Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.     

An adaptive image steganographic scheme based on Noise Visibility Function and an optimal chaotic based encryption method

Steganography is the science of hiding secret message in an appropriate digital multimedia in such a way that the existence of the embedded message should be invisible to anyone apart from the sender or the intended recipient. This paper presents an irreversible scheme for hiding a secret image in the cover image that is able to improve both the visual quality and the security of the stego-image while still providing a large embedding capacity. This is achieved by a hybrid steganography scheme incorporates Noise Visibility Function (NVF) and an optimal chaotic based encryption scheme. In the embedding process, first to reduce the image distortion and to increase the embedding capacity, the payload of each region of the cover image is determined dynamically according to NVF. NVF analyzes the local image properties to identify the complex areas where more secret bits should be embedded. This ensures to maintain a high visual quality of the stego-image as well as a large embedding capacity. Second, the security of the secret image is brought about by an optimal chaotic based encryption scheme to transform the secret image into an encrypted image. Third, the optimal chaotic based encryption scheme is achieved by using a hybrid optimization of Particle Swarm Optimization (PSO) and Genetic Algorithm (GA) which is allowing us to find an optimal secret key. The optimal secret key is able to encrypt the secret image so as the rate of changes after embedding process be decreased which results in increasing the quality of the stego-image. In the extracting process, the secret image can be extracted from the stego-image losslessly without referring to the original cover image. The experimental results confirm that the proposed scheme not only has the ability to achieve a good trade-off between the payload and the stego-image quality, but also can resist against the statistics and image processing attacks.     

Genetic algorithm and self organizing map based fuzzy hybrid intelligent method for color image segmentation

The grouping of pixels based on some similarity criteria is called image segmentation. In this paper the problem of color image segmentation is considered as a clustering problem and a fixed length genetic algorithm (GA) is used to handle it. The effectiveness of GA depends on the objective function (fitness function) and the initialization of the population. A new objective function is proposed to evaluate the quality of the segmentation and the fitness of a chromosome. In fixed length genetic algorithm the chromosomes have same length, which is normally set by the user. Here, a self organizing map (SOM) is used to determine the number of segments in order to set the length of a chromosome automatically. An opposition based strategy is adopted for the initialization of the population in order to diversify the search process. In some cases the proposed method makes the small regions of an image as separate segments, which leads to noisy segmentation. A simple ad hoc mechanism is devised to refine the noisy segmentation. The qualitative and quantitative results show that the proposed method performs better than the state-of-the-art methods.     

Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells

In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism’s ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells.     

Enhanced photoreactivity of MOFs by intercalating interlayer bands via simultaneous ?NCO and ?SCu modification

Herein, we propose a novel method to enhance the photoreactivity of an MOF catalyst by grafting isocyanate bonds ( NCO) and sulfhydryl-complexed copper ( SCu) onto ZIF-8 (NIF-SCu). The grafting process intercalated interlayer bands between the conduction and valence bands of ZIF-8, thereby providing a “ladder” for facile electron transition. The extreme improvement in the photoreactivity of NIF-SCu could be attributed to the enhancement in light responses in the range of 350–450 nm by  NCO groups and the widening of the visible light range of the MOF by  SCu groups. The formation of staggered energy levels in NIF-SCu could also narrow the band gap, lower the resistance, and facilitate the transfer of photogenerated carriers, thereby generating electrons with strong reduction potential in the  SCu conduction band. This study provides a new strategy for improving or even endowing the photoactivity of environmental functional materials with wide bandgaps.     

基于局部分型面的电器外壳注塑模具设计

电器外壳制品形状结构复杂,有两处侧凸(孔)较难处理。通过对矩形孔内侧凸的结构分析,在其局部设计了分型面,避免了使用侧向抽芯机构;对侧孔部位设计了斜顶杆侧向抽芯机构,其结构简单、紧凑。模具采用一模二腔、平衡式布局,采用经扁推杆由制品内部进料的潜伏式浇口,S型流道。在NX 8.0中完成了模具结构设计。经实践证明,该模具结构合理,产品合格。     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Compiler compatible 5.66 Mb/mm2 8T 1R1W register file in 14 nm FinFET technology

1-read/1-write (1R1W) register file (RF) is a popular memory configuration in modern feature rich SoCs requiring significant amount of embedded memory. A memory compiler is constructed using the 8T RF bitcell spanning a range of instances from 32 b to 72 Kb. An 8T low-leakage bitcell of 0.106 μm² is used in a 14 nm FinFET technology with a 70 nm contacted gate pitch for high-density (HD) two-port (TP) RF memory compiler which achieves 5.66 Mb/mm² array density for a 72 Kb array which is the highest reported density in 14 nm FinFET technology. The density improvement is achieved by using techniques such as leaf-cell optimization (eliminating transistors), better architectural planning, top level connectivity through leaf-cell abutment and minimizing the number of unique leaf-cells. These techniques are fully compatible with memory compiler usage over the required span. Leakage power is minimized by using power-switches without degrading the density mentioned above. Self-induced supply voltage collapse technique is applied for write and a four stack static keeper is used for read Vmin improvement. Fabricated test chips using 14 nm process have demonstrated 2.33 GHz performance at 1.1 V/25 °C operation. Overall V_min of 550 mV is achieved with this design at 25 °C. The inbuilt power-switch improves leakage power by 12x in simulation. Approximately 8% die area of a leading 14 nm SoC in commercialization is occupied by these compiled RF instances.     

Vapor absorption by LiBr aqueous solution in vertical smooth tubes

Heat and mass transfer in a falling film vertical in-tube absorber was studied experimentally with LiBr aqueous solution. The presented results include the effect of solution flow rate, solution subcooling and cooling water temperature on the absorption in a smooth copper tube 16.05 mm I.D. and 400 mm long. The experimental data in the previous report for a 1200-mm-long tube was also re-examined and compared. It was demonstrated by the observation of the flow in the tube that the break down of the liquid film into rivulets leads to deterioration of heat and mass transfer at lower film Reynolds number or in longer tubes. An attempt to evaluate physically acceptable heat and mass transfer coefficients that are defined with estimated temperature and concentration at the vapor–liquid interface was also presented.