Search

Variants in aminoacyl-tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB, display brain abnormalities, interstitial lung disease and facial dysmorphism. We investigated four children from two unrelated consanguineous families carrying two missense homozygous variants in FARSA with significantly reduced PheRS-mediated aminoacylation activity. In addition to the core ARS-phenotype, all patients showed an inflammatory profile associated with autoimmunity and interferon score, a clinical feature not ascribed to PheRS-deficient patients to date. JAK inhibition improved lung disease in one patient. Our findings expand the genetic and clinical spectrum of FARSA-related disease. [ABSTRACT FROM AUTHOR]

Summary: Since its inception, the resistive random access memory (RRAM) fuse has been a good example of how small numbers of RRAM devices can be combined to obtain useful behaviors unachievable by individual devices. In this work, we link the RRAM fuse concept with that of the complementary resistive switch (CRS), exploit that link to experimentally demonstrate a practical RRAM fuse using TiOx‐based RRAM cells, and explain its basic operational principles. The fuse is stimulated by trains of identical pulses where successive pulse trains feature opposite polarities. In response, we observe a gradual (analogue) drop in resistive state followed by a gradual recovery phase regardless of input stimulus polarity, echoing traditional, binary CRS behavior. This analogue switching property opens the possibility of operating the RRAM fuse as a single‐component step change detector. Moreover, we discover that the characteristics of the individual RRAM devices used to demonstrate the RRAM fuse concept in this work allow our fuse to be operated in a regime where one of the two constituent devices can be switched largely independently from the other. This property, not present in the traditional CRS, indicates that the inherently analogue RRAM fuse architecture may support additional operational flexibility through, for example, allowing finer control over its resistive state. [ABSTRACT FROM AUTHOR]

The coordination chemistry of 1,10‐phenanthroline (phen) and sodium 1,3‐benzothiazole‐2‐thiolate (SBT) with selected s‐block elements has been investigated. Four metal complexes were prepared and their structures were characterized using a variety of analytical techniques including infrared, UV–visible, 1H NMR and 13C NMR spectroscopies, elemental analysis, mass spectrometry and single‐crystal X‐ray diffraction. The reactions of phen and SBT with M(X)n (M = K(I), Cs(I), Mg(II), Sr(II); X = OH−, CO3−, Cl−; n = 1, 2) in MeOH–H2O yielded one‐dimensional chains of both potassium [K2(phen)2(BT)2(H2O)4]n (1) and caesium [Cs(phen)(BS)(H2O)]n (2) (where BT = 1,3‐benzthiazole‐2‐thiolate and BS = 1,3‐benzthiazole‐2‐sulfinothiolate) and mononuclear complexes of both magnesium {[Mg(phen)(H2O)4](BT)2·phen} (3) and strontium {[Sr(phen)2(H2O)4](BT)2} (4). In these complexes, phen binds via an N,N′ chelate pocket, while the monoanonic BT− ligands either coordinate in a bidentate fashion (in the case of 1) or remain uncoordinated (in the case of 3 and 4). In complex 2, SBT ligand was oxidized in situ into a new BS ligand. The sulfinothiolate oxygen atoms in BS coordinate with caesium in a tridentate fashion. Complexes 1–4 were evaluated against urease for enzyme inhibition. The complexes displayed significant inhibition with IC50 values in the range 10.8–45.8 μM. In order to examine the structure–activity relationship, the complexes were docked at the active site of urease. Docking results clearly demonstrate the binding of each complex within the active site of the enzyme. [ABSTRACT FROM AUTHOR]

Summary: Current innovative distributed architectures, proposing on‐line services, involve more and more computing resources. From a provider point of view, the platform management leads to challenging problematic relating to resource allocation, which involve different kind of quality of service parameters, the provider has to focus on to keep his platform reliable and efficient. MFHS is a modular generic framework, which can be adapted to any distributed computing environment. Structured in modules, MFHS allows to discover the existing computing resources in terms of computing performance, network throughput and disk I/O speeds (Resources Discovery module) and to predict how the experiment should behave (Pi value). As the setting up of real experiments is often complex, MFHS allows: to make theoretical experimentation (based on models), to use any kind of distributed emulators, or to deploy experiments on real‐experimental platforms. In this article, these three environments are used to highlight the reliability of MFHS (measured Pi=90% against 94% for the predicted Pi). Deployment and scheduling studies have also been achieved using an experimental Cloud based on OpenStack while Emulab test‐bed has been used as emulator. During experiments, four QoS parameters are taken into account (Resources Monitoring module): energy consumption, cost, resource utilization, and makespan. These studies also includes a new heuristic called MMin, based on Max‐Min and Min‐Min algorithms. Experimentation section, proposes a detailed comparative analysis of these algorithms in terms of QoS results, while the abilities of the proposed heuristic MMin regarding the makespan metric is shown. [ABSTRACT FROM AUTHOR]

Two new C-glucosyl chromones named aloeverasides A ( 1) and B ( 2) were isolated from the resin of Commiphora gileadensis (L.) C. Chr. The structures of the two new natural products were elucidated based on 1D- (1H- and 13C-NMR) and 2D-NMR (COSY, HSQC, and HMBC) spectroscopic techniques and mass spectrometry (ESI-MS). Aloeverasides A ( 1) and B ( 2) were evaluated for their anticancer activity, and both induced a 76.4 and 70.5% growth inhibition of the breast cancer cell line (MDA-MB-231) at a concentration of 100 μ m. Both compounds were also evaluated for their 1,1-diphenyl-2-picryl-hydrazyl antioxidant, urease enzyme, and α-glucosidase enzyme inhibition activities. Aloeverasides A ( 1) and B ( 2) displayed good urease enzyme inhibition activities (62 and 55%, resp.), as well as antioxidant activity in which aloeveraside A ( 1) had a value of 60% inhibition, while aloeveraside B ( 2) demonstrated a more potent antioxidant activity with 80% inhibition. [ABSTRACT FROM AUTHOR]

One new diacylglycoside named lyciumaside ( 1) and a new sesquiterpene lactone named lyciumate ( 2) were isolated from Lycium shawii Roem. & Schult. The structures of the two new compounds were elucidated based on 1D- (1H- and 13C- NMR and NOE) and 2D- NMR ( COSY, HSQC, and HMBC) spectroscopic techniques, and mass spectrometry ( ESI-MS). Preliminary evaluations demonstrated lyciumaside ( 1) possesses strong antioxidant activity with an IC50 = 30 μg/ml (80% inhibition) while it was inactive in α-glucosidase and urease enzymes assays. [ABSTRACT FROM AUTHOR]

TiO2 is commonly used as the active switching layer in resistive random access memory. The electrical characteristics of these devices are directly related to the fundamental conditions inside the TiO2 layer and at the interfaces between it and the surrounding electrodes. However, it is complex to disentangle the effects of film 'bulk' properties and interface phenomena. The present work uses hard X-ray photoemission spectroscopy (HAXPES) at different excitation energies to distinguish between these regimes. Changes are found to affect the entire thin film, but the most dramatic effects are confined to an interface. These changes are connected to oxygen ions moving and redistributing within the film. Based on the HAXPES results, post-deposition annealing of the TiO2 thin film was investigated as an optimisation pathway in order to reach an ideal compromise between device resistivity and lifetime. The structural and chemical changes upon annealing are investigated using X-ray absorption spectroscopy and are further supported by a range of bulk and surface sensitive characterisation methods. In summary, it is shown that the management of oxygen content and interface quality is intrinsically important to device behavior and that careful annealing procedures are a powerful device optimisation technique. [ABSTRACT FROM AUTHOR]

We demonstrate that indium tin oxide (ITO), when used as an active core material in metal-insulator-metal type devices, facilitates resistive switching. We fabricated devices both on silicon as well as quartz wafers, to demonstrate transparent devices. Furthermore, we investigated the influence of active core thickness on the devices' characteristics, showing that their switching threshold scales with the ITO thickness. Unipolar switching was observed for devices comprising thick ITO films while bipolar switching occurred for both thin and thick ITO films at the absence of high voltage forming steps. Our study demonstrates that ITO holds good potential for resistive memory applications. [ABSTRACT FROM AUTHOR]

Background Loose anagen hair (LAH) syndrome is a phenomenon in early childhood characterized by the presence of easily pluckable hair, where hair tufts can be pulled out easily and painlessly. Aims All reports in the English literature described mainly white patients with blond hair. We present the first report of LAH syndrome in dark-skinned children of Upper Egypt. Patients and methods Twenty-eight children with LAH were diagnosed and examined from 1996 to 2007. The main complaints were patchy or diffuse alopecia and/or slow growth of hair. Clinical examination, hair pull test, trichogram, and scanning electron microscopy (SEM) were performed. Results Children with LAH included 21 girls (75%) and seven boys (25%). Light microscopy of hair pull tests and trichograms disclosed a striking predominance of anagen hairs (90–100%) with misshapen hair bulbs and absent inner and outer root sheaths. SEM confirmed the misshapen anagen bulbs with ruffled appearance of cuticle and the longitudinal groove parallel to the long axis of the hair shaft. Most children improved spontaneously within few years, however, hair shed continued. Conclusion LAH syndrome occurs in dark-skinned children and could be under-diagnosed. The condition is of cosmetic concern and does not affect the general health. [ABSTRACT FROM AUTHOR]

Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (−13%, P = 0.020) and SOD patients (−12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (−11%, P = 0.079). All other metabolite ratios ( N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Some linear truncated analogs of endothelin-1 display potent agonistic activity at the ET[sub B] receptor, especially when the side chain of Trp[sup 21] is N-formylated. Then, the three-dimensional arrangements of six structurally reduced linear analogs, three formylated and three nonformylated, have been investigated by high resolution NMR spectroscopy and molecular modeling, in order to pinpoint the conformational features related to the biological activity. Two-dimensional double-quantum-filtered correlation spectroscopy (DQFCOSY), total correlation spectroscopy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY) were recorded and analyzed for each molecule. Interspatial distance constraints were derived from the intensity of the NOESY connectivities. The formation of hydrogen bonding was monitored from the temperature dependence of the NH chemical shifts. Molecular models calculated by means of distance geometry, simulated annealing and energy minimization, using the NMR constraints, strongly suggested a global elongated structure for the formylated analogs exhibiting biological activity, and a folded arrangement for the unformylated derivatives. Homology comparisons allowed the identification of a β-turn-like folding of the C-terminal segment Asp[sup 18]-Trp[sup 21] as a probable key-factor for activity. [ABSTRACT FROM AUTHOR]

Erythromycin A and some derivatives have been shown to act as agonists at the motilin receptor site (motilides) and a structural similarity between these molecules and the N-terminal fragment of motilin has been proposed. Conformational analysis and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods have been used to determine the homology between a series of erythromycin A derivatives and motilin 1-10. A total of 18 compounds has been studied to correlate the gastrointestinal motor stimulating (GMS) activity with the structure-related parameters determined by 3D-QSAR. Two models with good predictive power of the GMS activity are presented, leading to the prediction of motilin 1-10 activity. The models are consistent with the majority of the data available. The most significant parameters for GMS activity are a favorable dispersion interaction from the quaternary ammonium group of the desosamine ring. In motilin 1-10, the aromatic side chains of Phe1 and Tyr7 seem to play the same role as the quaternary ammonium group in models 1 and 2, respectively. Some hydroxyl groups of erythromycin A derivatives and hydrophobic groups of the Val2 and lie4 side chains of motilin also contribute to the GMS activity. The experimental GMS activities measured are in good agreement with the predicted values, with correlation coefficient values of 0.98 and 0.94 in models 1 and 2, respectively. [ABSTRACT FROM AUTHOR]

The solution structure of the Y1 receptor agonist, porcine [Leu31, Pro34]NPY, has been investigated by two-dimensional NMR and molecular modeling. A complete assignment of the NMR resonances was achieved and 201 inter-residue nuclear Overhauser enhancement spectroscopy (NOESY) connectivities could be identified, comprising several connectivities between the N- and C-terminal segments. A molecular model was calculated by distance geometry, simulated annealing and conjugate gradients energy minimization using the NOE constraints. The results indicate that, like NPY and other peptides of the family, [Leu31, Pro34]NPY adopts a folded hairpin structure with the terminal segments in close proximity. Analysis of the secondary chemical shifts for the CHα's and of the temperature dependence of the NH chemical shifts combined with the NOE constraints indicates a tendency toward helix structure for the segment 18-30 and the presence of turn structure for the C-terminal segment (residues 31-36). Native NPY and [Leu31, Pro34]NPY have most of their structures in common but differ slightly in their C-terminal portion. Based on the structures of NPY and of its specific agonists, [Leu31, Pro34]NPY and NPY 13-36, conclusions can be drawn about the structural requirements for binding to the Y1 and Y2 receptor subtypes. [ABSTRACT FROM AUTHOR]