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PubMedDate not supplied

[DNA interaction with low molecular ligands of different structure. II. Complexes of DNA with actinomine and its analogs].

DNA-complexes with actinomine and its analogues containing omega-dialkylaminoalkyl groups at 1,9 positions of the phenoxazone moiety were studied by technique of spectrophotometry, viscometry and flow birefringence. In the process of spectrophotometry titration two groups of spectra corresponding to different DNA--ligand ratio in a complex were observed. According to the experimental data the investigated compounds are bounded to DNA by means of intercalation and external binding. There within a region of low degrees of binding the intercalation type of the ligand--DNA interaction prevails. In virtue of the spectrophotometry data the intercalation binding share was calculated. The intrinsic viscosity of a complex increases in the case of ligand intercalation and does not change as it joins to the DNA double-helix from outside. Optical anisotropy of DNA molecule increases linearly irrespective of the way of ligand binding. Data on the flow birefringence permits to conclude that under external binding the angle between the normal to the ligand chromophore plane and the axis of DNA double-helix is about zero. During ligand intercalation the equilibrium rigidity of DNA molecules increases.

Chemical Phenomena↗
PubMed2005

Trends in the geographic distribution of human embryonic stem-cell research.

Human embryonic stem-cell (hESC) research offers substantial potential benefits but has generated politically influential controversies and, in the United States, funding restrictions. Some observers fear the United States has been falling behind nations more permissive in this field, but policy debate has remained largely anecdotal. This study reports citation data indicating that the share of hESC research publications credited to the United States in the six years following the introduction of key technologies was significantly less than in five less contentious biomedical-research areas. The United States share of hESC publications fell sharply in 2003 and remained near this reduced level in 2004. Putative explanations are reviewed and several implications discussed.

Asia↗
PubMed2002

OILing the way to machine understandable bioinformatics resources.

The complex questions and analyses posed by biologists, as well as the diverse data resources they develop, require the fusion of evidence from different, independently developed, and heterogeneous resources. The web, as an enabler for interoperability, has been an excellent mechanism for data publication and transportation. Successful exchange and integration of information, however, depends on a shared language for communication (a terminology) and a shared understanding of what the data means (an ontology). Without this kind of understanding, semantic heterogeneity remains a problem for both humans and machines. One means of dealing with heterogeneity in bioinformatics resources is through terminology founded upon an ontology. Bioinformatics resources tend to be rich in human readable and understandable annotation, with each resource using its own terminology. These resources are machine readable, but not machine understandable. Ontologies have a role in increasing this machine understanding, reducing the semantic heterogeneity between resources and thus promoting the flexible and reliable interoperation of bioinformatics resources. This paper describes a solution derived from the semantic web [a machine understandable world-wide web (WWW)], the ontology inference layer (OIL), as a solution for semantic bioinformatics resources. The nature of the heterogeneity problems are presented along with a description of how metadata from domain ontologies can be used to alleviate this problem. A companion paper in this issue gives an example of the development of a bio-ontology using OIL.

Algorithms↗
PubMed1995

Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure.

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.

Aging↗
PubMed1997

The effect of fatigue on multijoint kinematics and load sharing during a repetitive lifting test.

STUDY DESIGN: A repetitive lifting test in the sagittal plane was performed with a submaximal load at a maximal lifting rate to understand the effects of fatigue on kinematic and kinetic measures of performance. OBJECTIVES: To quantify the effect of fatigue during a highly repetitive lifting task, in terms of lifting force transmitted to the load, joint motion patterns, and internal joint load sharing. SUMMARY OF BACKGROUND DATA: Industrial surveillance and epidemiologic data suggest that repetitive lifting is a risk factor for low back pain. Previous studies examining the effect of fatigue have either been constrained to isolated trunk movement, or have not explored the internal load distribution and potential alteration in the loading patterns. METHODS: Sixteen healthy male subjects performed repetitive lifting in the sagittal plane with a load equal to 25% of their maximal lifting capacity, at a maximal lifting rate. Changes in lifting performance were determined from the power transferred to the box, joint kinematics, and joint kinetics. Data from three cycles at the start and end of the exercise were tested for the effect of fatigue using repeated-measures analysis of variance. RESULTS: Fatigue was documented by a reduction in average lifting force and hip and spine torque generation, whereas internal joint load sharing was relatively unchanged. The fatigue was associated with decreased knee and hip motion, and increased lumbar flexion. Decreased postural stability also was evident. CONCLUSIONS: The significant decrease in postural stability and force generation capability because of the repetitive lifting task indicated a higher risk of injury in the presence of unexpected perturbation. Multijoint coordinated lifting tasks provide a more realistic protocol to study neuromuscular fatigue.

Adult↗
PubMed1989

Care-related stress. A comparison of spouse and adult-child caregivers in shared and separate households.

This research examines the role that relationship and household arrangement have in explaining the levels of care-related stress effects experienced by spouse and adult-child caregivers in shared and separate residences. Data from 180 spouse and adult-child caregivers were analyzed to identify differences in caregiver health decline, relationship strain, and activity restriction across these settings when the effects of elder impairment, caregiver age, and use of social supports are controlled. Results show that spouse and adult children in shared households experience similar levels of care-related strain. However, comparison of adult children in shared and separate households show considerable cross-setting differences in strain, with those in shared households having significantly greater activity restriction but less relationship strain. These findings have implications for the delivery of social services, specifically for targeting health monitoring, respite, and family counseling services.

Activities of Daily Living↗
PubMed2006

Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth.

Genomic imprinting is an epigenetic mechanism of regulation that restrains the expression of a small subset of mammalian genes to one parental allele. The reason for the targeting of these approximately 80 genes by imprinting remains uncertain. We show that inactivation of the maternally repressed Zac1 transcription factor results in intrauterine growth restriction, altered bone formation, and neonatal lethality. A meta-analysis of microarray data reveals that Zac1 is a member of a network of coregulated genes comprising other imprinted genes involved in the control of embryonic growth. Zac1 alters the expression of several of these imprinted genes, including Igf2, H19, Cdkn1c, and Dlk1, and it directly regulates the Igf2/H19 locus through binding to a shared enhancer. Accordingly, these data identify a network of imprinted genes, including Zac1, which controls embryonic growth and which may be the basis for the implementation of a common mechanism of gene regulation during mammalian evolution.

Animals↗
PubMed2007

DroSpeGe: rapid access database for new Drosophila species genomes.

The Drosophila species comparative genome database DroSpeGe (http://insects.eugenes.org/DroSpeGe/) provides genome researchers with rapid, usable access to 12 new and old Drosophila genomes, since its inception in 2004. Scientists can use, with minimal computing expertise, the wealth of new genome information for developing new insights into insect evolution. New genome assemblies provided by several sequencing centers have been annotated with known model organism gene homologies and gene predictions to provided basic comparative data. TeraGrid supplies the shared cyberinfrastructure for the primary computations. This genome database includes homologies to Drosophila melanogaster and eight other eukaryote model genomes, and gene predictions from several groups. BLAST searches of the newest assemblies are integrated with genome maps. GBrowse maps provide detailed views of cross-species aligned genomes. BioMart provides for data mining of annotations and sequences. Common chromosome maps identify major synteny among species. Potential gain and loss of genes is suggested by Gene Ontology groupings for genes of the new species. Summaries of essential genome statistics include sizes, genes found and predicted, homology among genomes, phylogenetic trees of species and comparisons of several gene predictions for sensitivity and specificity in finding new and known genes.

Animals↗
PubMed1982

The sharing of amino acid short spans by ancestrally unrelated proteins may be the result of ubiquitous alpha and beta secondary structures.

Short homologies are often found when genetically unrelated proteins are compared but it is not known whether the rate at which they occur is or not above randomness. Comparing 190 pairs of unrelated proteins enable us to show that the frequency at which pairs of unrelated proteins share little spans of amino acids is compatible with chance. However, it appears that those short homologies are mainly located within protein subregions of identical secondary structure: the frequency at which pairs of unrelated proteins exhibit related spans of amino acids inside subregions of identical secondary structure is far above randomness. Those data suggest that the sharing of related spans of amino acids by genetically unrelated proteins could result from structural constraints imposed by the alpha or beta secondary structures.

Amino Acid Sequence↗
PubMed2006

Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.

This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.

Biomarkers, Tumor↗
PubMed2005

Comparisons of case-selection approaches based on allele sharing and/or disease severity index: application to the GAW14 simulated data.

For mapping complex disease traits, linkage studies are often followed by a case-control association strategy in order to identify disease-associated genes/single-nucleotide polymorphisms (SNPs). Substantial efforts are required in selecting the most informative cases from a large collection of affected individuals in order to maximize the power of the study, while taking into consideration study cost. In this article, we applied and extended three case-selection strategies that use allele-sharing information method for families with multiple affected offspring to select most informative cases using additional information on disease severity. Our results revealed that most significant associations, as measured by the lowest p-values, were obtained from a strategy that selected a case with the most allele sharing with other affected sibs from linked families ("linked-best"), despite reduction in sample size resulting from discarding unlinked families. Moreover, information on disease severity appears to be useful to improve the ability to detect associations between markers and disease loci.

Alleles↗
PubMed2004

ELISA for early diagnosis of histoplasmosis.

An ELISA was developed and evaluated as a method for detecting antibodies against glycosylated and deglycosylated histoplasmin (HMIN). Sera from patients with histoplasmosis, paracoccidioidomycosis, sporotrichosis, coccidioidomycosis, aspergillosis, cryptococcosis and healthy donors were tested by ELISA against purified, deglycosylated histoplasmin (ptHMIN) and compared with purified, native (i.e. glycosylated) histoplasmin (pHMIN). Although cross-reactivity was not abolished when ptHMIN was used in the test, it was reduced (pHMIN ELISA 93 % versus ptHMIN ELISA 96 %). However, there were statistically significant differences between the sensitivities of these two methods for the detection of antibodies (pHMIN ELISA 57 % versus ptHMIN ELISA 92 %; P < 0.001) and between the efficiency of the methods (pHMIN ELISA 83 % versus ptHMIN ELISA 95 %; P < 0.001). These parameters compare better than previously published data relating to the use of treated HMIN in diagnostic ELISAs. Some of the reactivities of serum samples were compared by immunoblotting using deglycosylated HMIN and by immunodiffusion using the crude antigen. The results demonstrated that cross-reactions with heterologous sera in both ELISAs could also be observed in immunoblotting and arose from shared protein epitopes. These data suggest that ELISA using deglycosylated HMIN is a very sensitive diagnostic method and, by using commercially available antigen, it can be easily standardized and performed faster than previous Western blot-based tests using the same antigen. It provides a useful adjunct to existing methods of diagnosis that could be applied even in situations where laboratory facilities were relatively limited.

Antibodies, Fungal↗
PubMed1999

Easy-to-read consumer communications: a missing link in Medicaid managed care.

Effective consumer communication is key to successfully moving Medicaid recipients into managed care systems and realizing the promised cost savings from the upheaval. Yet, little attention has been paid to educating these consumers with easy-to-read materials. The Maine Area Health Education Center (AHEC) Health Literacy Center, with the support of the Center for Health Care Strategies, Inc., addressed the problem by offering three national skills training workshops called Writing for the Medicaid Market. The training was marketed to public and private organizations providing Medicaid managed care services, including state Medicaid officials, health benefit counselor staff (enrollment brokers), managed care plan (HMO) staff, and consumer advocates. The training addressed the core issue in health literacy: the mismatch between the low literacy skills of the target population and the high reading level of most health and managed care materials. Posttraining survey data revealed that training was successful in skill building, but also that it addressed only the tip of the iceberg. Faulty and/or nonexistent communication planning limits the success not only of Medicaid, but of other large health and social programs as well. The authors outline the broad scope of the national health literacy problem, share their posttraining survey data, discuss lessons extrapolated from both their data and their experience, and propose a national agenda to address a vast and generally ignored public problem.

Adult↗
PubMed2006

SARS Grid--an AG-based disease management and collaborative platform.

This paper describes the development of the NCHC's Severe Acute Respiratory Syndrome (SARS) Grid project-An Access Grid (AG)-based disease management and collaborative platform that allowed for SARS patient's medical data to be dynamically shared and discussed between hospitals and doctors using AG's video teleconferencing (VTC) capabilities. During the height of the SARS epidemic in Asia, SARS Grid and the SARShope website significantly curved the spread of SARS by helping doctors manage the in-hospital and in-home care of quarantined SARS patients through medical data exchange and the monitoring of the patient's symptoms. Now that the SARS epidemic has ended, the primary function of the SARS Grid project is that of a web-based informatics tool to increase pubic awareness of SARS and other epidemic diseases. Additionally, the SARS Grid project can be viewed and further studied as an outstanding model of epidemic disease prevention and/or containment.

Cooperative Behavior↗
PubMed2006

High-capacity data hiding in halftone images using minimal-error bit searching and least-mean square filter.

In this paper, a high-capacity data hiding is proposed for embedding a large amount of information into halftone images. The embedded watermark can be distributed into several error-diffused images with the proposed minimal-error bit-searching technique (MEBS). The method can also be generalized to self-decoding mode with dot diffusion or color halftone images. From the experiments, the embedded capacity from 33% up to 50% and good quality results are achieved. Furthermore, the proposed MEBS method is also extended for robust watermarking against the degradation from printing-and-scanning and several kinds of distortions. Finally, a least-mean square-based halftoning is developed to produce an edge-enhanced halftone image, and the technique also cooperates with MEBS for all the applications described above, including high-capacity data hiding with secret sharing or self-decoding mode, as well as robust watermarking. The results prove much sharper than the error diffusion or dot diffusion methods.

Algorithms↗
PubMed1998

Effects of changes in the criteria for nationally shared kidney transplants for HLA-matched patients.

BACKGROUND: Nine years ago, a prospective trial began in all U.S. transplant centers to determine whether the results of renal transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to HLA-matched patients. Since then, the stringency of criteria for HLA matching have been liberalized twice, from sharing only those kidneys that matched at all six HLA-A, -B, -DR antigens, to sharing phenotypically HLA-matched kidneys, and most recently to sharing zero HLA-mismatched kidneys. METHODS: Data reported to the United Network for Organ Sharing Scientific Renal Transplant Registry from October 1987 to December 1996 were analyzed to examine the transplant results of nationally shared HLA-matched kidneys and the effects of changes to the HLA matching criteria on graft survival and the distribution of HLA-matched kidneys. RESULTS: The overall 1-year graft survival rate of 5102 HLA-matched transplants was 88% compared with 81% for 58,207 recipients of kidneys with at least one HLA mismatch (P < 0.001). HLA-matched kidneys had a projected 12-year graft half-life, 50% higher than the 8-year half-life of mismatched grafts (P < 0.01). After the first change in the match criteria in August 1990, 1365 phenotypically matched kidneys with fewer than six HLA antigens identified had an 89% 1-year graft survival rate compared with 84% for 466 six antigen-matched kidneys transplanted before the change. After March 1995, 1067 zero HLA-mismatched kidneys that were not phenotypically identical nor six antigen matched, had a 1-year graft survival rate of 88%. Graft survival has not decreased as a result of these changes in the criteria for national sharing, despite an increase in the percentage of matched transplants from 2.5% during the six antigen-match era to 15.5% during the zero antigen-mismatch era. CONCLUSIONS: Changes to the United Network for Organ Sharing policy for national sharing of HLA-matched kidneys have increased the number of patients, and especially minority patients, who can benefit by receiving a well-matched graft without compromising the high graft survival rates provided by an HLA-matched kidney.

Cadaver↗
PubMed1993

Identification of a key domain in annexin and 14-3-3 proteins that stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells.

Calcium-dependent secretion in digitonin-permeabilized adrenal chromaffin cells is stimulated by exogenous annexin II and 14-3-3 proteins. These proteins share a conserved domain that has been suggested to be involved in specific protein-protein interactions. We examined whether this domain was involved in secretion by using a synthetic peptide (P16) of sequence KGDYQKALLYLCGGDD corresponding to the C-terminus of annexin II. P16, but not truncated peptides, prevented the stimulation of secretion by 14-3-3 proteins and produced a partial inhibition of control secretion. These data suggest that the shared annexin/14-3-3 domain is important in the mechanisms controlling Ca(2+)-dependent secretion and may play a key role in protein-protein interactions during exocytosis.

14-3-3 Proteins↗