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At least 397 records · Page 22Linked to original sources

PubMed2006

Thermodynamics, structure, and dynamics in room temperature ionic liquids: the case of 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim][PF6]).

A detailed investigation of the phase diagram of 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim][PF(6)]) is presented on the basis of a wide set of experimental data accessing thermodynamic, structural, and dynamical properties of this important room temperature ionic liquid (RTIL). The combination of quasi adiabatic, continuous calorimetry, wide angle neutron and X-ray diffraction, and quasi elastic neutron scattering allows the exploration of many novel features of this material. Thermodynamic and microscopic structural information is derived on both glassy and crystalline states and compared with results that recently appeared in the literature allowing direct information to be obtained on the existence of two crystalline phases that were not previously characterized and confirming the view that RTILs show a substantial degree of order (even in their amorphous states), which resembles the crystalline order. We highlight a strong connection between structure and dynamics, showing the existence of three temperature ranges in the glassy state across which both the spatial correlation and the dynamics change. The complex crystalline polymorphism in [bmim][PF(6)] also is investigated; we compare our findings with the corresponding findings for similar RTILs. These results provide a strong experimental basis for the exploration of the features of the phase diagram of RTILs and for the further study of longer alkyl chain salts.

Journal Article↗

PubMed2003

Quantitative description of human skin water dynamics by a disposition-decomposition analysis (DDA) of trans-epidermal water loss and epidermal capacitance.

BACKGROUND: In vivo water assessment would greatly benefit from a dynamical approach since the evaluation of common related variables such as trans-epidermal water loss or "capacitance" measurements is always limited to instantaneous data. Mathematical modelling is still an attractive alternative already attempted with bi-exponential empirical models. A classical two-compartment interpretation of such models raises a number of questions about the underlying fundamentals, which can hardly be experimentally confirmed. However, in a system analysis sense, skin water dynamics may be approached as an ensemble of many factors, impossible to discretize, but conceptually grouped in terms of feasible properties of the system. The present paper explores the applicability of this strategy to the in vivo water dynamics assessment. METHODS: From the plastic occlusion stress test (POST) skin water balance is assessed by modelling trans-epidermal water loss (TEWL) and "capacitance" data obtained at skin's surface. With system analysis (disposition-decomposition analysis) the distribution function, H(t), modelled as a sum of exponential terms, covers only the distribution characteristics of water molecules traversing the skin. This may correspond macroscopically to the experimental data accessed by "corneometry". Separately, the hyperbolic elimination function Q(TEWL) helps to characterise the dynamic aspects of water influx through the skin. DISCUSSION AND CONCLUSION: In the observable range there seems to be a linear relationship between the net amount of water lost at the surface by evaporation, and the capability of the system to replenish that loss. This may be a specific characteristic of the system related to what may be described as the skin's "intrinsic hydration capacity" (IHC) a new functional parameter only identified by this strategy. These new quantitative tools are expected to find different applicabilities (from the in vivo skin characterisation to efficacy testing) contributing to disclose the dynamical nature of the skin water balance process.

Adult↗

PubMed1990

"Do I know you?" The role of significant others in general social perception.

This research used an idiographic method to examine the proposition that significant others are mentally represented as well-organized person categories that can influence social perception even more than representations of nonsignificant others, stereotypes, or traits. Together, Studies 1 and 2 showed that significant-other representations are richer, more distinctive, and more cognitively accessible than the other categories. Study 3 replicated the accessibility data and gauged inferential power by indirectly activating each category in a learning trial about a fictional person and then testing recognition memory. The results showed that participants made more category-consistent false-positive errors about targets who activated significant others vs. any other category. This constitutes the first experimental demonstration of transference and has implications both for social categorization and for basic personality processes.

Adult↗

PubMed1999

Target site selection for an RNA-cleaving catalytic DNA.

A small catalytic DNA, known as the 10-23 DNA enzyme or deoxyribozyme, has been shown to efficiently hydrolyze RNA at purine-pyrimidine (R-Y) junctions in vitro. Although these potentially cleavable junctions are ubiquitous, they are often protected from deoxyribozyme activity by RNA secondary structure. We have developed a multiplex cleavage assay for screening the entire length of a target RNA molecule for deoxyribozyme cleavage sites that are efficient, both in terms of kinetics and accessibility. This strategy allowed us to simultaneously compare the RNA cleaving activity of 80 deoxyribozymes for a model target gene (HPV16 E6), and an additional 60 deoxyribozymes against the rat c-myc target. The human papilloma virus (HPV) target was used primarily to characterize the multiplex system and determine its validity. The c-myc target, coupled with a smooth muscle cell proliferation assay, allowed us to assess the relationship between in vitro cleavage efficiency and c-myc gene suppression in cell culture. The multiplex reaction approach streamlines the process of revealing effective deoxyribozymes in a functional assay and provides accessibility data that may also be applicable to site selection for other hybridization-based agents.

Animals↗

PubMed2006

Human genetics in the Crescent City.

Genome-wide association studies are now being carried out for a variety of human traits. Announcements at the annual meeting of the American Society of Human Genetics, held recently in New Orleans, offer a glimpse into the changing landscape surrounding issues such as study design, reporting, analysis and data accessibility.

Genetics, Medical↗

PubMed1998

Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy.

The transmembrane organization of a potassium channel from Streptomyces lividans has been studied using site-directed spin labeling techniques and electron paramagnetic resonance spectroscopy. In the tetrameric channel complex, two alpha-helices were identified per monomer and assigned to the amino acid sequence. Probe mobility and accessibility data clearly establish that the first helix (TM1) is located in the perimeter of the channel, showing extensive protein-lipid contacts, while the second helix (TM2) is closer to the four-fold symmetric axis of the channel, lining the intracellular vestibule. A large conformational change in the C-terminal end of TM2 was measured when comparing conditions that favor either the open or closed states. The present data suggest that the diameter of the internal vestibule increases with channel opening.

Amino Acid Sequence↗

PubMed2005

Pattern profiling and mapping of the fat body transcriptome in Drosophila melanogaster.

In Drosophila, the fat body is a collective name for the masses and sheets of adipose tissue that are distributed throughout the fly body. Thus far, >386,000 Drosophila expressed sequence tags (ESTs) have been deposited to the GenBank database, including 10,443 derived from fat body in flies (data accessed on October 7, 2004). The objective of this study was to map the transcriptome of the fat body in flies and thus provide genomics and bioinformatics tools for developing a Drosophila model for addressing the genetic complexity of obesity in humans. The gene-EST Basic Local Alignment Search Tool (BLAST) matches revealed that these ESTs could represent 12,188 coding genes in the Drosophila genome. Among them, at least 2,261 are expressed in the fat body, including 41 identified as preferentially expressed genes with logarithm of odds >3.0. Self-organizing map analysis revealed a cluster of 290 genes favorably expressed in the fat body compared with genes expressed in five other tissues. Mapping of the fat body transcriptome identified a 1.7-Mb domain on 3L containing 35 genes that were expressed at a much higher level than in other tissues (transcript density factor = 1.0 approximately 2.3).

Animals↗

PubMed2026

Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo.

Enhancers control tissue-specific gene expression across animals1. Although deep learning2,3 has enabled enhancer prediction and design in mammalian cell lines and non-mammalian model organisms4-10 (reviewed in a previous publication11), it remains unclear whether such approaches can operate within the regulatory complexity of mammalian genomes and tissues in vivo. Here we present a general strategy for designing tissue-specific enhancers that function reliably in mice. We use deep learning to train compact convolutional neural networks on curated chromatin accessibility data and fine-tune them by transfer learning on validated human and mouse enhancers. Guided by these models, we design 15 synthetic enhancers for the heart, limb and central nervous system in mouse embryos, all of which are active in their intended target tissue. These results demonstrate that mammalian enhancer function can be reliably inferred from DNA sequence alone, enabling the predictive de novo design of tissue-specific synthetic enhancers from modest training sets. This work establishes a generalizable framework for programmable control of mammalian gene expression in vivo, opening new avenues in functional genomics, synthetic biology and gene therapy.

Animals↗

PubMed2003

Migraine prophylactic medication usage patterns in The Netherlands.

This study aims to investigate usage patterns of specific migraine prophylactic medications in ergotamine and triptan patients commencing this treatment for the first time during 1 January 1992 until 31 December 1998. Usage patterns of specific migraine prophylactic drugs were evaluated for each patient by accessing data from a large prescription database and were characterized as continued, switch or stop use during the patient observation period. Several patient and medication-related factors were explored in order to identify a possible relationship with the specific usage pattern defined. Approximately 75% of the study population (n = 729) had terminated (stop or switch) prophylactic treatment after 1 year. Age < 40 years (relative risk (RR) 1.9; 95% confidence interval (CI) 1.2-3.2) and the concomitant use of non-steroidal anti-inflammatory drugs (RR 3.2; 95% CI 1.2-5.5) or specific abortive migraine drugs resulted in a faster onset of treatment modification (switch). Overall, migraine prophylactic treatment is used for a relatively short period, probably attributable to the common limitations associated with migraine prophylaxis, such as poor compliance and/or limited therapeutic efficacy. Patterns of use can be influenced by a variety of factors, including age, type of prescriber and certain co-medication. Patient interview studies are required to clarify these issues further.

Adrenergic beta-Antagonists↗

PubMed2000

[Helicobacter pylori and gastroesophageal reflux disease].

The latest accessible data indicate, that Helicobacter pylori (H.p.) infection, particularly by cagA-positive strains, protects against the development of gastroesophageal reflux disease (GERD) and its complications. Various epidemiological, pathophysiological and clinical studies demonstrate this protective effect, which is dependent on the extent of H.p. induced gastritis. Severe corpus gastritis may cause a profound reduction of acid secretion. In regard to acute or chronic PPI therapy of GERD the biological antisecretory effect of H.p. is of minor benefit. Development of atrophic gastritis in patients with GERD treated chronically with PPI is still uncertain. On account of the protective effect of H.p. against GERD, it is prudent to reserve H.p. eradication for the well-established indications.

Gastritis↗

PubMed2005

Brownian dynamics investigation of magnetization and birefringence relaxations in ferrofluids.

Brownian dynamics simulations are used to investigate the dynamics of orientational properties of real charge-stabilized ferrofluids, i.e. stable colloidal dispersions of magnetic nanoparticles. The relaxation times of the magnetization and of the birefringence, data accessible by experimental techniques, have been computed at several volume fractions. Besides, the effect of hydrodynamic interactions has been investigated. Equilibrium simulations without field are found to be inadequate to determine the aforementioned relaxation times for the systems under study, the dipolar interaction being too weak. Thus a nonequilibrium simulation procedure that mimics the experimental operating mode has been developed. After equilibrium simulations under a magnetic field, both birefringence and magnetization decays are recorded once the field is suppressed. Birefringence and magnetization decays are markedly impeded as the volume fraction increases, whereas they are barely enhanced when the intensity of the initial magnetic field is increased at a fixed volume fraction. Eventually, hydrodynamic interactions exhibit a slight but systematic lengthening of the relaxation times.

Journal Article↗

PubMed2004

Pathways to chemical dependency treatment for adolescents in an HMO.

This study examines pathways to chemical dependency (CD) treatment for adolescents in a prepaid health plan, including factors influencing treatment referral and access. Data were collected from 419 adolescent CD treatment intakes ages 13 to 18 in a large, private health plan. The study examines predictors of referral from different sources and of mental health treatment prior to CD treatment. Referral patterns, problem severity, and psychiatric comorbidity differed by gender. Being male (p < .05) and higher scores on the Youth Self-Report (YSR) externalizing scale (p < .01) predicted a justice system referral. Using more types of substances predicted referral by medical and mental health providers (p < .05) and self-referral (p < .01). Higher YSR internalizing scores predicted referral from mental health (p < .01) and self-referral (p <.01). Being White versus African American (p < .05) or Latino (p < .01), older (p < .05), and having higher YSR internalizing scores (p < .05), a conduct disorder (p < .01), or a family member with a substance use problem (p < .01) predicted a mental health visit prior to CD intake. The findings raise questions regarding the role of health plans, clinicians, families, schools, and community agencies in referring and treating adolescents with substance use problems. They suggest that improved coordination of care may promote more integrated treatment practices, which could decrease substance use, mental health, and medical problem severity.

Adolescent↗

PubMedDate not supplied

London Archive of Longitudinal Growth Data.

An Archive of longitudinal growth data, accessible to research workers under the usual safeguards, has been set up in the Department of Growth and Development. The present S.I.R. database contains seven British and one Indian study. The Archive is open to receive other contributions if researchers wish.

Adolescent↗

PubMed2002

Water as a structural element in a channel: gating in the Kcsa channel, and implications for voltage-gated ion channels.

Water is becoming understood as a structural element in proteins. Here we are concerned with one particular type of protein, ion channels. The S. Lividans KcsA K(+) channel, the X-ray structure of which is known, is gated by protons (i.e, by a drop in pH). Ab initio calculations suggest that an H(5)O(2) group, partially charged, connects the E118 residues in the gating region, when the four residues have a -2 net charge, but that the hydrogen bonding is not strong enough to do this when the charge becomes -1. The H(5)O(2) group would block the channel, in the -2 state, and prevent motion of the four transmembrane (TM) segments of the protein, by binding them. With the weaker bond in the -1 state, the TM segments would be able to separate (as they have been found to do experimentally, opening the channel. Voltage gated channels have four additional TM segments for each of the four domains of the channel protein. These appear to allow motion of protons; in fact there is evidence that the initial step in gating must be the transfer of a proton. We have earlier shown that the transfer of a single proton between two methylamines under the influence of a field is possible, as proton tunneling. Subsequent steps are hypothesized to result from four proton transfer cascades of about three protons each, triggered by the initial proton transfer. We suggest that the extra 4 TM segments of the voltage gated channel act as a voltage to proton-current transducer. Water, held by hydrogen bonds, is also suggested as the source of the accessibility data found with MTS reagents, based largely on simulations, our earlier Monte Carlo simulations as well as molecular dynamics studies reported by others. These waters may also play a structural role in the protein.

Bacterial Proteins↗

PubMed1993

Training researchers in cancer prevention and control: a description and evaluation of NCI's Cancer Prevention Fellowship Program.

NCI's Cancer Prevention Fellowship Program recently initiated a continuing evaluation of the fellows' demographics, fellows' accomplishments in the program, fellow and preceptor expectations and satisfaction, program strengths and weaknesses, current employment for former fellows, and ex-fellows' perceptions of program training. Evaluation shows that the program attracts quality applicants (including minorities and females) nationwide from many disciplines. The program successfully educates about cancer prevention and provides a positive preceptor experience with publication opportunities. Areas for improvement are data access, stipend, office space, job assistance, and networking. Recommendations for other programs include committed enthusiastic staff; adequate budget, space, and support; a formal learning experience in public health fundamentals, research methods, and cancer prevention; individual mentored research within a productive scientific program; aggressive recruitment; competitive admissions policy; defined objectives for fellows; and ongoing formal program evaluation.

Attitude of Health Personnel↗

PubMed2001

Site-directed spin-labeling analysis of reconstituted Mscl in the closed state.

The mechanosensitive channel from Escherichia coli (Eco-MscL) responds to membrane lateral tension by opening a large, water-filled pore that serves as an osmotic safety valve. In an attempt to understand the structural dynamics of MscL in the closed state and under physiological conditions, we have performed a systematic site-directed spin labeling study of this channel reconstituted in a membrane bilayer. Structural information was derived from an analysis of probe mobility, residue accessibility to O(2) or NiEdda and overall intersubunit proximity. For the majority of the residues studied, mobility and accessibility data showed a remarkable agreement with the Mycobacterium tuberculosis crystal structure, clearly identifying residues facing the large water-filled vestibule at the extracellular face of the molecule, the narrowest point along the permeation pathway (residues 21-26 of Eco-MscL), and the lipid-exposed residues in the peripheral transmembrane segments (TM2). Overall, the present dataset demonstrates that the transmembrane regions of the MscL crystal structure (obtained in detergent and at low pH) are, in general, an accurate representation of its structure in a membrane bilayer under physiological conditions. However, significant differences between the EPR data and the crystal structure were found toward the COOH-terminal end of TM2.

Amino Acid Sequence↗

PubMed1999

The Tangled Web: Gene Genealogies and the Origin of Eukaryotes.

Accessing data from the genomes of organisms (individual genes) and analyzing these data using sophisticated alignment and phylogenetic methods led to the expectation that we would be able to paint a clear picture of the evolution of eukaryotes. Previous analyses based on morphology and ultrastructure failed to pinpoint both the sister taxon to eukaryotes and the branching order of eukaryotic lineages. However, the expectation that molecular data would provide resolution has not been met since a growing number of gene genealogies present conflicting hypotheses for the origin and diversification of eukaryotes. Instead of reconstructing a simple bifurcating tree of life, these gene genealogies have generated a complex picture of eukaryotic genomes whereby ancient lateral transfers (of individual genes or perhaps even entire genomes) has tangled the evolutionary history of eukaryotes. Resolution of these conflicting genealogies comes in recognizing that eukaryotes are chimeric, containing genetic information from multiple ancestral lineages.

Journal Article↗

PubMed2006

Diabetes information systems: a rapidly emerging support for diabetes surveillance and care.

BACKGROUND: With the rapid advances in information technology in the last decade, various diabetes information systems have evolved in different parts of the world. Availability of new technologies and information systems for monitoring and treating diabetes is critical to achieving recommended metabolic control, including glycosylated hemoglobin levels. The first step is to develop a registry, including a patient identifier that can link multiple data sources, which can then serve as a springboard to electronic mechanisms for practitioners to gain information on performance and results. OBJECTIVE: The aim is to review the provisions for diabetes surveillance in different parts of the world. This is a systematic review of national and regional information systems for diabetes surveillance. LITERATURE REVIEW: A comprehensive review was undertaken using Medline literature review, internet search using the Google search engine, and e-mail consultation with opinion leaders. TOPICS REVIEW: National/regional-level diabetes surveillance systems in Europe, the United States, Australia/New Zealand, and Asia have been reviewed. State-of-the-art diabetes information systems linking multiple data sources, with extensive audit and feedback capabilities, have also been looked at. RESULTS: National/regional-level audit databases have been tabulated. Diabetes information systems linking multiple data sources have been described. Most of the developed countries have now implemented systems such as diabetes registers and audits for diabetes surveillance in at least some regions, if not nationally. Developing nations are beginning to recognize the need for chronic disease management. CONCLUSIONS: With the advancements in information technology, the diabetes registers have the potential to rise beyond their traditional functions with dynamic data integration, decision support, and data access, as demonstrated by some diabetes information systems. With the rapid pace of development in electronic health records and health information systems, countries that are beginning to build their health information technology infrastructure could benefit from planning and funding along these lines.

Diabetes Mellitus↗