In an earlier study (Chua et al., 1998, 1999a), a 5:1 enlarged model of the Kyoto-NTN Magnetically Suspended Centrifugal Blood Pump (Akamatsu et al., 1995) with five different impeller blade profiles was designed and constructed. Their respective flow characteristics with respect to (1) the three different blade profile designs: forward, radial, and backward, (2) the number of blades used, and (3) the rotating speed were investigated. Among the five impeller designs, the results obtained suggested that impellers A and C designs should be adopted if higher head is required. Impellers A and C therefore were selected for the flow in between their blades to be measured using Laser Doppler Anemometer (LDA), so as to have a better understanding of the flow physics with respect to the design parameters.

A novel and fast integral-equation-based scheme is presented for analyzing transient electromagnetic scattering from homogeneous, isotropic, and nondispersive bodies. The computational complexity of classical marching-on-in-time (MOT) methods for solving time-domain integral equations governing electromagnetic scattering phenomena involving homogeneous penetrable bodies scales as O(NtNsNtNs log2Ns). Numerical results that demonstrate the accuracy and the efficacy of the scheme are presented.

The role of T cell-mediated immunity in the early phase of nephrotoxic serum nephritis (NTN) was examined by transfer of pan T, CD8-positive, and CD4-positive cells. The disease was induced by transferring rabbit gamma-globulin (RGG)-sensitized T cells to nude (rnu/rnu) rats pretreated with a subnephritogenic dose (a dose insufficient to cause proteinuria) of nephrotoxic serum. Mild but abnormal proteinuria was detected, and macrophages showed significant accumulation in glomeruli. Transfer of not only RGG-sensitized CD4-positive cells but also CD8-positive cells separated by the T cell markers OX8 and OX38 using the panning method caused an increased accumulation of macrophages in isolated glomeruli. No host antibody against rabbit immunoglobulins was demonstrated either in glomeruli by immunofluorescence or sera by ELISA in the early disease phase. These findings support a pathological role of T cells in initiation of glomerular injury in NTN.

The bacterial biofilm plays a key role in nosocomial infections, especially those related to medical devices in sustained contact with patients. The active dispersion of bacterial cells out of biofilms acts as a reservoir for infectious diseases. The formation of such biofilms is a highly complex process, which is coordinated by many regulatory mechanisms of the pathogen including quorum sensing (QS). Many bacteria coordinate the expression of key virulence factors dependent on their population density through QS. The inhibition of this system is called quorum quenching (QQ). Thus, preventing the development of biofilms is considered a promising approach to prevent the development of hard to treat infections. Enzymatic QQ is the concept of interfering with the QS system of bacteria outside the cell. PvdQ is an acylase with an N-terminal nucleophile (Ntn-hydrolase) that is a part of the pyoverdine gene cluster (pvd). It is able to cleave irreversibly the amide bond of long chain N-acyl homoserine lactones (AHL) rendering them inactive. Long chain AHLs are the main signaling molecule in the QS system of the gram-negative pathogen Pseudomonas aeruginosa PA01, which is known for surface-associated biofilms on indwelling catheters and is also the cause of catheter-associated urinary tract infections. Furthermore, PA01 is a well characterized pathogen with respect to QS as well as QQ. In this study, we immobilized the acylase PvdQ on polydimethylsiloxane silicone (PDMS), creating a surface with quorum quenching properties. The goal is to control infections by minimizing the colonization of indwelling medical devices such as urinary catheters or intravascular catheters. The enzyme activity was confirmed by testing the degradation of the main auto-inducer that mediates QS in P. aeruginosa. In this article we report for the first time a successful immobilization of the quorum quenching acylase PvdQ on PDMS silicone. We could show that immobilized PvdQ retained its activity after the coating procedure and showed a 6-fold reduction of the auto-inducer 3-oxo-C12 in a biosensor setup. Further we report significant reduction of a P. aeruginosa PA01 biofilm on a coated PDMS surface compared to the same untreated material.

Glomerular infiltration of blood-derived mononuclear cells contributes to the glomerular injury in the autologous phase of nephrotoxic nephritis (NTN). LysoPAF has recently been shown to be chemotactic for human monocytes, thus its accumulation might account for monocyte recruitment. We investigated [3H]lysoPAF metabolism in isolated glomeruli from normal and NTN rabbits studied both in the heterologous and in the autologous phases of the disease. [3H]lysoPAF was converted to [3H]1-O-alkyl-glycerol and [3H]1-O-alkyl-2-acyl-GPC by phospholipase C and acyltransferase, respectively, both in normal and NTN glomeruli. Glomerular metabolism of [3H]lysoPAF was normal during the heterologous phase of NTN. By contrast, in isolated glomeruli from NTN rabbits studied in the autologous phase of the disease, a significantly lower [3H]lysoPAF degradation occurred with respect to normal ones. This defective degradation resulted in a significantly reduced formation of [3H]1-O-alkyl-glycerol. The apparent Km for enzymatic conversion of [3H]lysoPAF to [3H]1-O-alkyl-glycerol, determined at 15 minutes as a function of [3H]lysoPAF concentration, was doubled in glomeruli from rabbits studied in the autologous phase of NTN as compared to normal ones, while Vmax values were similar in the two groups. These results show a defective glomerular lysoPAF degradation in the autologous phase of NTN, likely due to a decreased affinity of phospholipase C to lysoPAF. Altered lysoPAF metabolism results in glomerular accumulation of lysoPAF in the autologous phase of NTN, as shown by significantly higher levels of lysoPAF measured in nephritic glomeruli as compared to normal ones.

Lewis rats receiving subnephritic doses of nephrotoxic serum (NTS) showed increased albuminuria and glomerular histopathologic alterations during the autologous phase of nephrotoxic nephritis (NTN) when they received simultaneous footpad injections of Freund's complete adjuvant (FCA). Lymph nodal lymphocytes from such experimental rats showed increased in vitro cellular sensitization to the nephrotoxic IgG as measured by [3H]thymidine incorporation. Such a lymphocyte blastogenesis response was not detected in rats receiving the same doses of FCA or NTS alone. Antibody titers to the nephrotoxic rabbit IgG were not different in the two groups of rats as measured by enzyme-linked immunosorbent assay. The transfer of lymph nodal mononuclear cells from rats with NTN potentiated by FCA, was able to induce albuminuria and glomerular histopathologic alterations in recipients treated with NTS. In the above experimental model FCA appears to potentiate the autologous phase of NTN by cellular immune mechanisms.

OBJECTIVE

To investigate the effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, vascular endothelial growth factor (VEGF) and type X collagen (ColX) in impaired cartilage of rabbits with knee osteoarthritis (KOA) and explore its possible mechanisms.

METHODS

Forty New Zealand rabbits were randomized equally into normal control group, KOA model group, eletroacupuncture with close-to-bone needling group (CN group), and normal thrust needing group (NTN group). In the latter 3 groups, KOA was induced by Hulth-Telhag treatment and evaluated with X-ray examination, and 6 weeks after the modeling, eletroacupuncture for 20 min was administered in CN and NTN groups at the acupoints "Zusanli", "Waixiyan", "Neixiyan", "Liangqiu" and "Yinlingquan" in the left knee joints once daily for 5 days as a treatment cycle. After 5 treatment cycles, the rabbits were examined for behavioral changes, cartilage morphology, and Mankin scores; The protein and mRNA expressions of S0x9, VEGF, and ColX were examined using Westen blotting, immunohistochemistry, and RT-PCR as appropriate.

RESULTS

The rabbits in the model, CN and NTN groups showed significant changes in behaviors and cartilage histomorphology after the modeling and after the treatments. HE staining showed that cartilage injury was repaired and tended to recovery in CN and NTN groups. The cartilage pathologies was severer in the model group than in the normal control, CN and NTN groups (P<0.01); Sox9 protein increased and VEGF mRNA level decreased in CN and NTN groups after treatment as compared with those in the model group (P<0.01).

CONCLUSIONS

Eletroacupuncture with close-to-bone needling can effectively improve KOA in rabbits probably by enhancing Sox9 and reducing VEGF and ColX expressions in the cartilage to inhibit hypertrophic differentiation of the chondrocytes, maintain chondrogenic phenotype and repair cartilage cells.

Winning in the global market place with brilliant innovations is the recipe for success for the Swiss economy. Indeed, Switzerland always stands out in the global rankings when it comes to innovation. Yet there is nothing as dangerous as to rest on one's laurels, and this is particularly true for R&D-based businesses. For this reason CTI, the Commission for Technology and Innovation, offers Swiss companies quick and effective access to knowledge available at Swiss public research institutions, and to international R&D programs promoting application-oriented research. Knowledge and technology transfer are promoted - via its KTT support - through National Thematic Networks (NTNs), Innovation Mentors and information platforms. The following article highlights the activities of the National Thematic Networks and invites Swiss companies and research institutes to benefit from the multiple offers and services available.

This study aimed to quantify core surgical trainee (CST) differential attainment (DA) related to three cohorts; white UK graduate (White UKG) versus black and minority ethnic UKG (BME UKG) versus international medical graduates (IMGs). The primary outcome measures were annual review of competence progression (ARCP) outcome, intercollegiate Membership of the Royal College of Surgeons (iMRCS) examination pass and national training number (NTN) selection. Intercollegiate Surgical Curriculum Programme (ISCP) portfolios of 264 consecutive CSTs (2010-2017, 168 white UKG, 66 BME UKG, 30 IMG) from a single UK regional post graduate medical region (Wales) were examined. Data collected prospectively over an 8-year time period was analysed retrospectively. ARCP outcomes were similar irrespective of ethnicity or nationality (ARCP outcome 1, white UKG 60.7% vs BME UKG 62.1% vs IMG 53.3%, p=0.395). iMRCS pass rates for white UKG vs BME UKG vs IMG were 71.4% vs 71.2% vs 50.0% (p=0.042), respectively. NTN success rates for white UKG vs BME UKG vs IMG were 36.9% vs 36.4% vs 6.7% (p=0.023), respectively. On multivariable analysis, operative experience (OR 1.002, 95% CI 1.001 to 1.004, p=0.004), bootcamp attendance (OR 2.615, 95% CI 1.403 to 4.871, p=0.002), and UKG (OR 7.081, 95% CI 1.556 to 32.230, p=0.011), were associated with NTN appointment. Although outcomes related to BME DA were equitable, important DA variation was apparent among IMGs, with iMRCS pass 21.4% lower and NTN success sixfold less likely than UKG. Targeted counter measures are required to let equity prevail in UK CST programmes.

As many as 145 patients with painful syndromes in the face and head underwent immunologic examination. They manifested certain changes in cellular and humoral immunity. An increase in the content of secretory IgA in the saliva and in the serum and a decrease of the concentration of IgM and IgG in the serum were detected in the majority of patients. In patients with NTN of mainly peripheral genesis and with Horton's syndrome, the concentration of IgE in the serum was significantly (P less than 0.01) elevated. The changes in the immunologic status, seen in patients after the treatment are discussed.

OBJECTIVE

To explore the effects of tyrosine hydroxylase-neurturin (TH-NTN) gene modified bone marrow mesenchymal stem cell (BMSC) transplantation in Parkinson's disease (PD) model rats and the alternations of correlated proteins.

METHODS

The PD rat model was established by the 2-point injection of 6-hydroxydopamine (6-OHDA) into unilateral (right) striatum. Successful modeling rats were separated into PD, BMSC and TH-NTN-BMSC groups. BMSC and TH-NTN-BMSC groups were transplanted into BMSCs and TH-NTN gene modified BMSC cells separately into right striatum. After transplantation, ethology detection in all groups was made with an intraperitoneal injection of apomorphine (APO). Dopamine (DA) and Dihydroxyphenylacetic Acid (DOPAC) in striatum were detected by high performance liquid electrochemical analysis. TH and NTN proteins in right striatum were also analyzed by immunohistochemistry and Western blot. Finally the density of dopamine receptors in post synaptic density of dopaminergic synapses of corpus striatum were compared between each group by post-embedding immunogold electron microscopy.

RESULTS

After an injection of APO, rotation frequency decreased in TH-NTN-BMSC group, i.e. (5.7 ± 1.3) circles/min versus (10.8 ± 2.2), (9.9 ± 1.2) circles/min in PD and BMSC groups (P < 0.05). For proteins in right striatum, DA, (0.421 ± 0.113) and DOPAC, (0.093 ± 0.012) nmol/L increased significantly versus (0.208 ± 0.043), (0.043 ± 0.017) nmol/L in PD and (0.231 ± 0.082), (0.044 ± 0.023)noml/L in BMSC groups (P < 0.05). Also a lower density of D2 receptors at (623 ± 96)/µm(2) in TH-NTN-BMSC group versus (923 ± 132)/µm(2) in PD and (860 ± 116)/µm(2) in BMSC groups was also found.

CONCLUSIONS

The combined therapy of TH and NTN genes increases the synthesis of DA and also protects the dopaminergic neurons to achieve double therapeutic effects. It may provide potential innovations of PD genetic therapy.

Potato virus Y (PVY) is one of the main viruses affecting potato in Australia. However, molecular characterization of PVY isolates circulating in potato in different states of Australia has not yet been thoroughly conducted. Only nonrecombinant isolates of three biological PVY strains collected from potato were reported previously from Western Australia and one from Queensland. Here, PVY isolates collected from seed potato originating in Victoria, Australia, and printed on FTA cards, were subjected to strain typing by RT-PCR, with three isolates subjected to whole genome sequencing. All the 59 PVY isolates detected during two growing seasons were identified to be recombinants based on two RT-PCR assays. No nonrecombinant PVY isolates were identified. All the RT-PCR typed isolates belonged to the PVY^NTN strain. Sequence analysis of the whole genomes of three isolates suggested a single introduction of the PVY^NTN strain to Australia but provided no clues as to where this introduction originated. Given the association of the PVY^NTN strain with potato tuber damage, growers in Australia should implement appropriate strategies to manage PVY^NTN in potato.

Keywords: FTA; PTNRD; PVYNTN; multiplex PCR.

BACKGROUND

In order to evaluate the analgesic efficacy of low dose epidural bupivacaine infusion with and without morphine after caesarean section we performed combined spinal-epidural anesthesia (CSEA) using needle through needle method. Three different epidural analgesic regimens were compared retrospectively.

METHODS

The number of analgesic use during 24 hours after operation was compared. Patients were categorized into three groups; group N : intraoperative bolus epidural morphine (2.5 mg) alone, group L : bolus morphine (2.5 mg) plus epidural bupivacaine infusion (32 ml of 0.2% bupivacaine) at a rate of 2.1 ml x hr(-1), group M : bolus morphine (2.4 mg) plus epidural bupivacaine-morphine (33 ml of 0.2% bupivacaine containing morphine 2.3 mg) infusion at a rate of 2.1 ml x hr(-1). Used analgesics included pentazocine 15 mg i.m., diclofenac 25 mg suppo. and loxoprofen 60 mg p.o..

RESULTS

The mean number of analgesic use during the first 24 hours in group M (0.29 +/- 0.46) was significantly smaller than those of group N (0.97 +/- 0.91) and group L (0.84 +/- 0.95). Percentage of patients requiring no analgesic during the first 24 hours was significantly less in group M (70.8%) than in group N (33.4%) and group L (42.1%).

CONCLUSIONS

A 2.1 ml x hr(-1) infusion of epidural bupivacaine has no analgesic effect after caesarean section under CSEA using NTN method.

In mice, the initial stage of nephrotoxic serum-induced nephritis (NTN) mimics antibody-mediated human glomerulonephritis. Local immune deposits generate tumor necrosis factor (TNF), which activates pro-inflammatory pathways in glomerular endothelial cells (GECs) and podocytes. Because TNF receptors mediate antibacterial defense, existing anti-TNF therapies can promote infection; however, we have previously demonstrated that different functional domains of TNF may have opposing effects. The TIP peptide mimics the lectin-like domain of TNF, and has been shown to blunt inflammation in acute lung injury without impairing TNF receptor-mediated antibacterial activity. We evaluated the impact of TIP peptide in NTN. Intraperitoneal administration of TIP peptide reduced inflammation, proteinuria, and blood urea nitrogen. The protective effect was blocked by the cyclooxygenase inhibitor indomethacin, indicating involvement of prostaglandins. Targeted glomerular delivery of TIP peptide improved pathology in moderate NTN and reduced mortality in severe NTN, indicating a local protective effect. We show that TIP peptide activates the epithelial sodium channel(ENaC), which is expressed by GEC, upon binding to the channel's α subunit. In vitro, TNF treatment of GEC activated pro-inflammatory pathways and decreased the generation of prostaglandin E2 and nitric oxide, which promote recovery from NTN. TIP peptide counteracted these effects. Despite the capacity of TIP peptide to activate ENaC, it did not increase mean arterial blood pressure in mice. In the later autologous phase of NTN, TIP peptide blunted the infiltration of Th17 cells. By countering the deleterious effects of TNF through direct actions in GEC, TIP peptide could provide a novel strategy to treat glomerular inflammation.

OBJECTIVE

To investigate the role of c-Jun N-terminal kinase (JNK)-c-Jun/activator protein-1 (AP-1) signal pathway in expression of monocyte chemoattractant protein-1 (MCP-1) in experimental rat glomerulonephritis.

METHODS

Nephrotoxic sera nephritis (NTN) was induced by injection of anti-GBM antibody into the tail veins of rats. Electrophoretic mobility shift assay (EMSA) and non-radioactive kinase assay were used to detect the activity of AP-1 and JNK in kidneys and angiotensin II-stimulated human mesangial cells. Ribonuclear protection assay was used to detect MCP-1 expression in cultured human mesangial cells.

RESULTS

Significant up-regulation of JNK and AP-1 was observed in NTN rats (3.82 +/- 0.58) folds and (5.36 +/- 0.61) folds, as compared with the controls. Supershift assay demonstrated that c-Jun and c-Fos were the predominant subunits involved. Activation of JNK and AP-1 significantly correlated with MCP-1 expression in NTN rats. Angiotensin II enhanced the expression of MCP-1 and activation of JNK and AP-1 in cultured human mesangial cells in a dose-dependent manner, with maximal stimulation seen at 100 nmol/L (20.99 +/- 4.71) folds, (6.91 +/- 1.65) folds and (7.82 +/- 1.32) folds respectively. Significant down-regulation of AP-1 activation and MCP-1 expression were observed in angiotensin II-induced human mesangial cells pretreated with JNK specific inhibitor SP600125.

CONCLUSIONS

Angiotensin II and MCP-1 may play an important role in glomerulosclerosis via the JNK-c-Jun/AP-1 signal pathway.

Phospholipase-B-like (SVPLB-like) enzymes are present in relatively small amounts in a number of venoms, however, their biological function and mechanisms of action are un-clear. A three-dimensional model of the SVPLB-like enzyme from Crotalus adamanteus was generated by homology modeling based on the crystal structures of bovine Ntn-hydrolyases and the modeled protein possesses conserved domains characteristic of Ntn-hydrolases. Molecular dynamics simulations indicate that activation by autocatalytic cleavage results in the removal of 25 amino acids which increases accessibility to the active site. SVPLB-like enzymes possess a highly reactive cysteine and are hence amidases that to belong to the N-terminal nucleophile (Ntn) hydrolase family. The Ntn-hydrolases (N-terminal nucleophile) form a superfamily of diverse enzymes that are activated autocatalytically; wherein the N-terminal catalytic nucleophile is implicated in the cleavage of the amide bond.

A new copper metallothionein (TfCuMT) gene has been identified from a locally isolated ciliate Tetrahymena farahensis. It contains 327 nucleotides encoding a peptide chain of 108 amino acids and belongs to class MTT2 and subfamily 7b. Amplification from both gDNA and mRNA confirmed the intronless nature of this gene. Like most of the metallohtioneins, cysteine residues contribute nearly 30% content with the specific CKC motifs. Structural repeats present in peptide sequence of TfCuMT indicate internal duplication of gene at some stage of gene evolution. The predicted model of copper metallothionein protein showed that copper ions are mainly chelated by thiol sulfur of cysteine residues and are embedded in the folds of polypeptide chain. For in vivo expression of TfCuMT in Escherichia coli host cells the classical stop codons, which coded for glutamine in the ciliate were mutated to CAA and CAG through site directed mutagenesis. The mutated gene showed higher expression in pET28a expression vector compared with pET21a. Optimum expression was obtained after 6-8 h of 0.1 mM IPTG induction. Stability of His tagged TfCuMT in 5% SDS was low, with half-life of about 104 min. Presence of 1.0 μM copper increased the expression level by 1.65-fold. Presence of 100 μM Cysteine in culture medium caused 2.4-fold increase in expression level. His tagged TfCuMT was purified through affinity chromatography using NTN-His binding resin in the presence of 0.1 M imidazole and NaCl. The modeled structure of the TfCuMT showed a cleft for Cu binding with correct orientation of Cys residues in the motif CKC. J. Cell. Biochem. 117: 1843-1854, 2016. © 2016 Wiley Periodicals, Inc.

OBJECTIVE

To determine the prevalence of nontuberculous mycobacteria (NTM) colonization and disease in cystic fibrosis (CF) patients.

METHODS

All the CF patients followed-up from 2002 to 2012 with three acid-fast bacilli (AFB) cultures were included. The American Thoracic Society (ATS) criteria for NTM lung disease were applied.

RESULTS

Forty-four of the 53 patients being followed-up were included. The mean time of follow-up was 7.0 years. A total of 18 patients (40.9%) were NTM positive. The NTN mean annual prevalence was 14.1%. The risk of Mycobacterium abscessus complex was higher in the group of 10-14 years-old (p < 0.001). Ten patients (22.7% of the entire cohort) met the ATS microbiological criteria. The mean annual prevalence of NTM disease was 10.4%. Seven patients (four with Mycobacterium simiae and three with M. abscessus complex) with multiple positive cultures, positive AFB smears and clinical worsening were treated. Three patients with M. simiae and none of those with M. abscessus were cured.

CONCLUSIONS

Overall NTM prevalence of colonization and disease were high in our CF patients. Patients <15 years old had a higher risk of M. abscessus complex colonization. Multiple positive cultures or positive AFB smears were associated with disease.

Potato virus Y (PVY) is the most economically important virus infecting potatoes worldwide. Current-season spread of PVY occurs when aphids transmit the virus from infected to noninfected plants during the growing season. The impact of current-season PVY infection on yield and quality of chip processing potatoes is not well documented. In a replicated, greenhouse experiment conducted over 2 years, we measured the effect of current-season infection with four PVY strains (PVY^O, PVY^N-Wi, PVY^NTN, and PVY^N:O) on chip processing varieties Atlantic, Lamoka, and Snowden. PVY infection decreased yield and tuber specific gravity for some combinations of potato variety and virus strain but did not affect the appearance of chips including the prevalence of stem-end chip defects. This work suggests that current-season infection of chipping potatoes imposes a cost on producers and emphasizes the need for continued investment in seed certification and development of PVY-resistant cultivars.

Keywords: Potato virus Y-Wilga; Solanum tuberosum L.; chipping potato dry matter content; potato chip color; potato tuber sugar content.

N-acylethanolamine acid amidase (NAAA) is an N-terminal nucleophile (Ntn) enzyme with a catalytic cysteine residue that has highest activity at acidic pH. The most prominent substrate hydrolyzed is palmitoylethanolamine (PEA), which regulates inflammation. Inhibitors of NAAA have been shown to increase endogenous levels of PEA, and are of interest as potential treatments for inflammatory disorders and other maladies. Currently, there are no X-ray or NMR structures of NAAA available to inform medicinal chemistry. Additionally, there are a limited number of enzyme structures available that are within the Ntn-hydrolase family, have a catalytic cysteine residue, and have a high sequence homology. For these reasons, we developed expression and purification methods for the production of enzyme samples amenable to structural characterization. Mammalian cells are necessary for post-translational processing, including signal sequence cleavage and glycosylation, that are required for a correctly folded zymogen before conversion to active, and mature enzyme. We have identified an expression construct, mammalian cell line, specific media and additives to express and secrete hNAAA zymogen and we further optimized propagation conditions and show this secretion method is suitable for isotopic labeling of the protein. We refined purification methods to achieve a high degree of protein purity potentially suited to crystallography. Glycosylated proteins can present challenges to biophysical methods. Therefore we deglycosylate the enzyme and show that the activity of the mature enzyme is not affected by deglycosylation.

This paper introduces a nonsmooth (NS) neural network that is able to operate in a time-dependent (TD) context and is potentially useful for solving some classes of NS-TD problems. The proposed network is named nonsmooth time-dependent network (NTN) and is an extension to a TD setting of a previous NS neural network for programming problems. Suppose C(t), t ≥ 0, is a nonempty TD convex feasibility set defined by TD inequality constraints. The constraints are in general NS (nondifferentiable) functions of the state variables and time. NTN is described by the subdifferential with respect to the state variables of an NS-TD barrier function and a vector field corresponding to the unconstrained dynamics. This paper shows that for suitable values of the penalty parameter, the NTN dynamics displays two main phases. In the first phase, any solution of NTN not starting in C(0) at t=0 is able to reach the moving set C(·) in finite time th , whereas in the second phase, the solution tracks the moving set, i.e., it stays within C(t) for all subsequent times t ≥ t(h). NTN is thus able to find an exact feasible solution in finite time and also to provide an exact feasible solution for subsequent times. This new and peculiar dynamics displayed by NTN is potentially useful for addressing some significant TD signal processing tasks. As an illustration, this paper discusses a number of examples where NTN is applied to the solution of NS-TD convex feasibility problems.

U.S. studies show that the global point-of-care (POC) diagnostics market will reach $40.5 bn by 2022, with a compound annual growth rate (CAGR) of 10%. This is one of the reasons why HES-SO Valais-Wallis and CSEM, acting on behalf of the NTN Swiss Biotech thematic platform in vitro Diagnostics (TP IVD), invited interested parties on October 26, 2017 to the SWISS SYMPOSIUM in Point-of-Care Diagnostics (see CHIMIA No. 12/2017). We now bring the second report on the future prospects of POC diagnostics.

Computer-aided approaches are widely used in modern medicinal chemistry to improve the efficiency of the discovery phase. N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase belonging to the N-terminal nucleophile (Ntn) hydrolases that primarily degrades anti-inflammatory and analgesic lipid amide palmitoylethanolamide. In this chapter, we review our contribution to (i) the determination of the reaction mechanism of amide hydrolysis catalyzed by cysteine Ntn-hydrolases and (ii) the discovery and optimization of active-site-directed inhibitors of NAAA characterized by a β-lactone warhead. The combination of different computational tools, ranging from homology modeling, docking, and mechanistic simulations based on hybrid quantum mechanics/molecular mechanics potentials, contributed to the elucidation of the mechanism of action and inhibition of NAAA enzyme and to the design of more potent inhibitors.