Miracle-dz/UniFAR-FTUs huggingface dataset:
Computer-aided design (CAD) of Mn(II) complexes: superoxide dismutase mimetics with catalytic activity exceeding the native enzyme.

New Mn(II) macrocyclic pentaamine complexes derived from the biscyclohexyl-pyridine complex, M40403 ([manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3. 1.0. (4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]]), are described here. The complex M40403 was previously shown to be a superoxide dismutase (SOD) catalyst with rates for the catalytic dismutation of superoxide to oxygen and hydrogen peroxide at pH = 7.4 of 1.2 x 10(+7) M(-1) s(-1). (1) The use of the computer-aided design paradigm reported previously for this class of Mn(II) complexes(2,3) led to the prediction that the 2S,21S-dimethyl derivative of M40403 should possess superior catalytic SOD activity. The synthesis of this new macrocyclic Mn(II) complex, [manganese(II)dichloro[2S, 21S-dimethyl-(4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3. 1.0. (4,9)0(14,19)]hexacosa-1(26),22(23),24-triene]], 5, was accomplished via a high yield template condensation utilizing the linear tetraamine, N,N'-Bis[(1R,2R)-[2-(amino)]cyclohexyl]-1,2-diaminoethane, 1, 2,6-diacetylpyridine, and MnCl(2) to form the macrocyclic diimine complex, 2, which then is reduced. The two other possible dimethyl diastereomers of 5 (2R,21R-dimethyl,3, and 2R,21S-dimethyl, 6) were also prepared via reduction of the diimine complex 2. Two of these complexes, 3 and 5, were characterized by X-ray structure determination confirming their absolute stereochemistry as 2R,21R-dimethyl and 2S,21S-dimethyl, respectively. The results of the MM calculations which predict that the 2S,21S-dimethyl complex, 5, should be a high activity catalyst and that the 2R,21R-dimethyl complex, 3, should have little or no catalytic activity are presented. The catalytic SOD rates for these complexes are reported for each of these complexes and a correlation with the modeling predictions is established showing that 2R,21R-complex, 3, has no measurable catalytic rate, while the 2R,21S complex, 6, is identical to M40403, and the 2S,21S- complex, 5, possesses a very fast rate at pH = 7.4 of 1.6 x 10(+9) M(-1) s(-1) exceeding that of the native mitochondrial MnSOD enzymes.
Upregulation of Epac-1 in Hepatic Stellate Cells by Prostaglandin E2 in Liver Fibrosis Is Associated with Reduced Fibrogenesis

Exchange protein activated by cAMP (Epac-1) is an important signaling mechanism for cAMP-mediated effects, yet factors that change Epac-1 levels are unknown. Such factors are relevant because it has been postulated that Epac-1 directly affects fibrogenesis. Prostaglandin E2 (PGE2) is a well-known cAMP activator, and we therefore studied the effects of this cyclo-oxygenase product on Epac-1 expression and on fibrogenesis within the liver. Liver fibrosis was induced by 8 weeks carbon tetrachloride (CCL4) administration to mice. In the last 2 weeks, mice received vehicle, PGE2, the cyclo-oxygenase-2 inhibitor niflumic acid (NFA), or PGE2 coupled to cell-specific carriers to hepatocytes, Kupffer cells, or hepatic stellate cells (HSC). Results showed antifibrotic effects of PGE2 and profibrotic effects of NFA in CCL4 mice. Western blot analysis revealed reduced Epac-1 protein expression in fibrotic livers of mice and humans compared with healthy livers. PGE2 administration to fibrotic mice completely restored intrahepatic Epac-1 levels and also led to reduced Rho kinase activity, a downstream target of Epac-1. Cell-specific delivery of PGE2 to either hepatocytes, Kupffer cells, or HSC identified the latter cell as the key player in the observed effects on Epac-1 and Rho kinase. No significant alterations in protein kinase A expressions were found. In primary isolated HSC, PGE2 elicited Rap1 translocation reflecting Epac-1 activation, and Epac-1 agonists attenuated platelet-derived growth factor–induced proliferation and migration of these cells. These studies demonstrate that PGE2 enhances Epac-1 activity in HSC, which is associated with significant changes in (myo)fibroblast activities in vitro and in vivo. Therefore, Epac-1 is a potential target for antifibrotic drugs.
Therapeutics of postpartum depression

ABSTRACT Introduction: Postpartum depression is a prevalent disorder affecting many women of reproductive age. Despite increasing public awareness, it is frequently underdiagnosed and undertreated leading to significant maternal morbidity and adverse child outcomes. When identified, postpartum depression is usually treated as major depressive disorder. Many studies have identified the postpartum as a period of high risk for first presentations and relapses of bipolar disorder. Areas covered: This article reviews the acute and prophylactic treatment of postpartum major depressive disorder, bipolar depression and major depressive disorder with mixed features. The safety of antidepressant and mood stabilizing medications in pregnancy and breastfeeding will also be reviewed. Expert commentary: Differentiating postpartum major depressive disorder and postpartum bipolar depression can be difficult given their clinical similarities but accurate identification is vital for initiating proper treatment. Antidepressants are the mainstay of drug treatment for postpartum major depressive disorder, yet randomized controlled trials have shown conflicting results. A paucity of evidence exists for the effectiveness of antidepressant prophylaxis in the prevention of recurrences of major depressive disorder. Mood stabilizing medications reduce the risk of postpartum bipolar depression relapse but no randomized controlled trials have examined their use in the acute or prophylactic treatment of postpartum bipolar depression.
Formal verification of real-time software by symbolic model-checker

Verifications of real-time software are important. However, the state explosion problem is serious for model checking verifications. We present a symbolic model checking algorithm for real-time software, which can check CTL properties without computing exact states. Based on an approximation method, we formulate an approximation/refinement procedure for symbolic model checking, which recursively computes approximate states and iteratively refines approximations. The algorithm reduces the state explosion, using approximations of time zone and symbolic representations with DBMs (difference bounded matrices) and BDDs (binary decision diagrams). We have implemented the algorithm and experimented with the CSMA/CD protocol. Experimental results show that our method can verify large real-time systems which cannot be handled by conventional symbolic model checkers.
The photography of stillborn children and neonatal deaths.

When the Department of Medical Photography first became involved in assisting the Maternity Unit to photograph stillborn children, numbers were expected to be low, and so arrangements were very ad hoc Following an investigation into the rationale for taking photographs, what their intended use was and how the system was operating, it became obvious that little thought had been put into the photography side of a potentially very sensitive operation.The procedure was thus streamlined and is presented here as being more carefully controlled, more professional and much more effective. Owing to this the Department of Photography has become an invaluable and esteemed part of the Health Authority's neonatal bereavement counselling service.
Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe-4S] proteins.

Ulrich Mühlenhoff, Nadine Richter, Ophry Pines, Antonio J. Pierik, and Roland Lill There were several errors in this article. In Fig. 2E, the Rip1 immunoblots from Gal-ISA1 and Gal-ISU1 cells were unintentionally duplicated. In Fig. 3E, the Lys4-HA immunoblots were inadvertently mixed up. Additionally, the wrong Isa2 immunoblot for Gal-ISA2 cells was used. In Fig. 7B, the top portion showed the wrong immunoblot for the porin loading control. Both the porin and Isa1 immunoblots were replaced from a replicate experiment. In the lower portion of Fig. 7B, the two immunoblots were accidentally flipped horizontally. These errors have now been corrected and do not affect the results or conclusions of the work. ADDITIONS AND CORRECTIONS
A NON-UNITARY EXTENSION TO SPECTRAL ESTIMATION

This paper introduces a new parametric frequency estimation technique, ROCK MUSIC, for uncovering frequency components of a sum of complex exponentials in noise. The ROCK MUSIC method is similar to conventional frequency estimation methods, like MUSIC, that decompose the autocorrelation matrix into signal and noise subspaces. The distinguishing feature of this new method is that it does not use an eigenvector decomposition but a decomposition based on a Reduced Order Correlation Kernel. This new non-unitary basis compresses the signal space, thereby making it much more robust to incorrect subspace partitioning than previous subspace frequency estimation methods. Simulation of the ROCK MUSIC technique indicates that large signal spaces may be represented by just a few basis vectors. The signi cance of this nding is that one does not need to know the correct number of signals present in order to obtain classi cation of the frequencies. Thus the new ROCK MUSIC method resolves a fundamental limitation of conventional subspace frequency estimation techniques. Finally, a signi cant savings is possible, both in terms of computation and sample support, because only a small number of basis vectors are required.
Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell‐binding and catalytic domains

Cytotoxic necrotizing factor type 1 (CNF1) induces, in epithelial cells, the development of stress fibres via the GTPase Rho pathway. We showed that CNF1 is able to modify Rho both in vitro and in vivo. Recombinant N‐terminal 33 kDa (CNF1Nter) and C‐terminal 14.8–31.5 kDa (CNF1Cter) regions of the CNF1 protein allowed us to demonstrate that the N‐terminal region contains the cell‐binding domain of the toxin and that the C‐terminal region is responsible for its catalytic activity. CNF1Nter lowered the activity of CNF1 when provided to cells before the toxin whereas CNF1Cter had no effect on CNF1 cell toxicity. CNF1Cter was sufficient to induce a typical CNF1 phenotype when microinjected into African green monkey kidney cells (Vero cells), and was able to modify Rho as previously reported for CNF1. The C‐terminal domain lost its catalytic activity when deleted of various subdomains, suggesting a scattered distribution of catalytic‐site amino acids. Elucidation of the CNF1 functional organization and analysis of amino acid homologies between CNFs (CNF1, CNF2), Pasteurella multocida toxin (PMT) and dermonecrotic toxin of Bordetella pertussis (DNT) allowed us to postulate that CNFs and DNT act on Rho via the same enzymatic activity located in their C‐terminus, and that CNFs and PMT probably bind to analogous cell receptors.
Design of narrow-band 2.4 – 2.5 GHz notch filter using various materials

This paper deals with design, simulation and measurement of narrow-band notch filter from 2.4 GHz to 2.5 GHz using five dielectric materials with various dielectric constants (glass microfiber, ceramic reinforced PTFE, hydrocarbon or epoxy based material). This paper presents filters based on microstrip line structure with half wavelength L - resonators and bandstop characteristic. Various dimensions of each structure were designed due to characteristic of used dielectrics, characterised by dielectric constant εr. The scattering parameters at various frequencies are investigating by modelling this structure with linear network analyses and electromagnetic simulation provides by Ansoft Designer simulating tool from ANSYS and measurement was done by VNA (Vector Network Analyzer). This article presents results of simulation and real measurement of scattering parameters of designed microstrip line structure. This paper refers how used dielectric materials (Rogers RO3003C, Rogers RO4003C, RT/duroid 5880, RT/duroid 6010LM and FR4) influence quality of designed notch filter and which of used material is the most suitable for purpose of high frequency filter using microstrip transmission lines.
An Activating Mutation in sos-1 Identifies Its Dbl Domain as a Critical Inhibitor of the Epidermal Growth Factor Receptor Pathway during Caenorhabditis elegans Vulval Development

ABSTRACT Proper regulation of receptor tyrosine kinase (RTK)-Ras-mitogen-activated protein kinase (MAPK) signaling pathways is critical for normal development and the prevention of cancer. SOS is a dual-function guanine nucleotide exchange factor (GEF) that catalyzes exchange on Ras and Rac. Although the physiologic role of SOS and its CDC25 domain in RTK-mediated Ras activation is well established, the in vivo function of its Dbl Rac GEF domain is less clear. We have identified a novel gain-of-function missense mutation in the Dbl domain of Caenorhabditis elegans SOS-1 that promotes epidermal growth factor receptor (EGFR) signaling in vivo. Our data indicate that a major developmental function of the Dbl domain is to inhibit EGF-dependent MAPK activation. The amount of inhibition conferred by the Dbl domain is equal to that of established trans-acting inhibitors of the EGFR pathway, including c-Cbl and RasGAP, and more than that of MAPK phosphatase. In conjunction with molecular modeling, our data suggest that the C. elegans mutation, as well as an equivalent mutation in human SOS1, activates the MAPK pathway by disrupting an autoinhibitory function of the Dbl domain on Ras activation. Our work suggests that functionally similar point mutations in humans could directly contribute to disease.
Temporal serum creatinine increase and exacerbation of tubulointerstitial inflammation during the first two months in resolving polyomavirus BK nephropathy

Polyomavirus BK nephropathy (BKVN) is an important complication in kidney transplantation. After immunosuppressive agents are reduced, some patients experience a temporal increase in serum creatinine (sCr) before viral clearance. The histological characteristics of re‐biopsies were therefore investigated to evaluate the time course of remission.
Cutting Edge: Rho Activation and Actin Polarization Are Dependent on Plexin-A1 in Dendritic Cells1

We recently identified expression of the semaphorin receptor, plexin-A1, in dendritic cells (DCs); however, its function in these cells remains to be elucidated. To investigate function and maximize physiological relevance, we devised a retroviral approach to ablate plexin-A1 gene expression using small hairpin RNA (shRNA) in primary bone marrow-derived DCs. We show that plexin-A1 localizes within the cytoplasm of immature DCs, becomes membrane-associated, and is enriched at the immune synapse in mature DCs. Reducing plexin-A1 expression with shRNA greatly reduced actin polarization as well as Rho activation without affecting Rac or Cdc42 activation. A Rho inhibitor, C3, also reduced actin polarization. These changes were accompanied by the near-ablation of T cell activation. We propose a mechanism of adaptive immune regulation in which plexin-A1 controls Rho activation and actin cytoskeletal rearrangements in DCs that is associated with enhanced DC-T cell interactions.
Consensus of Linear Multi-Agent Systems by Distributed Event-Triggered Strategy

This paper studies the consensus problem of multi-agent systems with general linear dynamics. We propose a novel event-triggered control scheme with some desirable features, namely, distributed, asynchronous, and independent. It is shown that consensus of the controlled multi-agent system can be reached asymptotically. The feasibility of the event-triggered strategy is further verified by the exclusion of both singular triggering and Zeno behavior. Moreover, a self-triggered algorithm is developed, where the next triggering time instant for each agent is determined based on its local information at the previous triggering time instant. Continuous monitoring of measurement errors is thus avoided. The effectiveness of the proposed control schemes is demonstrated by two examples.
Trends 2010: A decade of change in European Higher

A free electronic version of this report is available through www.eua. be This project has been funded with the support from the European Commission. This publication reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein. Tables Table 1 (page 16) Q11. Besides the Bologna Process, what have been the three most important reforms implemented in your country? Table 2 (page 18) Q8. Over the past ten years how important have the following changes been to your institution? Table 3 (page 23) Q9. In the past fi ve years what have been the three most important developments in the funding of your institution? Table 4 (page 26) Q7a. Over the past three years, how important have the following developments been for your institutional strategy? Table 5 (page 30) Q6. In my institution, the realisation of the European Higher Education Area (EHEA) has been Table 6 (page 34) Q12. Does your institution have a degree structure based on either two or three main cycles (Bachelor, Master, PhD) in most academic fi elds? Table 7 (page 36) Q16. Has your institution reconsidered curricula in connection with the Bologna Process, particularly with regard to adapting programmes to the new degrees structures? Table 8 (page 37) Q14. If the following professional disciplines are taught at your institution, does the Bachelor/Master structure apply to them as well? Table 9 (page 40) Q32. What do you expect your students to do after the fi rst cycle (Bachelor) degree? Table 10 (page 42) Q.15 In the framework of the Bachelor/ Master structure, has your institution recently defi ned the entry requirements for Master level programmes? Table 11 (page 46) Q18a. Have you changed the organisation of study programmes from a system based on the academic year to one based on study units or modules? Table 12 (page 47) Q18b. If yes, has the modularisation of courses led to? Table 13 (page 47) Q18c. If yes, has the modularisation of courses led to? Table 14 (page 48) Q19. Have Learning Outcomes been developed? Table 15 (page 50) Q21. Does your institution have a credit transfer system for all Bachelor´s and Master´s programmes? Table 16 (page 52) Q20. Does your institution use a credit accumulation system for all Bachelor's and Master´s programmes? Table 17 (page 55) Q22. If your institution has a credit system, …
Fine spatial structures and associated electric field changes for an M-component observed with a VHF broadband interferometer system

The fine spatial evolutions and the associated electric field changes of an M-component occurred in a rocket-triggered lightning discharge were analyzed. The lightning discharge was observed with a broadband VHF lightning interferometer, a slow antenna system located and a camera system. With an appropriate approach of combination of the camera images and the VHF interferometer data, spatial evolutions of various processes in the discharge, especially the M-component, were examined.
Transcriptomic and Proteomic Patterns of Systemic Inflammation in On-Pump and Off-Pump Coronary Artery Bypass Grafting

Background— Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. Methods and Results— To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-&agr;, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-&ggr;, granulocyte colony–stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1&bgr;) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-&ggr;, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell–cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a “primed” phenotype of circulating peripheral blood mononuclear cells. Conclusions— Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.
Implementation of scientific computing applications on the Cell Broadband Engine

The Cell Broadband Engine architecture is a revolutionary processor architecture well suited for many scientific codes. This paper reports on an effort to implement several traditional high-performance scientific computing applications on the Cell Broadband Engine processor, including molecular dynamics, quantum chromodynamics and quantum chemistry codes. The paper discusses data and code restructuring strategies necessary to adapt the applications to the intrinsic properties of the Cell processor and demonstrates performance improvements achieved on the Cell architecture. It concludes with the lessons learned and provides practical recommendations on optimization techniques that are believed to be most appropriate.
Practical and Efficient Multi-view Matching

In this paper we propose a novel solution to the multi-view matching problem that, given a set of noisy pairwise correspondences, jointly updates them so as to maximize their consistency. Our method is based on a spectral decomposition, resulting in a closed-form efficient algorithm, in contrast to other iterative techniques that can be found in the literature. Experiments on both synthetic and real datasets show that our method achieves comparable or superior accuracy to state-of-the-art algorithms in significantly less time. We also demonstrate that our solution can efficiently handle datasets of hundreds of images, which is unprecedented in the literature.
Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells

Clinical evidence of retinal pigment epithelium (RPE) alterations after intra‐arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model.