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1.
Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.  相似文献   
2.
Lithium zirconium phosphate (LiZr2P3O12) thin films have been prepared on platinized silicon substrates via a chemical solution deposition approach with processing temperatures between 700°C and 775°C. Films that were subject to a single high-temperature anneal were found to crystallize at temperatures above 725°C. Crystallization was observed in films annealed after each deposited layer at 700°C and above. In both cases, grain size was found to increase with annealing temperature. Ion conductivity was found to increase with annealing temperature in singly annealed films. In per-layer annealed films ion conductivity was found to initially increase then decrease with increasing annealing temperature. A maximum ion conductivity of 1.6 × 10−6 S/cm was observed for the singly annealed 775°C condition, while a maximum ion conductivity of 5.8 × 10−7 S/cm was observed for the 725°C per-layer annealed condition. These results are consistent with an increasing influence of cross-plane, internal interface resistance and vapor phase carrier loss in the per-layer annealed samples. This work demonstrates that post-deposition processing methods can strongly affect the ion conducting properties of LiZr2P3O12 thin films.  相似文献   
3.
Wet filament winding technology has been extensively used for the manufacture of rotationally symmetric parts made of fiber-reinforced plastics (FRP). As the design and modeling of FRP-parts require numerous assumptions, deviations between calculated and achieved mechanical properties are expected. One aspect that contributes to this discrepancy is the assumption of a homogeneous rectangular cross-section of the fiber-band. In this work, the fiber-band geometry in a wet-winding process of carbon fiber cylinders is analyzed. An Infrared-optical system for the detection of the fiber bandwidth and winding-angle is implemented. The influence of the winding speed and the resin temperature is analyzed. An image processing algorithm for the automatic measurement of the fiber's bandwidth and winding-angle is developed. Manual and adaptive gamma corrections are implemented to improve image quality. A parameter study for the suitable selection of image processing parameters is performed.  相似文献   
4.
A modular method for functionalization of nonwoven fabrics was developed using a two-step process. In the first step, the fabrics were grafted with a linker molecule, 10-undecenoyl chloride, via esterification, followed by attachment of a functional material under UV irradiation. Perfluorodecanethiol and 3-mercaptopropionic acid (MPA) were connected to the linker-modified fabrics using thiol-ene click chemistry. Perfluorodecanethiol modified fabrics exhibited hydrophobicity with water contact angle of about 140° while MPA-modified fabrics were able to lower the pH of a solution by about 1.6. We additionally demonstrated the possibility to connect functional polymers to the linker-modified fabrics by radical graft polymerization of acrylic acid; this produced a thin layer of the polymer on the surface of the fabric. Fabrics modified with poly(acrylic acid) exhibited increased hydrophilicity with water contact angle of 0° for both cotton and viscose-polyester fabrics, while the water absorption capability for polypropylene fabrics increased from about 50 to 1200%.  相似文献   
5.
Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; Ki=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.  相似文献   
6.
We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case–control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18–31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m2, p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m2, p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m2, p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m2, p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m2, p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m2, p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = −0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.  相似文献   
7.
Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual-role, creating micro-conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low-voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.  相似文献   
8.
Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.  相似文献   
9.
In this study the effects of high temperature and moisture on the impact damage resistance and mechanical strength of Nextel 610/alumina silicate ceramic matrix composites were experimentally evaluated. Composite laminates were exposed to either a 1050°C isothermal furnace-based environment for 30 consecutive days at 6 h a day, or 95% relative humidity environment for 13 consecutive days at 67°C. Low velocity impact, tensile and short beam strength tests were performed on both ambient and environmentally conditioned laminates and damage was characterized using a combination of non-destructive and destructive techniques. High temperature and humidity environmental exposure adversely affected the impact resistance of the composite laminates. For all the environments, planar internal damage area was greater than the back side dent area, which in turn was greater than the impactor side dent area. Evidence of environmental embrittlement through a stiffer tensile response was noted for the high temperature exposed laminates while the short beam strength tests showed greater propensity for interlaminar shear failure in the moisture exposed laminates. Destructive evaluations exposed larger, more pronounced delaminations in the environmentally conditioned laminates in comparison to the ambient ones. External damage metrics of the impactor side dent depth and area directly influenced the post-impact tensile strength of the laminates while no such trend between internal damage area and residual strength could be ascertained.  相似文献   
10.
As potential waste forms for immobilizing actinide-rich radioactive wastes, Eu2Ti2O7 (Eu as a surrogate for minor actinides) pyrochlore glass-ceramics were fabricated via hot isostatic pressing (HIPing) at 1200°C. The structure and microstructure at the reaction interface between the glass-ceramic waste form and the stainless steel (SS) canister under HIPing conditions were carefully investigated with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and synchrotron single crystal X-ray diffraction (SC-XRD). The interactions at the reaction interface led to the formations of a ~10-µm-thick Cr2O3 layer as the oxidation front of the SS and a layer of a mixed oxide phase (Eu1.25SiCr0.8Ti1.2O7.5) on the glass-ceramic side of the reaction interface. The crystal structure of such a unique mixed oxide phase was revealed indubitably with a combination of synchrotron SC-XRD and TEM assisted with a focused ion beam (FIB) SEM system. The improved structural understanding of the reaction interface will help to support the utilization of HIPing as a versatile hot consolidation process for the treatment of radioactive wastes.  相似文献   
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