Market Microstructure: Theory and Empirics

This paper reviews the literature on market microstructure. Particular emphasis is given to the research dealing with the impact that a specific trading mechanism might have on price behaviour and with the comparison of the performance of alternative market structures. Theoretical models and empirical studies investigating their implications are explored. The major statistical properties and reguliarities of microstructural data are discussed.-

Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes

The aim of this study was to determine the effects of glucosamine on matrix metalloprotease (MMP) production, on mitogen-activated protein kinase (MAPK) phosphorylation, and on activator protein (AP)-1 transcription factor activation in human chondrocytes. The human immortalized cell line lbpva55 and healthy human chondrocytes (obtained from healthy donors) were subjected to challenge with 10 ng/ml IL-1β after pretreatment with 2.5 or 10 mmol/l glucosamine. MMP mRNA expression levels were evaluated using quantitative real-time PCR, and MMP protein production levels were evaluated in the culture supernatant using ELISA. MAPK phosphorylation was evaluated using Western blotting. AP-1 transcription factor activation was evaluated by measuring AP-1 DNA-binding activity. After IL-1β stimulation, levels of MMP-1, MMP-3 and MMP-13 production were markedly increased. Treatment with 2.5 and 10 mmol/l glucosamine reduced expression of these metalloproteases. MMP expression is regulated by transcription factors such as the AP-1 complex, which is activated by phosphorylated MAPKs. IL-1β stimulated phosphorylation of c-jun amino-terminal kinase, p38 MAPK and extracellular signal-regulated kinase-1/2. Glucosamine inhibited c-jun amino-terminal kinase and p38 phosphorylation, and consequently c-jun binding activity. These findings demonstrate, for the first time, that glucosamine inhibits IL-1β-stimulated MMP production in human chondrocytes by affecting MAPK phosphorylation

Targeted Phospholipidomic Analysis of Synovial Fluid as a Tool for Osteoarthritis Deep Phenotyping

[Abstract] Objective. The aim of this study was to carry out a targeted phospholipidomic analysis on synovial fluid (SF) from patients with different grades of osteoarthritis (OA) and controls, in order to search for specific phospholipid profiles that may be useful for the deep phenotyping of this disease. Design. Multiple reaction monitoring-mass spectrometry (MRM/MS) was applied to explore the potential phospholipidomic differences in the SF of knee OA patients (n ​= ​15) (subclassified into early- and late-stage OA) and non-OA controls (n ​= ​4). Multivariate statistical analyses conducted by partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) were performed to identify significantly altered phospholipids in OA, characterize phospholipidomic profiles associated with the radiographic stage of the disease and describe potential endotypes at early stages. Results. Significant discrimination of phospholipid profiles between non-OA controls and the early- and late-stage OA groups were found by PLS-DA and HCA. Compared to SF from non-OA controls, OA patients showed higher levels of most quantified phospholipid species, including phosphatidylcholines (PC), phosphatidylserines and phosphatidylinositols. Furthermore, several PC species showed significant differences in abundance between the two OA subgroups and were negatively correlated with cartilage damage. Finally, two distinct endotypes of early-stage OA were identified based on the phospholipidomic profile of SF. Conclusions. Our data provides a novel insight into the phospholipid profiles of OA synovial fluid, revealing specific alterations associated with the radiographic stage of the disease. This targeted phospholipidomic profiling also facilitated the characterization of two different OA endotypes at early stages of the disease.This work is supported by grants from Fondo Investigación Sanitaria-Spain (PI16/02124, PI17/00404, PI19/01206, PI20/00793 and RETIC-RIER-RD16/0012/0002), integrated in the National Plan for Scientific Program, Development and Technological Innovation 2013–2016 and funded by the ISCIII-General Subdirection of Assessment and Promotion of Research - European Regional Development Fund (FEDER) “A way of making Europe”. This study is also supported by AE CICA-INIBIC (ED431E 2018/03) and grants IN607A 2017/11, IN607A 2021/7 and IN607D 2020/10 from Axencia Galega de Innovacion - Xunta de Galicia. The Biomedical Research Networking Center (CIBER) is an initiative from Instituto de Salud Carlos III (ISCIII). The Proteomics Unit of GIR belongs to ProteoRed, PRB3- ISCIII (PT17/0019/0014)Xunta de Galicia; ED431E 2018/03Xunta de Galicia; IN607A 2017/11Xunta de Galicia; IN607A 2021/7Xunta de Galicia; IN607D 2020/1

Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: a useful tool for precision medicine strategies

[Abstract] Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision medicine strategies. In the present study, we investigated those systemic molecular changes that are associated with the RF and ACPA status of RA patients. To achieve this objective, we followed a proteomic biomarker pipeline from the discovery phase to validation. First, we performed an iTRAQ-based quantitative proteomic experiment on serum samples from the RA cohort of the Hospital of Santiago de Compostela (CHUS). In this discovery phase, serum samples from the CHUS cohort were pooled according to their RF/ACPA status. Shotgun analysis revealed that, in comparison with the double negative group (RF-/ACPA-), the abundance of 12 proteins was altered in the RF+/ACPA+ pool, 16 in the RF+/ACPA- pool and 10 in the RF-/ACPA+ pool. Vitamin D binding protein and haptoglobin were the unique proteins increased in all the comparisons. For the verification phase, 80 samples from the same cohort were analyzed individually. To this end, we developed a Multiple Reaction Monitoring (MRM) method that was employed in a comprehensive targeted analysis with the aim of verifying the results obtained in the discovery phase. Thirty-one peptides belonging to 12 proteins associated with RF and/or ACPA status were quantified by MRM. In a final validation phase, the serum levels of alpha-1-acid glycoprotein 1 (A1AG1), haptoglobin (HPT) and retinol-binding protein 4 (RET4) were measured by immunoassays in the RA cohort of the Hospital of A Coruña (HUAC). The increase of two of these putative biomarkers in the double seropositive group was validated in 260 patients from this cohort (p = 0.009 A1AG1; p = 0.003 HPT). The increased level of A1AG1 showed association with RF rather than ACPA (p = 0.023), whereas HPT showed association with ACPA rather than RF (p = 0.013). Altogether, this study has allowed a further classification of the RA seropositive patients into two novel clusters: RF+A1AG+ and ACPA+HPT+. The determination of A1AG1 and HPT in serum would provide novel information useful for RA patient stratification, which could facilitate the effective implementation of personalized medicine in routine clinical practice.Instituto de Salud Carlos III; PI16/02124Instituto de Salud Carlos III; PI17/00404Instituto de Salud Carlos III; PI19/01206Instituto de Salud Carlos III; PI20/00793Instituto de Salud Carlos III; RD16/0012/0002Instituto de Salud Carlos III; RD21/0002/0009Xunta de Galicia; IN607A2021/07Xunta de Galicia; IN607D2020/1

Oligomerization of Sulfolobus solfataricus

The recombinant amidase from the hyperthermophylic archaeon Sulfolobus solfataricus (SSAM) a signature amidase, was cloned, purified and characterized. The enzyme is active on a large number of aliphatic and aromatic amides over the temperature range 60–95 °C and at pH values between 4.0 and 9.5, with an optimum at pH 5.0. The recombinant enzyme is in the form of a dimer of about 110 kD that reversibly associates into an octamer in a pH-dependent reaction. The pH dependence of the state of association was studied using gel permeation chromatography, analytical ultracentrifugation and dynamic light scattering techniques

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Trading Mechanisms in Commodities Markets

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Liquidity provision in ETF markets : The basket and beyond

We provide a theory and empirical evidence showing that the liquidity (quoted spread) of an ETF is strongly determined by inventory-risk related variables. We consider a risk averse market maker who optimally chooses to either manage her ETF position through trading, or resort to the ETF creation/redemption mechanism to exchange her residual inventory for the underlying basket. The trade-off between the ETF price concession and the cost of trading the basket is key in explaining liquidity provision in ETFs. Using data on European equity ETFs, we provide supporting evidence that ETF spreads depend on the risks and costs of inventory management. We also find that the ETF liquidity is linked with the basket liquidity only when market conditions make on-exchange inventory management unsuitable.Nous développons un modèle théorique accompagné d’une analyse empirique montrant que la liquidé (fourchette de prix affichée) d’un ETF est fortement déterminée par des variables capturant le risque lié à la position détenue par le teneur de marché. Nous considérons la stratégie optimale de celui-ci dans un contexte où il lui est possible de gérer son stock d’ETF à la fois sur le marché secondaire du produit et via le mécanisme de création/rachat. Ce faisant, le teneur de marché doit arbitrer entre d’une part une concession sur le prix auquel il négocie l’ETF, et d’autre part le coût d’illiquidité qu’il supporte sur les actifs constituant le panier répliqué en cas de création/rachat. Nous montrons que cette concession est cruciale pour expliquer les caractéristiques de l’offre de liquidité sur un ETF. L’étude empirique réalisée sur un large échantillon d’ETF européens confirme le rôle clef joué par les variables liées au risque de position. Nous montrons en outre que la liquidité d’un ETF n’est liée à celle des actifs du panier qu’il réplique que lorsque le risque de position des teneurs de marché ne peut pas être géré efficacement sur le marché secondaire de l’ETF