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Comparative sugar recovery data from laboratory scale application of leading pretreatment technologies to corn stover.

Biological processing of cellulosic biomass to fuels and chemicals would open up major new agricultural markets and provide powerful societal benefits, but pretreatment operations essential to economically viable yields have a major impact on costs and performance of the entire system. However, little comparative data is available on promising pretreatments. To aid in selecting appropriate systems, leading pretreatments based on ammonia explosion, aqueous ammonia recycle, controlled pH, dilute acid, flowthrough, and lime were evaluated in a coordinated laboratory program using a single source of corn stover, the same cellulase enzyme, shared analytical methods, and common data interpretation approaches to make meaningful comparisons possible for the first time. Each pretreatment made it possible to subsequently achieve high yields of glucose from cellulose by cellulase enzymes, and the cellulase formulations used were effective in solubilizing residual xylan left in the solids after each pretreatment. Thus, overall sugar yields from hemicellulose and cellulose in the coupled pretreatment and enzymatic hydrolysis operations were high for all of the pretreatments with corn stover. In addition, high-pH methods were found to offer promise in reducing cellulase use provided hemicellulase activity can be enhanced. However, the substantial differences in sugar release patterns in the pretreatment and enzymatic hydrolysis operations have important implications for the choice of process, enzymes, and fermentative organisms.

Biomass↗

Orthographic repetition blindness.

Repetition blindness (RB) is the failure to report the second occurrence of a repeated word, when words are sequentially and briefly displayed (Kanwisher, 1987). RB is also observed for non-identical words, such as home, dome. Explanations for non-identity RB assume that similarity at the level of the whole word causes the second word to be suppressed ("similarity inhibition"). Three experiments demonstrate that RB is robust for diverse types of orthographic relatedness, including critical words that share only their first initial letter, their last two letters, first three letters, middle three letters, beginning and final letters, three alternating letters, and three non-aligned letters (as in chance hand). The theoretical construct of similarity inhibition may be able to account for these data, although one mechanism previously proposed in the literature, neighbourhood inhibition, is probably not a useful way to explain the data on RB for words sharing only one or two letters. We introduce an alternative explanation for orthographic RB: Only the repeated letters are suppressed, and amount of RB depends on how easily the perceiver can reconstruct the target word from the non-suppressed letters.

Adult↗

Sex influences on the penetrance of HLA shared-epitope genotypes for rheumatoid arthritis.

The association between rheumatoid arthritis (RA) and HLA DRB1 alleles may arise through linkage disequilibrium with a disease locus or the direct involvement of HLA alleles in RA. In support of the latter possibility, the shared-epitope hypothesis has been postulated, stating that conformationally similar DR beta chains encoded by several DRB1 alleles confer disease susceptibility. To examine these alternative hypotheses of marker-disease association and to investigate gender differences in RA susceptibility, we analyzed the distributions of PCR-based DRB1 genotypes of 309 Caucasian RA patients and 283 Caucasian controls. Initially, the marker-association-segregation chi 2 method was used to evaluate evidence for linkage disequilibrium and the direct involvement of markers DR4 Dw4, DR4 Dw14, and DR1 in RA susceptibility. Additional shared-epitope models that grouped DRB1 alleles into five classes (*0401, *0404/*0102, *0405/*0408/*0101, *1001, and all others) and postulated relationships between genotypes and RA susceptibility were also fitted to observed genotypic distributions by the method of minimal chi 2. For females, a linkage-disequilibrium model provided a good fit to the data, as did a shared-epitope model with RA most penetrant among individuals with the *0401,*0401 genotype. For males, the best model indicated highest RA penetrance among shared-epitope compound heterozygotes. Clinically, male RA patients had more subcutaneous nodules and greater use of slowly acting antirheumatic drugs, while female RA patients had earlier disease onset. This study therefore suggests that sex-related factors influence the RA penetrance associated with DRB1 shared-epitope genotypes and that DRB1 effects on RA prognosis and pathogenesis should be considered separately for men and women.

Alleles↗

Shared k-space echo planar imaging with keyhole.

Time-dependent phenomena are of great interest, and researchers have sought to shed light on these processes with MRI, particularly in vivo. In this work, a new hybrid technique based on EPI and using the concept of keyhole imaging is presented. By sharing peripheral k-space data between images and acquiring the keyhole more frequently, it is shown that the spatial resolution of the reconstructed images can be maintained. The method affords a higher temporal resolution and is more robust against susceptibility and chemical-shift artifacts than single-shot EPI. The method, termed shared k-space echo planar imaging with keyhole (shared EPIK), has been implemented on a standard clinical scanner. Technical details, simulation results, phantom images, in vivo images, and fMRI results are presented. These results indicate that the new method is robust and may be used for dynamic MRI applications. Magn Reson Med 45:109-117, 2001.

Artifacts↗

Uniform basic data sets for health statistical systems.

The United States approach to coordinating health statistics involves introduction of multipurpose basic data sets describing health status and the health care system. Standard reporting procedures have been used for many years for vital statistics. Recently designated data sets cover health manpower, inpatient facilities, short-stay hospital discharges, and use of ambulatory care services. A data set for long-term health care is in the design stage. Advantages of this approach in the United States and internationally are: basic comparisons can be made between health care settings are geographic areas while maintaining the variety and flexibility of existing public and private information systems; shared local, regional, and national data systems can be set up; and better coordination can be achieved between government-sponsored general-purpose and administrative data systems. Problem areas are: avoiding undue proliferation, e.g. of disease-specific data sets; adhering to the principle of minimal requirements; linking data sets and coordinating them with census and other social indicators; promoting widespread use; assuring data quality; establishing mechanisms for review and revision; and extending the concept internationally.

Data Display↗

Ancestry of an isolated subspecies of salamander, Ambystoma tigrinum stebbinsi Lowe: the evolutionary significance of hybridization.

Most phylogenetic systematists assume speciation results in dichotomously branching phylogenies. Hybridization that gives rise to a new lineage can produce character homoplasty that might obscure a species' true history. We report the results of a restriction-enzyme analysis of mitochondrial DNA (mtDNA) variation in three tiger salamander subspecies (Ambystoma trigrinum mavortium, Ambystoma tigrinum nebulosum, and Ambystoma trigrinum stebbinsi) and compare the results to studies of morphological and allozymic variation in these taxa. Allozymically, A. t. mavortium and A. t. nebulosum share most of their genomes (although each has several unique alleles), yet color pattern and mtDNA haplotypes are distinct. Color pattern and allozyme data suggest that A. t. stebbinsi shares a common ancestor with A. t. mavortium, while the A. t. stebbinsi mtDNA haplotype is derived from an A. t. nebulosum haplotype. Thus, our data suggest that A. t. stebbinsi originated through hybridization between A. t. mavortium and A. t. nebulosum. That hybridization can produce recognizably distinct evolutionary entities has long been recognized for plants, but the evolutionary significance of hybridization in animals should be examined more closely. Conservation agencies must recognize that hybrids and hybrid taxa are not necessarily evolutionary "mistakes," and they might have significant importance in the production of natural biodiversity.

Animals↗

Are efforts at expanding the donor pool misdirected?

BACKGROUND: The number of patients potentially benefiting from heart transplantation far exceeds the number of hearts available. This has led to an increasing interest in use of hearts from previously unacceptable donors. However, the long-term outcome of such hearts is largely unknown. Research on other parts of the donor process may provide a greater number of additional hearts of high quality. METHODS: Journal reviews were conducted to identify proposed methods for use of previously unacceptable donor hearts, as well as research regarding the consent process. Data from the United Network for Organ Sharing were obtained to identify the reason consented heart referrals were not recovered. Data from the Association of Organ Procurement Organizations were obtained for consent rates in the United States. Calculated estimates were made for the number of excess hearts potentially available by use of extended donor criteria versus increasing the consent rate. RESULTS: More than 40 articles proposing extended donor criteria were identified versus only 12 articles about consent. Of the 2199 consented heart referrals not recovered in 1995, more than 1300 fit into a category amenable to a proposed strategy for use of extended donors. If these strategies were used aggressively (50% of the time), 701 additional hearts would have been available. Alternatively, if the consent rate were increased a comparable amount, 1260 excess hearts of high quality would have been available. CONCLUSION: Although research into extended donor criteria is probably justified, transplantation programs should direct research efforts into the consent process as a potential source of additional hearts.

Heart Transplantation↗

The pursuit of equity in health: reflections on race and public health data in Southern Africa.

The United States shares with Zimbabwe and South Africa a history of racial subjugation. A revision of the US racial classification to allow membership in more than one group means race may no longer be an exclusive characteristic. These issues also have been debated in southern Africa. In this commentary, the author reviews race classification in southern Africa and the use of race-specific public health data. Comparisons of illness and death rates across race groups have shown the health consequences of White privilege and Black disadvantage. But current public health data are not divided by race. The consequences of this policy are discussed.

Censuses↗

The demand for dental care: evidence from a randomized trial in health insurance.

Using data from a randomized trial in health insurance, this paper examines the effect of cost sharing on use of dental services. The data come from a sample of the nonaged, noninstitutionalized civilian population of six urban and rural sites. We find that: reducing the level of cost sharing increases demand for dental services; and dental expenses rise 46% when the coinsurance rate falls from 95% to 0%, subject to a catastrophic limit on out-of-pocket expenses. Of this increase, two-thirds is attributable to an increase in the likelihood of visiting a dentist during the year. Moreover, there is a substantial surge in demand during the first year of more generous coverage. The first-year response to cost sharing is nearly twice the second-year response.

Adolescent↗

Comparative analysis by independent contrasts (CAIC): an Apple Macintosh application for analysing comparative data.

CAIC is an application for the Apple Macintosh which allows the valid analysis of comparative (multi-species) data sets that include continuous variables. Comparison among species is the most common technique for testing hypotheses of how organisms are adapted to their environments, but standard statistical tests like regression should not be used with species data. Such tests assume independence of data points, but related species often share traits by common descent rather than through independent adaptation. CAIC uses a phylogeny of the species in the data set to partition the variance among species into independent comparisons (technically, linear contrasts), each comparison being made at a different node in the phylogeny. There are two partitioning procedures--one used when all variables are continuous, the other when one variable is discrete. The resulting comparisons can be analysed validly in standard statistical packages to test hypotheses about correlated evolution among traits, to estimate parameters such as allometric exponents, and to compare rates of evolution. Previous versions of the package have already been used widely; this version is simpler to use and works on a wider range of machines. The package and manual are freely available by anonymous ftp or from the authors.

Data Interpretation, Statistical↗

Molecular identification of high-affinity glutamate transporters in sheep and cattle forestomach, intestine, liver, kidney, and pancreas.

Glutamate metabolism is essential to support many facets of metabolism. The objective of this study was to determine the tissue distribution of glutamate transporters known to support the tissue metabolism of glutamate. The expression of proteins capable of high-affinity glutamate transport (system X-(AG)) by epithelia isolated from the rumen, omasum, duodenum, jejunum, ileum, cecum, and colon and homogenates of liver, kidney, and pancreatic tissues from wethers (n = 4; BW = 28.4 +/- 8.4 kg) and steers (n = 3; BW = 426 +/- 32.3 kg) fed forage-based diets was evaluated by immunoblot analysis. Proteins EAAC1 (62, 93 kDa) and GLT-1 (142, 188, >202 kDa) were expressed by every tissue examined. In contrast, GLAST1 (140 kDa) was expressed only by the pancreas, and EAAT4 (67 kDa) was detected only in sheep brain. To corroborate protein expression data, the presence and size of transporter mRNA in ileal, liver, and pancreatic homogenates were evaluated by Northern analysis. GLAST1 mRNA (2.4, 4.3 kb) was detected only in the pancreas, whereas EAAC1 (2.2, 2.8 kb) and GLT-1 (12.1 kb) mRNA transcripts were detected in all three tissues. The expression of EAAT4 and GLT-1 mRNA was confirmed by reverse transcriptase-polymerase chain reaction analyses. Sequencing of the resulting partial-length ovine GLT-1 cDNA revealed 100% identity with the rat homolog. Overall, these data demonstrate that sheep and cattle share the same pattern of system X-(AG) transporter expression, which differed among tissues and transporter isoforms. Accordingly, these data provide the fundamental knowledge to initiate research that determines whether the expression of high-affinity glutamate transporters by ruminants is sensitive to ontogenic and(or) dietary regulation.

ATP-Binding Cassette Transporters↗

Implementation of a statewide perinatal automated medical network (PAM/NET) for Michigan.

PAM/NET is a computerized data base and conferencing system used by nine neonatal intensive care units in Michigan and Illinois. The system depends on the timesharing resource of a large university mainframe computer. The data base functions are managed by a sophisticated inverted file relational data base management system capable of mass storage and rapid and specific retrieval of individual cases or summary data. Data stored in the system are used to generate admission, discharge and developmental assessment clinic summaries that serve as such for the medical record and as letters to primary physicians. We report here the early experience in the design and dissemination of this database network to the participating hospitals. Conflicting goals of sharing and confidentiality of clinical data are addressed in the design of this system.

Ambulatory Care Facilities↗

A latent autoregressive model for longitudinal binary data subject to informative missingness.

Longitudinal clinical trials often collect long sequences of binary data. Our application is a recent clinical trial in opiate addicts that examined the effect of a new treatment on repeated binary urine tests to assess opiate use over an extended follow-up. The dataset had two sources of missingness: dropout and intermittent missing observations. The primary endpoint of the study was comparing the marginal probability of a positive urine test over follow-up across treatment arms. We present a latent autoregressive model for longitudinal binary data subject to informative missingness. In this model, a Gaussian autoregressive process is shared between the binary response and missing-data processes, thereby inducing informative missingness. Our approach extends the work of others who have developed models that link the various processes through a shared random effect but do not allow for autocorrelation. We discuss parameter estimation using Monte Carlo EM and demonstrate through simulations that incorporating within-subject autocorrelation through a latent autoregressive process can be very important when longitudinal binary data is subject to informative missingness. We illustrate our new methodology using the opiate clinical trial data.

Algorithms↗

Excess concordance of cancer incidence and lifestyles in married couples (Japan): survival analysis of paired rate data.

OBJECTIVE: A population-based cohort study was conducted to examine concordance of cancer incidence and lifestyle in married couples. METHODS: Cancer incidence from 1 September 1986 to 30 June 2000 was followed for a baseline cohort of 2601 community-living married couples aged 40-84 years who were cancer-free and had completed an epidemiologic questionnaire in 1986 in Saitama, Japan. We computed age-adjusted cross-ratios: spouse-with/spouse-without rate ratios as a measure of association for paired rate data, using a bivariate survival analysis method. RESULTS: Concordance of lifestyles for couples was high for dietary habits, and low for smoking and alcohol habits. During the 14 year follow-up, 464 cancer cases occurred (husbands only: 279, wives only: 119, both: 33 couples). Wives whose husbands developed cancer were at an increased risk of developing cancer themselves, compared with those whose husbands had not had cancer (CR: 1.70, 95% CI: 1.12-2.58). Mean age at diagnosis was 68.2 years for husbands and 66.0 years for wives. And correlation of cancer incidence was further seen among couples who shared habits of smoking and/or drinking. CONCLUSIONS: Our data suggest that shared lifestyles including smoking and drinking habits are associated with an excess concordance of cancer incidence among married couples.

Adult↗

Securing electronic health records without impeding the flow of information.

OBJECTIVE: We present an integrated set of technologies, known as the Hippocratic Database, that enable healthcare enterprises to comply with privacy and security laws without impeding the legitimate management, sharing, and analysis of personal health information. APPROACH: The Hippocratic Database approach to securing electronic health records involves (1) active enforcement of fine-grained data disclosure policies using query modification techniques, (2) efficient auditing of past database access to verify compliance with policies and track security breaches, (3) data mining algorithms that preserve privacy by randomizing information at the individual level, (4) de-identification of personal health data using an optimal method of k-anonymization, and (5) information sharing across autonomous data sources using cryptographic protocols. CONCLUSIONS: Our research confirms that policies concerning the disclosure of electronic health records can be reliably and efficiently enforced and audited at the database level. We further demonstrate that advanced data mining and anonymization techniques can be employed to analyze aggregate health records without revealing individual patient identities. Finally, we show that web services and commutative encryption can be used to share sensitive information selectively among autonomous entities without compromising security or privacy.

Access to Information↗

Identification of RB18A, a 205 kDa new p53 regulatory protein which shares antigenic and functional properties with p53.

Immunological screening with the anti-p53 moAb, PAb1801 of a cDNA expression library, prepared from human B lymphoma cells, led us to identify a new human 205 kDa protein called RB18A for 'Recognized By PAb1801 moAntibody'. Immunoblotting or immunoprecipitation of fusion protein or in vitro translated protein, respectively, demonstrated that RB18A protein was recognized by several anti-p53 moAb reacting with the N or C-terminal domains of p53. Full length sequence of RB18A cDNA and computer analysis demonstrated that despite common antigenic determinants between RB18A and p53 proteins, nucleotide and deduced protein sequences did not reveal any significant homologies. RB18A mRNA was detected in all tissues tested except in kidney. In addition, RB18A protein shared identical functions with p53 protein: binding to DNA or to p53 and self-oligomerization. Furthermore, RB18A regulated p53 specific binding on his DNA consensus binding site. These functions were associated to the C-terminal domain of RB18A protein and more specifically to the PAb421 binding site present in this domain. The activation by RB18A of p53 binding on DNA was induced through an unstable interaction between both proteins. Altogether, our data demonstrated that RB18A protein shares antigenic and functional properties with p53 and regulated p53 functions.

Amino Acid Sequence↗

The human placental growth hormone variant is mitogenic for rat lymphoma Nb2 cells.

Although there is evidence that human (h) placental GH variant (hGH-V) possesses a growth-promoting function, lactogenic activity by the hormone has not been demonstrated. Rat anterior pituitary tumor (GC) cells stably transfected with the hGH-V gene (GC [hGH-V] cells) synthesize and secrete hGH-V. This hormone shares considerable structural similarity with pituitary growth hormone (hGH-N) and chorionic somatomammotropin (hCS) at the nucleotide (greater than 90%) and amino acid (greater than 80%) levels. As expected, both hGH-N and hCS antibodies detect hGH-V by immunoblotting. However, hGH-V, but not hGH-N or hCS, cross-reacts with human or rat pituitary prolactin (PRL) antibodies. These data indicate that structural features shared by hGH-V and pituitary PRL are not present in hGH-N or hCS. Comparison of amino acid sequences implicates two regions that may account for a common epitope between hGH-V and hPRL, and structural difference from hGH-N and hCS. The possible lactogenic activity by hGH-V was assessed in a rat lymphoma Nb2 cell bioassay. Conditioned medium from GC[hGH-V] cells permitted growth of lactogen-dependent Nb2 lymphoma cells in culture. This activity was blocked by antibodies raised to rat PRL but not hPRL or hGH-N. Comparison of the hGH-V amino acid sequence with those from 14 other lactogenic hormones, including hPRL, hCS and hGH-N, reveals 6 conserved amino acids. These data indicate a lactogenic as well as growth-promoting function for the secreted hGH-V protein in vivo.

Amino Acid Sequence↗