Multimetal organic frameworks as drug carriers: Aceclofenac as a drug candidate

Background: Multimetal organic frameworks (M-MOFs) were synthesized by including a second metal ion with the main base metal in the synthesis process to enhance their applications for drug delivery. Aceclofenac (ACF), a nonsteroidal anti-inflammatory analgesic drug of low aqueous solubility, was selected as a candidate for the drug delivery system Purpose: This study aimed to evaluate the loading capacity (LC) and entrapment efficiency (EE) percentages of multi-Material of Institute Lavoisier (MIL)-100(Fe) (M-MIL-100(Fe)) for ACF. Materials and methods: Hydrothermal synthesis procedure was used to prepare multi-MIL-100(Fe) samples (Zn I-MIL-100(Fe), Zn II-MIL-100(Fe), Ca I-MIL-100(Fe), Ca II-MIL-100-(Fe), Mg I-MIL-100(Fe), Mg II-MIL-100(Fe), Mn I-MIL-100(Fe), and Mn II-MIL-100(Fe)). The characterization of M-MIL-100(Fe) samples was evaluated by X-ray powder diffraction (XRD), Fourier transform infrared spectra, scanning electron microscope (SEM), TGA, and N2 adsorption isotherms. The LC of M-MIL-100(Fe) and EE of ACF were determined. Nuclear magnetic resonance (NMR) and zeta-potential analyses were employed to confirm qualitatively the drug loading within M-MIL-100(Fe). Results: The ACF LC of MIL-100(Fe) was 27%, whereas the LC of M-MIL-100(Fe) was significantly increased and ranged from 37% in Ca I-MIL-100(Fe) to about 57% and 59% in Mn II-MIL-100(Fe) and Zn II-MIL-100(Fe), respectively. The ACF@M-MOFs release profiles showed slow release rates in phosphate buffer solutions at pH 6.8 and 7.4 as compared to the ACF@MIL-100(Fe). Conclusion: Therefore, M-MOFs showed a significant potential as a carrier for drug delivery systems

Physiological responses to shuttle repeated-sprint running

This study investigated the influence of 180° changes of direction during a repeated-sprint running test on performance, cardiorespiratory variables, muscle deoxygenation and post-exercise blood lactate ([La]b) levels. Thirteen team-sport athletes (22±3 yr) performed 6 repeated maximal sprints with (RSS, 6×[2×12.5 m]) or without (RS, 6×25 m) changes of direction. Best and mean running time, percentage speed decrement (%Dec), pulmonary oxygen uptake (V˙ O2), vastus lateralis deoxygenation (Hbdiff) and [La]b were calculated for each condition. Best and mean times for both protocols were largely correlated (r=0.63 and r=0.78, respectively), and were ‘almost certainly’ higher for RSS compared with RS (e. g., 5.30±0.17 vs. 4.09±0.17 s for mean time, with the qualitative analysis revealing a 100% chance of RSS time being greater than RS). In contrast, %Dec was‘possibly’ lower for RSS (2.6±1.2 vs. 3.2±1.3%, with a 79% chance of a real difference). Compared with RS,V˙ O2 (40.4±4.2 vs. 38.9±3.8 mL.min−1.kg−1, with a 90% chance of a real difference) and [La]b (10.0±1.7 vs. 9.3±2.4 mmol.L−1, with a 70% chance of a real difference) were‘possibly’ higher. Conversely, there were no differences in Hbdiff (11.5±3.2 vs. 10.9±3.0 μM, with the comparison rated as‘unclear’). To conclude, the present results suggest that the ability to repeat sprints can be considered as a general quality. They also suggest that repeated shuttle sprints might be an effective training practice for eliciting a greater systemic physiological load, but perhaps not a greater loading of the vastus lateralis

Dynamic behaviour of unbraced steel frames resting on soft ground

© 2019 Ernst & Sohn Verlag für Architektur und technische Wissenschaften GmbH & Co. KG, Berlin Many recent earthquakes clearly illustrate the importance of local ground properties for the dynamic response of structures. The dynamic response of an engineering structure is influenced by the medium on which it is founded. On solid rock, a fixed-base structural response occurs which can be evaluated by subjecting the foundation to the free-field ground motion occurring in the absence of the structure. However, on deformable ground, a feedback loop exists. In other words, when a feedback loop exists, the structure responds to the dynamics of the soil, while the soil also responds to the dynamics of the structure. Structural response is then governed by the interplay between the characteristics of the ground, the structure and the input motion. This study involved a numerical investigation of the dynamic behaviour of unbraced steel frames resting on soft ground. Two types of mid-rise unbraced steel frame, including 5- and 15-storey buildings on a soft soil deposit, were selected and analysed under the influence of three different earthquake acceleration records. The above-mentioned frames were analysed under two different boundary conditions: i) fixed-base (no soil-structure interaction) and ii) flexible-base (considering soil-structure interaction). The results of the analyses in terms of structural forces and lateral displacements for the above-mentioned boundary conditions are compared and discussed

Contrasts in top soil infiltration processes for degraded vs. Restored lands. a case study at the perijá range in Colombia

Governments are increasingly committing to significant ecological restoration. However, the impacts of forest restoration on local hydrological services are surprisingly poorly understood. Particularly, limited information is available about the impacts of tree planting on soil infiltration processes and runoff pathways. Thus, we investigated the saturated hydraulic conductivity (Ks ) and preferential flow pathways in three land-cover types: (i) Active Restoration, (ii) Degraded Land, and (iii) Reference Forest, with contrasting differences in soil profile and land use history in the municipality of La Jagua de Ibirico, César department, Colombia. We conducted soil sampling, using the Beerkan method to determine Ks values. We also measured vegetation attributes (i.e., canopy cover, vegetation height, diameter at breast height, and total number of trees) and carried out three dye tracer experiments for each study site. The blue dye experiments revealed that near surface matrix infiltration was dominant for Degraded Land, while at the Active Restoration and Reference Forest, this only occurred at local surface depressions. The general infiltration pattern at the three land uses is indicated as being macropore flow with mixed interaction with the matrix and highly affected by the presence of rock fragments. The deeper infiltration patterns occur by preferential flow due to the presence of roots and rock fragments. The mean Ks for the Active Restoration (240 mm h−1 ) was much higher than the Ks at Degraded Land (40 mm h−1 ) but still considerably lower than the Reference Forest (324 mm h−1 ). These results indicate that top soil infiltration capacity and soil physical parameters not only directly regulate the amount of infiltration but also infiltration patterns and runoff processes, leading to lower infiltration and increased excess overland flow for Degraded Land than for other land uses

Adult Neuroblastoma Complicated by Increased Intracranial Pressure: A Case Report and Review of the Literature

Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures. The patient was treated with systemic chemotherapy, I131 metaiodobenzylguanidine (MIBG) radiotherapy, and autologous stem cell transplant (SCT). Unfortunately the patient’s response to therapy was limited and she subsequently died. We aim to review neuroblastoma in the context of increased intracranial pressure and the limited data of neuroblastoma occurring in the adult population, along with proposed treatment options

Twisted topology and Bipolar Non-Hermitian Skin Effect induced by long-range asymmetric coupling

We investigate the twisted topology of the complex eigenspectrum of a one-dimensional non-Hermitian system under the influence of long-range unidirectional coupling. Unlike the complex energy spectrum of the conventional Hatano-Nelson chain, which takes the form of a single loop with a topological winding index of a definite sign, the introduction of long-range unidirectional hopping results in the creation of multiple twisted loops. These twisted loops exhibit opposite signs of the topological winding index, which correlate to alternating clockwise and anticlockwise energy windings. The simultaneous presence of both signs of the winding index translates into a bipolar non-Hermitian skin effect (NHSE), which challenges the conventional wisdom that the NHSE localization is dependent on the direction of the dominant nearest-neighbor interactions. In this bipolar NHSE, the exponents of the complex energy eigenvectors corresponding to clockwise and anti-clockwise windings, lie inside and outside of the complex unit circle, respectively. Interestingly, at the intersections of oppositely oriented energy loops where the sign of the topological winding index flips, the energy becomes real-valued, leading to a suppression of the NHSE. This marks the emergence of Bloch-like contact points, where both the bipolar NHSE and the traditional NHSE vanish. Based on the non-Hermitian model we provide analytical insights into the effects of long-range unidirectional coupling to the winding topology of its complex energy spectra and their broader implications for the field of condensed matter physics.Comment: 11 pages, 3 figure

Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia

Delayed oligodendrocyte (OL) maturation caused by hypoxia (Hx)-induced neonatal brain injury results in hypomyelination and leads to neurological disabilities. Previously, we characterized Sirt1 as a crucial regulator of OL progenitor cell (OPC) proliferation in response to Hx. We now identify Sirt2 as a critical promoter of OL differentiation during both normal white matter development and in a mouse model of Hx. Importantly, we find that Hx reduces Sirt2 expression in mature OLs and that Sirt2 overexpression in OPCs restores mature OL populations. Reduced numbers of Sirt2+ OLs were also observed in the white matter of preterm human infants. We show that Sirt2 interacts with p27Kip1/FoxO1, p21Cip1/Cdk4, and Cdk5 pathways, and that these interactions are altered by Hx. Furthermore, Hx induces nuclear translocation of Sirt2 in OPCs where it binds several genomic targets. Overall, these results indicate that a balance of Sirt1 and Sirt2 activity is required for developmental oligodendrogenesis, and that these proteins represent potential targets for promoting repair following white matter injury

Impedance responses and size-dependent resonances in topolectrical circuits via the method of images

Resonances in an electric circuit occur when capacitive and inductive components are present together. Such resonances appear in admittance measurements depending on the circuit's parameters and the driving AC frequency. In this study, we analyze the impedance characteristics of nontrivial topolectrical circuits such as one- and two-dimensional Su-Schrieffer-Heeger circuits and reveal that size-dependent anomalous impedance resonances inevitably arise in finite $LC$ circuits. Through the \textit{method of images}, we study how resonance modes in a multi-dimensional circuit array can be nontrivially modified by the reflection and interference of current from the structure and boundaries of the lattice. We derive analytic expressions for the impedance across two corner nodes of various lattice networks with homogeneous and heterogeneous circuit elements. We also derive the irregular dependency of the impedance resonance on the lattice size, and provide integral and dimensionally-reduced expressions for the impedance in three dimensions and above.Comment: 24 pages, 10 figure

Generating a checking sequence with a minimum number of reset transitions

Given a finite state machine M, a checking sequence is an input sequence that is guaranteed to lead to a failure if the implementation under test is faulty and has no more states than M. There has been much interest in the automated generation of a short checking sequence from a finite state machine. However, such sequences can contain reset transitions whose use can adversely affect both the cost of applying the checking sequence and the effectiveness of the checking sequence. Thus, we sometimes want a checking sequence with a minimum number of reset transitions rather than a shortest checking sequence. This paper describes a new algorithm for generating a checking sequence, based on a distinguishing sequence, that minimises the number of reset transitions used.This work was supported in part by Leverhulme Trust grant number F/00275/D, Testing State Based Systems, Natural Sciences and Engineering Research Council (NSERC) of Canada grant number RGPIN 976, and Engineering and Physical Sciences Research Council grant number GR/R43150, Formal Methods and Testing (FORTEST)

Insights into GABA receptor signalling in TM3 Leydig cells

gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Base