High-κ perovskite membranes as insulators for two-dimensional transistors.

The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.

Gut Microbiome Modulation by Antibiotics in Adult Asthma: A Human Proof-of-Concept Intervention Trial.

Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.1 Disruption and subsequent dysregulation of gut microbiota-related immunologic processes have also been linked to disease severity and response to treatment.2.

Impact of Particle Sedimentation in Pendant Drop Tensiometry.

Understanding the interface-stabilizing properties of surface-active components is key in designing stable macroscopic multiphase systems, such as emulsions and foams. When poorly soluble materials are used as an interface stabilizer, the insoluble material may sediment and interfere with the analysis of interfacial properties in pendant (or hanging) drop tensiometry. Here, the impact of sedimentation of particles on the interfacial properties determined by pendant drop tensiometry was evaluated using a model system of whey protein isolate and (non surface-active) glass beads (2.2-34.7 µm). Although the glass beads did not adsorb to the air-water interface, a 1% (w/w) glass bead solution appeared to decrease the surface tension by nearly 12 mN/m after 3 h. A similar effect was shown for a mixture of whey proteins and glass beads: the addition of 1% (w/w) of glass beads led to an apparent surface tension decrease of 31 mN/m rather than the 20 mN/m observed for pure whey proteins. These effects are attributed to the sedimentation of particles near the apex of the droplet, leading to droplet shape changes, which are interpreted as a decrease in surface tension using tensiometer software. The droplet density at the apex increases due to sedimentation, and this density increase is not accounted for when fitting the droplet shape with the Young-Laplace equation. The result is the observed apparent decrease in surface tension. In contrast to the significant impact of sedimenting material on the surface tension measurements, the impact on the results of oscillatory deformations was limited. These findings show that the impact of sedimentation should be considered when studying the interface-stabilizing properties of materials with reduced solubility, such as certain plant protein extracts. The presence of such particles should be carefully considered when conducting pendant drop tensiometry.

Enhanced electrical conductivity of anticorrosive coatings by functionalized carbon nanotubes: effect of hydrogen bonding.

Carbon nanotubes and nanofibers (CNFs) are well-known nano additives to produce coating materials with high electrical and thermal conductivity and corrosion resistance. In this paper, coating materials incorporating hydrogen bonding offered significantly lower electrical resistance. The hydrogen bonding formed between functionalized carbon nanotubes and ethanol helped create a well-dispersed carbon nanotube network as the electron pathways. Electrical resistivity as low as 6.8 Ω cm has been achieved by adding 4.5 wt% functionalized multiwalled carbon nanotubes (MWNT-OH) to 75%polyurethane/25%ethanol. Moreover, the thermal conductivity of polyurethane was improved by 332% with 10 wt% addition of CNF. Electrochemical methods were used to evaluate the anti-corrosion properties of the fabricated coating materials. 75%polyurethane/25%ethanol with the addition of 3.0 wt% of MWNT-OH showed an excellent corrosion rate of 5.105 × 10-3mm year-1, with a protection efficiency of 99.5% against corrosive environments. The adhesion properties of the coating materials were measured following ASTM standard test methods. 75%polyurethane/25%ethanol with 3.0 wt% of MWNT-OH belonged to class 5 (ASTM D3359), indicating the outstanding adhesion of the coating to the substrate. These nanocoatings with enhanced electrical, thermal, and anti-corrosion properties consist of a choice of traditional coating materials, such as polyurethane, yielding coating durability with the ability to tailor the electrical and thermal properties to fit the desired application.

Development of Joint Activity Angle Measurement and Cloud Data Storage System.

In this study, we developed a range of motion sensing system (ROMSS) to simulate the function of the elbow joint, with errors less than 0.76 degrees and 0.87 degrees in static and dynamic verification by the swinging and angle recognition modules, respectively. In the simulation process, the É£ correlation coefficient of the Pearson difference between the ROMSS and the universal goniometer was 0.90, the standard deviations of the general goniometer measurements were between ±2 degrees and ±2.6 degrees, and the standard deviations between the ROMSS measurements were between ±0.5 degrees and ±1.6 degrees. With the ROMSS, a cloud database was also established; the data measured by the sensor could be uploaded to the cloud database in real-time to provide timely patient information for healthcare professionals. We also developed a mobile app for smartphones to enable patients and healthcare providers to easily trace the data in real-time. Historical data sets with joint activity angles could be retrieved to observe the progress or effectiveness of disease recovery so the quality of care could be properly assessed and maintained.

Prekallikrein inhibits innate immune signaling in the lung and impairs host defense during pneumosepsis in mice.

Prekallikrein (PKK, also known as Fletcher factor and encoded by the gene KLKB1 in humans) is a component of the contact system. Activation of the contact system has been implicated in lethality in fulminant sepsis models. Pneumonia is the most frequent cause of sepsis. We sought to determine the role of PKK in host defense during pneumosepsis. To this end, mice were infected with the common human pathogen Klebsiella pneumoniae via the airways, causing an initially localized infection of the lungs with subsequent bacterial dissemination and sepsis. Mice were treated with a selective PKK-directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 h post-infection, including genome-wide messenger RNA profiling of lungs, or mice were followed for survival. PKK ASO treatment inhibited constitutive hepatic Klkb1 mRNA expression by >80% and almost completely abolished plasma PKK activity. Klkb1 mRNA could not be detected in lungs. Pneumonia was associated with a progressive decline in PKK expression in mice treated with control ASO. PKK ASO administration was associated with a delayed mortality, reduced bacterial burdens, and diminished distant organ injury. While PKK depletion did not influence lung pathology or neutrophil recruitment, it was associated with an upregulation of multiple innate immune signaling pathways in the lungs already prior to infection. Activation of the contact system could not be detected, either during infection in vivo or at the surface of Klebsiella in vitro. These data suggest that circulating PKK confines pro-inflammatory signaling in the lung by a mechanism that does not involve contact system activation, which in the case of respiratory tract infection may impede early protective innate immunity. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Composition-dependent chemical and structural stabilities of mixed tin-lead inorganic halide perovskites.

Alloying tin into lead-based halide perovskites is one of the strategies to reduce the chemical toxicities associated with lead-containing compounds, while retaining comparable physical properties. However, tin-based compounds possess their own shortcomings, with the most critical ones being their increased thermodynamic tendencies towards oxidative degradation, as well as vibrational anharmonicities due to the presence of shallow Sn-5s2 lone-pair electrons. Hereby, we performed density-functional-theory calculations to systematically examine the composition-dependent chemical and structural stabilities for Cs(PbxSn1-x)X3 (X = Cl, Br and I) alloys. We found that oxidative degradation to rhombohedral Cs2SnX6, SnO2 and cubic CsSnX3 tends to be the most favored pathway with no observable composition-dependent 'bowing behaviour', the latter is primarily governed by the bowing-effects in the demixing energies which are generated when the perovskite alloy phase-segregates into the two cubic end-members, which are two orders of magnitude smaller. Potential surface energy scans for the off-center B-site ion displacements further reveal the nonlinearity in the change of vibrational anharmonicity with respect to a linear change of Sn concentrations. Such nonlinearity is strongly modulated by the nature of the halide ions, in order to minimize the exchange repulsion between the charge densities of Sn-5s2 lone pairs and the octahedrally coordinating halogen anions.

Kininogen deficiency or depletion reduces enhanced pause independent of pulmonary inflammation in a house dust mite-induced murine asthma model.

High-molecular-weight kininogen is an important substrate of the kallikrein-kinin system. Activation of this system has been associated with aggravation of hallmark features in asthma. We aimed to determine the role of kininogen in enhanced pause (Penh) measurements and lung inflammation in a house dust mite (HDM)-induced murine asthma model. Normal wild-type mice and mice with a genetic deficiency of kininogen were subjected to repeated HDM exposure (sensitization on days 0, 1, and 2; challenge on days 14, 15, 18, and 19) via the airways to induce allergic lung inflammation. Alternatively, kininogen was depleted after HDM sensitization by twice-weekly injections of a specific antisense oligonucleotide (kininogen ASO) starting at day 3. In kininogen-deficient mice HDM induced in Penh was completely prevented. Remarkably, kininogen deficiency did not modify HDM-induced eosinophil/neutrophil influx, T helper 2 responses, mucus production, or lung pathology. kininogen ASO treatment started after HDM sensitization reduced plasma kininogen levels by 75% and reproduced the phenotype of kininogen deficiency: kininogen ASO administration prevented the HDM-induced increase in Penh without influencing leukocyte influx, Th2 responses, mucus production, or lung pathology. This study suggests that kininogen could contribute to HDM-induced rise in Penh independently of allergic lung inflammation. Further research is warranted to confirm these data using invasive measurements of airway responsiveness.

Complement factor C5 inhibition reduces type 2 responses without affecting group 2 innate lymphoid cells in a house dust mite induced murine asthma model.

BACKGROUND: Complement factor C5 can either aggravate or attenuate the T-helper type 2 (TH2) immune response and airway hyperresponsiveness (AHR) in murine models of allergic asthma. The effect of C5 during the effector phase of allergen-induced asthma is ill-defined. OBJECTIVES: We aimed to determine the effect of C5 blockade during the effector phase on the pulmonary TH2 response and AHR in a house dust mite (HDM) driven murine asthma model. METHODS: BALB/c mice were sensitized and challenged repeatedly with HDM via the airways to induce allergic lung inflammation. Sensitized mice received twice weekly injections with a blocking anti-C5 or control antibody 24 h before the first challenge. RESULTS: HDM challenge in sensitized mice resulted in elevated C5a levels in bronchoalveolar lavage fluid. Anti-C5 administered to sensitized mice prior to the first HDM challenge prevented this rise in C5a, but did not influence the influx of eosinophils or neutrophils. While anti-C5 did not impact the recruitment of CD4 T cells upon HDM challenge, it reduced the proportion of TH2 cells recruited to the airways, attenuated IL-4 release by regional lymph nodes restimulated with HDM ex vivo and mitigated the plasma IgE response. Anti-C5 did not affect innate lymphoid cell (ILC) proliferation or group 2 ILC (ILC2) differentiation. Anti-C5 attenuated HDM induced AHR in the absence of an effect on lung histopathology, mucus production or vascular leak. CONCLUSIONS: Generation of C5a during the effector phase of HDM induced allergic lung inflammation contributes to TH2 cell differentiation and AHR without impacting ILC2 cells.

Inhibition of the extrinsic or intrinsic coagulation pathway during pneumonia-derived sepsis.

Pneumonia is the most frequent cause of sepsis, and Klebsiella pneumoniae is a common pathogen in pneumonia and sepsis. Infection is associated with activation of the coagulation system. Coagulation can be activated by the extrinsic and intrinsic routes, mediated by factor VII (FVII) and factor XII (FXII), respectively. To determine the role of FVII and FXII in the host response during pneumonia-derived sepsis, mice were treated with specific antisense oligonucleotide (ASO) directed at FVII or FXII for 3 wk before infection with K. pneumoniae via the airways. FVII ASO treatment strongly inhibited hepatic FVII mRNA expression, reduced plasma FVII to ~25% of control, and selectively prolonged the prothrombin time. FXII ASO treatment strongly suppressed hepatic FXII mRNA expression, reduced plasma FXII to ~20% of control, and selectively prolonged the activated partial thromboplastin time. Lungs also expressed FVII mRNA, which was not altered by FVII ASO administration. Very low FXII mRNA levels were detected in lungs, which were not modified by FXII ASO treatment. FVII ASO attenuated systemic activation of coagulation but did not influence fibrin deposition in lung tissue. FVII ASO enhanced bacterial loads in lungs and mitigated sepsis-induced distant organ injury. FXII inhibition did not affect any of the host response parameters measured. These results suggest that partial inhibition of FVII, but not of FXII, modifies the host response to gram-negative pneumonia-derived sepsis.

Origins of possible synergistic effects in the interactions between metal atoms and MoS2/graphene heterostructures for battery applications.

The interactions between metals and two-dimensional materials, in particular, the adsorption energies, strongly determine the performances of rechargeable batteries. Previously, it has been demonstrated that heterostructures of two dimensional (2D) materials can lead to enhanced metal adsorptions, which were ascribed to the existence of 'synergistic' effects amongst metal atoms and two different 2D materials. However, further investigations are still required to reveal the physical mechanisms behind the contribution of these possible 'synergistic' effects for metal intercalations in 2D heterostructures. Here, we selected MoS2/graphene as a prototypical system, and we examined the adsorption and intercalation thermochemistry of monovalent atoms (Li, Na and K) and multivalent atoms (Mg, Ca and Al) using density-functional theory (DFT) calculations. The synergistic effects arising from charge polarizations in these systems were quantified using the three-body interaction energy terms. Our results show strong system dependencies whereby the interactions between the Mg or Ca atom with the MoS2/graphene heterostructures might exhibit cooperative bindings. Nevertheless, metal adsorptions on top of the graphene surface were all found to be anti-cooperative in this case. Our results suggest that enhancement of metal adsorptions using 2D heterostructures is predominantly driven by increasing dispersion interactions due to increases in the interaction surface areas.

Factor XI deficiency enhances the pulmonary allergic response to house dust mite in mice independent of factor XII.

Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor-dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system and its possible route of activation in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO), and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared. FXI KO mice showed increased influx of eosinophils into lung tissue, accompanied by elevated local levels of the main eosinophil chemoattractant eotaxin. Although gross lung pathology and airway mucus production did not differ between groups, FXI KO mice displayed an impaired endothelial/epithelial barrier function, as reflected by elevated levels of total protein and IgM in bronchoalveolar lavage fluid. FXI KO mice had a stronger systemic IgE response with an almost completely absent HDM-specific IgG1 response. The phenotype of FXII KO mice was, except for a higher HDM-specific IgG1 response, similar to that of WT mice. In conclusion, FXI attenuates part of the allergic response to repeated administration of HDM in the airways by a mechanism that is independent of activation via FXII.

Association of six CpG-SNPs in the inflammation-related genes with coronary heart disease.

BACKGROUND: Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. RESULTS: Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Further gender-based subgroup tests showed that one SNP (CD40 rs1800686) and two SNPs (FAM5C rs12732361 and CD36 rs2065666) were associated with CHD in females and males, respectively. And the age-based subgroup tests indicated that PLA2G7 rs9395208, IL1B rs16944, and CD40 rs1800686 were associated with CHD among individuals younger than 55, younger than 65, and over 65, respectively. CONCLUSIONS: In conclusion, all the six inflammation-related CpG-SNPs (rs16944, rs2071008, rs12732361, rs2065666, rs9395208, and rs1800686) were associated with CHD in the combined or subgroup tests, suggesting an important role of inflammation in the risk of CHD.

The clinical significance of snail protein expression in gastric cancer: a meta-analysis.

BACKGROUND: Snail is a typical transcription factor that could induce epithelial-mesenchymal transition (EMT) and cancer progression. There are some related reports about the clinical significance of snail protein expression in gastric cancer. However, the published results were not completely consistent. This study was aimed to investigate snail expression and clinical significance in gastric cancer. RESULTS: A systematic review of PubMed, CNKI, Weipu, and Wanfang database before March 2015 was conducted. We established an inclusion criterion according to subjects, method of detection, and results evaluation of snail protein. Meta-analysis was conducted using RevMan4.2 software. And merged odds ratio (OR) and 95 % CI (95 % confidence interval) were calculated. Also, forest plots and funnel plot were used to assess the potential of publication bias. A total of 10 studies were recruited. The meta-analysis was conducted to evaluate the positive rate of snail protein expression. OR and 95 % CI for different groups were listed below: (1) gastric cancer and para-carcinoma tissue [OR = 6.15, 95 % CI (4.70, 8.05)]; (2) gastric cancer and normal gastric tissue [OR = 17.00, 95 % CI (10.08, 28.67)]; (3) non-lymph node metastasis and lymph node metastasis [OR = 0.40, 95 % CI (0.18, 0.93)]; (4) poor differentiated cancer, highly differentiated cancer, and moderate cancer [OR = 3.34, 95 % CI (2.22, 5.03)]; (5) clinical stage TI + TII and stage TIII + TIV [OR = 0.38, 95 % CI (0.23, 0.60)]; (6) superficial muscularis and deep muscularis [OR = 0.18, 95 % CI (0.11, 0.31)]. CONCLUSIONS: Our results indicated that the increase of snail protein expression may play an important role in the carcinogenesis, progression, and metastasis of gastric cancer. And this result might provide instruction for the diagnosis, therapy, and prognosis of gastric cancer.

Cytological diagnosis of metastatic malignant melanoma by fine-needle aspiration biopsy.

Despite increased surveillance and public awareness, the incidence of melanoma is increasing. Frequently, fine-needle aspiration is employed for the diagnosis of metastatic disease, and aspirated material is used for cytogenetic and molecular studies to guide treatment options. The pairing of a significant diagnosis with the numerous morphologic variants of melanoma can make the cytologic evaluation disquieting. We present selected examples of our experiences and a brief review of the literature to provide cytodiagnostic clues for this malignancy. The clinical history is foremost, although the fine-needle aspiration (FNA) of metastatic melanoma can provide a diagnosis before identification of the primary lesion in up to 20% of cases. If a history of melanoma is assured, negative results in sampling of pulmonary and subcutaneous nodules should be suspected as false negatives. The smearing pattern usually features poorly cohesive cells. Frankly malignant, spindled, and epithelioid cell shapes are most common, and cytoplasmic vacuoles, if sought on Romanowsky-stained specimens, can usually be found. The telltale feature of melanin production, although diagnostic, is only present in 50% of cases. Finally, eccentric placement of nuclei, nucleoli, and nuclear pseudoinclusions are accessory features for the cytologic interpretation of melanoma. Numerous morphologic patterns of melanoma are potentially seen, but a stepwise approach to diagnosis usually produces a successful result.

Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P < 0.05) and decreased IL-4 levels (P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

A new statistical approach to combining p-values using gamma distribution and its application to genome-wide association study.

BACKGROUND: Combining information from different studies is an important and useful practice in bioinformatics, including genome-wide association study, rare variant data analysis and other set-based analyses. Many statistical methods have been proposed to combine p-values from independent studies. However, it is known that there is no uniformly most powerful test under all conditions; therefore, finding a powerful test in specific situation is important and desirable. RESULTS: In this paper, we propose a new statistical approach to combining p-values based on gamma distribution, which uses the inverse of the p-value as the shape parameter in the gamma distribution. CONCLUSIONS: Simulation study and real data application demonstrate that the proposed method has good performance under some situations.