Categories of comodules and chain complexes of modules

Let \lL(A) denote the coendomorphism left $R$-bialgebroid associated to a left finitely generated and projective extension of rings $R \to A$ with identities. We show that the category of left comodules over an epimorphic image of \lL(A) is equivalent to the category of chain complexes of left $R$-modules. This equivalence is monoidal whenever $R$ is commutative and $A$ is an $R$-algebra. This is a generalization, using entirely new tools, of results by B. Pareigis and D. Tambara for chain complexes of vector spaces over fields. Our approach relies heavily on the non commutative theory of Tannaka reconstruction, and the generalized faithfully flat descent for small additive categories, or rings with enough orthogonal idempotents.Comment: The title has been changed, the first part is removed and the construction of the coendomorphim bialgebroid is now freely used in the statement of the main Theorem

Noninteracting control with stability for Hamiltonian systems

Published versio

Design of controllers for hybrid linear systems with impulsive inputs and periodic jumps

In this study, the problem of designing a controller for a hybrid system with impulsive input and periodic jumps is addressed. In particular, it is shown that any hybrid system with impulsive inputs and periodic jumps can be recast into a discrete-time, linear, time-invariant system, which, in turn, can be used to design a controller by using classical methods. Furthermore, it is shown that, once such a controller has been designed, it can be readily used to control the hybrid system by mean of an interfacing system that is based just on the continuous-time dynamics of the plant to be controlled. Several examples, spanning from aerospace to biomedical applications, are reported in order to corroborate the theoretical results

Ergonomics and Workflow Evaluation of Automatic Doppler Angle Technology Implemented in a Diagnostic Ultrasound System

AbstractCommonly available Pulsed Wave Doppler (PW) flow velocity measurements for Ultrasound (US) investigation require the operator to manually set the direction of the flow velocity vector along the blood vessel axis on the US image, in order to determine the Doppler angle and then to estimate the real flow velocity. The present work investigates the possibility to implement on a commercially available US system an innovative Automatic Doppler Angle (ADA) Technology by analyzing the best workflow in terms of higher execution speed, lower keystrokes/adjustments helping in the prevention of Work-related Musculoskeletal Disorders (WRMSD) and a Doppler angle correction precision, comparable to the one obtained manually by expert sonographer. Ergonomics and workflow tests, then accuracy and repeatability evaluations of the Doppler velocity measurement, were performed on a portable US system (MyLabAlpha, Esaote S.p.A., Florence, Italy) by an expert sonographer. Ergonomics and workflow Tests were performed to analyze the potential of ADA in terms of reduction of muscular activation applied (by SEMG), number of activations (by cameras optoelectronic system) and time needed using ADA, in comparison to manual procedure. Accuracy and intra-operator repeatability tests of the velocity measurement were performed to evaluate the precision of the obtained PW trace velocity measurements with ADA technology, compared to manual ones. Results provided evidence that ADA tool allowed: a reduction of muscular activation (from 12% for trapezius descendens, to 25% for deltoideus anterior) a lower total number of keystrokes and a reduction of the US scan time of about 56%. The maximal variation between PW Doppler trace velocity measurement set automatically by ADA and set manually by sonographer was 11%. ADA technology can provide a Doppler angle correction precision comparable to the manual one, while decreasing the risk of WRMSD

Diabetes promotes invasive pancreatic cancer by increasing systemic and tumour carbonyl stress in Kras G12D/+mice

Background: Type 1 and 2 diabetes confer an increased risk of pancreatic cancer (PaC) of similar magnitude, suggesting a common mechanism. The recent finding that PaC incidence increases linearly with increasing fasting glucose levels supports a central role for hyperglycaemia, which is known to cause carbonyl stress and advanced glycation end-product (AGE) accumulation through increased glycolytic activity and non-enzymatic reactions. This study investigated the impact of hyperglycaemia on invasive tumour development and the underlying mechanisms involved. Methods: Pdx1-Cre;LSL-Kras G12D/+ mice were interbred with mitosis luciferase reporter mice, rendered diabetic with streptozotocin and treated or not with carnosinol (FL-926-16), a selective scavenger of reactive carbonyl species (RCS) and, as such, an inhibitor of AGE formation. Mice were monitored for tumour development by in vivo bioluminescence imaging. At the end of the study, pancreatic tissue was collected for histology/immunohistochemistry and molecular analyses. Mechanistic studies were performed in pancreatic ductal adenocarcinoma cell lines challenged with high glucose, glycolysis- and glycoxidation-derived RCS, their protein adducts AGEs and sera from diabetic patients. Results: Cumulative incidence of invasive PaC at 22 weeks of age was 75% in untreated diabetic vs 25% in FL-926-16-gtreated diabetic and 8.3% in non-diabetic mice. FL-926-16 treatment suppressed systemic and pancreatic carbonyl stress, extracellular signal-regulated kinases (ERK) 1/2 activation, and nuclear translocation of Yes-associated protein (YAP) in pancreas. In vitro, RCS scavenging and AGE elimination completely inhibited cell proliferation stimulated by high glucose, and YAP proved essential in mediating the effects of both glucose-derived RCS and their protein adducts AGEs. However, RCS and AGEs induced YAP activity through distinct pathways, causing reduction of Large Tumour Suppressor Kinase 1 and activation of the Epidermal Growth Factor Receptor/ERK signalling pathway, respectively. Conclusions: An RCS scavenger and AGE inhibitor prevented the accelerating effect of diabetes on PainINs progression to invasive PaC, showing that hyperglycaemia promotes PaC mainly through increased carbonyl stress. In vitro experiments demonstrated that both circulating RCS/AGEs and tumour cell-derived carbonyl stress generated by excess glucose metabolism induce proliferation by YAP activation, hence providing a molecular mechanism underlying the link between diabetes and PaC (and cancer in general)

Increased tumor necrosis factor alpha-converting enzyme activity induces insulin resistance and hepatosteatosis in mice

Tumor necrosis factor alpha-converting enzyme (TACE, also known as ADAM17) was recently involved in the pathogenesis of insulin resistance. We observed that TACE activity was significantly higher in livers of mice fed a high-fat diet (HFD) for 1 month, and this activity was increased in liver > white adipose tissue > muscle after 5 months compared with chow control. In mouse hepatocytes, C(2)C(12) myocytes, and 3T3F442A adipocytes, TACE activity was triggered by palmitic acid, lipolysaccharide, high glucose, and high insulin. TACE overexpression significantly impaired insulin-dependent phosphorylation of AKT, GSK3, and FoxO1 in mouse hepatocytes. To test the role of TACE activation in vivo, we used tissue inhibitor of metalloproteinase 3 (Timp3) null mice, because Timp3 is the specific inhibitor of TACE and Timp3(-/-) mice have higher TACE activity compared with wild-type (WT) mice. Timp3(-/-) mice fed a HFD for 5 months are glucose-intolerant and insulin-resistant; they showed macrovesicular steatosis and ballooning degeneration compared with WT mice, which presented only microvesicular steatosis. Shotgun proteomics analysis revealed that Timp3(-/-) liver showed a significant differential expression of 38 proteins, including lower levels of adenosine kinase, methionine adenosysltransferase I/III, and glycine N-methyltransferase and higher levels of liver fatty acid-binding protein 1. These changes in protein levels were also observed in hepatocytes infected with adenovirus encoding TACE. All these proteins play a role in fatty acid uptake, triglyceride synthesis, and methionine metabolism, providing a molecular explanation for the increased hepatosteatosis observed in Timp3(-/-) compared with WT mice. Conclusion: We have identified novel mechanisms, governed by the TACE-Timp3 interaction, involved in the determination of insulin resistance and liver steatosis during overfeeding in mice

Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: Neurophysiological and skin biopsy longitudinal analysis

OBJECTIVE - The purpose of this study was to evaluate whether islet transplantation may stabilize polyneuropathy in uremic type 1 diabetic patients (end-stage renal disease [ESRD] and type 1 diabetes), who received a successful islet-after-kidney transplantation (KI-s). RESEARCH DESIGN AND METHODS - Eighteen KI-s patients underwent electroneurographic tests of sural, peroneal, ulnar, and median nerves: the nerve conduction velocity (NCV) index and amplitudes of both sensory action potentials (SAPs) and compound motor action potentials (CMAPs) were analyzed longitudinally at 2, 4, and 6 years after islet transplantation. Skin content of advanced glycation end products (AGEs) and expression of their specific receptors (RAGE) were also studied at the 4-year follow-up. Nine patients with ESRD and type 1 diabetes who received kidney transplantation alone (KD) served as control subjects. RESULTS - The NCV score improved in the KI-s group up to the 4-year time point (P = 0.01 versus baseline) and stabilized 2 years later, whereas the same parameter did not change significantly in the KD group throughout the follow-up period or when a cross-sectional analysis between groups was performed. Either SAP or CMAP amplitudes recovered in the KI-s group, whereas they continued worsening in KD control subjects. AGE and RAGE levels in perineurium and vasa nervorum of skin biopsies were lower in the KI-s than in the KD group (P < 0.01 for RAGE). CONCLUSIONS - Islet transplantation seems to prevent long-term worsening of polyneuropathy in patients with ESRD and type 1 diabetes who receive islets after kidney transplantation. No statistical differences between the two groups were evident on cross-sectional analysis. A reduction in AGE/RAGE expression in the peripheral nervous system was shown in patients receiving islet transplantation. © 2007 by the American Diabetes Association

Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells.

Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone-responsive cell functions and viability. We used high-density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17b-estradiol (E2), ICI 182,780 (ICI), 4OH- tamoxifen (Tamoxifen), and raloxifene (RAL) in ER-positive ZR-75.1 cells, a suitable model to investigate estrogen and antiestrogen actions in hormone-responsive BC. The expression of 601 genes was significantly affected by E2 in these cells; in silico analysis reveals that 86 among them include one or more potential ER binding site within or near the promoter and that the binding site signatures for E2F-1, NF-Y, and NRF-1 transcription factors are significantly enriched in the promoters of genes induced by estrogen treatment, while those for CAC-binding protein and LF-A1 in those repressed by the hormone, pointing to novel transcriptional effectors of secondary responses to estrogen in BC cells. Interestingly, expression of 176 E2- regulated mRNAs was unaffected by any of the antiestrogens tested, despite the fact that under the same conditions the transcriptional and cell cycle stimulatory activities of ER were inhibited. On the other hand, of 373 antiestrogen-responsive genes identified here, 52 were unresponsive to estrogen and 25% responded specifically to only one of the compounds tested, revealing non-overlapping and clearly distinguishable effects of the different antiestrogens in BC cells. As some of these differences reflect specificities of the mechanism of action of the antiestrogens tested, we propose to exploit this gene set for characterization of novel hormonal antagonists and selective estrogen receptor modulators (SERMs) and as a tool for testing new associations of antiestrogens, more effective against BC

The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing

OBJECTIVE: The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS: Skin wounds were created in wild-type (WT) and p66Shc(-/-) control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and beta-catenin. Response to hind limb ischemia was also evaluated. RESULTS: Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of beta-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc(-/-) than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and beta-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc(-/-) dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS: p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication

Notulae to the Italian native vascular flora: 11.

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions. A new combination in the genus Pilosella is proposed. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1