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Acute effects of vibration from a chipping hammer and a grinder on the hand-arm system.

OBJECTIVES: The purpose of this study was to compare various effects on the hand-arm system of vibration exposure from a chipping hammer and a grinder with the same frequency weighted acceleration. Grip and push forces were measured and monitored during the exposure. The various effects were: muscle activity (measured with surface electrodes), discomfort ratings for different parts of the hand-arm system (made during and after exposure), and vibration perception threshold (for 10 minutes before and 10 minutes after the exposure). RESULTS: No increase in muscle activity due to exposure to vibration was found in the hand muscle studied. In the forearm, conversely, there was an increase in both muscle studied. For the upper arm the muscle activity only increased when exposed to impact vibration. Subjective ratings in the hand and shift in vibration perception threshold were effected more by the grinder than the hammer exposure. CONCLUSION: These results show that the reaction of the hand-arm system to vibration varies with frequency quantitatively as well as qualitatively. They do not support the notion that one single frequency weighted curve would be valid for the different health effects of hand-arm vibration (vascular, musculoskeletal, neurological, and psychophysiological).

Adult↗

Carpal conformation in relation to carpal chip fracture.

An objective radiological method of assessing the degree to which horses are conformationally 'back at the knee' (hyper-extended) is described. The effects on the measurements of variations in the direction of the incident X-ray beam and variations in weight bearing by the horse were assessed. A change from a lateromedial projection towards a plamaro-lateral-dorsomedial oblique projection consistently tended to reduce the observed degree of hyperextension of the carpus. Raising the contralateral limb to increase the load on the carpus had little effect on the measurements. The carpi of 21 thoroughbred racehorses with carpal chip fractures were not significantly more hyperextended than those of 10 thoroughbred racehorses with normal carpi. Back at the knee conformation was unlikely to have played a major role in the aetiopathogenesis of the carpal injuries.

Animals↗

Removal of chip fractures of the femoral trochlear ridges of three horses by arthroscopy.

Clinical and radiographic examinations of three horses with histories of trauma and/or wounds to the stifle revealed chip fractures from the medial trochlear ridge of the femur of one of them and from the lateral ridges of the femurs of the others. The joints were evaluated and the fragments of bone were removed by arthroscopy. The results were good in all three horses.

Animals↗

CMOS realization of a 2-layer CNN universal machine chip.

Some features of the biological retina can be modelled by a 2-layer cellular neural network (CNN) composed of locally connected elementary nonlinear processors. In order to explore these complex spatiotemporal dynamics for image processing, a prototype chip has been designed and fabricated in a 0.5 microm CMOS technology. Design challenges, trade-offs, the building blocks and the tests results for this system with 0.5 x 10(6) transistors, most of them operating in analog mode, are presented in this paper.

Microcomputers↗

On-chip learning with analogue VLSI neural networks.

Results from simulations of weight perturbation as an on-chip learning scheme for analogue VLSI neural networks are presented. The limitations of analogue hardware are modelled as realistically as possible. Thus synaptic weight precision is defined according to the smallest change in the weight setting voltage which gives a measurable change at the output of the corresponding neuron. Tests are carried out on a hard classification problem constructed from mobile robot navigation data. The simulations show that the degradation in classification performance on a 500-pattern test set caused by the introduction of realistic hardware constraints is acceptable: with 8-bit weights, updated probabilistically and with a simplified output error criterion, the error rate increases by no more than 7% when compared with weight perturbation implemented with full 32-bit precision.

Algorithms↗

An ASIC-chip for stereoscopic depth analysis in video-real-time based on visual cortical cell behavior.

In a stereoscopic system both eyes or cameras have a slightly different view. As a consequence small variations between the projected images exist ("disparities") which are spatially evaluated in order to retrieve depth information. We will show that two related algorithmic versions can be designed which recover disparity. Both approaches are based on the comparison of filter outputs from filtering the left and the right image. The difference of the phase components between left and right filter responses encodes the disparity. One approach uses regular Gabor filters and computes the spatial phase differences in a conventional way as described already in 1988 by Sanger. Novel to this approach, however, is that we formulate it in a way which is fully compatible with neural operations in the visual cortex. The second approach uses the apparently paradoxical similarity between the analysis of visual disparities and the determination of the azimuth of a sound source. Animals determine the direction of the sound from the temporal delay between the left and right ear signals. Similarly, in our second approach we transpose the spatially defined problem of disparity analysis into the temporal domain and utilize two resonators implemented in the form of causal (electronic) filters to determine the disparity as local temporal phase differences between the left and right filter responses. This approach permits video real-time analysis of stereo image sequences (see movies at http://www.neurop.ruhr-uni-bochum.de/Real- Time-Stereo) and a FPGA-based PC-board has been developed which performs stereo-analysis at full PAL resolution in video real-time. An ASIC chip will be available in March 2000.

Animals↗

Supersequences of masks for oligo-chips.

On a very small surface, a chip, several thousands of oligonucleotides, can be synthesized using a mask technology. Given a set of oligos, the problems tackled here are: What is the minimum number of masks necessary to synthesize one copy of each oligo? How long will be the series of masks if each oligo is synthesized twice, such that the two copies are realized with two completely different series of masks? We establish that, for 20,000 oligos of 20 bases a single copy can be synthesized with around 67 masks and for two copies with less than the double.

Algorithms↗

Blood-on-a-chip.

Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.

Animals↗

Protein chip discovery of secreted proteins regulated by the phosphatidylinositol 3-kinase pathway in ovarian cancer cell lines.

Ovarian cancer has the highest mortality among the gynecologic malignancies. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated, leading to increased cell survival. This study aimed to identify secreted proteins regulated by the PI3K pathway in ovarian cancer cell lines. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry with cation-exchange protein-chips was used to analyze secreted proteins from five ovarian cancer cell lines (SKOV-3, PE01, OVCAR-3, OV167, and OV207). To activate the PI3K pathway, cells were treated with 50 ng/mL epidermal growth factor (EGF) with or without 10 micromol/L LY294002, a PI3K inhibitor. Proteins induced by EGF and inhibited by LY294002, in the m/z range 7,500 to 9,500, were purified chromatographically, identified by peptide mass fingerprinting and NH(2)-terminal sequencing, and confirmed by immunodepletion. Two immunologically related proteins, m/z approximately 8,385 and 8,922, were identified as truncated and intact forms, respectively, of interleukin 8, a chemokine previously shown to be elevated in serum of ovarian cancer patients. Another protein, m/z 7,866, was identified as CXC chemokine ligand 1 (CXCL1) or GRO-alpha, a chemokine associated with melanoma formation and some epithelial cancers. EGF-stimulated CXCL1 levels were variably decreased by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase and p38 MAPK inhibition in the five cell lines, but only LY294002 fully reversed the EGF effect in all cell lines. Immunoreactive CXCL1 levels in 160 conditioned media were highly correlated with corresponding peak intensities at m/z 7,866 by mass spectrometry, indicating the quantitative nature of these analyses. We conclude that proteomic analysis of cell models of human disease may facilitate the discovery of pathway-dependent proteins.

Blotting, Western↗

Coupling an aVLSI neuromorphic vision chip to a neurotrophic model of synaptic plasticity: the development of topography.

We couple a previously studied, biologically inspired neurotrophic model of activity-dependent competitive synaptic plasticity and neuronal development to a neuromorphic retina chip. Using this system, we examine the development and refinement of a topographic mapping between an array of afferent neurons (the retinal ganglion cells) and an array of target neurons. We find that the plasticity model can indeed drive topographic refinement in the presence of afferent activity patterns generated by a real-world device. We examine the resilience of the developing system to the presence of high levels of noise by adjusting the spontaneous firing rate of the silicon neurons.

Models, Neurological↗

Novel transducers for nano-optical biosensor chips based on biological and synthetic polymers with analyte-dependent swelling/shrinking behavior.

Analyte-dependent swelling/shrinking properties of ultrathin polymer layers are an appropriate means for the detection of various analytes. Optical metal nanoclusters can be used to determine the change of the layer's thickness, which is shown by a change in the color of the chip. By using different cross-linking agents and different polymers (biological or artificial as well) it was possible to design various sensitive layers showing different swelling/shrinking behaviors. Sensitivity on various analytes could be observed, since the different types of polymers employed differed in structure, functional groups, or biorecognitive properties.

Biopolymers↗

Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles.

PURPOSE: Leber congenital amaurosis (LCA) is an early-onset inherited disorder of childhood blindness characterized by visual impairment noted soon after birth. Variants in at least six genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) have been associated with a diagnosis consistent with LCA or early-onset retinitis pigmentosa (RP). Genetically heterogeneous inheritance complicates the analyses of LCA cases, especially in patients without a family history of the disorder, and conventional methods are of limited value. METHODS: To overcome these limitations, arrayed primer extension (APEX) technology was used to design a genotyping microarray for early-onset, severe retinal degenerations that includes all of the >300 disease-associated variants currently described in eight genes (in addition to the six just listed, the early-onset RP genes LRAT and MERTK were added). The resultant LCA array allows simultaneous detection of all known disease-associated alleles in any patient with early-onset RP. The array was validated by screening 93 confirmed patients with LCA who had known mutations. Subsequently, 205 novel LCA cases were screened on the array, followed by segregation analyses in families, if applicable. RESULTS: The microarray was >99% effective in determining the existing genetic variation and yielded at least one disease-associated allele in approximately one third of the novel patients. More than two (expected) variants were discovered in a substantial fraction (22/300) of the patients, suggesting a modifier effect from more than one gene. In support of the latter hypothesis, the third allele segregated with a more severe disease phenotype in at least five families. CONCLUSIONS: The LCA genotyping microarray is a robust and cost-effective screening tool, representing the prototype of a disease chip for genotyping patients with a genetically heterogeneous condition. Simultaneous screening for all known LCA-associated variants in large LCA cohorts allows systematic detection and analysis of genetic variation, facilitating prospective diagnosis and ultimately predicting disease progression.

Alleles↗

The natural history of "chipping".

The authors present five case histories illustrating controlled use of opiates ("chipping"). Long-term chippers tend to develop consistent social use patterns that permit and also limit use. The authors conclude that controlled use of opiates is possible and that large numbers of people are involved in such use, although they are hard to locate and identify. Controlled users are differentiated from compulsive users more by their development and maintenance of social drug use rituals than by such variables as availability of the drug and personality and family background of the user.

Adult↗

Buried chip skin grafting in neuropathic diabetic foot ulcers following vacuum-assisted wound bed preparation: enhancing a classic surgical tool with novel technologies.

In patients with diabetes mellitus, complications such as polyneuropathy and peripheral angiopathy inevitably lead to diabetic foot complications including foot ulcers, gangrene, and osteoarthropathy. These conditions necessitate minor or major amputation as part of treatment. In patients with Charcot's arthropathy and predominant neuropathy, recurrent foot ulcers are common in areas of high pressure. Such high pressure is caused by the degrading of the architecture of the foot and inadequate footwear. These patients are a clinical challenge. A select group of such patients may benefit from free surgical tissue transfer, though free or local flap surgery is often difficult or even impossible owing to an impaired arterial circulation. In such wounds, surgical debridement followed by skin grafts often fail due to bacterial burden in the wounds. To circumvent these problems, the authors developed a therapeutic approach using buried chip skin grafting to close granulation wound beds in diabetic feet. Locally applied vacuum therapy (VAC) for wound bed preparation of chronic, nonresponsive foot ulcers and subsequent grafting using the burying technique with a minute fraction of skin was used. Firm closure was achieved. The closed wound was resistant to mechanical irritation.

Journal Article↗

Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer binding proteins alpha and epsilon (C/EBP alpha and C/EBP epsilon ) and CDP/cut in myeloid maturation-induced lactoferrin gene expression.

In vitro models of granulopoiesis involving the inducible expression of either CCAAT enhancer binding protein alpha (C/EBP alpha) or C/EBP epsilon in myeloid cells have been shown to lead to the induction of a granulocytic maturation program accompanied by the expression of myeloid-specific genes. Since members of the C/EBP family of transcription factors recognize and bind to similar DNA-binding motifs, it has been difficult to elucidate the specific role of each of the C/EBP family members in eliciting myeloid gene expression. In order to address this issue, we focused on the expression of the lactoferrin (LF) gene. LF expression is transcriptionally regulated in a C/EBP-dependent manner in myeloid cells. Using chromatin immunoprecipitation (ChIP) analysis we demonstrate that C/EBP alpha binds to the LF promoter in nonexpressing cells. Upon induction of maturation, C/EBP epsilon binds to the LF promoter, which correlates with LF expression. Lack of LF expression in the acute promyelocytic leukemia cell line NB4, which harbors the t(15;17) translocation, cannot be correlated with aberrant binding at the C/EBP site in the LF promoter. It is, however, associated with the persistent binding of the silencer CCAAT displacement protein (CDP/cut) to the LF promoter in these cells. We conclude that C/EBP alpha, C/EBP epsilon, and CDP/cut all play definitive roles in regulating late gene expression during normal myeloid development.

CCAAT-Enhancer-Binding Protein-alpha↗

Alternative mapping of probes to genes for Affymetrix chips.

BACKGROUND: Short oligonucleotide arrays have several probes measuring the expression level of each target transcript. Therefore the selection of probes is a key component for the quality of measurements. However, once probes have been selected and synthesized on an array, it is still possible to re-evaluate the results using an updated mapping of probes to genes, taking into account the latest biological knowledge available. METHODS: We investigated how probes found on recent commercial microarrays for human genes (Affymetrix HG-U133A) were matching a recent curated collection of human transcripts: the NCBI RefSeq database. We also built mappings and used them in place of the original probe to genes associations provided by the manufacturer of the arrays. RESULTS: In a large number of cases, 36%, the probes matching a reference sequence were consistent with the grouping of probes by the manufacturer of the chips. For the remaining cases there were discrepancies and we show how that can affect the analysis of data. CONCLUSIONS: While the probes on Affymetrix arrays remain the same for several years, the biological knowledge concerning the genomic sequences evolves rapidly. Using up-to-date knowledge can apparently change the outcome of an analysis.

Base Sequence↗

Simultaneous measurement of sensor-protein dynamics and motility of a single cell by on-chip microcultivation system.

Measurement of the correlation between sensor-protein expression, motility and environmental change is important for understanding the adaptation process of cells during their change of generation. We have developed a novel assay exploiting the on-chip cultivation system, which enabled us to observe the change of the localization of expressed sensor-protein and the motility for generations. Localization of the aspartate sensitive sensor protein at two poles in Escherichia coli decreased quickly after the aspartate was added into the cultivation medium. However, it took more than three generations for recovering the localization after the removal of aspartate from the medium. Moreover, the tumbling frequency was strongly related to the localization of the sensor protein in a cell. The results indicate that the change of the spatial localization of sensor protein, which was inherited for more than three generations, may contribute to cells, motility as the inheritable information.

Journal Article↗