How to Date Nothing With Cosmogenic Nuclides

A cave is a natural void in the rock. Therefore, a cave in itself cannot be dated, and one has to resort to datable sediments to get ideas about the age of the void itself. The problem then is that it is never very certain that the obtained age really is coincident with the true age of the cave. Here, we present the use of a method which couples sedimentary and morphologic information to get a relative chronology of events. Datings within this relative chronology can be used for assessing ages of forms, processes, and sediments, and the obtained dates also fix some milestones within the chronology, which then can be used to retrace, among other things, paleoclimatic variations. For many cave systems, the dating limits of the most widely used U/Th method on speleothems are too low (350 to max. 700 ka) to get ages that inform us about the age of the cave. The recent use of cosmogenic nuclides on quartz-containing sediment permits to push the datable range back to 5 Ma. While the theoretical background is explained elsewhere (Granger, this volume), we concentrate on the Siebenhengste example (Switzerland

UIS Cave Symbols: The definitive List

Predstavljen je seznam jamskih simbolov, ki jih Mednarodna speleološka zveza priporoča pri risanju načrtov podzemnih jam. Seznam simbolov so leta 1999 izvolili delegati iz dvanajstih držav. Kjer je potrebno, je poleg simbola še krajša razlaga. V prispevku je na kratko predstavljena tudi podkomisija za topografijo pri Mednarodni speleološki zvezi.A set of cave symbols used for underground mapping has been voted by national delegates of 12 countries in 1999. This symbol set is shown and, when necessary, explained. The UIS subcommission on topography is briefly presented and its aims outlined.

Late Quaternary and Holocene paleoclimate and paleoenvironmental reconstruction - a multi-proxy approach on Swiss speleothems

Detailed knowledge of the past climate and environmental variability is vital in order to predict future scenarios with more confidence. High resolution and highly-resolved natural archives are therefore in growing demand (PAGES report, 2009). This thesis is part of a coordinated effort, STALCLIM project, where a series of state-of-theart methods in speleothems proxies were used in order to develop the full potential of speleothemsas paleoclimate and paleoenvironmental archive. The thesis investigates climate variations as recorded by speleothems from Schafsloch and Milandre caves, spanning time intervals of high scientific interest: 0 to 14 550 years BP and 130 000 to 230 000 years BP. The locations of the caves, Jura Mountains and the Alpstein Mountains (Swiss Alps) are regions highly sensitive to climate-induced changes in temperature, atmospheric pathways and/or environment evolution. In order to establish new climate records and resolve the paleoclimate questions, continuous geochemical analyses were applied, with high resolution stable isotopic and trace elements analysis and 230Th age measurements, and these were combined with thin section analysis of the calcite petrology. Where possible, we conducted continuous and temporal measurements in the caves where the samples were collected, to provide a better understanding of the cave environment. Chapters 2 and 3 highlight the sensitivity of high altitude speleothem proxies to small changes in temperature and water availability, both induced by internal and external climate drivers. The MF3 stalagmite, from Schafsloch Cave, provides a unique opportunity to investigate a regional expression of millennial-scale climate variability in Central Europe during MIS 6 and Late MIS 7. The sample records in high detail the structure of the penultimate deglaciation in the Alps, and brings new evidence regarding the nature of this important climatic transition. Chapters 4 and 5 show the high resolution composite δ18O record and elemental composition of speleothems from Milandre Cave, covering the Lateglacial- Holocene interval. A detailed comparison with Greenland ice cores and Gerzensee lake sediments (Central Switzerland) indicates similarities in the long timescale changes of atmospheric circulation patterns in the whole North Atlantic region after the last deglaciation. In contrast, during the Holocene, the signature pattern in the isotopic calcite δ18O data differs to that seen in Central Europe. This provides important insights into the regional teleconnections and local environmental reaction to changes in the temperature, seasonality of precipitation and atmospheric processes. The use of a robust δ18O/temperature transfer function has enabled a high resolution temperature reconstruction of the autumn to spring temperatures at the Milandre site for the last 14 550 y BP. In summary, this thesis provides new results on environmental and climatic variability in Switzerland during specific intervals over the last 230 000 years. It suports large teleconnections over the northern hemisphere and emphasizes the role of insolation and obliquity as important climate triggers in the region. These new high-resolution and precisely dated records of δ18O and cold season temperature reconstruction for the Jura Mountains over the last 14 550 y BP, are proposed as being representative for Central Europe

Cave Genesis and its relationship to surface processes: investigations in the Siebenhengste region (BE, Switzerland)

Du point de vue spéléologique, la région des Siebenhengste est l’une des plus importantes du monde. La densité exceptionnelle des galeries souterraines, qui s’étendent sur plus de 1500 m de dénivelé, en fait un site privilégié pour l’étude de la paléogéomorphologie alpine et de la paléoclimatologie glaciaire. La présente thèse se concentre sur la grotte de St. Béat et le Bärenschacht, situés au sud de ladite région. Les résultats obtenus, qui concernent la tectonique, l’hydrogéologie, la spéléogenèse, la paléogéographie et la paléoclimatologie, sont présentés sommairement ci-dessous. Tectonique et stratigraphie: Le rejet de la faille de Hohgant-Sundlauenen (HSV) est de l’ordre de 1 km. L’épaisseur stratigraphique du Schrattenkalk et de la série du Hohgant permet l’observation de l’activité synsédimentaire de la HSV à partir du Crétacé inférieur jusqu’à l’Eocène. L’histoire complexe de l’activité tectonique et de la sédimentation pendant cette période est esquissée. La Waldegg est une structure en Horst et Graben. Hydrogéologie: Des observations dans la grotte de St. Béat ont démontré que les eaux du karst sont capables de former des cavités à l’intérieur et au travers de formations imperméables. De plus, les diffluences vadoses sont très courantes, et les transfluences ne nécessitent pas une couche imperméable pour leur mise en place. Certains résultats «étranges» des essais de traçage peuvent être expliqués par ces observations. Un essai de traçage a permis de délimiter les bassins versants de la grotte de St. Béat et des Siebenhengste. Une revue de tous les traçages effectués dans la région des Siebenhengste-Hohgant est présentée et permet de faire une synthèse des systèmes hydrogéologiques au nord d’Interlaken. Spéléogenèse: La morphologie des galeries dans la zone épiphréatique actuelle indique que la corrosion en temps de crue, bien que temporaire, prédomine sur l’érosion vadose pérenne, avec pour corollaire la forme phréatique des galeries qui se situent dans la zone épiphréatique. La transition méandre-tube se fait au toit de cette zone, qui est responsable de la dernière étape morphogénétique des cavités alpines. Les phases spéléogénétiques sont liées à la zone épiphréatique. Des soutirages vidangent la zone épiphréatique en temps d’étiage. Leur genèse est intimement liée à l’existence d’une zone de battement. La transition d’une phase à l’autre se fait assez rapidement. Par contre, un équilibre entre la taille des galeries et le débit total n’est atteint qu’asymptotiquement et après un temps considérable. Reconstitution de la paléogéographie: On a trouvé douze phases spéléogénétiques, d’âges différents. On assume que leur source était en relation avec un ancien fond de vallée. Ainsi, les phases spéléogénétiques indiqueraient l’approfondissement progressif de la vallée. Les phases traitées dans le présent travail se situent à 558, 660, 700, 760, 805 et 890 m d’altitude. L’analyse statistique des petites cavités confirme ces phases. Des observations morphologiques et sédimentologiques suggèrent une genèse des galeries les plus anciennes aux Siebenhengste pendant le dernier dépôt de molasse, au Mio/Pliocène, avant l’approfondissement de la vallée de l’Aare. Datation des phases et information paléoclimatique: L’érosion laisse toujours des restes de sédiment à l’intérieur d’une cavité, que l’on peut utiliser pour une reconstitution du paléoclimat. La genèse des cavités et le dépôt de concrétions a lieu pendant les périodes chaudes, tandis que les glaciations causent l’arrêt de la spéléogenèse et le dépôt des limons varvés dus à l’ennoyement des galeries. Plusieurs profils sédimentaires, principalement dans la grotte de St. Béat, ont été étudiés. La succession sédimentaire permet une reconstitution chronologique des évènements, combinée ensuite avec les phases spéléogénétiques. On obtient ainsi des indications sur l’âge relatif des profils et des phases spéléogénétiques correspondantes. La datation de cette chronologie permet de retracer les phases spéléogénétiques et, en même temps, les avancées et retraits glaciaires. Les résultats montrent six avancées, à >350 ka, 235-180 ka, 157-135 ka, 114-99 ka, 76-54 ka et 39-16 ka. La phase spéléogénétique 760 était active à >350-235 ka, la phase 700 à 180-157 ka, la phase 660 à 135-39 ka, et la phase actuelle 558 entre 39 ka et aujourd’hui. L’analyse intégrale d’un système souterrain fournit des informations paléoclimatiques bien plus significatives que l’étude d’échantillons isolés dans un système essentiellement ouvert. La présente étude a été rendue possible grâce à la topographie souterraine bénévole effectuée par des générations de spéléologues.Die Region der Siebenhengste ist eine der grössten Höhlengebiete weltweit. Ihre hohe Dichte an Höhlengängen, die sich über mehr als 1500 Höhenmeter erstrecken, machen sie zu einem idealen Ort zum Studium der alpinen Paläogeomorphologie und glazialen Paläoklimatologie. Die vorliegende Arbeit konzentriert sich auf die St. Beatus-Höhle und den Bärenschacht, die sich am südlichen Ende der Höhlenregion befinden. Die Resultate über Tektonik, Hydrogeologie, Höhlenentstehung, Paläogeographie und Paläoklimatologie werden im Folgenden summarisch präsentiert. Tektonik und Stratigraphie: Der Versatz der Hohgant-Sundlauenen-Verwerfung (HSV) liegt bei 1 km. Die stratigraphischen Mächtigkeiten des Schrattenkalkes und der Hohgantserie erlauben, eine synsedimentäre Aktivität der HSV bereits ab der Unterkreide bis zum Eozän zu belegen. Eine komplexe Geschichte der Bruchaktivität und Sedimentation dieses Zeitalters wird nachgezeichnet. Die Waldegg ist eine Horst-Graben-Struktur. Hydrogeologie: Beobachtungen in der St. Beatus-Höhle haben gezeigt, dass Karstwässer auch innerhalb und quer zu undurchlässigen Schichten Höhlen bilden können. Zusätzlich sind vadose Diffluenzen sehr häufig, und Transfluenzen sind nicht auf Gebiete mit undurchlässigen Schichten beschränkt. Durch diese Beobachtungen können „seltsame“ Resultate von Färbversuchen erklärt werden. Ein Färbversuch erlaubte die Abgrenzung der Einzugsgebiete der St. Beatus-Höhle von demjenigen der Siebenhengste. Eine Übersicht über alle je in der Region durchgeführten Färbversuche wurde erstellt und erlaubt einen Überblick über die hydrogeologischen Systeme nördlich von Interlaken. Höhlenentstehung: Die Gangmorphologie zeigt, dass in der heutigen epiphreatischen Zone die zeitweilige Hochwasserkorrosion über die ständige Niederwassererosion dominiert, was eine phreatische Morphologie innerhalb der epiphreatischen Zone ergibt. Der Übergang Mäander-Röhre geschieht im Dach dieser Zone, welche für die letzte Morphogenese zumindest in alpinen Höhlen verantwortlich ist. Die speläogenetischen Phasen sind in Zusammenhang mit der epiphreatischen Zone. Soutirages entleeren die epiphreatische Zone während Niederwasser. Ihre Genese ist von der Existenz einer Hochwasserzone abhängig. Der Übergang von einer speläogenetischen Phase zur nächsten geschieht verhältnismässig schnell; ein Gleichgewicht zwischen Schüttung und Ganggrösse stellt sich jedoch sehr wahrscheinlich nur asymptotisch und nach einer sehr langen Zeit ein. Rekonstruktion der Paläogeographie: Es wurden zwölf speläogenetische Phasen verschiedenen Alters gefunden, deren Quelle wohl in Zusammenhang mit einem alten Talboden steht. Aus diesem Grunde sollten die speläogenetischen Phasen die Abfolge der Taleintiefung darstellen. Die in der vorliegenden Arbeit besonders studierten Phasen liegen auf 558, 660, 700, 760, 805 und 890 m ü.M. Die statistische Analyse von Kleinhöhlen bestätigt diese Phasen. Morphologische und sedimentologische Befunde legen eine Entstehung der ältesten Gänge auf den Siebenhengsten zur Zeit der Molasseablagerung, also im Mio-Pliozän, nahe, bevor das Aaretal begann zu existieren. Datierung der Phasen und paläoklimatische Informationen: Die Erosion verschont zumeist Überreste der Sedimente. Aus diesem Grund sind Höhlen zur Rekonstruktion des Paläoklimas geeignet. Höhlenentstehung und Tropfsteinablagerung geschieht während Warmzeiten, während Eiszeiten die Speläogenese behindern und wegen des Wasserspiegelanstiegs gewarvte Silte ablagern. Einige Sedimentprofile, zumeist aus der St. Beatus-Höhle, wurden untersucht. Die sedimentäre Abfolge erlaubt eine chronologische Rekonstruktion von Ereignissen, die dann mit den spelägenetischen Phasen kombiniert wird und so Angaben über die relative Abfolge der Profile untereinander sowie über die Alterszusammenhänge der Phasen liefert. Die Datierung dieser Chronologie erlaubt sodann die zeitliche Einstufung der speläogenetischen Phasen sowie der Eisvorstösse und -rückzüge. Die Resultate zeigen sechs Eisvorstösse bei >350 ka, 235-180 ka, 157-135 ka, 114-99 ka, 76-54 ka und 39-16 ka. Die speläogenetische Phase 760 war zwischen >350-235 ka aktiv, Phase 700 zwischen 180-157 ka, Phase 660 wiederum zwischen 135-39 ka, und die heutige Phase 558 seit 39 ka. Eine Gesamtanalyse der Höhle ergibt sinnvollere Resultate als die punktuelle Analyse von Einzelproben in einem grundsätzlich offenen System. Diese Arbeit war nur möglich dank der ehrenamtlichen Höhlenvermessung durch Generationen von Höhlenforschern.The Siebenhengste region is one of the most significant cave areas in the world. Its high density of cave passages that extend over 1500 m in altitude makes it a key site for the study of Alpine paleogeomorphology and paleoclimatology. The present thesis concentrates on St. Beatus Cave and Bärenschacht at the southern rim of the cave region. The tectonics, hydrogeology, speleogenesis, paleogeography, and paleoclimatology are summarised as follows: Tectonics and stratigraphy: The throw of the Hohgant-Sundlauenen fault (HSV) is around 1 km. The stratigraphical thickness of the Schrattenkalk and Hohgant series allow an examination of the synsedimentary activity of the HSV from the Lower Cretaceous up to the Eocene. A complicated history of faulting activity and sedimentation in this timespan is retraced. The Waldegg is found to be a Horst-Graben structure. Hydrogeology: Observations in St. Beatus Cave have shown that karst waters not only can generate caves across and within impermeable formations; in addition vadose diffluences are common, and transfluences do not necessarily require an impermeable layer to form. These findings allow an explanation of complex results of water tracings to be formulated. A tracing experiment permitted delineation of the catchment areas of St. Beatus Cave and Siebenhengste. A review of all tracing experiments performed in the Siebenhengste-Hohgant area is made, and allows an overview of the hydrogeologic systems to the north of Interlaken. Speleogenesis: The passage morphology shows that in the present epiphreatic zone, temporal floodwater corrosion prevails over perennial low-water erosion, resulting in a phreatic morphology of the tubes within the epiphreatic zone. The transition from meandering canyon to tubetype passages occurs at the top of this zone, which is responsible for the latest stage of tube morphogenesis in Alpine caves. The speleogenetic phases are related to the top of the epiphreatic zone. Soutirages empty the epiphreatic zone in low water condition. Their genesis is intimately connected to the existence of a floodwater zone. The transition from one speleogenetic phase to another happens rapidly; however, equilibrium between passage size and total discharge most probably is reached only asymptotically and needs considerable time. Reconstruction of paleogeography: Twelve speleogenetic phases of different age can be found. The spring responsible for their formation is thought to be related to an old valley bottom. Therefore, the speleogenetic phases should directly indicate the successive deepening of the valley. The six phases that are investigated in the present study are found at 558, 660, 700, 760, 805, and 890 m a.s.l. The statistical analysis of small caves near the surface supports the definition of these phases. Morphologic and sedimentologic findings suggest the genesis of the oldest conduits at Siebenhengste to be contemporaneous with the last Molasse deposition in Mio-Pliocene, before the Aare valley existed. Phase-dating and paleoclimatic information: Erosion always leaves some sedimentary traces within the cave, which therefore yields paleoclimatic information. Cave genesis and speleothem deposition occurs during warm periods, whereas during glaciations, speleogenesis stops. Instead, varved silts are deposited as a result of waterlevel rise. Several sediment profiles are investigated, most of them within the St. Beatus Cave. The sedimentary succession allows a chronological reconstruction of events that, when combined with the speleogenetic phases, gives information about the relative age of each profile, and thus about the age of the speleogenetic phase. The dating of this chronology then allows the estimation of ages for the speleogenetic phases and glacial advances and retreats. The results show six glaciations at >350 ka, 235-180 ka, 157-135 ka, 114-99 ka, 76-54 ka, and 39-16 ka. The speleogenetic phase 760 was present at >350-235 ka, phase 700 was active at 180-157 ka, phase 660 again at 135-39 ka, and the present phase 558 between 39 ka and today. A comprehensive analysis of a cave system gives much more meaningful results than the analysis of single points and structures in a basically open system. The present study was made possible by of the volunteer mapping efforts of generations of speleologists

Dating of Caves by Cosmogenic Nuclides: Method, Possibilities, and the Siebenhengste Example

Kozmični žarki povzročajo nastanek kozmogenih nuklidov na površini zemlje in tik pod njo. Za datiranje jamskih sedimentov sta posebej pomembna 10Be in 26Al, ki nastajata v kremenu. Ko je kamen na površini in izpostavljen kozmičnemu sevanju, nastajata v stalnem razmerju. Ko ga zanese v podzemlje, se tvorba kozmogenih nuklidov ustavi, nadaljuje pa se njihov radioaktivni razpad. Ker 26 Al razpada hitreje, lahko iz razmerja med njima izračunamo čas, ki je potekel odkar je kremen pod zemljo. Metodo lahko uporabimo na sedimentih, ki so pokopani oziroma v jami med 0.1 in 5 milijoni let. Na ta način lahko v idealnih primerih izračunamo hitrost vrezovanja dolin. Z opisano metodo smo določili starost najstarejših delov sistema Siebenhengste v Švici. Najstarejši sediment je star 4.4 ± 0.6 Ma in nakazuje, da je na tem območju potekalo zakrasevanje že v pliocenu.  Cosmic rays produce nuclides at and near the Earthʼs surface. 10Be and 26Al in quartz are of particular interest for dating cave sediments. These two nuclides are produced at the surface at a fixed ratio. If the quartz is carried from the surface into a cave, the sediment is shielded from additional cosmogenic nuclide production, and the inherited 10Be and 26Al decay radioactively. Because 26Al decays more rapidly than 10Be, the ratio of these two nuclides indicates the time since the sediment was washed underground. The burial dating method can be applied to sediments in the age range of approximately 0.1 to 5 Ma. In ideal cases, we get information about valley lowering rates. If the provenance of the sediment is known, averaged erosion rates of the source area can be estimated. The oldest cave phases of the Siebenhengste system, Switzerland, were dated using cosmogenic nuclides. The oldest sediment is 4.4 ± 0.6 Ma and thus indicates Pliocene karstification of the Siebenhengste.   

EU privacy and data protection law applied to AI: unveiling the legal problems for individuals

AI-powered emotion recognition, typing with thoughts or eavesdropping virtual assistants: three non-fictional examples illustrate how AI may impact society. AI-related products and services increasingly find their way into daily life. Are the EU's fundamental rights to privacy and data protection equipped to protect individuals effectively? In addressing this question, the dissertation concludes that no new legal framework is needed. Instead, adjustments are required. First, the extent of adjustments depends on the AI discipline. There is nothing like 'the AI'. AI covers various concepts, including the disciplines machine learning, natural language processing, computer vision, affective computing and automated reasoning. Second, the extent of adjustments depends on the type of legal problem: legal provisions are violated (type 1), cannot be enforced (type 2) or are not fit for purpose (type 3). Type 2 and 3 problems require either adjustments of current provisions or new judicial interpretations. Two instruments might be helpful for more effective legislation: rebuttable presumptions and reversal of proof. In some cases, the solution is technical, not legal. Research in AI should solve reasoning deficiencies in AI systems and their lack of common sense.Effective Protection of Fundamental Rights in a pluralist worl

A model of osteoporosis impact in Switzerland 2000-2020

The aim of our study was to develop a modeling framework suitable to quantify the incidence, absolute number and economic impact of osteoporosis-attributable hip, vertebral and distal forearm fractures, with a particular focus on change over time, and with application to the situation in Switzerland from 2000 to 2020. A Markov process model was developed and analyzed by Monte Carlo simulation. A demographic scenario provided by the Swiss Federal Statistical Office and various Swiss and international data sources were used as model inputs. Demographic and epidemiologic input parameters were reproduced correctly, confirming the internal validity of the model. The proportion of the Swiss population aged 50 years or over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000 person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person-years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per 1,000 person-years in the case of distal forearm fracture. Osteoporosis-attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related direct medical inpatient costs per year will rise from 713.4million Swiss francs (CHF) to CHF946.2million. These figures correspond to 1.6% and 2.2% of Swiss health care expenditures in 2000. The modeling framework described can be applied to a wide variety of settings. It can be used to assess the impact of new prevention, diagnostic and treatment strategies. In Switzerland incidences of osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%, and 19%, respectively, between 2000 and 2020, if current prevention and treatment patterns are maintained. Corresponding absolute fracture numbers will rise by 36%, 31%, and 23%. Related direct medical inpatient costs are predicted to increase by 33%; however, this estimate is subject to uncertainty due to limited availability of input dat

E-selectin-monocyte interactions facilitate pulmonary metastasis

Metastasis is a multistep process depending on complex interactions between tumor cells and the stromal compartment which also contains immune cells and soluble factors such as chemokines. The presence of certain classes of monocytes in malignant tumors is frequently a result of chemoattractants such as CCL2 and correlates with enhanced tumor cell extravasation and metastasis. Selectins are vascular adhesion receptors, well-known to facilitate metastasis by mediating the contact between tumor cells and cells in the metastatic environment. Particularly E-selectin is thought to mediate the arrest of tumor cells in the vasculature by binding to E-selectin ligands on tumor cells and thereby promoting metastasis. This study aimed to elucidate whether E-selectin facilitates metastasis by interacting with other constituents of the metastatic microenvironment. Experimental metastasis of tumor cells without E-selectin ligands to the lungs was attenuated in E-selectin deficient mice. This phenotype can already be determined during early metastatic phases. Lung analysis within the first hours after tumor cell injection revealed reduced expression of endothelial activation markers and the chemokine CCL2 in E-selectin deficient mice. Endothelial activation includes E-selectin up-regulation in C57BL/6 mouse lungs and was shown to be partially dependent on tumor cell-derived CCL2. However, endothelial cells and recruited monocytes were identified as the main sources of CCL2 in the metastatic lungs. The total pool of CCL2 in metastatic lungs was decreased in the absence of E-selectin. This is linked to the reduced leukocyte infiltration observed in E-selectin deficient lungs upon tumor cell injection. Association of infiltrated leukocytes with tumor cells was E-selectin dependent. Moreover, monocyte-supported tumor cell transmigration required binding of E-selectin to monocyte ligands. In the presence of E-selectin, tumor cells together with monocytes induced endothelial cell retraction. Accordingly, the lung vasculature was less permeable in E-selectin deficient or monocyte-depleted mice after tumor cell injection. E-selectin deficient mice also showed decreased spontaneous lung metastasis. Our study identifies a novel mechanism how E-selectin-leukocyte interactions supported by CCL2 induce vascular permeability, which promotes tumor cell extravasation and metastasis

Nitric oxide and proteoglycan biosynthesis by human articular chondrocytes in alginate culture

AbstractInterleukin-1α and β induced the production of large amounts of nitric oxide by normal, human articular chondrocytes in alginate culture; at the same time the biosynthesis of proteoglycan was strongly suppressed. In a dose-dependent manner, NG-monomethyl-l-arginine both inhibited nitric oxide formation and relieved the suppression of proteoglycan synthesis. However concentrations of NG-monomethyl-l-arginine which completely prevented nitric oxide production only partially restored proteoglycan biosynthesis, even at low doses of interleukin-1 where suppression of proteoglycan synthesis was modest. The organic donor of nitric oxide, S-nitrosyl-acetyl-d,l- penicillamine also inhibited proteoglycan biosynthesis, but not as extensively as interleukin-1. These data suggest that interleukin-1 suppresses synthesis of the cartilaginous matrix through more than one mechanism, at least one of which is dependent upon the production of nitric oxide