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PubMed2005

Three-dimensional contrast-enhanced steady-state free precession for improved catheter-directed coronary magnetic resonance angiography.

PURPOSE: To demonstrate the feasibility of three-dimensional thick-partition, contrast-enhanced, catheter-directed coronary artery magnetic resonance angiography (MRA) and test the hypothesis that three-dimensional imaging improves coronary artery background contrast-to-noise ratio (CNR) compared to two-dimensional imaging. MATERIALS AND METHODS: Catheters were advanced into the coronary arteries of swine (N = 6) under MR guidance. Three-dimensional coronary MRA was performed after intracoronary injection of a small dose of contrast media using magnetization-prepared steady-state free precession (SSFP) with two thick partitions. For comparison, two magnetization-prepared two-dimensional SSFP scans were also performed, one with no signal averaging and one with two signal averages. All sequences had the same coverage and in-plane spatial resolution. RESULTS: The coronary artery was successfully catheterized in all (6/6) animals. CNR for three-dimensional imaging was 11.1 +/- 1.2 for proximal arterial segments and 4.3 +/- 0.4 for distal segments. Without averaging, two-dimensional imaging CNRs for proximal and distal segments were 5.0 +/- 0.7 and 1.2 +/- 0.2, respectively. With averaging, two-dimensional imaging CNRs for proximal and distal segments were 9.4 +/- 1.5 and 2.9 +/- 0.4, respectively. Three-dimensional imaging showed a statistically significant increase in CNR over all two-dimensional imaging for both proximal and distal segments (P < 0.05). CONCLUSION: Three-dimensional thick-partition, contrast-enhanced, catheter-directed coronary MRA is feasible and improves CNR over two-dimensional projection imaging.

Animals↗

PubMed2006

Recording high quality speech during tagged cine-MRI studies using a fiber optic microphone.

PURPOSE: To investigate the feasibility of obtaining high quality speech recordings during cine imaging of tongue movement using a fiber optic microphone. MATERIALS AND METHODS: A Complementary Spatial Modulation of Magnetization (C-SPAMM) tagged cine sequence triggered by an electrocardiogram (ECG) simulator was used to image a volunteer while speaking the syllable pairs /a/-/u/, /i/-/u/, and the words "golly" and "Tamil" in sync with the imaging sequence. A noise-canceling, optical microphone was fastened approximately 1-2 inches above the mouth of the volunteer. The microphone was attached via optical fiber to a laptop computer, where the speech was sampled at 44.1 kHz. A reference recording of gradient activity with no speech was subtracted from target recordings. RESULTS: Good quality speech was discernible above the background gradient sound using the fiber optic microphone without reference subtraction. The audio waveform of gradient activity was extremely stable and reproducible. Subtraction of the reference gradient recording further reduced gradient noise by roughly 21 dB, resulting in exceptionally high quality speech waveforms. CONCLUSION: It is possible to obtain high quality speech recordings using an optical microphone even during exceptionally loud cine imaging sequences. This opens up the possibility of more elaborate MRI studies of speech including spectral analysis of the speech signal in all types of MRI.

Acoustics↗

PubMed1994

Spatially restricted imprinting of mouse chromosome 7.

Three of the four known imprinted genes (Igf-2, H19, and Snrpn) map to mouse chromosome 7. We used mRNA phenotyping to examine the tissue-specific transcription of Igf-1r, H-ras-1, and Gabrb3, which map to chromosome 7 between Snrpn and the Igf-2/H19 domain, and Myod-1, which maps proximal to Snrpn. We found that all of these genes were expressed by both parental alleles in tissues from day 1 neonates. The fact that imprinted genes can flank or map closely to genes that escape such epigenetic modification suggests that autosomal imprinting is not manifested globally along imprinted chromosomes but rather is spatially restricted, perhaps even defined by specific DNA consensus sequences or an "imprint box" associated with imprintable genes.

Alleles↗

PubMed2005

Common SENSE (sensitivity encoding using hardware common to all MR scanners): a new method for single-shot segmented echo planar imaging.

A new method is presented that enables image acquisition to be segmented into two readouts. This is achieved using a new pulse sequence that creates two components of magnetization with different spatial profiles. Each component of the magnetization is measured in one of the readouts. This produces two images with complimentary "sensitivity profiles" and near identical contrast. The images can be acquired with a reduced data matrix that corresponds to shorter periods of data acquisition. The reduced matrix images are then combined to produce a full matrix image using reconstruction methods previously applied to images from multiple RF coils in the sensitivity encoding (SENSE) technique. The most promising application for this technique is in improving the performance of echo planar imaging (EPI) at high field. In this application, common SENSE obtains two segments of data in a single excitation of the magnetization (i.e., two readouts are performed per shot). The combination of these segments in image space avoids the difficulties normally associated with segmented EPI methods, namely, increased ghosting from discontinuities in the k-space data. The main advantages are a reduction in distortion and blurring. Common SENSE is compatible with parallel imaging and partial Fourier methods.

Echo-Planar Imaging↗

PubMed1996

Maze learning by honeybees.

This study examines whether honeybees can learn to fly through complex mazes, in the presence or the absence of specific visual cues. The results are summarized as follows: 1. Bees can learn to fly through a complex maze by following a trail of colored marks. 2. Bees, initially trained to follow color marks through an initial part of the maze, are immediately able to use the same sign-tracking cue to find their way through the rest of the maze, which is unfamiliar to them. 3. Bees trained to follow color marks through a particular maze can use the same cue to negotiate a novel maze. 4. Bees trained to use a particular color to negotiate a maze can immediately use a novel color to negotiate the same maze or even a novel maze. 5. After learning to negotiate a maze by following colored marks, bees can find their way through the maze even when the marks are removed, albeit at reduced levels of accuracy. Thus, the trained bees do not rely solely on sign-tracking to find their way through the maze: they also acquire a spatial memory of the maze or at least a sequence of motor commands describing the correct path through it. 6. Bees can learn to use color as a signal even when it indicates the path through the maze in a symbolic way, for example, blue indicating a turn to the right and green a turn to the left. 7. Bees can learn an unmarked maze. Performance under these conditions is poorer than when marks are provided, but is still significantly better than chance level. 8. Control experiments rule out the use of external landmarks in all of these situations.

Animals↗

PubMed1997

[Conventional magnetic resonance angiography and contrast enhanced magnetic resonance angiography of extracranial blood vessel segments].

The introduction of fast gradient systems allows a reliable visualization of the extracranial carotid vessels by the magnetic resonance angiography (MRA) which meanwhile is implemented into clinical routine. By the mainly applied time-of-flight (TOF) technique, vessels can be imaged without contrast agent (CA). Due to the application of ultra-fast gradient-echo-sequences, the first-pass evaluation of an intravenous bolus-injection of Gadolinium in the carotids from the aortic arch up to the skull base can be performed in less than 30 s. In this study. Advantages and disadvantages of both techniques are discussed. For a qualitatively optimal contrast enhanced MRA (CE-MRA) timing parameters like injection delay, flow rate and the adjustment of sequence parameters have to be considered in relation to the fast venous return from the sinus to the jugular veins. First, the optimal time point of the data acquisition have been determined at a model and with a computer simulation in reference to the presence of CA in the arteries. As a result, 90% of the contrast contribution is defined by 16% of the symmetrically acquired central k-space lines. A measuring protocol for clinical use was obtained by a gradual variation of spacial resolution, measuring time and CA-injection parameters and was proved in normal volunteers and patients. An exact determination of the bolus-arrival-time by means of a test-bolus injection was acquired. The best qualitative results were achieved by a double-dose- injection at 2 ml/s injection rate. The temporal reserves of ultra-fast sequences should be invested in the improvement of the spatial resolution. To date, further investigations related to the problem of optimal CA-application may improve the potentials of CE-MRA procedures.

Carotid Arteries↗

PubMed1996

Random selection algorithms for spatial and temporal sampling.

Seven BASIC programs are presented that use algorithms for selection of treatments and samples in spatial and temporal contexts. Program (1) takes a natural sequence of samples (such as logs cut from a tree trunk) and divides them into groups (equal to the number of samples divided by treatments), and then selects non-redundantly from each group a sample at random for each treatment. Program (2) matches items from different categories equally to any number of treatments in proportion to the numbers of items of each category. Program (3) selects sampling times or segment lengths of specified interval and number from within a time period or perimeter distance. These samples can be spaced apart by at least a specified amount of time or distance but otherwise are chosen at random. In program (4), a series of sample coordinates (x,y) are chosen at random from a rectangular area so that no points are closer than a specified minimum distance to any other. For each of the sample points, the Cartesian and polar coordinates are given. Program (5) generates any possible Latin square, while program (6) generates Latin cubes, and program (7) makes Graeco-Latin cubes. Examples of program use and output are presented for experiments with bark beetles (Coleoptera: Scolytidae) responding to pheromone blends and colonizing host trees.

Animals↗

PubMed1991

The oblique muscle organizer in Hirudo medicinalis, an identified embryonic cell projecting multiple parallel growth cones in an orderly array.

The oblique muscle layer in the leech body wall is built upon the processes of a unique identified embryonic cell, the Comb- or C-cell. Each C-cell is composed of a spindle-shaped soma that projects approximately 70 parallel processes through the developing body wall at an angle oblique to the long axis. The morphogenesis of this cell and the navigation of its growth cones were examined by intracellular dye filling and antibody staining. At the earliest stages described each C-cell had about six processes, with those near the center of the cell oriented obliquely. As processes were added at the axial ends of the soma they often projected along previously developed longitudinal or circular muscle founder cells and then secondarily aligned themselves parallel to the older processes from the same C-cell. All growth cones initially extended to a particular location in the body wall, where they ceased growing until all 70 processes had been added (over the course of about 5 days). As adjacent segmental homologs met, their growth cones intermingled, eventually sorting out to align parallel. When one of these cells was ablated early--but not later--in development, the remaining adjacent segmental homologs expanded into the vacant territory, consistent with a hypothesis of mutual avoidance between segmental homologs. Most processes that expanded into the experimentally induced vacancy remained correctly oriented and parallel; the few exceptions projected instead along the mirror-image trajectory. Thus, expression of specific avoidance between adjacent C-cell processes is developmentally regulated and functions as a guidance mechanism in vivo, in that it serves to restrict possible trajectories. After aligning its growth cones, each cell stopped adding processes and the processes rapidly extended in concert along relatively precise trajectories. Processes of contralateral homologs cross to form the orthogonal grid used as a scaffold by myocytes to form the oblique muscles. The advancing fronts of growth cones reached the dorsal midline at about the same time as body closure occurs (at about Embryonic Day 20) at which time the C-cells became granular, lost processes, and presumably died. This sequence of developmental events is consistent with temporal and spatial regulation of different morphogenetic strategies, including--but not limited to--specific avoidance, and further suggests testable hypotheses of mechanisms of growth cone navigation in the intact embryo.

Animals↗

PubMed1991

Properties of some density-dependent integrodifference equation population models.

Integrodifference equations may be used as models of populations with discrete generations inhabiting continuous habitats. In this paper integrodifference equation models are formulated for annual plant populations without a seed bank; these models differ in the stage of the life cycle at which intraspecific competition acts to reduce vital rates. The models exhibit a sequence of period-doubling bifurcations leading to chaotic spatial and temporal behavior. The behavior of the models when modal dispersal distances are at the origin is compared with their behavior when these distances are displaced away from the origin. The models are capable of predicting stable, cyclical, and chaotic asymptotic behavior. They also predict that the variance of dispersal distances is an important indicator of the colonizing ability of a species.

Animals↗

PubMed1989

Isolation and structure analysis of components from venom of the spider Argiope lobata.

Homologous low molecular weight compounds, blocking postsynaptic glutamate receptors, were isolated from the venom of the spider Argiope lobata by ion exchange chromatography and reverse phase HPLC. Structures of nine blocking agents were determined by 1H-NMR and mass spectroscopy. Two-dimensional COSY spectra were used to identify spin systems of the protons coupled via two or three chemical bonds. The spin systems were combined into the sequence by means of the nuclear Overhauser effect between spatially close protons. Ionogenic groups were identified from pH dependences of the proton chemical shifts. Molecular structures thus obtained were checked against amino acid analysis and mass spectrometry data. The antagonists can be divided into three groups: argiopin, argiopinins and pseudoargiopinins depending on features of the chromophoric moiety (2,4-dihydroxyphenylacetic acid, 4-hydroxy-indole-3-acetic acid or indole-3-acetic acid).

Amino Acids↗

PubMed1985

Stationary patterns suppress the perception of stroboscopic motion.

Two spatially separated vertical bar stimuli briefly flashed in temporal sequence produced strong sensations of stroboscopic apparent motion; particularly at intermediate onset asynchronies. The sustained presence of two additional stationary vertical bars flanking the two movement-inducing bars during their presentation significantly decreased the rated magnitude of the sensation of stroboscopic motion. Control experiments rule out contrast reduction of the movement-inducing bars by the stationary flanking bars as a source of the decrease of the rated magnitude of stroboscopic motion. These results are related to similar effects observed in metacontrast and suggest that sustained channels responding to stationary patterns inhibit transient channels responding to brief or rapid image displacements giving rise to perception of stroboscopic motion.

Adult↗

PubMed1986

Repression of a mutant derivative of the pRE promoter of bacteriophage lambda by its activator, CII.

A 2-bp insertion between the -10 and -35 regions of the pRE promoter of bacteriophage lambda reverses the effect of the activator protein, CII, on transcription from pRE in vitro. The mutant promoter is weakly constitutive in the absence of cII protein and repressed in its presence. This is in sharp contrast to wild-type pRE which is inactive in the absence of cII protein and stimulated at least 1000-fold in its presence (Shih and Gussin, 1984a; McClure and Hoopes, 1985). These effects are explained by the creation of a new -35 region with weak homology to the -35 consensus sequence for Escherichia coli promoters, and by the altered spatial relationship between the -35 region and the CII-binding site. This interpretation was confirmed by analysis of double mutants containing known cy (pRE) mutations together with the 2-bp insertion. Insertion of 4 bp or deletion of 2 bp completely inactivates pRE in the presence or absence of cII protein, again indicating that activation is dependent upon proper spacing between the -35 region and the transcription start point.

Bacteriophage lambda↗

PubMed2026

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥ 50%; however, up to 30% of patients experience early progression or death, including cases of hyperprogressive disease (HPD). High baseline levels (≥ 30.5%) of circulating CD10- low-density neutrophils (LDNs) have been associated with increased HPD occurrence. Emerging evidence suggests that combining ICI with platinum-based chemotherapy (PCT) may mitigate the risk of HPD. Currently, no prospective studies have addressed HPD prevention in this context. PATIENTS AND METHODS: HYPERBOLIC (NCT07274384) is a phase 2, randomized, open-label, multicenter, international trial evaluating whether adding 3 cycles of PCT to first-line cemiplimab reduces HPD rate in stage IV NSCLC with PD-L1 ≥ 50% and CD10- LDNs (identified by flow cytometry as CD15⁺CD11b⁺ within the PBMC fraction, with immature cells defined by loss of CD10) ≥ 30.5%. Seventy-four patients will be randomized (1:1 ratio) to receive cemiplimab alone or cemiplimab plus 3 PCT cycles, followed by cemiplimab maintenance. Randomization will be stratified by Lung Immune Prognostic Index. The first computed tomography scan at week 7 after treatment start will assess HPD occurrence, defined as RECIST v 1.1. disease progression with a delta tumor growth rate (ΔTGR) ≥ 50% and/or TGR ratio ≥ 2. The primary endpoint will be the combined rate of HPD and early death (death within 12 weeks with no radiological evaluation). Secondary endpoints will be HPD rate according to alternative definitions, overall survival, progression free survival, objective response rate, and safety. An extensive translational research platform will include spatial transcriptomics of tumor tissue, single-cell RNA sequencing of PBMCs, circulating-free DNA and plasma factors profiling, and saliva/stool microbiome genomics and metabolomics, to longitudinally explore tumor-host dynamic interactions during treatment. CONCLUSION: to our knowledge, HYPERBOLIC is the first prospective, biomarker-driven trial investigating early treatment escalation based on HPD risk in PD-L1-high NSCLC.

CD10↗

PubMed2005

Stretching of single DNA molecules complexed with restriction endonuclease by Langmuir-Blodgett method.

We have proposed a new technique for stretching single double-stranded DNA molecules on solid substrates by the Langmuir-Blodgett (LB) method. The polyion complex monolayer of a cationic amphiphile and DNA molecules formed at the air-water interface was transferred on a clean glass substrate. Vertical lifting up of the glass substrate provided the transferred monolayer consisting the stretched individual DNA molecules aligned parallel to the lifting direction on the glass. The DNA molecules complexed with the restriction endonuclease (EcoRI) were employed for stretching by using this method. Fluorescence images of the transferred monolayer showed that the EcoRI-binding DNA molecules could be stretched and immobilized on the glass substrate. A specific sequence of DNA recognized by EcoRI was detected as spatial positions of the stretched DNA molecules.

Bacteriophage lambda↗

PubMed2004

Phosphohippolin expression in the rat central nervous system.

The FXYD family is a small single-span membrane protein family; recently, we have identified a novel member of this family from the cDNA library of the rat hippocampus and named phosphohippolin (Php) (Mol. Br. Res. vol. 86, 2001). The deduced amino acid sequence of this novel Php comprises 93 residues with a core motif of FXYD and a single transmembrane domain. This indicates that Php belongs to FXYD6 subfamily of the seven FXYD subfamilies (FXYD1-7). Php shows a 48.1% homology with rat phospholemman (FXYD1), a transmembrane family protein. In this study, polyclonal antibodies against the carboxyl-terminal sequence of rat Php were raised and purified. The spatial expression of the Php protein was in the neuronal fibers of the medial part of lateral habenula nucleus, thalamus, hypothalamus, stria terminalis, zona incerta, amygdaloid body and cingulum, olfactory bulb, hippocampus, cerebral cortex and cerebellum. A unique Php distribution was identified in the cerebellum, with a predominant expression pattern in the granule layer of lobules VI-IX of the posterior lobe. Developmental studies demonstrated that the highest level of Php expression was seen in the postnatal (PN) 3-week-old rat brain, and a significant amount of Php still existed in the adult brain. These findings suggest that Php may play an important role in the excitability of neurons in the central nervous system during postnatal development, as well as those in the adult brain.

Aging↗

PubMed2006

Primary visual cortex activation on the path of apparent motion is mediated by feedback from hMT+/V5.

Apparent motion (AM) is the illusory perception of real motion created when two spatially distinct stationary visual objects are presented in alternating sequence. In common with many other illusory percepts, activation during AM can be identified in unstimulated regions of V1 representing the illusory motion path. However, little is known about the mechanisms underlying such activation and its relationship with motion-sensitive area hMT+/V5. Using fMRI and a novel AM stimulus, we replicated previous findings showing a correlate of the perceived AM path in V1. To more closely characterize the mechanisms underlying these activations, we performed analyses of effective connectivity and found that the AM-induced activations on the illusory AM path were associated with enhanced feedback (but not feedforward) connectivity from hMT+/V5. These findings provide for the first time evidence for the involvement of cortico-cortical coupling in generating an illusory percept of AM. They therefore emphasize the role of recurrent processing between visual cortical areas in human perceptual awareness.

Adult↗

PubMed2005

From brainstem to cortex: computational models of saccade generation circuitry.

The brain circuitry of saccadic eye movements, from brainstem to cortex, has been extensively studied during the last 30 years. The wealth of data gathered allowed the conception of numerous computational models. These models proposed descriptions of the putative mechanisms generating this data, and, in turn, made predictions and helped to plan new experiments. In this article, we review the computational models of the five main brain regions involved in saccade generation: reticular formation saccadic burst generators, superior colliculus, cerebellum, basal ganglia and premotor cortical areas. We present the various topics these models are concerned with: location of the feedback loop, multimodal saccades, long-term adaptation, on the fly trajectory correction, strategy and metrics selection, short-term spatial memory, transformations between retinocentric and craniocentric reference frames, sequence learning, to name the principle ones. Our objective is to provide a global view of the whole system. Indeed, narrowing too much the modelled areas while trying to explain too much data is a recurrent problem that should be avoided. Moreover, beyond the multiple research topics remaining to be solved locally, questions regarding the operation of the whole structure can now be addressed by building on the existing models.

Animals↗

PubMed2006

Genetic organization and embryonic expression of the ParaHox genes in the sea urchin S. purpuratus: insights into the relationship between clustering and colinearity.

The ANTP family of homeodomain transcription factors consists of three major groups, the NKL, the extended Hox, and the Hox/ParaHox family. Hox genes and ParaHox genes are often linked in the genome forming two clusters of genes, the Hox cluster and the ParaHox cluster, and are expressed along the major body axis in a nested fashion, following the relative positions of the genes within these clusters, a property called colinearity. While the presences of a Hox cluster and a ParaHox cluster appear to be primitive for bilaterians, few taxa have actually been examined for spatial and temporal colinearity, and, aside from chordates, even fewer still manifest it. Here we show that the ParaHox genes of the sea urchin Strongylocentrotus purpuratus show both spatial and temporal colinearity, but with peculiarities. Specifically, two of the three ParaHox genes-discovered through the S. purpuratus genome project-Sp-lox and Sp-Cdx, are expressed in the developing gut with nested domains in a spatially colinear manner. However, transcripts of Sp-Gsx, although anterior of Sp-lox, are detected in the ectoderm and not in the gut. Strikingly, the expression of the three ParaHox genes would follow temporal colinearity if they were clustered in the same order as in chordates, but each ParaHox gene is actually found on a different genomic scaffold (>300 kb each), which suggests that they are not linked into a single coherent cluster. Therefore, ParaHox genes are dispersed in the genome and are used during embryogenesis in a temporally and spatially coherent manner, whereas the Hox genes, now fully sequenced and annotated, are still linked and are employed as a complex only during the emergence of the adult body plan in the larva.

Amino Acid Sequence↗