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• Band alignments of the various oxides that create oxide dipole layers to set gate voltages in CMOS transistors. A density functional analysis of oxide dipole layers used to set the threshold voltages in high-K/metal CMOS gate stacks is given in terms of the band alignments and chemical trends of these component oxide layers. The oxides SrO, La 2 O 3 , HfO 2 and Al 2 O 3 are found to have similar band gaps and form a 'staircase' of band alignments, allowing them to shift the metal electrode Fermi level in both n-type and p-type directions. This analysis supersedes previous largely empirical models based on metal oxide ion densities or electronegativity scales. [ABSTRACT FROM AUTHOR]

Objective: There is considerable evidence for relationship between gut microbiota and osteoarthritis (OA), but no studies have investigated their causal relationship.Method: This study utilized large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and OA risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for OA. Comprehensively sensitive analyses were performed to validate the robustness of results and novel multivariable MR analyses were further conducted to ensure the independence of causal association. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. Finally, enrichment analyses were used to investigate the biofunction.Results: After correction, three microbial taxa were identified to be causally associated with diverse joint OA (PFDR < 0.100), namely Methanobacteriaceae family for knee OA (PFDR = 0.043) and any OA (PFDR = 0.028), Desulfovibrionales order for knee OA (PFDR = 0.045) and Ruminiclostridium5 genus for knee OA (PFDR = 0.063). In addition, we also identified five suggestive microbial taxa that were significant with three different methods under the nominal significance (P < 0.05). Sensitive analysis excluded the influence of heterogeneity and horizontal pleiotropy and multivariable MR analysis ruled out the possibility of horizontal pleiotropy of BMI. GO enrichment analysis illustrates the protective mechanism of the identified taxa against OA.Conclusions: This study found that several microbial taxa were causally associated with diverse joint OA. The results enhanced our understanding of gut microbiota in the pathology of OA. [ABSTRACT FROM AUTHOR]

Unicystic ameloblastoma is a unique histopathological type of ameloblastoma, and treatment is controversial. Marsupialisation is effective in reducing the size of cystic lesions and their complications. We have retrospectively analysed the clinical, histopathological, and prognostic data of affected patients who were treated by marsupialisation between 2003 and 2013 in three Chinese hospitals. Our aim was to evaluate the effects and prognosis, and the factors associated with outcome. A total of 116 patients with mandibular unicystic ameloblastomas were included, and 74, 26, and 16 patients were histopathologically classified as being luminal, intraluminal, and mural subtypes, respectively. Most responded well to marsupialisation, with an overall recurrence rate of 12%. Resorption of the root (p < 0.001), perforation of the cortical bone (p = 0.005), and histopathological subtype (p = 0.013) were the main factors that predicted the outcome. Perforation of the cortical bone was the only reliable predictor of recurrence (p < 0.001). Disease-free survival function curves indicated that patients with the mural subtype were at a higher risk of recurrence than patients with the other two subtypes (p = 0.003). Poor outcomes of marsupialisation were treated surgically and, to date, no subsequent recurrences have been reported. Marsupialisation is effective for these patients, with a recurrence rate similar to that of radical treatment. The outcomes can be predicted using characteristics of the lesion such as resorption of the root, perforation of the cortical bone, and histopathological subtypes. However, additional studies are required to corroborate these findings. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to compare the outcomes of three surgical techniques for the treatment of patients with benign parotid tumours: superficial parotidectomy (SP; group 1), partial superficial parotidectomy (PSP; group 2), and ultrasonic scalpel-assisted minimal extracapsular dissection (US-MECD; group 3). Groups 1 and 2 received the conventional surgical technique, while group 3 underwent surgery with an ultrasonic scalpel. A total of 281 patients treated during 2012–2016 were included: 98 in group 1, 91 in group 2, and 92 in group 3. The mean surgical time and blood loss during surgery, as well as drainage time and amount, were significantly lower for US-MECD (P < 0.01). The great auricular nerve and parotid fascia were both preserved with US-MECD (P < 0.01), while the rate of capsule rupture with US-MECD was slightly higher than in the other groups (P > 0.05). There was less transient facial nerve paralysis and Frey syndrome with US-MECD (P < 0.01). No significant difference in wound infection, sialocele, or permanent facial nerve paralysis was observed among the three groups. Patients enrolled during 2012–2013 were selected to evaluate the recurrence rates, and no statistically significant differences were found among the groups. In conclusion, US-MECD showed similar effectiveness and fewer side effects than SP and PSP. The long-term effects of the new technique require further study. [ABSTRACT FROM AUTHOR]

Abstract Multilayered steel composites consisting of alternating martensitic and austenite layers were successfully fabricated with a combination of high strength and ductility. In situ SEM tensile experiments were performed to investigate the fracture processes. Results indicated that the martensitic layer distributed between two ductile austenite layers has better deformation ability, and the dimple fracture mode dominated the fracture of the whole specimen. In situ synchrotron microbeam X-ray diffraction experiments were carried out to study the microscopic deformation in austenitic layer and martensitic layer ahead of notch root under incremental tensile loading. Results indicated that for austenite layer, the maximum strain is located in the middle of the layer at the lower applied load. When at the higher applied load, larger strain is concentrated on the notch root. For martensitic layer, uniform strain is distributed at the region at the lower applied load, with increasing the applied load, small strain appears in the middle of martensitic layer. However, the variation in the strain in the martensitic layer is relatively smaller, which is actually affected by both the notch and the ferrite content in the martensitic layer. The changing trends of the strain in the austenite layer and martensitic layer can still show the better combination of brittle martensitic phase and ductile austenite phase. Highlights • In situ SEM tensile experiments were performed to investigate the fracture processes. • In situ synchrotron x-ray diffraction were carried out to study the microscopic deformation in MLS steel. • The changing trends of the strain in the austenite layer and martensitic layer have been revealed. [ABSTRACT FROM AUTHOR]

The microstructure and mechanical properties of 2Cr13/316L composite plates by hot-rolling at different rolling temperatures of 1130 °C, 1180 °C, 1250 °C, 1300 °C are investigated in details. With the increase of the rolling temperature, the tensile strength and bending strength of 2Cr13/316Lwere reduced first and then increased slightly due to the coarsening of grains and the increasing of ferrite content in 2Cr13 layers. The highest tensile elongation is obtained at the composite plate with rolling temperature of 1180 °C. 2Cr13/316L composite plates obtained by hot rolling processes were able to withstand larger bending deformation, and no cracks or interfacial delamination can be found in the bending process because of a strong combined interface. [ABSTRACT FROM AUTHOR]

Background: Synchronization can measure the interaction between different brain regions, but how alcoholics and non-alcoholic subjects differ in synchronization is still not fully clear. Methods: The synchronization analyses in present study on EEG synchronization are almost all based on the scalp EEG data. However, due to the volume conductor effect, there may be pseudo relevance between the scalp electrodes, which further affects the measurement of synchronization. Based on eLORETA and the self-defined regions of interest (ROIs), the synchronization between ROIs was measured. Our study used synchronization likelihood to measure the synchronization difference between 28 alcoholics and 28 controls (nonalcoholics) during certain cognitive tasks based on the scalp EEG and the cortical ROI. Results: The results indicated that the synchronization for the alcoholic group is lower in multiple bands than in the control group when performing the same cognitive task. Moreover, the synchronization for the control group can reflect the complexity levels of the cognitive tasks, whereas the alcoholics only display erratic changes. Conclusions: These two results indicate that in alcoholics, brain synchronization is reduced, and the connection between different brain regions is inhibited, meaning brain cognitive function is impaired. In addition, the synchronization method based on the cortical ROI is more effective and more valuable than the scalp EEG. Our research provides strong evidence that long-term alcoholism causes functional damage to the brain from an entirely new perspective. [ABSTRACT FROM AUTHOR]

The performance of nanoelectronics devices critically depends on the distribution of active dopants inside these structures. For this reason, dopant profiling has been defined as one of the major metrology challenges by the international technology roadmap of semiconductors. Scanning spreading resistance microscopy (SSRM) has evolved as one of the most viable approaches over the last decade due to its excellent spatial resolution, sensitivity and quantification accuracy. However, in case of advanced device architectures like fins and nanowires a proper measurement of the spreading resistance is often hampered by the increasing impact of parasitic series resistances (e.g. bulk series resistance) arising from the confined nature of the aforementioned structures. In order to overcome this limitation we report in this paper the development and implementation of a novel SSRM mode (fast Fourier transform-SSRM: FFT-SSRM) which essentially decouples the spreading resistance from parasitic series resistance components. We show that this can be achieved by a force modulation (leading to a modulated spreading resistance signal) in combination with a lock-in deconvolution concept. In this paper we first introduce the principle of operation of the technique. We discuss in detail the underlying physical mechanisms as well as the technical implementation on a state-of-the-art atomic force microscope (AFM). We demonstrate the performance of FFT-SSRM and its ability to remove substantial series resistance components in practice. Eventually, the possibility of decoupling the spreading resistance from the intrinsic probe resistance will be demonstrated and discussed. [ABSTRACT FROM AUTHOR]

Metal nanowires are usually strong but are not able to maintain a high plastic flow due to a lack of strain hardening. In this study, we investigated the tensile deformation of a new category of metal nanowires with hollow interiors by atomistic simulations – the so-called metal nanotubes – and revealed that they possess a combination of ultrahigh strength and plastic flow. In particular, it was found that by controlling the wall thickness and axial orientation, ultrahigh plastic flow stress of more than 2 GPa could be maintained at up to ∼60% tensile strain in Au nanotubes, whereas the solid Au nanowires of similar size yielded at tensile strain of less than 5%, after which the stress dropped immediately below 1 GPa. Furthermore, a universal trend of surface reconstruction to the energetically favorable close-packed {1 1 1} orientation was found in Au nanotubes regardless of the initial orientation, which may be responsible for the unique plasticity in Au nanotubes with extremely thin walls. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cold metal transfer welding–brazing of titanium to copper was performed. [•] Increasing wire feed speed or groove angle will get satisfied Ti/Cu joint. [•] Increasing wire feed speed or groove angle will increase tensile load. [•] Ti/Cu CMT butt joint has dual characteristics of fusion welding and brazing. [Copyright &y& Elsevier]

Highlights: [•] Ti–Cu joints can be successfully performed by cold metal transfer technology. [•] Ti–Cu joints can be joined by series of Ti–Cu intermetallic compounds. [•] Ti–Cu joint has a tensile strength of 194N/mm. [ABSTRACT FROM AUTHOR]

Abstract: Circadian (24-h) rhythms influence virtually every aspect of mammalian physiology. The main rhythm generation center is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and work over the past several years has revealed that rhythmic gene transcription and post-translational processes are central to clock timing. In addition, rhythmic translation control has also been implicated in clock timing; however the precise cell signaling pathways that drive this process are not well known. Here we report that a key translation activation cascade, the mammalian target of rapamycin (mTOR) pathway, is under control of the circadian clock in the SCN. Using phosphorylated S6 ribosomal protein (pS6) as a marker of mTOR activity, we show that the mTOR cascade exhibits maximal activity during the subjective day, and minimal activity during the late subjective night. Importantly, expression of S6 was not altered as a function of circadian time. Rhythmic S6 phosphorylation was detected throughout the dorsoventral axis of the SCN, thus suggesting that rhythmic mTOR activity was not restricted to a subset of SCN neurons. Rather, rhythmic pS6 expression appeared to parallel the expression pattern of the clock gene period1 (per1). Using a transgenic per1 reporter gene mouse strain, we found a statistically significant cellular level correlation between pS6 and per1 gene expression over the circadian cycle. Further, photic stimulation triggered a coordinate upregulation of per1 and mTOR activation in a subset of SCN cells. Interestingly, this cellular level correlation between mTOR activity and per1 expression appears to be specific, since a similar expression profile for pS6 and per2 or c-FOS was not detected. Finally, we show that mTOR activity is downstream of the ERK/MAPK signal transduction pathway. Together these data reveal that mTOR pathway activity is under the control of the SCN clock, and suggests that mTOR signaling may contribute to distinct aspects of the molecular clock timing process. [Copyright &y& Elsevier]

Abstract: This work investigated the variations of Charpy V toughness which was measured in various parts of welding joints of a 980MPa steel. The welding joints were composed of multi-pass weld metal, heat affected zones (HAZs) and base metal. Two types of weld metals, one with inferior toughness and the other with comparable toughness to the base metal, were used to reveal the effects of weld metal property and fraction on the toughness of the welding joint as a whole. The notches of Charpy V specimens were located at various sections of the welding joints where the ligaments comprised various fractions of weld metal. The results revealed that the weld metal with inferior toughness, even in a fraction as low as 20%, caused remarkable deterioration on the impact toughness of the welding joint. The weld metal with comparable toughness had little effect on the properties of the welding joint. The microstructures and fracture surfaces were observed to analyze the mechanism of the inferior toughness in a MAG weld metal. [Copyright &y& Elsevier]

Abstract: Superconducting Nb thin films with a spacing-graded array of holes were prepared by electron beam lithography. Two films with different hole gradients were fabricated. The ac-driven vortices were investigated in Nb superconductors with a spacing-graded array of holes. The measurements revealed pronounced rectified voltage when the vortex lattice is driven by an ac injected current. The rectified voltage is mainly caused by the strength of the vortex–vortex interaction. The rectified motion of a vortex is affected by the pinning potential of the spacing-graded array and the applied magnetic field. The vortex–vortex interaction strength changes the effective pinning landscape of the vortices and an asymmetric potential is formed. Vortices depin easily from high concentration to low concentration of pinning sites. In both samples, the ac-driven vortices exhibit a variety of dynamical responses and the rectified voltage is tunable with the applied magnetic field. [Copyright &y& Elsevier]

Abstract: Tensile tests, compression tests, in situ tensile tests, bending tests, tensile fatigue tests and bending fatigue tests were carried out for a TiAl alloy. Based on the global experimental results and microscopic observations of the fracture surfaces and cracking behaviour on the side surfaces of tested specimens, the fracture mechanisms of fully lamellar (FL) TiAl alloys under various loading modes are summarized as following: (1) Cracks initiate at grain boundaries and/or interfaces between lamellae. (2) When a crack extends to a critical length, which matches the fracture loading stress the crack propagates catastrophically through entire specimen. (3) The crack with the critical length can be produced promptly by the applied load in the tensile and bending test or be produced step-by-step by a much lower load in the fatigue tensile test. (4) For fatigue bending tests, the fatigue crack initiates and extends directly from the notch root, then extends step-by-step with increasing the fatigue bending loads. The fatigue crack maybe extends through entire specimen at a lower fatigue load or triggers the cleavage through the whole specimen at a higher load. (5) In compressive tests, cracks initiate and propagate in directions parallel or inclined to the compressive load after producing appreciable plastic strains. The specimen can be fractured by the propagation of cracks in both directions. [Copyright &y& Elsevier]

Abstract: Notched specimens of a fully lamellar TiAl alloy and a duplex TiAl alloy were in situ tensile tested with repeated loading–unloading–reloading processes in a scanning electron microscope (SEM). The step-by-step processes of initiation and extension of the main crack were captured by SEM. The fracture surfaces were observed and one-sector-to-one-sector related to the crack extension. Effects of loading–unloading damage on the fracture behavior were evaluated by combining the pictures of propagating crack configurations, corresponding fracture surfaces and the load locus. The results revealed the following events: (1) at the elastic regime, the loading–unloading process had negligible effect on the fracture behavior produced by subsequent reloading; (2) at the plastic regime, even at a value much lower than that of the preload, the reload extended further the existing main crack; (3) after a heavy loading–unloading process, the main crack extended and resulted in final fracture at a value of the reload, which was lower than that of the preload and (4) microcracks produced in the loading–unloading process had minor effects on the fracture behavior. [Copyright &y& Elsevier]

Abstract: A superconducting thin film with regular triangular arrays has been fabricated to explore the anisotropic vortex pinning behavior. We found that the critical currents for these films depend strongly on the current directions. Some interesting temperature-dependent phenomena are observed and discussed. We also made molecular dynamic simulations to study the dynamics of the vortex motion. The simulation results confirm the anisotropic features we found in the experiments. [Copyright &y& Elsevier]

Abstract: Ultra-fine grained γ-Ni–xFe (x =20, 50, and 64 (nominal)) dispersed Al2O3-matrix composites were fabricated by a mechano-chemical process plus hot-pressing, and their mechanical and magnetic properties were explored. The results indicated that all composites incorporated with different γ-Ni–xFe alloys possessed high densities (relative density D ⩾98%) and sub-micrometer-sized matrix dispersed with γ-Ni–xFe particles of sizes below ∼500nm. As compared to other two composite systems, γ-Ni–20Fe/Al2O3 had finer microstructures and displayed superior fracture toughness and strength. In high iron-contained γ-Ni–64Fe/Al2O3 composite undesired FeAl2O4 phase formed on the matrix grain boundaries, which is mainly responsible for its inferior mechanical properties. Although Young’s modulus and hardness of Ni–20Fe/Al2O3 composite system decreased, its fracture toughness increased monotonously with increasing the alloy content in the composition range investigated. Moreover, incorporation of ferromagnetic γ-Ni–xFe particles led all the composite systems to display ferromagnetism with their saturation magnetization increasing almost linearly with increasing alloy content. In addition, experiments showed that their ferromagnetism had high thermal stability (T c =∼580°C), no obvious magnetism degradation and magnetic interactions of the alloys with the matrix being observed. The combination of good mechanical properties with excellent magnetic performance would make this material be very valuable in industry. [Copyright &y& Elsevier]

Abstract: High-dense (relative density D ≥98%) ultra-fine grained γ-Ni–20Fe/Al2O3 composites were fabricated by using a mechano-chemical process plus hot-pressing. Microstructure investigations revealed that fine γ-Ni–20Fe particles with the dimensions of several hundreds of nanometers dispersed homogeneously at the matrix grain boundaries. Mechanical tests indicate that fracture toughness increases monotonously from 4.7MPam1/2 for monolithic alumina to 8.4MPam1/2 for ∼19vol.% Ni–20Fe/Al2O3 composites. Fracture strength σ f increased with addition of Ni–20Fe phase as Ni–20Fe content was low (≤5vol.%). However, σ f decreased with further increase of Ni–20Fe content, exhibiting a maximum strength of ∼600MPa at ∼5vol.% Ni–20Fe. The improvement of the mechanical properties could be ascribed to the microstructure refinement of the composites and increase of cracking resistance introduced by the dispersed Ni–Fe phase, which was supported by fracture characteristic observations. [Copyright &y& Elsevier]

Abstract: The study was done using notched two-colony thick tensile specimens of a directionally solidified cast fully lamellar TiAl alloy. In-situ observations of fracture processes in scanning electron microscope (SEM) were combined with section-to-section related observations of fracture surfaces to investigate the crack growth process. Finite element method (FEM) calculations are carried out to evaluate the stresses for propagating cracks. The results reveal that: (1) the reason why enhancement of applied load is required to propagate the main crack, was attributed to that the main crack observed at the surface did not extend all the way through the specimen''s thickness thus the stress field was still controlled by the notch, in which a definite stress required for extending a crack tip should be kept by increasing the applied load. (2) Crack propagation resistance is enhanced at colony boundaries, only when a change occurs from an inter-lamellar propagation to a trans-lamellar propagation (3) Ligament bridging toughening phenomena can be integrated into aforementioned mechanism. As a whole the processes of new crack nucleation with bridging ligament formation decreases the crack propagation resistance rather than increasing it. (4) In case the majority of microcracks are surface cracks, the effect of microcrack shielding is not obvious. [Copyright &y& Elsevier]

Abstract: To further our SAR study on the chemistry and antitumor activity/neurotoxicity of β-carboline alkaloids, several series of β-carboline derivatives with various substituents were designed and synthesized from the starting material l-tryptophan on the basis of harmine chemical structure. Cytotoxic activities of these compounds were investigated in vitro. The results showed that some β-carboline derivatives had significant cytotoxic activities against human tumor cell lines. Among all the synthesized β-carboline derivatives, the compounds 27, 28 and 32, having a benzyl substituent at both position-2 and 9, respectively, were found to be the most potent compounds with IC50 value lower than 50 μM against all human tumor cell lines examined. Acute toxicities and antitumor activities of the selected β-carboline derivatives in mice were also evaluated. The results demonstrated that a benzyl substituent at position-2 increased the antitumor activity as well as acute toxicity significantly. However an (ethoxycarbonyl)amino substituent at position-3 reduced the acute toxicity as well as antitumor activity remarkedly. These data suggested that (1) the antitumor potencies of β-carboline derivatives were enhanced by the introduction of benzyl substituent into the position-2; (2) the acute toxicity of β-carboline derivatives reduced dramatically by the introduction of an appropriate substituent into the position-3 and 9; (3) the β-carboline structure might be an important basis for the design and synthesis of new antitumor drugs with significant antitumor activity and low toxicity. [Copyright &y& Elsevier]

Dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein, 32 kDa (DARPP-32) is a key element of dopamine/D1/DARPP-32/protein phosphatase-1 (PP-1) signaling cascades of mammalian brain. We are interested in the expression patterns of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in DARPP-32-containing neurons, which may constitute morphological basis for interaction between dopamine and ionotropic glutamate receptors in dopaminoceptive cells. Double immunofluorescence was performed to visualize neurons showing coexpression of DARPP-32 with NMDA or AMPA receptor subunits (i.e., NR1, NR2a/b, glutamate receptor subunit 1 [GluR1], GluR2/3, and GluR4) in the forebrains of rats. Distribution of DARPP-32-positive neurons completely or partially overlapped with that of NMDA receptor- or AMPA receptor-immunoreactive ones in the frontal and parietal cortex, hippocampus and neostriatum, and neurons double-labeled with DARPP-32/NR1, DARPP-32/NR2a/b, DARPP-32/GluR1, DARPP-32/GluR2/3, or DARPP-32/GluR4 immunoreactivity were numerously observed. Semiquantification analysis indicated that most of DARPP-32-containing neurons (86–98%) expressed NR1, NR2a/b and GluR2/3, while less of them (14–90%) expressed GluR1 and GluR4. Although high rates (90–98%) of DARPP-32-positive cells expressed NMDA receptors in all regions above, variant percentages of them expressing AMPA receptor subunits were observed among the cortex (54–90%), hippocampus (59–97%) and neostriatum (14–97%).The study presents differential expression patterns of NMDA and AMPA receptors in DARPP-32-postive neurons in these forebrain regions. Taken together with previous reports, the present data suggest that interaction between dopamine and glutamate receptors may occur in the dopaminoceptive neurons with distinct receptor compositions and may be involved in modulating neuronal properties and excitotoxicity in mammalian forebrain. [Copyright &y& Elsevier]

By using a double immunofluorescence, we have examined the distribution of striatal GABAergic neurons that expressed substance P receptor (SPR) in the basal ganglia of adult C57 mice. The distribution of GABA-immunoreactive neurons completely or partially overlapped with that of SPR-immunoreactive neurons in the striatum (i.e. the caudate-putamen), globus pallidus, ventral pallidum, and nucleus accumbens. Neurons showing both GABA- and SPR-immunoreactivities were, however, predominantly found in the caudate-putamen, and most of them were characterized by their large-sized aspiny neuronal profile. Semi-quantification indicated that only about 13% of the total GABA-immunoreactive neurons (including large and medium-sized) displayed SPR-immunoreactivity, and these double-labeled neurons constituted about 31% of the total SPR-immunoreactive cells in the striatum. Neurons double-labeled with GABA- and SPR-immunoreactivities were hardly detected in other aforementioned regions of the basal ganglia. In addition, double immunofluorescence also showed co-localization of SPR- with glutamic acid decarboxylase-immunoreactivity, but not with parvalbumin-immunoreactivity, in the striatal neurons.Taken together with previous reports, the present study has suggested that a sub-population of striatal GABA-ergic neurons, most possibly GABA-ergic interneurons, may also receive direct physiological modulation by tachykinins through SPR in the basal ganglia of mammals. [Copyright &y& Elsevier]

The impacts of climate change need to be mitigated by controlling the emissions of carbon dioxide. The restriction of carbon dioxide emissions will limit fossil-fuel-fired electricity and affect water consumption in energy-related industries. In this study, a chance-constrained urban agglomeration energy model is developed to plan a cooperative energy-water nexus system with carbon dioxide emission constraints at the regional scale. The model can not only reflect uncertainties expressed as random variables and interval values but also manage energy-water nexus systems under cooperation mechanism effectively. The model is applied to the Guangzhou-Shenzhen-Dongguan region, wherein two scenarios with/without cooperative carbon dioxide emission strategies under different water resource risks are analyzed. Results reveal that the system cost of the study region would decrease under the cooperative carbon dioxide emission strategy. Compared with the case without mitigation cooperation, the cost of those with cooperation would reduce by [4.3, 4.8] % (with 6.2% more carbon dioxide emission) in Shenzhen. The results also demonstrate that water consumption would increase as constraint-violation level decreases from 0.2 to 0. The developed model is efficient for facilitating regional dynamic analyses of carbon dioxide emission mitigation and the associated economic cost under different policy scenarios and system risks. • A chance-constrained urban agglomeration energy model is developed. • The model can address interregional carbon cooperation and diminish the uncertainty. • The model is formulated for Guangzhou-Shenzhen-Dongguan of Pearl River Delta, China. • Tradeoffs between economic sustainability and environmental cost are analyzed. • Results are used for policymaker to generate cost-effective energy-water plan. [ABSTRACT FROM AUTHOR]

Abstract: It has been recognized that delayed xenograft rejection (DXR) is the major barrier to the acceptance of xenotransplantation after overcoming hyperacute rejection. Objectives: This study sought to investigate the pathogenesis and pathology of delayed xenograft rejection following pig-to-rhesus monkey heart xenotransplantation. Methods: Heterotopic xenogeneic heart transplants in the abdominal cavity were performed using piglet donors to four monkey recipients. Complete complement depletion was achieved in the recipients with repetitive doses of high-activity cobra venom factor (Y-CVF). The recipients were immunosuppressed with a combination of cyclosporine, cyclophosphamide, and steroids. Sera were analyzed for C3 and C4 levels and complement activity and anti-pig endothelial xenoantibody. The grafts were examined histopathologically and immunohistochemically for C3, C4;C5b-9, IgM, IgG, tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1(ICAM-1), CD57(NK cells), CD68 (macrophages), CD4, and CD8. Results: Xenografts survived 8, 10, 13, and 13 days respectively, all developing DXR. Venous thrombosis was the outstanding feature within DXR xenografts, complicated by interstitial edema, local hemorrhage, myocardial necrosis, and mild to moderate cellular infiltration. The serum C3 levels and complement activity decreased to almost 0 from the day of transplantation due to treatment with Y-CVF. The C4 level began to decrease 2 to 4 days before the cardiac xenografts lost their function. Anti-pig endothelial xenoantibody also decreased after transplantation, slightly increasing during DXR. All rejected xenografts showed C3, C4, C5b-9, IgG, and IgM deposits to various degrees. Large numbers of macrophages (50% of total leukocytes) infiltrated the entire xenograft with a few natural killer cells (8% to 10%), as well as some CD4+ T cells (15%) and CD8+ T cells (25%). Upregulation of ICAM-1 on graft endothelial cells and TNF-alpha in the interstitium were also demonstrated in the rejected heart. Conclusion: Both humoral and cell-mediated immunologic reactions may play important roles in the pathogenesis of DXR. Besides C3, C4, C5b-9, IgM, and IgG destroying the xenograft, NK cells, macrophages, and CD4+ and CD8+ T cells may further aggravate the development of DXR. [Copyright &y& Elsevier]