Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats

Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.     

Low energy electron storage ring with tunable compaction factor

A low energy electron storage ring is designed to have many desirable properties, such as varying momentum compaction factor, damping partition numbers, favorable betatron tunes for multiturn accumulations, and excellent dynamic aperture. This storage ring can be used for debunching rf linac beams in one turn, for compression of linac pulses, and more importantly for a compact photon source based on inverse Compton scattering of laser beams.     

Influence of bearing damping on instability of asymmetric shafts, part IV: Effects of fluid-film bearings

The influence of fluid-film bearings on the parametric instability of asymmetric shafts is investigated. Since fluid-film bearings may have non-isotropic stiffness and damping, the system equations are time-varying coefficients in a rotating reference frame and the complete solution of transition curves includes coupled modes. Thus, the analytical modal method provided by our previous studies has been modified in this part for the determination of approximate solutions from a truncated Hill's determinant. In numerical examples, a plain cylindrical type and a tilting four-pad type are considered to estimate the effects of bearing parameters concerning static load, oil viscosity, and clearance on unstable regions.     

Field and numerical analysis of in-situ air sparging: a case study

An in-situ air sparging operation was used to remediate the sandy subsurface soils and shallow groundwater under a drum storage site near Chicago, IL, where either periodic or random spillage of a light non-aqueous phase liquid (LNAPL) occurred between 1980 and 1987. Both field measurements and model simulations using commercially available computer software suggested that microbial degradation was the most significant contributor to the removal of contaminant mass. Toluene, ethylbenzene and total xylenes (TEX), which were of major concern with regards to reaching clean-up criteria at the site, were observed to decline by 88% in concentration. Furthermore, up to 97% of the total mass removed through microbial degradation consisted of TEX. Of the total contaminant spill, up to 23% of initial organic chemical mass was removed through microbial degradation compared to less than 6% by physical stripping. Greater loss to microbial degradation is most likely attributed to the relatively low air injection rate used during the course of the air sparging remediation. Evaluation of air sparging at the site using model simulations supported this analysis by estimating 140 and 620 kg of total contaminant mass being removed through volatilization and biodegradation, respectively. An evaluation of several system design parameters using model simulations suggested that only the type of sparging operation (i.e. pulsed or continuous) was significant in terms of total contaminant removal time, while both the sparging operation and air injection rate were significant in terms of removal of a critical species, total xylenes.     

Bioinformatics of Differentially Expressed Genes in Phorbol 12-Myristate 13-Acetate-Induced Megakaryocytic Differentiation of K562 Cells by Microarray Analysis

Megakaryocytes are large hematopoietic cells present in the bone marrow cavity, comprising less than 0.1% of all bone marrow cells. Despite their small number, megakaryocytes play important roles in blood coagulation, inflammatory responses, and platelet production. However, little is known about changes in gene expression during megakaryocyte maturation. Here we identified the genes whose expression was changed during K562 leukemia cell differentiation into megakaryocytes using an Affymetrix GeneChip microarray to determine the multifunctionality of megakaryocytes. K562 cells were differentiated into mature megakaryocytes by treatment for 7 days with phorbol 12-myristate 13-acetate, and a microarray was performed using RNA obtained from both types of cells. The expression of 44,629 genes was compared between K562 cells and mature megakaryocytes, and 954 differentially expressed genes (DEGs) were selected based on a p-value < 0.05 and a fold change >2. The DEGs was further functionally classified using five major megakaryocyte function-associated clusters—inflammatory response, angiogenesis, cell migration, extracellular matrix, and secretion. Furthermore, interaction analysis based on the STRING database was used to generate interactions between the proteins translated from the DEGs. This study provides information on the bioinformatics of the DEGs in mature megakaryocytes after K562 cell differentiation.     

Shock Initiation of PBX-9404 by electrically driven flyer plates

The shock initiation threshold of PBX-9404 has been studied over the pressure range 3.1 GPa-28 GPa with pulse lengths ranging from 0.007 μs-0.63 μs. The short-duration, high pressure pulses were produced by the impact of thin plastic flyer plates accelerated by electrically exploded metal foils. We performed the experiments on explosive pellets 25.4 mm in diameter with thicknesses of 6.0 mm, 10.1 mm and 19.1 mm. No dependence of the initiation threshold on pellet thickness was observed. The data are represented reasonably well by either the critical initiation energy or by the constant P²τ initiation criteria.     

Effect of surface structure on biomechanical properties and osseointegration

The purpose of this study is to improve the bone-bonding ability between titanium implants and living bone through the control of geometric design and chemical compositions of an implant surface. We compared the tissue healing response and resulting implant stability for three surface designs by characterizing the histological and mechanical properties of the healing tissue around smooth-surfaced Ti–6Al–4V (SS), CP-Ti plasma-spray-coated (PSC), alkali- and heat-treated (AHT) implants. The implants were transversely inserted into a dog thighbone and evaluated at 4, 8, and 12 weeks. Histological examination indicated that initial matrix mineralization leading to osseointegration occurred more rapidly with the AHT implant. During the 4, 8, and 12 week healing periods, new bone on the surface of AHT implant showed denser growth than that on the SS and PSC implants. The more extensive tissue integration and more rapid matrix mineralization with the AHT implant were reflected in the mechanical test data, which demonstrated superior attachment strength and interfacial stiffness for the AHT implant after healing for 4, 8 and 12 weeks of healing because of the mechanical interlocking in the micrometer sized rough surface and the large bonding area between bone and implant caused by the nanosized porous surface structure. Histological and mechanical data demonstrate that with the appropriate surface design selection, bone bone-bonding ability can be improved and can induce acceleration of the healing response, thereby improving the potential for implant osseointegration.     

Amyloid Formation in Nanoliter Droplets

Processes that monitor the nucleation of amyloids and characterize the formation of amyloid fibrils are vital to medicine and pharmacology. In this study, we observe the nucleation and formation of lysozyme amyloid fibrils using a facile microfluidic system to generate nanoliter droplets that can control the flow rate and movement of monomer-in-oil emulsion droplets in a T-junction microchannel. Using a fluorescence assay, we monitor the nucleation and growth process of amyloids based on the volume of droplets. Using the microfluidic system, we demonstrate that the lag phase, which is vital to amyloid nucleation and growth, is reduced at a lower droplet volume. Furthermore, we report a peculiar phenomenon of high amyloid formation at the edge of a bullet-shaped droplet, which is likely due to the high local monomer concentration. Moreover, we discovered that amyloid fibrils synthesized in the nanoliter droplets are shorter and thicker than fibrils synthesized from a bulk solution via the conventional heating method. Herein, a facile procedure to observe and characterize the nucleation and growth of amyloid fibrils using nanoliter droplets is presented, which is beneficial for investigating new features of amyloid fibril formation as an unconventional synthetic method for amyloid fibrils.