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1.  Musings on our meetings: MLA conventions, 'ninety-eight to date. 
Annual meetings of the Medical Library Association have been a part of the culture of medical librarians in North America since 1898. With only four exceptions (one during WWI and three during WWII) medical librarians have met annually for nearly 100 years to conduct their business, share ideas, present papers, attend continuing education courses, view exhibits, and have fun. Based on the writer's research and personal experience, his reflections contain a summary of the history and development of these meetings since the first one in Philadelphia in 1898, an assessment of their content and value, and recommendations.
PMCID: PMC226319  PMID: 9583936
2.  Musings on genome medicine: Crohn's disease 
Genome Medicine  2009;1(11):103.
The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, pose a fascinating challenge to specialists in gastroenterology, infectious diseases, immunology and genetics and an often crushing burden to patients and their families.
doi:10.1186/gm103
PMCID: PMC2808738  PMID: 19891793
3.  Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases 
Genome Medicine  2009;1(12):114.
The lysosomal storage diseases, such as Gaucher's disease, mucopolysaccharidosis I, II and IV, Fabry's disease, and Pompe's disease, are rare inherited disorders whose symptoms result from enzyme deficiency causing lysosomal accumulation. Until effective gene-replacement therapy is developed, expensive, and at best incomplete, enzyme-replacement therapy is the only hope for sufferers of rare lysosomal storage diseases. Preventive strategies involving carrier detection should be a priority toward the successful management of these conditions.
doi:10.1186/gm114
PMCID: PMC2808730  PMID: 20017892
4.  Musings about the effects of environment on photosynthesis 
Annals of Botany  2009;103(4):543-549.
Understanding of how plants respond to their environment, particularly to extreme conditions to which their metabolisms are not adapted, is advancing on many fronts. An enormous matrix of plant and environmental factors exists from which mechanisms and assessments of quantitative responses must be developed if further progress in understanding how to improve plant (and particularly crop) production is to be achieved. This Special Issue contains assessments of different areas of plant sciences, ranging from genome to field, but with a focus on photosynthesis. Photosynthesis is central to all aspects of plant biology as the provider of energy and assimilates for growth and reproduction, yet how it is regulated by abiotic stresses, such as salinity and water deficits, and by biotic stresses, such as insect herbivory, is still unclear. Differences in responses of C3, C4 and CAM plants are still uncertain and mechanisms unclarified. Gene distribution and transfer between chloroplasts and nucleus on an evolutionary time scale may reflect conditions in the cell and organelles relevant to the short-term effects of water deficits on photosynthetic rate and the function of ATP synthase. Regulation of conditions in tissues and cells depends not only on chloroplast functions but on mitochondrial activity, and their interaction and differences in responses have implications for understanding many aspects of cell metabolism. Adaptation of plant structure, such as stomatal frequency and composition of the photosynthetic machinery by changes to gene expression controlled by transcription factors, or arising from regulation of gene expression by redox state, is of major importance with implications for adaptation in the short- and long-term. The incisive and thought-provoking reviews in this Special Issue offer analyses of experimental information and develop concepts within the complex matrix, relating photosynthesis and associated metabolism to the environment and addressing mechanisms critically with a balanced assessment of the current state of the science.
doi:10.1093/aob/mcn256
PMCID: PMC2707351  PMID: 19205084
Photosynthesis; environment; water deficit; drought; salinity; gene expression; C3; C4; CAM; ATP; RuBP
5.  MUlti-Dimensional Spline-Based Estimator (MUSE) for Motion Estimation: Algorithm Development and Initial Results 
Annals of biomedical engineering  2008;36(12):1942-1960.
Image registration and motion estimation play central roles in many fields, including RADAR, SONAR, light microscopy, and medical imaging. Because of its central significance, estimator accuracy, precision, and computational cost are of critical importance. We have previously presented a highly accurate, spline-based time delay estimator that directly determines sub-sample time delay estimates from sampled data. The algorithm uses cubic splines to produce a continuous representation of a reference signal and then computes an analytical matching function between this reference and a delayed signal. The location of the minima of this function yields estimates of the time delay. In this paper we describe the MUlti-dimensional Spline-based Estimator (MUSE) that allows accurate and precise estimation of multidimensional displacements/strain components from multidimensional data sets. We describe the mathematical formulation for two- and three-dimensional motion/strain estimation and present simulation results to assess the intrinsic bias and standard deviation of this algorithm and compare it to currently available multi-dimensional estimators. In 1000 noise-free simulations of ultrasound data we found that 2D MUSE exhibits maximum bias of 2.6 × 10−4 samples in range and 2.2 × 10−3 samples in azimuth (corresponding to 4.8 and 297 nm, respectively). The maximum simulated standard deviation of estimates in both dimensions was comparable at roughly 2.8 × 10−3 samples (corresponding to 54 nm axially and 378 nm laterally). These results are between two and three orders of magnitude better than currently used 2D tracking methods. Simulation of performance in 3D yielded similar results to those observed in 2D. We also present experimental results obtained using 2D MUSE on data acquired by an Ultrasonix Sonix RP imaging system with an L14-5/38 linear array transducer operating at 6.6 MHz. While our validation of the algorithm was performed using ultrasound data, MUSE is broadly applicable across imaging applications.
doi:10.1007/s10439-008-9564-2
PMCID: PMC2584164  PMID: 18807190
Motion estimation; Image registration; Strain estimation; Elasticity imaging; Splines
6.  Helicobacter pylori, musings from the epidemiologic armchair. 
Epidemiology and Infection  1992;109(1):81-85.
The literature on Helicobacter pylori has become enormous, but the epidemiology of the infection remains an enigma. Guided by epidemiologic principles we have tried to interpret the available data on the epidemiologic aspects of H. pylori. We conclude that conflicting results on familial clustering and seroprevalence curves might have logical explanations. However, the exact way this organism spreads among humans remains to be solved.
PMCID: PMC2272237  PMID: 1499674
7.  Musings on genome medicine: Hepatitis C 
Genome Medicine  2010;2(1):4.
Hepatitis C is a viral disease transmitted principally by blood, which affects millions of people worldwide. A significant proportion of those affected develop severe liver disease as a result. Only a fraction of patients are responsive to interferon treatment, highlighting the need for further research into genetic factors involved in response to therapy in order to optimize treatment. The only current approach for end-stage disease is liver transplant, which ironically does not cure the condition, and thus poses a clinical dilemma in the face of liver-donor shortage.
doi:10.1186/gm125
PMCID: PMC2829929  PMID: 20193049
9.  Musings on a quarter of a century in pediatric cardiac technology 
Annals of Pediatric Cardiology  2009;2(2):146-148.
doi:10.4103/0974-2069.58316
PMCID: PMC2922662  PMID: 20808627
12.  Musings on the Wanderer: What’s New in our Understanding of Vago-Vagal Reflexes? 
Vago-vagal reflex circuits modulate digestive functions from the oral cavity to the transverse colon. Previous articles in this series have described events at the level of the sensory receptors encoding the peripheral stimuli, the transmission of information in the afferent vagus, and the conversion of this data within the dorsal vagal complex (DVC) to impulses in the preganglionic efferents. The control by vagal efferents of the postganglionic neurons impinging on the glands and smooth muscles of the target organs has also been illustrated. Here we focus on some of the mechanisms by which these apparently static reflex circuits can be made quite plastic as a consequence of the action of modulatory inputs from other central nervous system sources. A large body of evidence has shown that the neuronal elements that constitute these brain stem circuits have nonuniform properties and function differently according to status of their target organs and the level of activity in critical modulatory inputs. We propose that DVC circuits undergo a certain amount of short-term plasticity that allows the brain stem neuronal elements to act in harmony with neural systems that control behavioral and physiological homeostasis.
doi:10.1152/ajpgi.00413.2002
PMCID: PMC3055655  PMID: 12529266
dorsal motor nucleus of the vagus; nucleus of the solitary tract; brain stem; gastrointestinal motility
13.  Saving Darwin's muse: evolutionary genetics for the recovery of the Floreana mockingbird 
Biology Letters  2009;6(2):212-215.
The distribution of mockingbird species among the Galápagos Islands prompted Charles Darwin to question, for the first time in writing, the ‘stability of species’. Some 50 years after Darwin's visit, however, the endemic Floreana mockingbird (Mimus trifasciatus) had become extinct on Floreana Island and, today, only two small populations survive on two satellite islets. As Darwin noted, rarity often precedes extinction. To avert extinction, plans are being developed to reintroduce M. trifasciatus to Floreana. Here, we integrate evolutionary thinking and conservation practice using coalescent analyses and genetic data from contemporary and museum samples, including two collected by Darwin and Robert Fitzroy on Floreana in 1835. Our microsatellite results show substantial differentiation between the two extant populations, but our coalescence-based modelling does not indicate long, independent evolutionary histories. One of the populations is highly inbred, but both harbour unique alleles present on Floreana in 1835, suggesting that birds from both islets should be used to establish a single, mixed population on Floreana. Thus, Darwin's mockingbird specimens not only revealed to him a level of variation that suggested speciation following geographical isolation but also, more than 170 years later, return important information to their place of origin for the conservation of their conspecifics.
doi:10.1098/rsbl.2009.0778
PMCID: PMC2865062  PMID: 19923141
museum specimens; genetic diversity; conservation; Galápagos; Nesomimus
14.  Muse+TriposScore: a ligand-based de novo design approach 
Journal of Cheminformatics  2011;3(Suppl 1):P26.
doi:10.1186/1758-2946-3-S1-P26
PMCID: PMC3083581
15.  Molecular musings in microbial ecology and evolution 
Biology Direct  2011;6:58.
A few major discoveries have influenced how ecologists and evolutionists study microbes. Here, in the format of an interview, we answer questions that directly relate to how these discoveries are perceived in these two branches of microbiology, and how they have impacted on both scientific thinking and methodology.
The first question is "What has been the influence of the 'Universal Tree of Life' based on molecular markers?" For evolutionists, the tree was a tool to understand the past of known (cultured) organisms, mapping the invention of various physiologies on the evolutionary history of microbes. For ecologists the tree was a guide to discover the current diversity of unknown (uncultured) organisms, without much knowledge of their physiology.
The second question we ask is "What was the impact of discovering frequent lateral gene transfer among microbes?" In evolutionary microbiology, frequent lateral gene transfer (LGT) made a simple description of relationships between organisms impossible, and for microbial ecologists, functions could not be easily linked to specific genotypes. Both fields initially resisted LGT, but methods or topics of inquiry were eventually changed in one to incorporate LGT in its theoretical models (evolution) and in the other to achieve its goals despite that phenomenon (ecology).
The third and last question we ask is "What are the implications of the unexpected extent of diversity?" The variation in the extent of diversity between organisms invalidated the universality of species definitions based on molecular criteria, a major obstacle to the adaptation of models developed for the study of macroscopic eukaryotes to evolutionary microbiology. This issue has not overtly affected microbial ecology, as it had already abandoned species in favor of the more flexible operational taxonomic units. This field is nonetheless moving away from traditional methods to measure diversity, as they do not provide enough resolution to uncover what lies below the species level.
The answers of the evolutionary microbiologist and microbial ecologist to these three questions illustrate differences in their theoretical frameworks. These differences mean that both fields can react quite distinctly to the same discovery, incorporating it with more or less difficulty in their scientific practice.
Reviewers
This article was reviewed by W. Ford Doolittle, Eugene V. Koonin and Maureen A. O'Malley.
doi:10.1186/1745-6150-6-58
PMCID: PMC3254073  PMID: 22074255
Ribosomal RNA genes; diversity, lateral gene transfer; microbial ecology; microbial evolution; evolutionary microbiology; ecological microbiology; Tree of Life
16.  Muse cells and induced pluripotent stem cell: implication of the elite model 
Cellular and Molecular Life Sciences  2012;69(22):3739-3750.
Induced pluripotent stem (iPS) cells have attracted a great deal attention as a new pluripotent stem cell type that can be generated from somatic cells, such as fibroblasts, by introducing the transcription factors Oct3/4, Sox2, Klf4, and c-Myc. The mechanism of generation, however, is not fully understood. Two mechanistic theories have been proposed; the stochastic model purports that every cell type has the potential to be reprogrammed to become an iPS cell and the elite model proposes that iPS cell generation occurs only from a subset of cells. Some reports have provided theoretical support for the stochastic model, but a recent publication demonstrated findings that support the elite model, and thus the mechanism of iPS cell generation remains under debate. To enhance our understanding of iPS cells, it is necessary to clarify the properties of the original cell source, i.e., the components of the original populations and the potential of each population to become iPS cells. In this review, we discuss the two theories and their implications in iPS cell research.
doi:10.1007/s00018-012-0994-5
PMCID: PMC3478511  PMID: 22527723
Stochastic model; Elite model; Tumorigenicity; Adult stem cells; Mesenchymal stem cells
17.  Washington Musings 
PMCID: PMC3564297  PMID: 23393433
18.  To amuse the muse of the brain by heart 
Netherlands Heart Journal  2013;21(4):181-182.
doi:10.1007/s12471-013-0387-x
PMCID: PMC3673609  PMID: 23468404
19.  The silver lining of a mind in the clouds: interesting musings are associated with positive mood while mind-wandering 
The negative effects of mind-wandering on performance and mood have been widely documented. In a recent well-cited study, Killingsworth and Gilbert (2010) conducted a large experience sampling study revealing that all off-task episodes, regardless of content, have equal to or lower happiness ratings, than on-task episodes. We present data from a similarly implemented experience sampling study with additional mind-wandering content categories. Our results largely conform to those of the Killingsworth and Gilbert (2010) study, with mind-wandering generally being associated with a more negative mood. However, subsequent analyses reveal situations in which a more positive mood is reported after being off-task. Specifically when off-task episodes are rated for interest, the high interest episodes are associated with an increase in positive mood compared to all on-task episodes. These findings both identify a situation in which mind-wandering may have positive effects on mood, and suggest the possible benefits of encouraging individuals to shift their off-task musings to the topics they find most engaging.
doi:10.3389/fpsyg.2013.00583
PMCID: PMC3755259  PMID: 24009599
mind-wandering; mood; daydreaming; experience sampling; emotion
21.  Musing in Oncology: When Oncology Meets Music Something Special Happens 
The Oncologist  2013;18(1):112-113.
doi:10.1634/theoncologist.2012-0140
PMCID: PMC3556247  PMID: 23287881
22.  Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells 
Cells  2012;1(4):1045-1060.
Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.
doi:10.3390/cells1041045
PMCID: PMC3901150  PMID: 24710542
pluripotent stem cells; mesenchymal stem cells; transdifferentiation; tissue repair; cell therapy
23.  A robust multi-shot scan strategy for high-resolution diffusion weighted MRI enabled by multiplexed sensitivity-encoding (MUSE) 
NeuroImage  2013;72:41-47.
Diffusion weighted magnetic resonance imaging (DWI) data have been mostly acquired with single-shot echo-planar imaging (EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in single-shot EPI, even when the parallel imaging (usually at an acceleration factor of 2) is incorporated. Multi-shot acquisition strategies could potentially achieve higher spatial resolution and fidelity, but they are generally susceptible to motion-induced phase errors among excitations that are exacerbated by diffusion sensitizing gradients, rendering the reconstructed images unusable. It has been shown that shot-to-shot phase variations may be corrected using navigator echoes, but at the cost of imaging throughput. To address these challenges, a novel and robust multi-shot DWI technique, termed multiplexed sensitivity-encoding (MUSE), is developed here to reliably and inherently correct nonlinear shot-to-shot phase variations without the use of navigator echoes. The performance of the MUSE technique is confirmed experimentally in healthy adult volunteers on 3 Tesla MRI systems. This newly developed technique should prove highly valuable for mapping brain structures and connectivities at high spatial resolution for neuroscience studies.
doi:10.1016/j.neuroimage.2013.01.038
PMCID: PMC3602151  PMID: 23370063
diffusion weighted imaging; inherent phase correction; multiplexed sensitivity-encoding; interleaved echo-planar imaging; multi-shot echo-planar imaging
24.  Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy 
In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were introduced to the scientific community, offering potential resolution to the issue of teratoma formation that plagues both embryonic stem (ES) and induced pluripotent (iPS) stem cells. Isolated from human bone marrow, dermal fibroblasts, adipose tissue and commercially available adipose stem cells (ASCs) under severe cellular stress conditions, Muse cells self-renew in a controlled manner and do not form teratomas when injected into immune-deficient mice. Furthermore, Muse cells express classic pluripotency markers and differentiate into cells from the three embryonic germ layers both spontaneously and under media-specific induction. When transplanted in vivo, Muse cells contribute to tissue generation and repair. This review delves into the aspects of Muse cells that set them apart from ES, iPS, and various reported adult pluripotent stem cell lines, with specific emphasis on Muse cells derived from adipose tissue (Muse-AT), and their potential to revolutionize the field of regenerative medicine and stem cell therapy.
doi:10.1186/2001-1326-3-12
PMCID: PMC4041046  PMID: 24940477
Adult pluripotent stem cells; Muse cells; Non-tumorigenic; Quiescence; Regenerative medicine
25.  Musings on Sketches, Artists, and Mosquito Nets 
Emerging Infectious Diseases  2014;20(8):1429-1430.
doi:10.3201/eid2008.AC2008
PMCID: PMC4111204
art science connection; emerging infectious diseases; art and medicine; James Abbott McNeill Whistler; Man at Table beneath Mosquito Net; Musings on sketches; artists; and mosquito nets; mosquitoes; mosquito nets; West Point; Aesthetic Movement; vector-borne disease; malaria; about the cover

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