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The aim of this study is to analyze the latest evidence on the effects of losartan or Ang II receptor antagonists on cartilage repair, with a focus on their clinical relevance.The PubMed, Embase, and Cochrane Library databases were searched up to November 12th 2021 to evaluate the effects of losartan or Ang II receptor antagonists on cartilage repair in in vitro studies and in vivo animal studies. Study design, sample characteristics, treatment type, duration, and outcomes were analyzed. The risk of bias and the quality of the eligible studies were assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias assessment tool and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES).A total of 12 studies were included in this systematic review. Of the 12 eligible studies, 2 studies were in vitro human studies, 3 studies were in vitro animal studies, 1 study was an in vitro human and animal study, and 6 studies were in vivo animal studies. The risk bias and quality assessments were predominantly classified as moderate. Since meta-analysis was difficult due to differences in treatment type, dosage, route of administration, and method of outcome assessment among the eligible studies, qualitative evaluation was conducted for each study.Both in vitro and in vivo studies provide evidence to demonstrate beneficial effects of Ang II receptor antagonists on osteoarthritis and cartilage defect models across animal species.

Resume Introduction L’incendie de l’usine chimique Lubrizol a Rouen le 26 septembre 2019 a genere une immense colonne de fumee dirigee nord-est vers l’agglomeration. L’œil pouvant particulierement etre touche par les fumees et autres degagements toxiques de l’incendie, nous avons evalue l’impact de cette catastrophe industrielle et ecologique sur les pathologies irritatives de surface oculaire dans la semaine suivant l’accident. Materiel et methode Nous avons recueilli retrospectivement les donnees medicales des patients qui se sont presentes aux urgences ophtalmologiques (UOph) du CHU de Rouen (seul service d’UOph ouvert pendant les jours suivant l’accident) pendant la semaine suivant l’incendie (semaine S1). Nous avons compare ces donnees a celles des patients ayant consulte dans la semaine precedant l’incendie (semaine S-1). Nous avons egalement recueilli la frequentation aux urgences generales en semaine S-1 et S1, dont le nombre de consultations en lien direct avec l’incendie. Resultats Nous avons accueilli 361 patients aux UOph durant la semaine S1 suivant l’incendie, versus 384 en S-1. Parmi ces patients, 83 (23 %) presentaient une pathologie de la surface oculaire en S1, versus 76 (20 %) en S-1. Une conjonctivite etait retrouvee chez 54 patients en S1 (39 d’allure virale, 9 d’allure allergique, 6 indeterminee) versus 44 en S-1 (27 d’allure virale, 12 d’allure allergique, 5 indeterminee). Un syndrome sec irritatif existait chez 29 patients en S1 versus 32 en S-1. Seuls 4 patients ont mentionne que leurs symptomes etaient en lien direct avec l’incendie : 2 conjonctivites virales, une conjonctivite allergique et un patient inquiet (respectivement a J2, J5, J7 et J7 de l’incendie). Discussion Le nombre de consultants aux urgences ophtalmologiques n’a pas varie dans la semaine suivant l’incendie de l’usine Lubrizol (sauf une baisse le jour meme liee au confinement). On note un nombre plus eleve de consultants en S1 pour des conjonctivites, surtout d’allure virale et probablement sans lien direct avec l’incendie. Les consultations pour syndrome sec irritatif etaient comparables entre les 2 semaines. Malgre une mediatisation majeure de l’evenement au niveau national et un niveau d’inquietude tres important dans la population, l’incendie ne semble pas avoir eu de repercussions sur l’activite aux UOph du CHU de Rouen, pas plus que sur l’activite des urgences generales. Le confinement a domicile de la population le premier jour a eu possiblement un effet protecteur, evitant une exposition directe aux fumees. Les consequences a long terme des depots de suie sur le sol au passage du nuage de fumee restent indeterminees et sous surveillance. Une revue de la litterature sur les consequences oculaires des accidents industriels est presentee. Conclusion Les urgences ophtalmologiques n’ont pas connu de suractivite dans la semaine suivant l’incendie de l’Usine Lubrizol a Rouen et les pathologies de la surface oculaire n’ont pas donne lieu a plus de consultations que la semaine precedente. Ceci permet de conclure a une toxicite oculaire immediate absente ou minime des fumees de l’incendie.

A fire at the Lubrizol chemical factory in Rouen on September 26, 2019 generated a huge column of smoke directed northeast toward the city. As the eye might be particularly affected by the smoke and other toxic emissions from the fire, we assessed the impact of this industrial and ecological disaster on irritative eye surface disease in the week following the accident.We retrospectively collected the medical data of the patients who presented to the Ophthalmology Emergency Department (OED) of Rouen University Hospital (the only OED open during the days following the accident) during the week following the fire (W1). We compared these data with those of patients who presented during the week before the fire (W-1). We also collected data on patients presenting to the ED in general during W-1 and W1, including the number of visits directly related to the fire.361 patients presented to the OED during W1 following the fire, compared with 384 in W-1. Of these patients, 83 (23%) had ocular surface disease in W1, versus 76 (20%) in W-1. Conjunctivitis was found in 54 patients in W1 (39 viral, 9 allergic, 6 undetermined) versus 44 in W-1 (27 viral, 12 allergic, 5 undetermined). A dry irritative syndrome was present in 29 patients in W1 versus 32 in W-1. Only 4 patients directly attributed their symptoms to the fire: 2 viral conjunctivitis, 1 allergic conjunctivitis and 1 worried patient (at D2, D5, D7 and D7 following the fire respectively).The number of emergency eye consultations did not change in the week following the Lubrizol factory fire (except for a decrease the day of the accident, related to the lock-down). There was a higher number of consultations in W1 for conjunctivitis, mostly viral in appearance and probably not directly related to the fire. The number of consultations for dry irritative syndrome was comparable between the two periods. Despite major media coverage of the event at the national level and a very high level of concern among the population, the fire does not seem to have had an effect on OED activity at Rouen University Hospital, nor on general ED visits. The stay-at-home order on the first day may have had a protective effect, avoiding direct exposure to smoke. The long-term consequences of the soot deposits on the ground as the smoke cloud passed over remain undetermined and are under surveillance. A review of the literature on the ocular consequences of industrial accidents is presented.The Ophthalmology Emergency Department did not record increased activity in the week following the Lubrizol Rouen fire, and ocular surface disease did not give rise to more consultations than the week before the fire. This suggests that there was no or minimal immediate ocular toxicity of the smoke from the fire.

There are many reports on the occurrence of anomalous changes in the ionosphere prior to large earthquakes. However, whether or not these changes are reliable precursors that could be useful for earthquake prediction is controversial within the scientific community. To test a possible statistical relationship between ionospheric disturbances and earthquakes, we compare changes in the total electron content (TEC) of the ionosphere with occurrences of M ≥ 6.0 earthquakes globally for 2000 - 2014. We use TEC data from the global ionosphere map (GIM) and an earthquake list declustered for aftershocks. For each earthquake, we look for anomalous changes in GIM-TEC within 2.5° latitude and 5.0° longitude of the earthquake location (the spatial resolution of GIM-TEC). Our analysis has not found any statistically significant changes in GIM-TEC prior to earthquakes. Thus, we have found no evidence that would suggest that monitoring changes in GIM-TEC might be useful for predicting earthquakes.

In order to improve our understanding of impact history and surface geology on the Moon, we obtained 40 Ar– 39 Ar incremental heating age data and major + trace element compositions of anorthositic and melt breccia clasts from Apollo 16 feldspathic fragmental breccias 67016 and 67455. These breccias represent the Descartes terrain, a regional unit often proposed to be ejecta from the nearby Nectaris basin. The goal of this work is to better constrain the emplacement age and provenance of the Descartes breccias. Four anorthositic clasts from 67016 yielded well-defined 40 Ar– 39 Ar plateau ages ranging from 3842 ± 19 to 3875 ± 20 Ma. Replicate analyses of these clasts all agree within measurement error, with only slight evidence for either inheritance or younger disturbance. In contrast, fragment-laden melt breccia clasts from 67016 yielded apparent plateau ages of 4.0–4.2 Ga with indications of even older material (to 4.5 Ga) in the high-T fractions. Argon release spectra of the 67455 clasts are more variable with evidence for reheating at 2.0-2.5 Ga. We obtained plateau ages of 3801 ± 29 to 4012 ± 21 Ma for three anorthositic clasts, and 3987 ± 21 Ma for one melt breccia clast. The anorthositic clasts from these breccias and fragments extracted from North Ray crater regolith ( Maurer et al., 1978 ) define a combined age of 3866 ± 9 Ma, which we interpret as the assembly age of the feldspathic fragmental breccia unit sampled at North Ray crater. Systematic variations in diagnostic trace element ratios (Sr/Ba, Ti/Sm, Sc/Sm) with incompatible element abundances show that ferroan anorthositic rocks and KREEP-bearing lithologies contributed to the clast population. The Descartes breccias likely were deposited as a coherent lithologic unit in a single event. Their regional distribution suggests emplacement as basin ejecta. An assembly age of 3866 ± 9 Ma would be identical with the accepted age of the Imbrium basin, and trace element compositions are consistent with a provenance in the Procellarum-KREEP Terrane. The combination of age and provenance constraints points toward deposition of the Descartes breccias as ejecta from the Imbrium basin rather than Nectaris. Diffusion modeling shows that the older apparent plateau ages of the melt brecia clasts plausibly result from incomplete degassing of ancient crust during emplacement of the Descartes breccias. Heating steps in the melt breccia clasts that approach the primary crystallization ages of lunar anorthosites show that earlier impact events did not completely outgas the upper crust.

Lunar impact melt breccias provide a unique record of the timing and frequency of collisional events during the early history of the inner Solar System prior to the development of a significant rock record on Earth. The predominance of ages clustering between 3.8 and 4.0 Ga was a major, unexpected discovery obtained from geochronological studies of lunar impact melts, and is the basis of the concept that a cataclysmic bombardment of large planetesimals struck the Earth and Moon, and possibly the entire inner Solar System, about 3.85 ± 0.10 billion years ago. As a test of the cataclysm hypothesis, we measured high-resolution (20–50 steps) 40 Ar– 39 Ar age spectra on 25 samples of Apollo 16 impact melt breccias using a continuous laser heating system on sub-milligram fragments. Twenty-one of these 25 breccias produced multi-step plateaus that we interpret as crystallization ages, with 20 of these ages falling in the range 3.75–3.96 Ga. We propose that at least four different melt-producing impact events can be distinguished based on the ages, bulk compositions, and petrographic characteristics of Apollo 16 melt breccias. The recognition of multiple impact events within the Apollo 16 melt breccia suite shows that numerous impact events occurred on the lunar surface within a relatively narrow time interval, providing additional evidence of a heavy bombardment of the Moon during the early Archean.

Timing measurements for gigahertz clock frequencies require high accuracy and resolution. This paper proposes a scalable built-in self-test (BIST) method that measures accumulated period jitter over a programmable number of periods, without using another reference clock. This on-chip method uses a charge pump to convert time to a voltage, which is digitized by an all-digital flash analog-to-digital converter (ADC). The ADC employs multiple chains of inverter strings composed of three series inverters instead of the popular analog comparators. The inverter thresholds set the reference voltages for triggering given an input dc value. The output is calibrated and converted to jitter measurement. The design using a 0.25 /spl mu/m BiCMOS process, with an input range of 625 MHz-1 GHz, shows that a resolution of 70 ps root mean square (rms) jitter can be achieved, while occupying 0.0575 mm/sup 2/ area with a very conservative layout style. The design has been fabricated and tested, and the test results are presented.

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches.

Robotic, high-throughput microscopy is a powerful tool for small molecule screening and classifying cell phenotype, proteomic and genomic data. An important hurdle in the field is the automated classification and visualization of results collected from a data set of tens of thousands of images. We present a method that approaches these problems from the perspective of flow cytometry with supporting open-source code. Image analysis software was created that allowed high-throughput microscopy data to be analysed in a similar manner as flow cytometry. Each cell on an image is considered an object and a series of gates similar to flow cytometry is used to classify and quantify the properties of cells including size and level of fluorescent intensity. This method is released with open-source software and code that demonstrates the method's implementation. Accuracy of the software was determined by measuring the levels of apoptosis in a primary murine myoblast cell line after exposure to staurosporine and comparing these results to flow cytometry.

Cet article decrit un capteur a fibres optiques de gaz carbonique par absorption moleculaire dans l'infrarouge moyen (4,3 μm) correspondant au mode fondamental ν3. La liaison entre le site de mesure et le site de controle est assuree par une fibre optique standard 50/125 apres une transposition de longueur d'onde de 4,3 μm a 860 nm par opto-alimentation. La simulation de l'absorption a ete obtenue par modelisation originale du spectre d'absorption et l'etablissement des courbes d'etalonnage prevoit une marge d'erreur minimale de 100 μbar, ce qui est suffisant pour l'application du dispositif a la regulation de taux de CO 2 dans les serres agricoles enrichies par ce gaz.

An intrinsic optical fibre temperature sensor which uses modal interference in a tapered monomode fibre is described. The sensor is demodulated by an interferometer designed to measure a phase by the coherence multiplexing technique. A theoretical description is given, followed by experimental results which are compared with numerical simulations.

Volcanic samples collected with the Monterey Bay Aquarium Research Institute's ROV Tiburon from eight seamounts at the continental margin offshore central to southern California comprise a diverse suite of mainly alkalic basalt to trachyte but also include rare tholeiitic basalt and basanite. All samples experienced complex crystal fractionation probably near the crust/mantle boundary, based on the presence in some of mantle xenoliths. Incompatible trace elements, poorly correlated with isotopic compositions, suggest variable degrees of partial melting of compositionally heterogeneous mantle sources, ranging from MORB-like to relatively enriched OIB. High-precision 40Ar/39Ar ages indicate episodes of volcanic activity mainly from 16 to 7 Ma but document one eruption as recent as 2.8 Ma at San Juan Seamount. Synchronous episodes of volcanism occurred at geographically widely separated locations offshore and within the continental borderland. Collectively, the samples from these seamounts have age ranges and chemical compositions similar to those from Davidson Seamount, identified as being located atop an abandoned spreading center. These seamounts appear to have a common origin ultimately related to abandonment and partial subduction of spreading center segments when the plate boundary changed from subduction-dominated to a transform margin. They differ in composition, age, and origin from other more widespread near-ridge seamounts, which commonly have circular plans with nested calderas, and from age progressive volcanoes in linear arrays, such as the Fieberling-Guadalupe chain, that occur in the same region. Each volcanic episode represents decompression melting of discrete enriched material in the suboceanic mantle with melts rising along zones of weakness in the oceanic crust fabric. The process may be aided by transtensional tectonics related to continued faulting along the continental margin.

Davidson Seamount, a volcano located about 80 km off the central California coast, has a volume of ∼320 km3 and consists of a series of parallel ridges serrated with steep cones. Davidson was sampled and its morphology observed during 27 ROV Tiburon dives. During those dives, 286 samples of lava, volcaniclastite, and erratics from the continental margin were collected, with additional samples from one ROV-collected push core and four gravity cores. We report glass compositions for 99 samples and 40Ar-39Ar incremental heating age data for 20 of the samples. The glass analyses are of hawaiite (62%), mugearite (13%), alkalic basalt (9%), and tephrite (8%), with minor transitional basalt (2%), benmoreite (2%), and trachyandesite (2%). The lithologies are irregularly distributed in space and time. The volcano erupted onto crust inferred to be 20 Ma from seafloor magnetic anomalies. Ages of the lavas range from 9.8 to 14.8 Ma. The oldest rocks are from the central ridge, and the youngest are from the flanks and southern end of the edifice. The compositions of the 18 reliably dated volcanic cones vary with age such that the oldest lavas are the most fractionated. The melts lost 65% to nearly 95% of their initial S because of bubble loss during vesiculation, and the shallowest samples have S contents similar to lava erupted subaerially in Hawaii. Despite this similarity in S contents, there is scant other evidence to suggest that Davidson was ever an island. The numerous small cones of disparate chemistry and the long eruptive period suggest episodic growth of the volcano over at least 5 Myr and perhaps as long as 10 Myr if it began to grow when the spreading ridge was abandoned.

Resume On calcule la reflexion et la transmission de la lumiere au niveau d'une epissure centree entre deux fibres faiblement guidantes. Ces fibres, unimodales dans le sens qu'elles guident un seul mode de noyau, peuvent toutefois supporter un grand nombre de modes de gaine si celle-ci est de dimension finie. Ces modes guides forment alors une base suffisament grande pour pouvoir decomposer correctement les champs et negliger les modes de radiation.

A BIST method to measure jitter without external references is presented. Measured data from 0.25- m BiCMOS chips show jitter resolution about 30 to 50 ps over 8 cycles of a 1 GHz input signal. The measurement technique uses the clock signal under test to control the charging of the input capacitance of an ADC. One advantage of this design is that it does not require an external jitter-free reference clock or a voltage reference. Design improvements from architectures to circuits are discussed and the method has potentials in other timing measurement applications.

Fractures in osteoporotic bones or segment defects are problematic bone lesions with a reduced biological capability of regeneration. We tested the hypothesis that cell-mediated ex vivo gene therapy to deliver BMP4 can heal critically sized defects and improve bone healing in osteoporotic rats. Primary muscle-derived cells were isolated from the hindlimb muscle of rats and retrovirally transduced to express bone morphogenic protein 4 (BMP4). The bone formation was evaluated following local application of these cells in critically sized defects and in fractures of osteoporotic bones. Radiographic analysis revealed bridging callus formation in a critically sized defect in all specimens using muscle-derived cells expressing BMP4 at 12 weeks. These findings were confirmed by histological evaluation, which revealed callus bone formation with good integration to the distal and proximal bone. Following treatment with muscle-derived cells expressing BMP4, the bone healing process in the osteoporotic bone was improved to the level similar to that of normal bone. The ex vivo gene therapy could be a promising tool for the treatment of osteoporotic fractures and critically sized defects. The reduced number of complications (nonunions, loss of reduction, and fragment dislocation), shortening of hospitalization period, and improvement of bone strength are decisive advocates for this treatment option.

Polarization of light is a consequence of the vectorial nature of electromagnetic waves. This concept must be taken into account in a large number of optical phenomena such as birefringence, modulation of light, and propagation in optical devices. A representation of the states of polarization will first be analyzed. The propagation of light in linear or circular anisotropic media is carried out in the context of the phase velocity of the eigenstates of propagation. The evolution of a state of polarization traveling through a complex optical device will be finally presented. Keywords: polarization; birefringence; Jones vectors; Jones matrices; Stokes parameters; Poincare sphere; optical rotary power

Growth and regeneration of skeletal muscle fibers in response to injury are made possible by the presence of resident myogenic progenitor cells. Researchers have attempted to isolate and transplant these cells to regenerate new muscle in cases involving injury, disease, or genetic deficiencies. Reports from such experiments underscore the functional diversity of progenitors obtained from skeletal muscle; however, currently there is no reliable means by which to positively identify and isolate the most desirable muscle progenitor populations. Taking a cue from the hematopoietic community, researchers in this area have begun to investigate cell surface protein expression in progenitor populations. Previous findings in cultured myogenic cells and our results in cells obtained directly from dissociated muscle suspensions indicate that cells sorted based on their expression of the commonly-studied myogenic cell surface proteins Sca-1 and CD34 exhibit differing regenerative abilities. However, results obtained to date are insufficient to clearly delineate whether the expression of either of these proteins is an exclusive characteristic of efficient myogenic progenitors. Nonetheless, observations from these studies clearly suggest that progenitor heterogeneity should be an important consideration during the development and implementation of muscle regeneration strategies. Additional research is necessary to establish reliable selection criteria for the isolation of efficient progenitors, which will facilitate therapeutic discoveries and enhance our understanding of factors affecting regeneration outcomes.

A BIST method measures accumulated jitter over N periods and requires no external references. Simulation using a 0.25um process shows a 625MHz - I GHz input range with resolution of 70ps RMS jitter occupying 0.05 75mmz area.

Skeletal muscle injuries are a common problem in trauma and orthopaedic surgery. Muscle injuries undergo the healing phases of degeneration, inflammation, regeneration, and fibrosis. Current and experimental therapies to improve muscle regeneration and limit muscle fibrosis include conservative and surgical principles with the adjuvant use of non-steroidal anti-inflammatory drugs (NSAIDs) and growth factor manipulation. NSAIDs appear to have a paradoxical effect on the healing of muscle injuries with early signs of improvement and subsequent late impairment in functional capacity and histology. In vitro and in vivo studies have explored the role of the cyclooxygenases and prostaglandins in the biological processes of healing muscle, including precursor cell activation, myoblast proliferation, myoblast fusion, and muscle protein synthesis. Through use of more specific cyclooxygenase inhibitors, we may be able to better understand the role of inflammation in muscle healing.

To determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection.The inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats.Throughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH2O, compared with naive animals with a basal ICP of 5 (6) cmH2O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 micro mol/L in the adeno-myoblast penis.Myoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.

Articular cartilage has very limited intrinsic healing capacity. Although numerous attempts to repair full-thickness articular cartilage defects have been conducted, no methods have successfully regenerated long-lasting hyaline cartilage. One of the most promising procedures for cartilage repair is tissue engineering accompanied by gene therapy.With gene therapy, genes encoding for therapeutic growth factors can be expressed at a high level in the injured site for an extended period of time. Chondrocytes have been intensively studied for cell transplantation in articular cartilage defects.However, recent studies have shown that chondrocytes are not the only candidate for cartilage repair. Muscle-derived cells have been found capable of delivering genes and represent a good vehicle to deliver therapeutic genes to improve cartilage repair. More importantly, recent studies have suggested the presence of pluripotent stem cells in muscle-derived cells.New techniques of cell therapy and molecular medicine for the treatment of cartilage lesions are currently undergoing clinical trials. This paper will summarize the current status of gene therapy for cartilage repair and its future application.

It is shown that a tapered monomode fibre can be used as a simple, compact, remote sensor by using the coherence multiplexing method. A device is presented in which the fibre taper is coupled to a Michelson interferometer used as a demodulator. Experimental results are compared with theoretical predictions for two different external media.

Recent advances in bone tissue engineering are established on the understanding of an engineered scaffold, the molecular milieu within the osteogenic site, and the cell(s) predisposed to an osteogenic lineage. Advances in the incorporation of a generative vehicle into a skeletal defect require temporal and spatial distribution of the scaffold, growth factor, and cell compatible with enhanced bone healing. Monitoring events culminating in osteogenesis has focused on phenotypic and intracellular indicators. Phenotypic and intracellular indicators include the presence of receptors and intracellular signals that enable cell proliferation and differentiation. Progress in the areas of scaffold design, growth factor utilization, bone cell lineage, and intracellular signaling are reviewed.

Articular cartilage injuries are commonly encountered problems in sports medicine and orthopaedics. The treatment of chondral and osteochondral lesions, which possess only a very limited potential for healing, still represents a great challenge to clinicians and to scientists. Experimental investigations reported over the last 20 years have shown that a variety of methods, including implantation of periosteum, perichondrium, artificial matrices, growth factors, and transplanted cells, can stimulate formation of new cartilage. Genetic engineering--a combination of gene transfer techniques and tissue engineering--will facilitate new approaches to the treatment of articular cartilage injuries.

Efficient adenoviral gene delivery to mature skeletal muscle has been hindered by different factors. The low levels of adenoviral attachment receptor (CAR) that have been reported in this tissue may be a limiting factor. Therefore, adenoviral transduction of mature muscle may be improved by extending the tropism of the adenoviral vectors to attachment receptors that are highly expressed in mature myofibers. In this study, we have investigated whether an extended tropism adenoviral vector which additionally attaches to the broadly expressed heparan-containing receptors (AdPK) can bypass the maturation-dependent adenoviral transducibility of mouse skeletal muscle.The adenoviral vector AdPK carrying the LacZ gene was evaluated as a gene delivery vehicle in mouse skeletal muscle at different maturities in vitro and in vivo. The viral transduction efficiencies were determined by histochemical and ONPG analysis of the beta-galactosidase activity level.Higher transduction efficiencies were detected in immature muscle from normal mice, and in mature muscle from merosin-deficient dy/dy mice (carrying myofibers with an impaired extracellular matrix) and dystrophin-deficient mdx mice (showing a high level of myoblast activity) when compared to mature muscle from normal mice.Despite the enhanced attachment characteristics, the extended tropism adenoviral vector is, similarly to the wild-type adenoviral vector in previous studies, still hindered by both a protective extracellular matrix and the diminished myoblast-mediation in mature muscle.

Muscle-based somatic gene therapy is a novel way to alleviate a biochemical deficiency.Muscle-derived cells are very promising in the field of gene therapy and tissue engineering. First, most muscle tissue is accessible by injection. Second, muscle tissue consists of multinucleated, postmitotic myofibers, which enable a long-term expression of the transduced gene. Third, muscle tissue can be biopsied easily. It is available in abundance and the biopsy does not compromise the health and function of the patient. Finally, muscle tissue is highly vascularized, which makes systemic delivery feasible.Muscle-derived cells can promote muscle healing and bone healing. Implanted cells maintain a long-term transgene expression of therapeutic proteins. Isolated, muscle-derived stem cells can differentiate in osteoblasts.Based on these characteristics, we present four possible applications: inherited muscular diseases, muscle injury, bone healing, and intraarticular disorders.

Duchenne muscular dystrophy (DMD) results from mutations that prevent the expression of functional dystrophin in muscle fibers. Herpes simplex virus type-1 (HSV-1) represents a potentially useful vector for treatment of DMD because it has the capacity to accommodate the 14-kb full-length dystrophin cDNA and can efficiently transduce muscle cells. We have tested the ability of first- and second-generation replication-defective HSV vectors to deliver full-length dystrophin to dystrophin-deficient mdx muscle cells in vitro and in vivo.First-generation replication-defective HSV vectors harboring full-length or truncated (Becker) dystrophin expression cassettes and lacking a single viral immediate-early (IE) gene were constructed and tested by immunofluorescence and immunoblotting for their ability to direct dystrophin expression in infected mdx cells in culture. To reduce vector cytotoxicity and safety concerns, a second-generation dystrophin vector missing additional IE genes was constructed and tested in vitro and in vivo.Dystrophin expression was observed in infected mdx myotubes in vitro in all cases. Confocal microscopy showed exclusive localization of full-length dystrophin to the cell membrane whereas the Becker variant was also found abundantly throughout the cytoplasm. Dystrophin expression in mdx mice was restored in muscle cells near the site of vector injection.Highly defective HSV-1 vectors which lack the ability to spread systemically and are greatly reduced in toxicity for infected cells, thus removing an impediment to prolonged transgene expression, can direct the delivery and proper expression of full-length dystrophin whose considerable size is compatible with few other modes of delivery. These vectors may offer a legitimate opportunity toward the development of effective gene therapy treatments for DMD.

The Pittsburgh Tissue Engineering Initiative (PTEI) is the prime catalyst for tissue-engineering research and the development of a viable for-profit tissue-engineering industry in southwestern Pennsylvania. PTEI operates targeted programs that support commercializable research; provide professional and community education; and facilitate interactions between academic medical centers, regional government, and industry to support the development of a vibrant tissue-engineering industry. This article discusses the types of research and education programs provided by PTEI and provides a brief summary of some of the tissue-engineering-related research in the region.

The principle of an interferometric single-mode fiber optic sensor using birefringent components and a broadband source is described. This device is sensitive to the magnetic field variation or to the mechanical rotations of its components. In this paper, we show that only one additional birefringent element is needed to make this fiber optic sensor. Besides, this device can be used for characterizing optical fibers or any birefringent element inside the Sagnac.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A new remote optical fiber sensor is presented for the detection of carbon dioxide by molecular absorption in the near infrared corresponding to fundamental mode v3 equals 2349 cm-1 (4.257 micrometers ). To overcome this problem of the strong attenuation signal of optical fibers in the infrared, the opto power supply, technique is used which changes the working wavelength from 4.3 micrometers to 860 nm and permits the use of standard 50/125 multimode optical fibers. The simulation of absorption has been obtained by modeling the carbon dioxide absorption spectrum. The relative absorption versus the partial pressure of carbon dioxide have been compared to different theoretical models. The establishment of the calibration curves indicate that the sensor detects partial pressures greater than 100 (mu) bar with a minimal error margin of 100 (mu) bar, which is acceptable considering the future use of the device. The sensor was designed to monitor carbon dioxide concentrations in enriched greenhouses.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The main results obtained with optical devices using coherence multiplexing are described. The demodulation methods for interferometers illuminated by low coherence sources are studied. The applications of coherence multiplexing in the field of fiber-optics sensors and telecommunications together with the future developments are also presented.

Herpes simplex virus type 1 (HSV-1) has a broad host range although in natural human infections the virus is neurotropic, establishing latent infections in sensory neurons where the viral DNA persists as an intact episome. The establishment of latency does not depend on viral replication functions, suggesting that infection of non-neuronal cells, including tissue of myogenic origin, by replication defective mutants may result in genome persistence in a similar episomal state. In this report a replication defective HSV-1 recombinant vector containing the beta-galactosidase reporter gene under transcriptional control of the strong human cytomegalovirus immediate-early gene promoter (HCMV IEp-lacZ) was used to infect muscle cells in vitro and in vivo. This replication defective mutant virus (d120), deleted for both copies of the essential immediate-early gene (ICP4) and thus incapable of expressing early and late viral genes, displayed highly reduced cytotoxicity in myogenic cells. This vector infected both myoblasts and myotubes in culture with transgene expression persisting for at least 8 days. The transduction efficiency in myotubes was similar to myoblasts at several multiplicities of infection (MOIs), suggesting that HSV could infect differentiated muscle fibers and that myoblast differentiation would neither prevent expression of the cellular receptor(s) for the virus nor inhibit viral penetration. Direct inoculation of mouse muscle fibers in vivo with 10(6) to 10(8) plaque forming units (p.f.u.) of vector was sufficient to transduce significant numbers of muscle fibers in newborn mice and some fibers in adult normal and mdx mice. These results suggest that recombinant HSV-1 vectors may be useful for gene transfer to muscle.

One of the key factors that determines the efficacy of adenovirus-mediated gene therapy in genetic diseases, is the degree and extent of transduction of the target cells by adenovirus (AV)-recombinants carrying the therapeutic gene or cDNA. In this paper we provide experimental evidence which indicates that the route of administration of the AV-recombinants has a major influence on the transduction of various tissues in young rats. The heart, diaphragm, intercostal muscles and thymus show high transduction after intra-arterial (left cardiac ventricle) injection. By contrast, the liver shows a high transduction after intravenous injection. A substantial viremia develops within 2 h of gastric-rectal, intraperitoneal and intracardiac administration of AV recombinants. The number of adenoviral DNA copies per nucleus of transduced cells ranged from one to three in most tissues. These numbers correlated well with the overall transduction efficiency of the tissue determined by reporter gene expression. The various factors that determine which route of administration favors a high transduction rate in a particular tissue can be analyzed and this can lead to an improved efficiency of gene therapy in targeting a particular tissue in a disease.

This paper reports how to realize a new type of tunable filter using the Faraday effect. The properties of a Fabry-Perot etalon whose cavity is made with a Faraday rotator are recalled. The analysis of the polarization state of the emergent light permits us to find the configuration of the device to realize such a tunable filter. This latter finds application in wavelength demultiplexing.

In order to demodulate optical fiber interferometric sensors in the coherence multiplexing scheme it is worthwhile using static interferomers. Measurement of a physical parameter is obtained by matching the optical path difference (OPD) of each interferometric sensor with a receiver. An attractive solution consists in using grating interferometer as a demodulator. Indeed, it permits one to record correlation peaks (each one corresponding to a sensor) on a photodiode array, thus making demultiplexing easier. On the other hand, it is possible to record only the peak envelope if the grating interferometer is adjusted in a well defined configuration. In this paper we concern ourselves with the theoretical determination of the conditions needed to simplify calculations and interpretation of the experimental results.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We show that a grating interferometer can be used as a receiver for quasi-distributed fibre optic sensors using white light interferometry. We report the results obtained when the sensor is based on an embedded fibre optic polarimetric interferometer for strain measurement of carbon/epoxy composites.

Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into certain target cells, such as skeletal muscle cells for gene therapy. Here we show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV) recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can very efficiently transduce cultured human myoblasts. However, transduction efficiency is about one order of magnitude less in cultured myotubes 16 days postfusion. The high transduction of myoblasts by AV-RSV-Lux could be effectively blocked by an arginine-glycine-asparagine (RGD) oligopeptide that serves as a ligand for the natural internalization receptor of AV. The normalized level of beta 3/beta 5-integrin, the main component of the internalization receptor for AV is about three times as abundant in myoblasts than in myotubes. This could contribute, among other things, to the relatively high susceptibility of myoblasts to AV infection and AV-mediated gene transduction.

Normal human myoblasts were cloned and transplanted in the tibialis anterior of immunodeficient nude and SCID mice and in mdx mice under different immunosuppressive treatments (cyclosporine A, CsA; antilymphocyte serum, ALS) or not immunosuppressed. This permitted us to show the interaction of the immune system in the myoblast transplantation. The graft success was assessed by verifying signs of humoral and cellular immune reactions and the presence of dystrophin produced by the fusion of the donor myoblasts. This study showed that clones of human myoblasts were able to fuse and produce dystrophin in injected muscles of immunodeficient mice and mdx mice receiving an effective immunosuppressive treatment (i.e., ALS+CsA). However, the same pool of human myoblasts injected in mdx mice inadequately immunosuppressed (i.e., CsA alone or ALS alone) triggered an immune reaction and was rejected. Cells expressing CD4 and CD8 antigens were observed in the injected muscles of mice treated with CsA alone. Therefore, evidence of humoral and cellular rejection was observed following human myoblasts transplantation.