by calculation of a secant modulus from measurements in tension of load and extension, and related to the powder/liquid mixing ratio. The impact strengths of autopolymerising, heat-cure and commercial resins were compared. It was found that while the stiffness of autopolymerising resins was unaffected by variations in powder/liquid mixing ratio, extension to failure was greater with lower powder/liquid ratios. The impact strength of autopolymerising resins was found to be greater than that of heat-cure resins, and a tentative explanation is offered. These findings may help to explain the pattern of failure of acrylic resin denture bases.

Acrylic Resins↗

Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail.

BACKGROUND: Angiogenesis, the formation of new vessels from the existing vasculature, is a critical process during early development as well as in a number of disease processes. Tie2 (also known as Tek) is an endothelium-specific receptor tyrosine kinase involved in both angiogenesis and vasculature maintenance. RESULTS: We have determined the crystal structure of the Tie2 kinase domain to 2.2 A resolution. The structure contains the catalytic core, the kinase insert domain (KID), and the C-terminal tail. The overall fold is similar to that observed in other serine/threonine and tyrosine kinase structures; however, several unique features distinguish the Tie2 structure from those of other kinases. The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an "activated-like" conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated. CONCLUSION: Regulation of the kinase activity of Tie2 is a complex process. Conformational changes in the nucleotide binding loop, activation loop, C helix, and the C-terminal tail are required for ATP and substrate binding.

Amino Acid Substitution↗

Expression, purification, and characterization of the human receptor activator of NF-kappaB ligand (RANKL) extracellular domain.

Receptor activator of NF-kappaB ligand (RANKL) is a type II transmembrane protein found on osteoblasts which functions as a major determinant of osteoclast differentiation and activation. RANKL mediates bone homeostasis through binding to the cognate ligand on osteoclasts, RANK, and a soluble decoy receptor, osteoprotegerin (OPG). We designed a construct encoding the extracellular domain of human RANKL that conformed to reports of native processing. To encourage folding and posttranslational modification of a normally membrane-inserted moiety, we expressed the RANKL truncate as a secreted protein using the signal sequence from OPG in a Trichoplusia ni cell line using a baculovirus expression vector. RANKL was purified by a three-step process including an OPG-Fc affinity column. SDS-PAGE and mass spectral analysis indicated that the protein was >99% pure and glycosylated. Circular dichroism spectra revealed that the protein exhibited structural elements similar to tumor necrosis factor-alpha. By BIAcore analysis, RANKL bound to OPG with an affinity of 6.7 nM. Sedimentation equilibrium analytical ultracentrifugation analyses established that our protein existed as a trimer. We conclude that our expressed human RANKL truncate is folded, is functional, and exhibits self-association consistent with other family members.

Amino Acid Sequence↗

Do better qualified dentists make fewer hospital referrals?

OBJECTIVE: To assess the influence of further qualifications and length of clinical experience on the number of referrals of complete denture problems made by GDPs to secondary care. DESIGN: An audit was made of complete denture referrals to Sheffield Dental Hospital between January 1997 and June 1999. METHOD: All complete denture referrals (n=257), either single complete denture or 2 complete dentures, made by locally practising NHS registered dentists (n=211) to Sheffield Dental Hospital, were recorded, along with the year of qualification and any additional clinical qualifications of referring practitioner. RESULTS: Fewer referrals were made by better qualified dentists (p=0.003). Better qualified dentists also appeared willing to treat more difficult cases. In the absence of a further clinical qualification, length of clinical experience had no effect on the number of referrals made. CONCLUSIONS: Better qualified dentists make fewer complete denture referrals, emphasising the importance of continuing education in reducing referral rates and improving patient service.

Clinical Competence↗

Monoclonal antibodies generated against recombinant ATM support kinase activity.

We report on the rapid generation of two monoclonal antibodies, ATM A16.35 and ATM D16.11, that bind to the kinase domain of mutated ataxia telangiectasia (ATM). These antibodies were generated against E. coli-expressed recombinant protein using the RIMMS strategy. We show that ATM A16.35 binds ATM by Western blot analysis, and ATM D16.11 forms immune complexes with native ATM in immunoprecipitations without neutralizing kinase activity.

Animals↗

Monoclonal antibody B9-2 recognizes an 8 amino acid sequence that spans an autocatalytic cleavage site between the two subunits of human procaspase 8.

Caspase 8 is synthesized in a zymogen form and must be proteolytically cleaved to be activated. The catalytically active enzyme is composed of two of the four cleavage products. We have determined that the monoclonal antibody B9-2 recognizes the octomer EMDLSSPQ. This sequence is shared by two of the cleavage products: a decamer linker region released after autocatalysis and the smaller subunit of the active enzyme.

Amino Acid Sequence↗

Production and characterization of an estrogen receptor beta subtype-specific mouse monoclonal antibody.

An important step in differentiating the unique physiological roles of the alpha and beta forms of estrogen receptor is to determine the precise expression pattern of each of these receptors. We report the generation and characterization of a murine IgG1 monoclonal antibody (MAb), ER15.64A that is ERbeta subtype-specific and capable of recognizing full-length human ERbeta as well as all of its known protein isoforms. ER15.64A, raised against a ERbeta peptide (aa2-18)-keyhole limpet hemocyanine conjugate, reacted to the immunizing peptide and the full-length E. coli expressed ERbeta in ELISA and BIAcore assays. It also immunostained nuclei of Sf9 insect cells that were infected with an ERbeta-baculovirus. In Western analysis, ER15.64A recognized ERbeta1 and ERbeta2 proteins from a reticulocyte in vitro transcription/translation preparation. This antibody did not cross-react with recombinant ERalpha in ELISA, BIAcore, immunocytochemistry, or Western blot analysis. The specificity of ER15.64A should make this antibody a useful tool for monitoring expression of ERbeta and its isoforms at the protein level and should aid in distinguishing the pattern of ERbeta receptor expression from that of ERalpha.

Animals↗

Rates of GDP referral of complete dentures to a teaching hospital.

PURPOSE OF STUDY: To identify areas and sites of excessive referral of complete dentures by GDPs, allowing for factors which might distort referral rates. METHODS: Two hundred and six consecutive valid referrals of patients over the age of 50 years with complete dentures to a local dental teaching hospital and originating from the 29 Sheffield electoral wards were audited from the beginning of 1995 to the end of 1997. The referring practitioner and electoral ward were recorded. RESULTS: Referral rates were calculated according to the size of the 50+ population within each ward and were found to be normally distributed, following exclusion of two wards with much higher referral rates than normal (3.5 and 6 SDs [standard deviations] from the mean). After calculating mean numbers referred per full-time equivalent (FTE) GDP for all wards, practices and practitioners originating excessive numbers of referrals within a high-referring ward could be identified. CONCLUSION: After taking into account factors which might permit a high referral rate to be acceptable, practices with inappropriately high referral rates can be identified and remedial teaching need pinpointed.

Aged↗

Investigation of trunk and extremity movement associated with passive head turning in newborns.

BACKGROUND AND PURPOSE: Physical therapist examination of pediatric clients or clients with neurological conditions often includes the observation of stereotypical movement patterns such as the asymmetrical tonic neck reflex and righting reactions. The purpose of this study was to investigate whether extremity and trunk responses to passive head turning could be documented in newborn infants. SUBJECTS AND METHODS: Forty-two newborns with no known medical problems were videotaped within 5 days of birth while an investigator turned their heads left and right. Videotapes were stopped at 5-second intervals to record the direction of head turn with the rest of the body obscured. A second investigator recorded trunk and extremity position with the head obscured. RESULTS: The direction of head turning affected upper- and lower-extremity position, with extension stronger on the face side. The direction of trunk convexity was also affected by head position, with the trunk convex to the side to which the face was turned. CONCLUSION AND DISCUSSION: Extremity responses and trunk responses to passive head turning can be documented corresponding to patterns reported for the asymmetrical tonic neck reflex and righting reflexes in neonates with no known medical problems more frequently than would occur by chance.

Back↗

Adherence to guidelines for antiretroviral therapy and for preventing opportunistic infections in HIV-infected adults and adolescents in Ryan White-funded facilities in the United States.

To determine adherence by health care providers to guidelines for antiretroviral therapy and for prevention of opportunistic infections (OIs) in adults with HIV infection in federally funded facilities in the United States, we reviewed records of HIV-infected adults (>13 years) in 11 Ryan White Title III facilities in four states for information on eight standard-of-care recommendations during November 1996 through September 1997. Eligibility required a visit to the facility within 6 months before record abstraction and a lowest CD4+ lymphocyte count <500 cells/microl. Reviews were completed for 148 patients in Maryland, 355 in New York, 370 in Georgia, and 538 in Illinois. Adherence to prevention measures by health care providers was >85% for HIV plasma RNA testing, prescription of antiretroviral therapy, Pneumocystis carinii pneumonia (PCP) prophylaxis, anti-Toxoplasma antibody testing, and obtaining Papanicolaou (Pap) smears but lower (69%-80%) for Mycobacterium avium complex (MAC) prophylaxis, tuberculin skin testing (TST), and pneumococcal vaccination. Adherence was similar by patient age, gender, racial/ethnic group, urban versus rural, and hospital versus clinic setting but was generally lower for injecting drug users (IDUs) than for patients with other HIV exposures (p < .05 by multivariate analysis for TST, anti-Toxoplasma antibody testing, Pap smear, and measurement of HIV plasma RNA). Adherence by health care providers to guidelines for preventing OIs in these federally funded facilities is generally high but could be improved for some prevention measures, for instance, MAC prophylaxis, TST, and pneumococcal vaccination, especially for IDUs.

AIDS-Related Opportunistic Infections↗