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Thermal boundary conductance of copolymer of polyurethane and thioctic acid with aluminum (Al) interface shows a remarkable increase 2–5 times than that of traditional polymers/Al interfaces owing to the highly matched and bonded interface.

Supplementary Table S5. Mutation summary in patients.

Purpose: The role and clinical implication of the transmembrane protein with EGF and two follistatin motifs 2 (TMEFF2) in gastric cancer is poorly understood.Experimental Design: Gene expression profile analyses were performed and Gene Set Enrichment Analysis (GSEA) was used to explore its gene signatures. AGS and MKN45 cells were transfected with TMEFF2 or control plasmids and analyzed for gene expression patterns, proliferation, and apoptosis. TMEFF2 expression was knocked down with shRNAs, and the effects on genome stability were assessed. Interactions between TMEFF2 and SHP-1 were determined by mass spectrometry and immunoprecipitation assays.Results: Integrated analysis revealed that TMEFF2 expression was significantly decreased in gastric cancer cases and its expression was negatively correlated with the poor pathologic stage, large tumor size, and poor prognosis. GSEA in The Cancer Genome Atlas (TCGA) and Jilin datasets revealed that cell proliferation, apoptosis, and DNA damage–related genes were enriched in TMEFF2 lower expression patients. Gain of TMEFF2 function decreased cell proliferation by increasing of apoptosis and blocking of cell cycle in gastric cancer cells. The protein tyrosine phosphatase SHP-1 was identified as a binding partner of TMEEF2 and mediator of TMEFF2 function. TMEFF2 expression positively correlated with SHP-1, and a favorable prognosis was more likely in patients with gastric cancer with higher levels of both TMEFF2 and SHP-1.Conclusion: TMEFF2 acts as a tumor suppressor in gastric cancer through direct interaction with SHP-1 and can be a potential biomarker of carcinogenesis. Clin Cancer Res; 20(17); 4689–704. ©2014 AACR.

Supplementary Figure S1. Identification of TMEFF2 as a key regulator in gastric cancer progression and the expression of TMEFF2 decreased in gastric carcinogenesis. Supplementary Figure S2. Gene Set Enrichment Analysis (GSEA) in TMEFF2-higher/lower expression patients. Supplementary Figure S3. The mRNA levels of the top-score tumorigenesis genes were measured in gastric cells after transfection of TMEFF2 overexpression plasmid or siRNA Supplementary Figure S4. Functional impact of TMEFF2 Supplementary Figure S5. Cell proliferation assays were performed in MKN45 cells after overexpression of SHP-1WT/ΔSH2D1/ΔSH2D2/ΔPTPD or these constructs combined with TMEFF2. n = 3, non-parametric Mann-Whitney test. Supplementary Figure S6. Correlation of TMEFF2 and SHP-1 expression in human GC.

Covalent adaptable networks incorporating supramolecular interactions are constructed to produce poly(thioctic acid)/aluminum (poly(TA)/Al) self-healing and stretchable composite elastomers for thermal management of advanced electronic devices.

Direct alkynylation of tryptamines with functionalized alkynyl sulfones to afford C3-alkynyl pyrroloindolines via a visible-light-induced intramolecular 5-endo-trig radical cyclization/intermolecular radical addition/elimination process.

With the rapid development of advanced microelectronic equipment, thermal interface materials with high thermal conductivity and excellent mechanical properties have become an urgent need.

A sequentially responsive nanocarrier was fabricated with three-in-one functional integration: bio-imaging, tumor microenvironment responsive chemotherapy and cascade activation of upconversion photodynamic therapy. The designed DNA outer nanoshell displayed site-specific degradation and controlled degradation speed. Significantly, the developed controllable nanotheranostic agent displayed high cell apoptosis ratios and obvious tumor inhibition.

Most elastomers suffer from poor thermal conductivity, which limits their further applications in various fields, especially for electronic devices. A common method to enhance thermal conductivity is to introduce thermally conductive fillers into elastomers. Unfortunately, thermal conductivity and compliance are often correlated and coupled: large amounts of fillers are required to increase thermal conductivity while damaging the compliance dramatically. In this study, we report thermally conductive and compliant polyurethane elastomer composites by constructing a tri-branched polymer network. The resultant polyurethane elastomer composites exhibit excellent superhigh stretchability (2000%), low Young's modulus (640 kPa), and low thermal resistance (0.11 K cm

Acoustic-based imaging techniques, including ultrasonography and photoacoustic imaging, are powerful noninvasive approaches for tumor imaging owing to sound transmission facilitation, deep tissue penetration, and high spatiotemporal resolution. Usually, imaging modes were classified into "always-on" mode and "activatable" mode. Conventional "always-on" acoustic-based probes often have difficulty distinguishing lesion regions of interest from surrounding healthy tissues due to poor target-to-background signal ratios. As compared, activatable probes have attracted attention with improved sensitivity, which can boost or amplify imaging signals only in response to specific biomolecular recognition or interactions. The tumor microenvironment (TME) exhibits abnormal physiological conditions that can be used to identify tumor sections from normal tissues. Various types of organic dyes and biomaterials can react with TME, leading to obvious changes in their optical properties. The TME also affects the self-assembly or aggregation state of nanoparticles, which can be used to design activatable imaging probes. Moreover, acoustic-based imaging probes and therapeutic agents can be coencapsulated into one nanocarrier to develop nanotheranostic probes, achieving tumor imaging and cooperative therapy. Satisfactorily, ultrasound waves not only accelerate the release of encapsulated therapeutic agents but also activate therapeutic agents to exert or enhance their therapeutic performance. Meanwhile, various photoacoustic probes can convert photon energy into heat under irradiation, achieving photoacoustic imaging and cooperative photothermal therapy. In this review, we focus on the recently developed TME-triggered ultrasound and photoacoustic theranostic probes for precise tumor imaging and targeted tumor therapy.

Ultralight graphene/phenolic resin composite aerogels (GPFs) were prepared through the chemical reduction and self-assembly of graphene oxide (GO) in water-soluble phenolic resin, followed by a freeze-drying process; carbonized foams (GPFs(T)) were obtained by the subsequent heat treatment of GPFs at a relatively low temperature (500–700 °C). Although GPFs do not show the qualified reflection loss value of below −10dB, GPFs(T) achieve the greatly enhanced electromagnetic-wave absorbing performance. Specifically, the minimum reflection loss value of GPF1 (500) reaches −22.7 dB at 14.4 GHz with the absorber thickness of 2.0 mm and the effective absorption bandwidth is up to 5.4 GHz (12.4–17.8 GHz). The evolution of electromagnetic-wave absorbing properties from GPFs to GPFs(T) at different temperatures related with different graphene content is explored. GPFs(T) are expected to exhibit high thermal stability and excellent corrosion resistance property, and especially still maintain ultralight nature (e.g the density of GPF1 (500) is only 24.3 mg/cm3). Most importantly, little graphene (as low as 7.5 wt% of GO addition for GPF1(T)) in GPFs(T) guarantees the facile formation of three-dimension (3D) skeleton network and greatly cut downs the carbonization temperature of phenolic resin to achieve the required electromagnetic-wave energy losing ability. The present work provides an effective method to fabricate an ultralight material with exceptional performances including the good electromagnetic-wave absorbing property and the high stability.

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.

Particle-laden composites are typical thermal interfacial materials (TIMs) in the electronic applications, which are widely used in the electron packaging fields. The effective thermal conductivity (effective TC) of the particle-laden composites is dominant by the particle-matrix and particle-particle interfacial thermal resistance (ITR). The reliable identification of ITR is essential for the accurate prediction of TC of the composites, which has potential in the design of TIMs. In this work, we propose an efficient strategy to identify the interfacial thermal resistance in the particle-laden composites combining the numerical simulation, high-throughput computation, machine learning algorithm and simple experimental measurement. Firstly, the high-throughput computation is conducted based on the numerical modeling of the standard samples, in which the input parameters are ITRs in the composites. Afterwards, a prototypical function-based machine learning strategy is employed on the database to describe the numerical relation between the effective TC and the input parameters. Finally, comparing the numerical predictions from the machine learning model with the experimental measurement of the effective TC, a high-throughput screening of the ITRs is executed for the identification of their values. The reliability of the strategy is validated by an example of Al2O3-AlN/silicone composites, showing that the particle-particle ITR is higher than particle-matrix ITR.

Soft elastomers have attracted wide applications, such as soft electronic devices and soft robotics, due to their ability to undergo large deformation with a small external force. Most elastomers suffer from poor toughness and thermal conductivity, which limits their use. The addition of inorganic fillers can enhance the thermal conductivity and toughness, but it deteriorates the softness (low Young's modulus and high stretchability). Integrating thermal conductivity, toughness, and softness into one elastomer is still a challenge. Here, we report a strategy of interfacial coordination interaction to achieve soft elastomer composites with high thermal conductivity and high toughness. We demonstrate the strategy by using poly(lipoic acid) elastomer and silver-coated aluminum filler as model, where silver-sulfur coordination cross-links are formed at the interface. The resultant elastomer composite shows high streachability (450%), high thermal conductivity (2.35 W m

The heat conduction of thermal interface materials (TIMs) is derived from the transport of electrons and phonons in the materials. Investigation on the thermal transport of electrons and phonons in TIMs will aid in promoting the advancement of TIMs with high performance. In this review, we summarize the current strategies for regulating the thermal transport of electrons and phonons during the preparation of TIMs. The interplay between the polymer matrix and fillers and the thermally conductive network formed by fillers is discussed. In addition, we present some new thermal measurement techniques to measure the interfacial thermal resistance. The reduction of interfacial thermal resistance is helpful for obtaining TIMs with larger thermal conductivity. Finally, we provide possible future research directions for the material design and measurement of interfacial thermal resistance.

Indolocarbazole alkaloids and their derivatives were discovered to have potent protein kinase and topoisomerase I inhibitory activities. Disclosed herein is the photochemical synthesis of the indolocarbazole ring system from

Thermal interface materials (TIMs) used between the chip and the heat spreader play an indispensable role in effective heat removal to ensure the chip's performance and reliability. As they suffer from stresses in practical applications, TIMs need to have high toughness to resist fracture. The notch sensitivity of TIMs is considered an important parameter to evaluate its toughness. However, the notch sensitivity of TIMs is seldom mentioned, and the mechanism to enhance the toughness is still unclear. Here, using polymer-based TIMs consisting of polydimethylsiloxane/aluminum as a model, we specifically investigate notch sensitivity of TIMs and analyze the mechanical mechanism in detail from the macroscopic and microscopic scales. It was found that a transition from notch insensitive to notch sensitive will happen with a notch length of 2.0 mm, which is much higher than typical soft materials, such as hydrogels. We interpret the notch sensitivity of the TIM by finite element analysis at macroscopic scales and the Lake–Thomas theory at microcosmic scales. The relationship between the area of the strain concentration region to the notch length in finite element analysis is in good agreement with the fracture stretch ratio with different notch lengths measured in a uniaxial tensile experiment. This investigation gives an insight into designing notch-insensitivity TIM and understanding their fracture behavior.

Introduction: Esophageal stenosis after chemotherapy in breast cancer patients is rare. It is important to distinguish esophageal stenosis from esophageal metastasis caused by breast cancer.Case presentation: We present the case of a 62-year-old woman who was diagnosed with breast cancer 4 months prior, had dysphagia and was referred to our department for further treatment after 2 cycles of chemotherapy. She suffered from severe mouth ulcers, painful swallowing and large areas of skin pigmentation with overlying scaliness after every chemotherapy session. Endoscopy revealed that the lumen of the lower esophagus was obviously narrow with ulceration above the stenosis. Histological results demonstrated inflammatory fibrinous necrosis and granulation tissue, with no clear neoplastic component. Conclusion: Short-term esophageal stenosis after chemotherapy may be caused by local mucosal injury, but malignant tumors need to be excluded.

The challenge of the heat dissipation of electronic packaging comes from the continuous increase in power consumption and power density of high-power devices. The demand for the use of thermal interface materials (TIMs) with excellent thermal conductivity between the surface of the heat source and the heat dissipation module is thus increasing. In addition to thermal performance, TIMs are also required to have good reliability and thermal degradation. In this paper, the reliability were evaluated for three types of TIM, including high-temperature storage (HTS), Highly accelerated temperature and humidity stress test (HAST) and high and low temperature cycling (HLTC). The trend of thermal resistance change and thermal degradation under various reliability test conditions were analyzed. The results show that after HAST and high and low temperature cycle evaluation, the sample can maintain the original characteristics. However, the thermal degradation of TIMs is more serious after high-temperature storage test. Therefore TIMs are more sensitive to long-term exposure to high temperature environments.

As the filler between the flip chip and lid, thermal interface material (TIM1) plays a role in heat dissipation to maintain the good performance of chips, lower power during operation. However, as the performance of the device itself continues to improve, in order to maintain reliability, the design demands for packaging materials such as TIM1 are increasing accordingly. Through the observation and analysis of TIM1 after working for a long time, the failure of the material is often due to the separation between the TIM1 and the chip or lid, which indicates that the interface interaction of the designed TIM1, that is, the adhesion is weak. Such problems can lead to a huge thermal resistance so that the thermal performance of TIM1 will be affected. In addition to the thermal resistance resulted from material failure, the contact thermal resistance of TIMl also can defeat its ability of thermal transport. Herein, the adhesion and contact thermal resistance of TIM1 are studied. In order to learn the term of contact thermal resistance, two types thermal testing method, laser flash and photo-thermal radiation are proposed. The research result shows that the adhesion has negative correlation with contact thermal resistance, two proposed method can work for the contact thermal resistance measurement. A method is probably to be used to improve the quality of TIM1 that is introducing adhesion promoter into it to enhance the adhesion at interface and defeat contact thermal resistance simultaneously.

With the continuous and rapid development of microelectronics technology, the power consumption of microelectronic device increased with the improvement of performance. The increasing power consumption may cause thermal-induced failures and greatly affect the reliability of the device. To avoid this problem, heat sinks and thermal interface materials (TIMs) are used for effective thermal management. The TIM1 is used inside the device between the chip and the metal lid to eliminate the interstitial air gaps from the interface by conforming to the topography of the surfaces in contact. However, in practical application, TIM1might be affected by thermal-induced deformation, resulting in the change of bond line thickness (BLT), loss of corner areas, and increase of interface thermal resistance, which may have a significant impact on the heat dissipation in return. In this paper, the effect of TIM1 on the junction temperature of chip in a flip-chip structure with heat sink and fan are systematically investigated using computational fluid dynamics (CFD) method. The temperature profile is obtained and the heat transfer in the out-of-plane and in-plane directions are analyzed. The effect of reduced in TIM1 coverage, warpage-induced change in bond-line-thickness (BLT) and contact resistance are discussed in detail.

Thermal interface material (TIM) has attracted numerous attentions to provide excellent performance and reliability of chip. To achieve outstanding thermal conductivity, high loading thermally conductive fillers have to be added in TIM, which weak the material's processability and mechanical properties. In this work, we fabricated a novel aluminum/zinc oxide/silicone composite. We studied the viscosity, mechanical and thermal properties of TIM with different filler content, and tried to discuss the relationship between them. When the content is 70%, the tensile properties of the material is up to the maximum value 420%. This work reveals the relationship between thermally conductive fillers and the macro-mechanical properties, and provides theoretical guidance for the preparation and application of high-performance TIM.

The booming growth of flexible and stretchable electronic devices with increasing power density calls for novel highly efficient thermal interface materials (TIMs) with versatile functions, such as high deformability and excellent resilience. Soft polymer composites such as silicone gap pad are expected to reduce the contact resistance and thermal impedance, but the huge mismatch of the thermal expansion coefficient between the heat sink and the microelectronic chip and stretching behavior make them under stress, especially in the way of tensile stress in stretchable electronic devices. So far, few researchers have reported study about the effect of tensile behavior on the properties of TIMs. In this work, DMA (dynamic mechanical analysis) was used to characterize the resilience, creep and stress relaxation characteristics of silicones gap padsIt was found that as the strain increases, the rebound ratio increases at the first and then decreases, reaching the maximum at 20% of its maximum stretching length. When the term of time is considered, the plasticity of the tensile behavior is not linearly related to time but decelerates as time increases. In five cycles of loading-unloading, the increase in stretch length can enhance the degree of plastic deformation significantly, while the stretch rate has no correspond with it. This research can provide important guidance for the application of TIMs in stretchable electronic devices industry.

The thermal interface material (TIM) located above the chip in a package is a key factor in determining the heat dissipation of a chip. The deformation or warpage of the package significantly affect the performance of the TIM, which induces stress that causes failures such as cracking and interface delamination. Therefore, a detailed analysis of the stress state of the TIM in the package is essential for the thermal management of the chip. Most polymer materials used in package are viscoelastic, showing obvious correlation with temperature and time. However, in most finite element analysis (FEA) the polymer materials are usually treated as linear elastic, which may lead to the deviation of simulation from the actual situation. In this paper, we use inverse analysis method to obtain the viscoelastic constitutive parameters of TIM based on the Prony series derived from the experimental stress relaxation test. The viscoelastic constitutive of the TIM is applied to FEA for studying the cooling process in a flip-chip package. We find that the viscoelastic TIM may absorb more stress than the elastic material does, leading to less deformation from the bottom side of package transferring to the upper lid due to stress relaxation. In addition, the stress and strain distribution in the plane of viscoelastic TIM also shows characteristics different from that derived using linear properties. This work will help to improve the understanding of the actual mechanical behavior of TIM during the deformation of a package.

As an important class of thermal management material, thermal gel is widely used to fille the gaps between heat generating devices and the heat sink. The performance of thermal gel varies when withstanding high environment temperature. Real-time monitoring the intrinsic thermal conductivity ${(k)}$ of thermal gels, and the variation of interfacial thermal resistance ${(R}_{i})$ at the thermal gel/substrate interface during the aging process is urgently-needed for exploring the anti-aging mechanism and further improve the overall transfer performance. In this study, laser flash method was applied as to characterize the thermal performance. We experimentally demonstrate that there exists strong dependence of $\boldsymbol{k}$ -thickness in single-layered test and thus introducing great data error. Double-layered test could largely weaken the $\boldsymbol{k}$ -thickness dependence of thin thermal gel layer and provide the detailed $\boldsymbol{R}$ i value for conference simultaneously. The results illustrate that the double layers-based laser flash method could be a crucial tool to real-time characterize $\boldsymbol{k}$ and $\boldsymbol{R}$ i of thermal gel-metal system during the aging process.