Endoglin Targeting: Lessons Learned and Questions That Remain

Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab^®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.     

综采工作面设备安装开切眼的支护设计及现场监测

针对开切眼跨度大造成工作面受到地质灾害的问题,以8702工作面为例,在研究其地质、顶底板情况的基础上,提出开切眼支护的原则,并结合现场情况完成锚杆+锚索+金属网的联合支护参数的设计,最后设计监测方案,对开切眼支护方案的有效性进行验证.实践表明,所采用的的支护方式应用效果良好.     

A Potent,Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K_d of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.     

Prediction models for multiphase-flow-induced corrosion of API X80 steel in CO2/H2S environment

In the offshore oil and gas industry, mainly focusing on the use of rigid or flexible pipes of subsea infrastructure applied to risers or flowlines, one of the greatest difficulties is the interpretation of the combined effects of the various correlated phenomena (hydrodynamic effects of intermittent flow, the effects of corrosivity of the environment in addition to variations in pressure, temperature, and dynamic loading). On the basis of this scenario, defining the degree of severity of each of the correlated system variables becomes of fundamental importance for establishing reliable criteria for selecting materials for subsea application. The established flow pattern directly affects the corrosion rate (or the pipe material mass loss), but the balance of other variables including possible changes in the physical and transported fluid chemical properties may increase the damage up to an order of magnitude, which is a piece of information normally not foreseen in design criteria. Therefore, to improve the understanding of the corrosion study influenced by multiphase flow, a testing loop was designed and assembled at the Corrosion and Protection Laboratory of the Institute for Technological Research, in which API X80 steel coupons were positioned in locations with a 0° and 45° inclinations. Tests were conducted by varying the partial pressure of the gaseous phase containing blends of CO₂ and H₂S with N₂ balance, mixed with the liquid phase containing light oil and heavy oil in water with salinity (NaCl)-simulating oil well conditions with 80% water cut. The main objective of this study is to establish models that can predict the corrosion intensity in conditions close to those obtained experimentally. To achieve results, the multiple regression and Box–Cox transformation methods were applied. These models will make possible damage prediction and optimization of matrix parameters for the multiphase-loop test.     

Studies on waterline corrosion processes and corrosion product characteristics of carbon steel in 3.5 wt% NaCl solution

The waterline corrosion behaviors of carbon steel partially immersed in a 3.5 wt% NaCl solution were investigated using the wire beam electrode technique, and the effects of corrosion products on the processes of waterline corrosion were analyzed. The results demonstrated that the initial stage and development stage of waterline corrosion were mainly controlled by the concentration and diffusion of dissolved oxygen, respectively, and the deceleration stage of waterline corrosion was mainly affected by corrosion products. The main component of the yellow corrosion products was γ-FeOOH, and γ-FeOOH that exhibited a high reduction reactivity could be involved in the cathodic reaction. The black corrosion products were mainly composed of Fe₃O₄ with strong thermodynamic stability and the processes of dissolved oxygen diffusion and ion transports were obviously affected due to the continuous accumulation of Fe₃O₄ on the surface of the electrodes. Polarity reversals were observed on the single electrodes below the waterline, but the reasons for the phenomena were different from each other.     

Evaluation of atmospheric galvanic aluminum corrosion in electrical transmission towers at different sites in the Valparaíso region,Chile. Wire-on-Bolt Test (CLIMAT)

This study evaluates environmental aggressiveness and atmospheric galvanic corrosivity categories in Chile (Classification of Industrial and Marine ATmospheres test) by installing bolts in electrical transmission towers in the Valparaiso region across four exposure sites: Playa Ancha, San Sebastián, Las Vegas, and San Felipe. Classifications of marine corrosion index (MCI), industrial corrosion index (ICI), and atmospheric corrosion index (ACI) used different galvanic couples: aluminum/steel for MCI, aluminum/copper for ICI, and aluminum/polyethylene for ACI. Corrosion indices varied by season (summer, autumn, winter, and spring), for which couples were exchanged every 3 months. Intraseason variation depended mainly on the meteorochemical variables of the zone, the Cl⁻/SO₂ ratio, and the presence of general and pitting corrosion in the aluminum. The results indicate that, regardless of environmental condition, the aluminum in Al/steel (MCI) and Al/copper (ICI) couples presented a higher corrosion rate than when not forming a galvanic couple (ACI). Moreover, under higher environmental chloride, these differences increase. The Playa Ancha station presented the highest ACI.     

Micromembrane absorber with deep-permeation nanostructure assembled by flowing synthesis

A micromembrane adsorber with deep-permeation nanostructure (DPNS) has been successfully fabricated by flowing synthesis. The nanoparticles are in-situ assembled in membrane pores and immobilized in each membrane pore along the direction of membrane thickness. The nanoparticles with a lower size and thinner size distribution can be achieved owing to the confined space effect of the membrane pores. As a concept-of-proof, the nano ZIF-8 and ZIF-67 are fabricated in porous membrane pores for methyl orange (MO) and rhodamine B (RhB) adsorption. The adsorption rate is increased significantly owing to the enhanced contact and mass transfer in the confined space. The adsorption capacity for the RhB is also increased, since the size of the nanoparticles assembled in membrane pores is smaller with more active sites exposed. This micromembrane adsorber with DPNS has good reusability and can provide a promising prospect for industrial application.     

Precise quantification of the antibacterial activity of chitosan by NB medium neutralizer

In the present research,nutrient broth(NB)medium was identified to be able to neutralize the antibac-terial activity of chitosan and its derivatives.Therefore,an improved test method independent of NB medium was proposed to precisely quantify the antibacterial effectiveness and efficiency of chitosan.The minimum bactericidal concentration(MBC)of chitosan was 60 μg mL-1 against S.aureus and E.coli,and 0.01％(w/v)chitosan could kill 100％of bacteria within 3 min.From another point of view,the neutralizing efficiency of NB could be tripled by adding 25 g L-1 of sodium chloride.Then the neutraliz-ing mechanism of NB medium was ascribed to flocculation between chitosan and protein.Adding extra sodium chloride could significantly reduce the size of floccules,and smaller floccules would lose the ability of binding with bacteria directly,showing higher neutralizing rate on the macro scale.     

氧化铝纤维束织造过程中摩擦磨损性能研究

运用往复线性摩擦试验方法,搭配自制的摩擦试验夹具,模拟织造过程中氧化铝纤维束-筘齿的摩擦行为,研究加载力、预加张力和摩擦频率对悬空状态下氧化铝纤维束摩擦磨损性能的影响.结果表明:随着加载力的增加,氧化铝纤维束所受摩擦力及长丝断裂根数增加,摩擦系数减小;在预加张力为0.40 N时,氧化铝纤维束所受摩擦力和摩擦系数出现最小值,磨损程度也最小;在摩擦稳定阶段,摩擦频率增加,则氧化铝纤维束所受摩擦力先下降,后略有上升,当摩擦频率增加至5 Hz时,氧化铝纤维束的摩擦系数较1 Hz时增加18.7％,磨损程度也最为严重.     

Adsorption of anionic dye on eco-friendly synthesised reduced graphene oxide anchored with lanthanum aluminate: Isotherms,kinetics and statistical error analysis

In the present study we made an effort to deploy eco-friendly synthesized reduced graphene oxide/Lanthanum Alluminate nanocomposites (RGO-LaAlO₃) and Lanthanum Alluminate (LaAlO₃) as adsorbents to remove dye from the synthetic media. XRD, SEM, BET surface area and EDX have been used to characterize the above-mentioned adsorbents. The impacts of different factors like adsorbent dosage, the concentration of adsorbate and PH on adsorption were studied. The best fit linear and nonlinear equations for the adsorption isotherms and kinetic models had been examined. The sum of the normalized errors and the coefficient of determination were used to determine the best fit model. The experimental data were more aptly fitted for nonlinear forms of isotherms and kinetic equations. Pseudo-second-order and Freundlich isotherm model fits the equilibrium data satisfactorily. Methyl orange (MO) has been used as model dye pollutant and maximum adsorption capacity was found to be 469.7 and 702.2 mg g^?1 for LaAlO₃ and RGO-LaAlO₃, respectively.