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At least 703 records · Page 39Linked to original sources

PubMed2003

Integrating mobile technology into a health professions curriculum: using flexible technology to meet expectations.

The diverse needs of students, faculty, administrators, and the curriculum itself, create formidable challenges when attempting to integrate mobile technology into a health professions curriculum. Single technology solutions often fail in this environment because they cannot meet user needs. Multiple platform and device agnostic solutions can provide the flexibility to address curricular needs without significantly adding technological complexity.

Computers, Handheld↗

PubMed2006

MT-103 Micromet/MedImmune.

Micromet AG and Medlmmune Inc are developing MT-103, a single-chain bispecific recombinant antibody from Micromet's BiTE (bispecific T-cell engager) product platform that binds both the CD19 antigen and the T-cell receptor (CD3), for the potential treatment of B-cell lymphoma. The company is also investigating the compound for the potential treatment of chronic lymphocytic leukemia and acute lymphoblastic leukemia.

Animals↗

PubMed1988

Wheat germ cytoplasmic ribosomes. Structure of ribosomal subunits and localization of N6,N6-dimethyladenosine by immunoelectron microscopy.

Cytoplasmic ribosomes have been isolated from wheat germ, and the structure of ribosomal subunits has been examined by electron microscopy of negatively stained preparations. Small (40 S) subunits show structural features generally regarded as characteristic of eukaryotic particles, while large (60 S) subunits show shapes that are equally well described by models of prokaryotic 50 S particles. Small subunit 18 S RNA contains 2 residues of N6,N6-dimethyladenosine 19 and 20 residues from the 3'-end (Hagenbüchle, O., Santer, M., Steitz, J. A., and Mans, R. J. (1978) Cell 13, 551-563). Nucleoside analysis by high performance liquid chromatography shows no other residues of this component in the RNA. Anti-dimethyladenosine immunoglobulins were reacted with wheat germ 40 S subunits, and the resulting complexes were studied by electron microscopy in order to localize the nucleoside. In about 90% of the complexes observed, antibody-subunit contact was consistent with a single binding site. We place the dimethyladenosine residues at or near the end of the platform of the 40 S particle in a position nearly equivalent to that previously identified in prokaryotic and chloroplast subunits (Trempe, M. R., and Glitz, D. G. (1981) J. Biol. Chem. 256, 11873-11879).

Adenosine↗

PubMedDate not supplied

HIS/RIS/PACS integration: getting to the gold standard.

The technology for acquiring, storing, retrieving, displaying, and distributing images has advanced dramatically in recent years. The push is toward enterprise-wide image management solutions, where digital images from radiology, cardiology, and other "ologies" are seamlessly linked with information from clinical information systems and other databases, and they are accessed seamlessly from a single point of end-user interaction. The "gold standard" of system integration would provide the platform for improved workflow, patient throughput and patient safety, as well as decreased cost. Unfortunately, the gold standard remains elusive in most healthcare environments, even those with new systems. One of the earliest issues that plagued the progress of hospital information system/radiology information systems/picture archiving and communication systems (HIS/RIS/PACS) integration was a matter of language between Health Level-7 (HL7) and DICOM. This barrier was solved by the broker--a software and hardware device that accepts HL7 messages from the RIS then translates, or maps, the data to produce DICOM messages for transmission to the PACS. Technologist workflow requires patient and exam information from the RIS to flow to the modality. The broker provides support for this by taking advantage of the DICOM Modality Worklist (DMWL). Two primary problems are inherent in most brokered configurations. Workflow is driven by paper, and RIS information flows in 1 direction only, which leads to duplicative databases. Overcoming the limitations of HIS/RIS/PACS connectivity requires industry accepted communication protocols/rules. To facilitate this, the Integrating the Health Care Enterprise (IHE) initiative was developed. The goal of IHE is to provide end-users improved access to critical patient and clinical information across all systems within the healthcare delivery network. While the IHE initiative began to facilitate more efficient, predictable, and functional integration between disparate systems, vendors still had technology hurdles to overcome. System integration continues to be significantly hampered, not by technology limitations, but instead by business and political issues. In response to these challenges, several vendors have begun to offer consolidated RIS/PACS solutions and/or HIS/RIS/PACS solutions. Consequently, the prospect of the gold standard appears to be on the horizon. Single vendor consolidated systems are not, however, feasible for deployment in many healthcare organizations, and they are not necessarily the panacea.

Database Management Systems↗

PubMed2005

Illumina, Inc.

Illumina, Inc., based in San Diego (CA, USA), is a genomics tool company that develops and markets integrated array-based systems and assays for a broad range of applications including genotyping, gene expression and epigenetics. Product offerings range from focused assay sets (up to 1,536 multiplexed assays) to whole-genome analysis (>100,000 assays/sample). Illumina's two microarray platforms, the Sentrix Array Matrix and the Sentrix BeadChip, are characterized by small (3 microm) feature size, dense feature packing (over 10 million features can be deployed on a single microarray) and the ability to analyze, in parallel, multiple samples on the same device. Illumina has developed a spectrum of proprietary assays (GoldenGate, Infinium, and DASL) for application on our microarray platform. These assays have been successfully employed for a number of applications, including collection of the majority of the Phase I genotyping data for the International HapMap Project. Illumina are focusing our activities on extending the applications of the above assays and developing new assays for future products. Illumina's goal is to deliver high-performance, high-throughput solutions that enable researchers to expand experimental scale while reducing the cost of large-scale research.

Gene Expression↗

PubMed2004

Dissecting tBHQ induced ARE-driven gene expression through long and short oligonucleotide arrays.

This paper compares the gene expression profiles identified by short (Affymetrix U95AV2) or long (Agilent Hu1A) oligonucleotide arrays on a model for upregulation of a cluster of antioxidant responsive element-driven genes by treatment with tert-butylhydroquinone. MAS 5.0, dCHIP, and RMA were applied to normalize the Affymetrix data, and Lowess regression was considered for Agilent data. SAM was used to identify the differential gene expression. A set of biological markers and housekeeping genes were chosen to evaluate the performance of multiple normalization approaches. Both arrays illustrated a definite set of overlapping genes between the data sets regardless of data mining tools used. However, unique gene expression profiles based on the platform used were also revealed and confirmed by quantitative RT-PCR. Further analysis of the data revealed by alternative approaches suggested that alternative splicing, multiple vs. single probe(s) measurement, and use or nonuse of mismatch probes may account for the discrepant data. Therefore, these two microarray technologies offer relatively reliable data. Integration of the gene expression profiles from different array platforms may not only help for cross-validation but also provide a more complete view of the transcriptional scenario.

Alternative Splicing↗

PubMed2006

Oxytocin null mice ingest enhanced amounts of sweet solutions during light and dark cycles and during repeated shaker stress.

Central oxytocin (OT) pathways appear to limit consumption of sweet solutions. Male and female C57BL/6 mice that lack the gene for oxytocin (OT KO mice) displayed an initial and sustained enhanced intake of sucrose solution over water compared to wild type (WT) mice when the solutions were presented as a two-bottle choice [Amico JA, Vollmer RR, Cai HM, Miedlar JA, Rinaman R. Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol: Regul Integr Comp Physiol 2005;289:R1798-806]. In this study we examined the ingestion of a non-nutritive sweetener, 0.2% saccharin in sucrose-experienced OT KO and WT mice given a two-bottle choice between saccharin solution and water available ad libitum for 4 days. Compared to WT mice, OT KO mice consumed significantly greater volumes of saccharin solution during the dark and light photoperiods on the first day and subsequent days of the study. The results were replicated when the experiment was repeated in the same animals. In another experiment, we determined that daily exposure to platform shaker stress did not alter the marked sucrose consumption in OT KO mice. OT KO mice drank significantly more sucrose than WT mice during periods of stress and non-stress. We conclude that the avid consumption of sweetened solutions by OT KO mice is not restricted to a single photoperiod, occurs independent of caloric content of the sweetened solution, and is not altered by exposure to the daily stress of platform shaker. The cumulative results from our studies of sucrose and saccharin ingestion in OT KO and WT male and female mice suggest a special role for sweet taste in the recruitment of OT neurons.

Administration, Oral↗

PubMed2003

Standardized determination of real-time PCR efficiency from a single reaction set-up.

We propose a computing method for the estimation of real-time PCR amplification efficiency. It is based on a statistic delimitation of the beginning of exponentially behaving observations in real-time PCR kinetics. PCR ground fluorescence phase, non-exponential and plateau phase were excluded from the calculation process by separate mathematical algorithms. We validated the method on experimental data on multiple targets obtained on the LightCycler platform. The developed method yields results of higher accuracy than the currently used method of serial dilutions for amplification efficiency estimation. The single reaction set-up estimation is sensitive to differences in starting concentrations of the target sequence in samples. Furthermore, it resists the subjective influence of researchers, and the estimation can therefore be fully instrumentalized.

Algorithms↗

PubMed2004

Annotation and cross-indexing of array elements on multiple platforms.

On the surface, transcript profiling using microarrays seems to offer a way of looking at the global response of the cell to perturbation, with a focus on changes in gene expression. The difficulty, however, is that the response of a particular gene is actually measured on the array by an element that is a short, defined nucleic acid sequence. Sequences that map back to the same genetic locus may actually be given different names and descriptions when they are deposited in public sequence databases; when such sequences are used in microarray construction, elements that monitor the same genetic locus may have different names and descriptions. The algorithm described here uses a hierarchical approach to assign a single best annotation to the elements in a given microarray in such a fashion that elements from one microarray platform may be cross-indexed with those of another. The algorithm relies on the nucleic acid accession number for a given array element, and uses that to retrieve annotation from the most recent versions of LocusLink and UniGene. Both database resources are searched, with a priority being given to annotation derived from the curated LocusLink database. In lieu of annotation found in these databases, the default GenBank annotation is used. As a final outcome, a cross-chip identifier is generated that may be used to cross-index array elements. The program is available as a practical extraction and report language (Perl) script that can run under any Perl interpreter.

Algorithms↗

PubMed2026

Unveiling tumor heterogeneity by single cell RNA-sequencing: From basic considerations to clinical applications.

Tumor heterogeneity-encompassing diverse cellular phenotypes, genomic alterations, and microenvironmental contexts-is a principal barrier to effective cancer therapy. Single-cell RNA sequencing (scRNA-seq) has transformed our ability to resolve this complexity by capturing transcriptomes at single-cell resolution. Here, we review the technical foundations required for high-quality scRNA-seq studies. We then trace the evolution of scRNA-seq platforms from manual micromanipulation to high-throughput systems, and describe the computational pipelines that enable reliable data interpretation. The application of scRNA-seq is exemplarily shown in the context of lung cancer, where single-cell profiling has revealed (i) the clonal and sub-clonal architecture of tumors, (ii) extensive remodeling of the immune microenvironment, iii) key mechanisms underlying resistance to targeted agents and immune-checkpoint blockade, and (iv) the dynamics of neo-antigen-specific T-cell responses. Integrating machine-learning techniques-such as deep-learning classifiers and graph-based models-with single-cell transcriptomic data has markedly sped up biomarker discovery, produced more accurate risk-stratification scores, and enabled the generation of patient-specific therapeutic predictions. We surveyed the major trial registry ClinicalTrials.gov and identified ∼380 ongoing or completed studies that explicitly incorporate scRNA-seq as a correlative or pharmacodynamic endpoint. Overall, the analysis shows that scRNA-seq becomes an increasingly important component of modern trials, providing high-resolution cellular and molecular readouts that complement conventional imaging and bulk-omics endpoints. While key challenges remain, ranging from costs, scalability and need for rigorous validation before routine clinical deployment, ongoing technological advances continue to expand the potential of scRNA-seq as a cornerstone of precision medicine.

Humans↗

PubMed2026

Dose-dependent IFN programs in myeloid cells after mRNA and adenovirus COVID-19 vaccination.

BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and its target genes (e.g., MX1, MX2, DDX58), with transcriptional and epigenetic profiles distinct from the robust IFN program observed after mRNA boosting or a single Ad26.COV2.S dose (ISG-high). In vitro stimulation of human monocytes showed that IFN-α alone recapitulates ISG-dim, whereas both IFN-α and IFN-γ are required for ISG-high.CONCLUSIONThese findings define dose-dependent IFN programming in human myeloid cells and highlight mechanistic differences between priming and boosting, with implications for optimizing vaccine platform choice, dose scheduling, and formulation.FUNDINGNIH grants AI142086, U19 AI135972, U01 AI165452, U01 AI165452, R01 AI160706, and P30 AG067988.

Humans↗

PubMed2004

Single-molecule imaging analysis of Ras activation in living cells.

A single-molecule fluorescence resonance energy transfer (FRET) method has been developed to observe the activation of the small G protein Ras at the level of individual molecules. KB cells expressing H- or K-Ras fused with YFP (donor) were microinjected with the fluorescent GTP analogue BodipyTR-GTP (acceptor), and the epidermal growth factor-induced binding of BodipyTR-GTP to YFP-(H or K)-Ras was monitored by single-molecule FRET. On activation, Ras diffusion was greatly suppressed/immobilized, suggesting the formation of large, activated Ras-signaling complexes. These complexes may work as platforms for transducing the Ras signal to effector molecules, further suggesting that Ras signal transduction requires more than simple collisions with effector molecules. GAP334-GFP recruited to the membrane was also stationary, suggesting its binding to the signaling complex. The single-molecules FRET method developed here provides a powerful technique to study the signal-transduction mechanisms of various G proteins.

Boron Compounds↗

PubMed2004

Recovery from perturbations during paced walking.

The aim of the current study was to develop a safe, standardized, stability test and to explore a set of metrics to characterize the recovery of gait stability in healthy individuals following a single mechanical perturbation during steady locomotion. Balance perturbations were mechanically applied to the right foot of 12 healthy subjects during paced walking by translating a platform embedded in a 12 m walkway diagonally (+45/-135 degrees ) relative to the direction of travel approximately 200 ms after heel strike. We examined the medio-lateral (ML) displacement of the sternum before, during and after the platform translation. Measurements of ML position of the right and left shanks in relation to the position of the sternum were used as step-by-step estimates of the moment arm controlling ML motion of the body. We hypothesized that when gait is perturbed in the single stance phase of the step cycle via a translation of the support surface, a series of steps after the perturbation input will be altered reflecting an effort by the CNS to maintain the center of mass (COM) within the base of support and to stabilize the upper body for continued gait. Specifically, if the foot is perturbed laterally during mid-stance a widening of the upcoming step will occur and if the foot is perturbed medially a narrowing of the upcoming step will occur. This behavior was frequent for most subjects. Recovery of non-perturbation behavior was achieved on the third step after the platform translation. An additional strategy was seen for some subjects during lateral perturbation inputs. Instead of widening the upcoming step, these subjects acquired the support to stabilize the body by putting their left foot down very quickly with minimal change in stance width. The recovery profiles of the sternum, though directionally asymmetric, were similar in shape among subjects and roughly proportional to the magnitude of the platform translation. Five to six steps were required for complete recovery in the subjects tested in this study.

Adult↗

PubMed2003

Electrophysiological and pharmacological characteristics of nigral dopaminergic neurons in the conscious, head-restrained rat.

Extracellular single-unit recordings of nigral dopamine (DA) neurons were obtained from conscious rats habituated to having their body suspended in a cloth jacket and their head immobilized in the stereotaxic frame by means of a "restraining platform" permanently fixed to the skull. The electrophysiological characteristics of DA neurons from head-restrained rats and their responses to apomorphine and haloperidol were compared with single-unit recordings obtained from rats lightly and deeply anesthetized with chloral hydrate and from mesencephalic slices. Head-restrained rats showed a higher number of spontaneously active DA neurons and a higher percentage of bursting neurons than lightly and deeply anesthetized rats. Indeed, bursting activity was rare in deeply anesthetized rats and was totally absent in slices. Haloperidol was more potent and effective in stimulating the firing rate and bursting activity in head-restrained than in lightly anesthetized rats, while it was virtually ineffective in deeply anesthetized rats and totally ineffective in slices. On the other hand, DA neurons in head-restrained rats showed the same average firing rate as DA neurons in lightly and deeply anesthetized rats and in slices. The potency of apomorphine in inhibiting the firing rate, and that of haloperidol in reversing apomorphine effect, did not vary among the different in vivo preparations. The results suggest that chloral hydrate anesthesia blunts or suppresses not only the excitatory inputs which normally sustain the number of spontaneously active DA neurons and their bursting activity, but also the feedback excitation of DA neurons following haloperidol-induced D(2) receptor blockade. On the other hand, chloral hydrate anesthesia modifies neither D(2) autoreceptor sensitivity to apomorphine and haloperidol nor the automatic genesis of action potentials. The head-restrained rat appears to be an important model for studies into the pharmacology and physiology of DA neurons.

Action Potentials↗

PubMed1998

A novel annuloplasty system with rigid and flexible elements: initial experimental results in sheep and the case for untreated autologous pericardium.

BACKGROUND AND AIMS OF THE STUDY: A precise annuloplasty is difficult to perform with pericardium as the ring material because unwanted plication of the pericardium itself typically occurs when the sutures are tied. A novel annuloplasty system has been developed which should allow a predictably precise measured plication of the annulus without plication of the pericardium itself. A feasibility study was designed to evaluate this new concept. METHODS: Three juvenile sheep underwent implantation of a new annuloplasty system into the posterior mitral annulus without tissue annulus plication. Small rigid titanium suture-platforms 7 x 3 x 1 mm with two-suture holes 3 mm apart were individually affixed to the posterior mitral tissue annulus each with a single horizontal mattress suture. A longitudinal strip of untreated autologous pericardium, corresponding to the perimeter dimension of the free edge of the anterior leaflet, was sutured to the posterior annulus including both fibrous trigones, covering the suture-platforms with the mesothelial surface up, using two different suture techniques. No postoperative anticoagulation was utilized. Serial transthoracic echocardiograms and necropsy at five to six weeks post implant were performed. RESULTS: When the pericardium was affixed to the annulus with a continuous suture exposing only the mesothelial surface to the blood, completely covering the suture-platforms and their suture knots or folded in upon itself as a tube above the suture-platforms, it appeared to maintain all of its original implant dimensions and flexibility. There was no functional or anatomical distortion of any part of the mitral apparatus; fibrotic reaction was minimal and there was no thrombus formation with this suture technique. CONCLUSIONS: This annuloplasty system, combining rigid and flexible elements, 'melts' into the tissue annulus with a low profile, providing overall annular flexibility with no shrinkage of the overlying untreated autologous pericardium, no distortion of any part of the mitral apparatus, minimal fibrous reaction and no thrombus formation.

Animals↗

PubMed2006

Detection and analysis of protein-protein interactions in organellar and prokaryotic proteomes by native gel electrophoresis: (Membrane) protein complexes and supercomplexes.

It is an essential and challenging task to unravel protein-protein interactions in their actual in vivo context. Native gel systems provide a separation platform allowing the analysis of protein complexes on a rather proteome-wide scale in a single experiment. This review focus on blue-native (BN)-PAGE as the most versatile and successful gel-based approach to separate soluble and membrane protein complexes of intricate protein mixtures derived from all biological sources. BN-PAGE is a charge-shift method with a running pH of 7.5 relying on the gentle binding of anionic CBB dye to all membrane and many soluble protein complexes, leading to separation of protein species essentially according to their size and superior resolution than other fractionation techniques can offer. The closely related colorless-native (CN)-PAGE, whose applicability is restricted to protein species with intrinsic negative net charge, proved to provide an especially mild separation capable of preserving weak protein-protein interactions better than BN-PAGE. The essential conditions determining the success of detecting protein-protein interactions are the sample preparations, e.g. the efficiency/mildness of the detergent solubilization of membrane protein complexes. A broad overview about the achievements of BN- and CN-PAGE studies to elucidate protein-protein interactions in organelles and prokaryotes is presented, e.g. the mitochondrial protein import machinery and oxidative phosphorylation supercomplexes. In many cases, solubilization with digitonin was demonstrated to facilitate an efficient and particularly gentle extraction of membrane protein complexes prone to dissociation by treatment with other detergents. In general, analyses of protein interactomes should be carried out by both BN- and CN-PAGE.

Electrophoresis, Polyacrylamide Gel↗

PubMed2002

A room with a view and a polarizing cue: individual differences in the stimulus control of place navigation and passive latent learning in the water maze.

We investigated individual differences in the stimulus control of navigational behavior in the water maze by comparing measures of place learning in one environment to measures of latent learning (via passive placement on the goal platform) in a novel environment. In the first experiment, 12 rats were trained to find a slightly submerged hidden platform at a fixed location in room A for 10 days (4 trials/day). Fast and slow place learners were identified by their mean escape latency and cumulative distance to the goal during acquisition. The same animals were then given a 2-min passive placement on the submerged platform in room B. Latent learning was assessed by the animal's escape latency on a single swim trial immediately following the placement in room B. The results showed that the good latent learners in room B were not necessarily the fast place learners in room A. This weak correlation may be related to the fact that some rats swam near the area in room B that corresponded to the former goal location in room A relative to a common polarizing cue (i.e., the door/entrance to both rooms). When the view of the door was blocked in a second experiment a significant positive correlation between place acquisition and the latent learning test was obtained, although escape performance following passive placement was not improved. These findings suggest that while place navigation and latent learning via passive placement may involve some common cognitive-spatial function, other associative (S-S and/or S-R) processes that occur during place navigation/active movement may be required for animals to exhibit truly accurate navigational behavior characteristic of asymptotic escape performance in the water maze. Additional implications for neurobiological studies using a procedural pretraining design are discussed.

Animals↗

PubMed2005

An adaptable microvalving system for on-chip polymerase chain reactions.

On-chip genetic analysis systems are beginning to provide a viable alternative to conventional gene profiling and amplification devices, through minimal reagent use, high detection resolution, and the potential for high-throughput parallel testing of the genetic material, even from single cells. Despite the advantages, there are many difficulties inherent in creating an integrated microfluidic diagnostic platform. One major challenge is the accurate control and manipulation of fluid, and particularly the immobilization of reaction mixtures during heating phases of polymerase chain reactions (PCR). In this paper we present a pumping and valving system based on the use of three servomotor-controlled valve fingers that actuate microchannels within a poly-dimethylsiloxane (PDMS) fluidic chip. We characterize the valving ability of the system in terms of fluid loss and show the successful fluid retention of the system over 35-cycle PCR runs at temperatures of up to approximately 96 degrees C. In addition, we demonstrate the system's ability to perform PCR by successfully amplifying a sample of beta2 microglobulin transcript obtained from the peripheral blood of a patient with multiple myeloma. This work has proven to be a successful approach to multi-use valving and a viable method of alleviating the fluid control difficulties inherent in performing a PCR reaction in an on-chip environment. In addition, it opens the door for further automation and integration with other chip-based genetic analysis platforms.

Humans↗