Search

Figure S1-S5

DNA repair mechanisms are crucial for cell survival. It increases the cancer cell's ability to resist DNA damage. FEN1 is involved in DNA replication and repair, specifically long-patch base excision repair. Although the gene function and post-translational modification of FEN1 are well studied, the regulatory mechanism of FEN1 by upstream signal pathways remains unclear. In this article, we have identified AKT as a regulator of FEN1 activity in lung cancer cells. Sustained activation of AKT can phosphorylate nuclear transcription factor NF-κB/p65. NF-κB/p65 directly binds to FEN1 promoter to promote a high transcription level of FEN1, revealing the contribution of the AKT signaling pathway to drug resistance of cancer cells. The combination of an AKT inhibitor and cisplatin efficiently suppressed lung cancer cell growth both in vitro and in vivo. Our study illustrated an upstream regulatory mechanism of FEN1, which will contribute to the development of effective lung cancer therapies.These findings identified AKT as a regulator of FEN1 activity and revealed the AKT signaling pathway's contribution to drug resistance, which will contribute to the development of effective lung cancer therapy.

In this study, a rapid solder melting process has been examined through a self-propagating exothermic reaction using Al/Ni nanofoil as a localized heat source. Four kinds of tin-based solder preforms were partly melted under this process, and the thicknesses of the fusion zone in solder preforms around the Al/Ni nanofoil were experimentally analyzed. The microstructure and morphology of the fusion zone in different kinds of solder preforms were studied by metallographic analysis. In Sn42Bi58 solder, the mean grain size of Bi-rich phases in the fusion zone was finer than the original structure, and decreased from ~ 2.7 μm to ~ 0.8 μm away from the Al/Ni nanofoil. Similar trends of mean size of grains in the fusion zone were also found in the Sn, Sn-3 wt.%Ag-0.5 wt.%Cu(SAC), and SnPb solder preforms. The widths of the fusion zone in the Sn, SAC, SnPb, and SnBi solder preforms were 150 μm, 173 μm, 188 μm, and 233 μm, respectively. In addition, the nano-hardness and distribution in the fusion zones were evaluated. The results show that the value of nanohardness increased along with the decrease of distance from Al/Ni nanofoil. The average hardness and the lower and upper bounds of Sn, SnPb, SAC, and SnBi solder in the fusion zone are 0.260 (−0.045, +0.039) GPa, 0.246 (−0.059, +0.114) GPa, 0.260 (−0.014, +0.070) GPa, and 0.404 (−0.072, +0.134) GPa, respectively. The statistical significance of solder hardness is related to its alloy component, element content, and microstructure.

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial intima. As AS represents the most common type of vascular disease, it affects millions of individuals and is a source of high morbidity and mortality rates worldwide. Overwhelming evidence indicates that AS-related inflammation is mediated by proinflammatory cytokines, chemokines, adhesion molecules and inflammatory signaling pathways, with each of these factors being shown to play critical roles during the entire progression of AS. While a number of drugs have been approved for use in the treatment of AS, their benefits are modest, which underscores the urgency for the development of new drug therapies. In part, these deficits in effective drugs can be attributable to the lack of a clear understanding of the molecular mechanisms of AS. In this study, we investigate the capacity for thrombin to trigger inflammation and induce cell proliferation in vascular smooth muscle cells (VSMCs). We then assessed the effects of baicalin and its potential mechanisms on VSMC inflammation as induced by thrombin. Baicalin, which is a natural bioactive compound of S. baicalensis Georgi (SBG), exerted a protective effect against thrombin-induced VSMC inflammation as resulting from the upregulation of PAR-1. This protection as exerted by baicalin appears to reside in its capacity to produce an inhibitory effect on the thrombin-induced activation of the ERK1/2 pathway. These findings suggest that baicalin may be a promising candidate for the treatment of atherosclerosis.

DNA repair mechanisms are crucial for cell survival. It increases the cancer cell's ability to resist DNA damage. FEN1 is involved in DNA replication and repair, specifically long-patch base excision repair. Although the gene function and post-translational modification of FEN1 are well studied, the regulatory mechanism of FEN1 by upstream signal pathways remains unclear. In this article, we have identified AKT as a regulator of FEN1 activity in lung cancer cells. Sustained activation of AKT can phosphorylate nuclear transcription factor NF-κB/p65. NF-κB/p65 directly binds to FEN1 promoter to promote a high transcription level of FEN1, revealing the contribution of the AKT signaling pathway to drug resistance of cancer cells. The combination of an AKT inhibitor and cisplatin efficiently suppressed lung cancer cell growth both in vitro and in vivo. Our study illustrated an upstream regulatory mechanism of FEN1, which will contribute to the development of effective lung cancer therapies. These findings identified AKT as a regulator of FEN1 activity and revealed the AKT signaling pathway's contribution to drug resistance, which will contribute to the development of effective lung cancer therapy.

The most common kind of kidney cancer with poor prognosis is clear cell renal cell carcinoma (ccRCC). Pyroptosis is shown to be an inflammatory type of programmed cell death in recent years. In this research, we utilized pyroptosis-related differentially expressed lncRNAs in ccRCC to develop a predictive multi-lncRNA signature. We uncovered 14 lncRNAs with different expression patterns that were linked to ccRCC prognosis. Kaplan–Meier analysis identified a signature of high-risk lncRNAs related to poor prognosis for ccRCC. Furthermore, the AUC of the lncRNA signature was 0.771, indicating that they can be used to predict ccRCC prognosis. In predicting ccRCC prognosis, our risk analysis approach outperformed standard clinicopathological characteristics. In the low-risk group, GSEA indicated tumor-related pathways. T-cell functions such as T-cell coinhibition and T-cell costimulation were found to be expressed differently in two groups. Immune checkpoints including PD-1, LAG3, CTLA4, and BTLA were also differently expressed between the two groups. In patients with ccRCC, we created a 14-lncRNA-based predictor as a robust prognostic and predictive tool for OS.

When and where do states coercively alter their internal demography? We build a theory that predicts under what conditions states alter the demographic “facts on the ground” by resettling and expelling ethno-national populations. We predict that, under particular scope conditions, states will employ demographic engineering to shore up control over (1) nonnatural frontiers, and (2) areas populated by ethnic minorities who are co-ethnics with elites in a hostile power. We then substantiate our predictions using new subnational data from both China and the USSR. Causally identifying the spatially differential effect of international conflict on demographic engineering via a difference-in-differences design, we find that the Sino-Soviet split (1959–1982) led to a disproportionate increase in the expulsion of ethnic Russians and resettlement of ethnic Han in Chinese border areas lacking a natural border with the USSR, and that resettlement was targeted at areas populated by ethnic Russians. On the Soviet side, we similarly find that the Sino-Soviet split led to a significant increase in expulsion of Chinese and the resettlement of Russians in border areas, and that resettlement was targeted at areas populated by more Chinese. We develop the nascent field of political demography by advancing our theoretical and empirical understanding ofwhen, where, andto whomstates seek to effect demographic change. By demonstrating that both ethnic group concentration and dispersion across borders are endogenous to international conflict, our results complicate a large and influential literature linking ethnic demography to conflict.

Nowadays, traditional human–machine interface has been converted into digital human–computer interface in most industrial control rooms, then, cognitive process and reliability are also bound to be different from traditional human–machine interface. Aiming at the situation, the authors in this paper propose a cognitive reliability model with influencing factors based on Bayesian network. Taking a nuclear power plant (Npp) as research background, taking simulative experiment as study way, parameter values in cognitive reliability mathematical model are obtained by analyzing much experimental data. The proposed model is reasonable, accurate, sensitive and convergent by analyzing experiment data. Cognitive error probabilities of some tasks regarding a hot transmission system (HTS) leak accident in a Npp are obtained according to the proposed model and simulative experiments. The model provides a simple and feasible approach to analyze cognitive reliability of operating process in digital human–computer interface.

We model the cultural outcomes of ‘sons of the soil’ conflicts. These are conflicts between the local inhabitants of a particular region and migrants to the region, typically belonging to a dominant national culture. Our goal is to understand the conditions under which migrants assimilate into the local culture, or in which locals assimilate into the national culture. The model has two main actors: a national elite of a dominant ethnic group, and a regional elite seeking to promote the traditional culture of the sons of the soil. Both actors have parallel strategies, viz. assimilating the other group into their culture, controlling the size of the migrant population, doing both, or allowing market forces to determine outcomes. The model has three possible cultural outcomes: the culture tips to that of the sons of the soil; the culture tips to that of the migrant group; or the region remains bicultural, with each group retaining its own culture. We illustrate these outcomes through four cases: (i) Bengalis and Assamese in the Indian state of Assam; (ii) Russians and Estonians in the Ida-Virumaa county of Estonia; (iii) Tamils and Sinhalese in Jaffna and the Eastern Province of Sri Lanka; and (iv) Castilians and Catalans in the autonomous community of Catalonia in Spain.

Thrombin plays a pivotal role in the pathogenesis of atherosclerosis. Baicalin, an active flavonoid compound, was shown to attenuate the development of atherosclerosis, but the mechanism remains elusive. In the present study, the role and mechanism of baicalin in thrombin-induced cell injury was investigated in human umbilical vein endothelial cells (HUVECs). Our results showed that baicalin significantly reduced thrombin-induced apoptosis of HUVECs. Additional experiments showed that baicalin inhibited thrombin-induced NF-κB activation and PAR-1 expression. In addition, baicalin decreased thrombin-induced PAR-1 expression by inhibiting ERK pathway. These results indicated that baicalin has protective effects on thrombin-induced cell injury in HUVECs possibly through inhibition of PAR-1 expression and its downstream NF-κB activation, which was mediated by ERK1/2 activation.

With Chinese economy developing rapidly, the pressure put on individuals and the number of special family type has been increasing dramatically, mental health problems therefor plaguing an increasing number of children. Because the school plays an important role on children’s psychological development, the social issue above can be solved most effectively in the school environment. Play therapy, a psychological therapy which is most suitable for children, can tackle students' cognitive, social and behavioral problems when applied at school. We also provide an idea of how to apply play therapy in the school environment.

This paper provides an innovative way of improving the quality of the lives of those living with Alzheimer's by designing and implementing a cost-effective Alzheimer's Artificial Intelligence Technologies (AAIT) system. Specifically, this paper describes the solution architecture as well as the design, deployment, and realization of an artificial intelligence enabled system with Internet of Things services, alert services, big data collection, scenarios, and patient data analysis tools. In order to create a faster prototype system for AAIT, a sandbox based approach is presented to leverage workflow automation and Internet services connection platforms. Finally, the conclusions and future directions of AAIT are presented.

The future technologies should center around the human beings. How to let human interact with various state-of-the-art technologies in a straightforward and intuitive way is a grand challenge. Currently human uses hands to interact with the world, however, there are so many scenarios that human is not able to use his hands to control multiple devices/equipment at the same time, for instance, while the hands are busy at carrying stuffs, driving or riding a bicycle. Oftentimes, people do not want to use voice command either. But humans are really good at multi-model interactions using body languages, eye and facial gestures to communicate with each other. It provides a good hint to use eye movements and facial expressions as a compensation to other existing interaction interfaces. In this research project, we aim to build a wearable device that is extremely compact, non-obtrusive, which can be worn comfortably for long hours to identify eye movements and facial expressions. We develop our product - EXGbuds to evaluate this idea of controlling the games in an engaging way.

Screen images are a combination of text, graphics and natural images. They extensively appear in such applications as desktop sharing, remote education, video conference, and so on. Ideal compression efficiency on screen contents is unaffordable by classic image or video coder. This paper proposes a new scheme based on H.264 and Hue-Saturation-Value (HSV) color quantization, which performs color quantification prior to regular H.264 encoding. The experimental results show that the proposed scheme improves more than 1–2 dB at most bit rate settings compared with the traditional compression algorithm.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. 5-Fluorouracil (5-FU) is widely used in the treatment of cancers, but its antineoplastic activity is limited in drug-resistant cancer cells. To investigate the detailed mechanism of 5-FU resistance, we developed a model of 5-FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell line. We found that the drug-resistant cells demonstrated high expression of TCF4 and β-catenin, indicating an upregulated Wnt pathway. A microarray analysis revealed that the suppression of the checkpoint kinase 1 (CHK1) pathway explained the resistance to 5-FU, especially in p53 wild-type cancer cells such as HCT-8. Our data also demonstrated that the CHK1 pathway is suppressed by the Wnt pathway in 5-FU-resistant cells. In summary, we have discovered a novel mechanism for 5-FU resistance mediated by histone deacetylation, which also revealed the crosstalk between the Wnt pathway and CHK1 pathway., Colorectal cancer: pathways to drug resistance The interaction between two signaling pathways may be related to resistance to a leading cancer drug in colorectal cancer cells. The drug 5-fluorouracil (5-FU) is widely used to limit malignant cell proliferation, but some cancers, including colorectal cancers, are resistant to 5-FU. Zhigang Guo at Nanjing Normal University, China, and co-workers have uncovered the signaling pathways behind 5-FU resistance in colorectal cancer cell lines. They found that 5-FU-resistant cells expressed high levels of two proteins indicative of an over-active Wnt signaling pathway, a crucial pathway in healthy development, the disruption of which is implicated in many diseases. This upregulated pathway suppressed another signaling pathway, leading to reduced cancer cell death. This interaction between the pathways could prove to be a valuable therapeutic target to limit resistance to 5-FU.

Self-propagating exothermic reaction has been developed as a heat source to melt solder alloy during interconnection process for its high combustion heat and short duration. The solidification of solder alloy has occurred in a rapid cooling condition, which would be different from the situation of traditional reflow soldering. In this paper, the self-propagating exothermic reaction of Al/Ni multilayer foil was applied to heat the different types of tin-based solder alloys, the corresponding solidification microstructure has been observed with the focus on fusion zone and the interface between solder and Al/Ni multilayer foil. The result indicates that the thickness of fusion zone is within the range of 150.32∼233.10 µm and which is different in Sn, Sn42Bi58, Sn63Pb37 and SAC305 preforms. Moreover, the grains in fusion zone were refined and the unsteady IMCs with small size were generated in fusion zone.

Al/Ni self-propagating nanofoil can be used as a localized and rapid heat source to melt solder and achieve material connection. In this paper, air natural convection, thermal insulation and contacting heat transfer of the bonding process were considered separately to analyze the maximum fusion zone size of Sn solder by FEA model. The simulation works analyzed the temperature field and temperature history of self-propagating reaction of Al/Ni foil with Sn coating. Meanwhile, with the help of the observation of microstructure of tin solder and the temperature measurement data by K-type thermocouple, the finite element model were verified and the cause of different size of grains distribution was analyzed. In addition, preheating temperature and the thickness of Cu or Si substrates were also considered for simulate the maximum thickness of Sn solder layer for soldering process.

Global developmental delay (GDD) affects ~1-3% of children, many of whom will also have intellectual disability (ID). Fragile X is the major genetic cause of GDD with mental retardation (MR) in males, accounting for ~20% of all X-linked MR. As Fragile X has serious genetic implications, the overwhelming majority of developmental delay (DD) cases referred to our laboratory are concerned with the exclusion of a diagnosis of Fragile X, along with simultaneous karyotype analysis to confirm chromosome aberrations. Critically, molecular laboratories have generally experienced a falling positive detection frequency of Fragile X. In this context, the recent implementation of array‑based techno-logy has significantly increased the likelihood of detecting chromosome aberrations that underpin DD. In the current study, we report a Fragile X mutation detection frequency for DD referrals that is comparable with the falling UK detection frequencies. In addition, we find that there is a 9‑fold greater likelihood of detecting clinically significant chromosomal aberrations than of detecting a full Fragile X mental retardation 1 (FMR1) gene CGG repeat expansion in cases referred on the basis of DD. We propose a more efficent sequential testing algorithm that involves an initial molecular karyotype, cascading to FMR1 gene analysis in the event of a negative result.

Self-propagating exothermic reaction of Al/Ni multilayer film has been developed as a heat source with small heat region and high reaction rate in the field of bonding. In this paper, using this kind of localized and rapid heat source, solder preforms with different melting point such as SAC305 (217°C), Au80Sn20 (278°C) and A88Ge12 (356°C) have been applied to achieve the Si/Si bonding includes stacked Si bonding with the condition of 125°C preheating and 2MPa pressures, and the cross-sectional microstructure of bonding joints were observed. Subsequently, the shear tests of Si/Si bonding joints have been conducted and the results proved that the self-propagating exothermic reaction of Al/Ni multilayer is an efficient heat source to achieve the strong Si/Si bonding.

The oral delivery of macromolecular drugs, including proteins and nucleic acids, is one of the greatest unmet needs in modern biomedicine. Although engineering solutions have been used to overcome enzymatic degradation and the low pH in the stomach, poor absorption across the intestinal epithelium into the bloodstream continues to pose the most significant challenge to clinical translation. One common approach to increase the flux of macromolecules across the intestinal epithelium is the use of chemical permeation enhancers. Unfortunately, the vast majority of effective enhancers have been thwarted by toxicity, and the structural and molecular parameters that contribute to this behavior are poorly understood. Previous work has shown that select piperazine-derived molecules favorably affect transepithelial and intracellular delivery outcomes, suggesting that piperazine-derived molecules interface uniquely with cellular barriers. To gain a better understanding of piperazine-mediated permeation enhancement, this work examined piperazine and 13 of its simple, hydrocarbon-substituted derivatives using Caco-2 monolayers as a model of the intestinal epithelium. After evaluating each piperazine for permeation enhancement efficacy and cytotoxicity at three concentrations, it became clear that piperazine derivatives consistently enhance permeability with each derivative resulting in noncytotoxic permeation enhancement at one or more concentrations. In attempting to identify structure-function relationships for the piperazine derivatives, it was found that treatment concentration, structural characteristics, and molecular pKa were not reliable indicators of permeation potential. Interestingly, the pH of the enhancer solution was identified as a controlling parameter even when accounting for the effects from pH change alone. Specifically, piperazine treatments with a pH between 9.2 and 9.6 guaranteed noncytotoxic efficacy. Furthermore, all effective treatments resulted in pH values between 8.7 and 9.6, behavior that was not shared by the other small, noncyclic amines studied. These data have important implications in the design of oral biologic delivery systems that employ permeation enhancers and underscore the need to carefully control the final treatment pH of the local intestinal epithelial environment.

Modern instrumental analytical techniques pervade chemical analyses in the authentication, quality control and research in wines. A potential alternative approach that does not involve the use of expensive analytical equipment, though dependent on availability of suitable chemical receptors, is array sensing. A 3 × 3 array of sensing ensembles that function via indicator displacement assays, and are composed of previously explored boronic acid receptors and indicators, was used for the discrimination of three organic acids commonly found in wine. This array, after finding it suitable for discriminating malate, tartrate and citrate, was used for the pattern-based discrimination of six wine varietals. Linear discriminant analysis of spectroscopic data obtained from the addition of the organic acids and wines to the array showed satisfactory discrimination of all analytes. Such a sensor array is envisioned to ultimately be able to classify wine varietals.

Dedifferentiated liposarcomas (DDLPSs) result in worse patient outcomes than well-differentiated tumors despite shared molecular derangements. Prevalence and pattern of DDLPS systemic metastases have not been extensively reported; information regarding diagnosis, treatment, and outcomes of metastatic DDLPS patients is limited. Our study seeks to address this knowledge gap.Metastatic patients were identified from a clinical database consisting of 277 DDLPS patients treated at the University of Texas M D Anderson Cancer Center (UTMDACC) (1993-2010). Only patients with radiologically demonstrable distant metastases were included. Patient, tumor, treatment, and outcome variables were recorded. Available imaging studies and tumor FFPE blocks were assessed.A total of 40 patients were identified, translating into a DDLPS metastatic rate of 14% (17% for de novo DDLPS and 9% for secondary dedifferentiation). The average patient age was 61 years with a male predilection. The retroperitoneum and lungs were the most common primary and metastatic tumor sites. Any of the 4 described DDLPS morphological subtypes harbored metastatic potential; MFH/UPS-like morphology was the most common. The median time from primary diagnosis to metastasis was 25 months; more than 50% of metastases developed without local failure. The median survival of metastatic patients was 11.5 months; the 5-year DSS was 5.2%. Patients amenable to complete surgical extirpation (n = 14) faired significantly better (P = .001; log rank).Metastatic spread is an ominous consequence of DDLPS, especially regarding de novo tumors. Occurring relatively early in the course of disease and exhibiting a pulmonary predilection, these lesions are highly aggressive and commonly fatal. Further studies to identify metastatic biomarkers are needed.

Porous carbon spheres were prepared through two steps: (a) coating a Na2SnO3 or Na2SiO3 protective layer onto the surface of porous starch, and then (b) carbonizing the products. The carbon spheres were characterized with X-ray diffraction, scanning electron microscopy and Raman spectroscopy. The porous carbon spheres inherited the morphology and texture of the porous starch during carbonization. A mechanism for the morphology preservation of the porous starch is proposed. The electrochemical performance of carbon spheres as anode material of lithium ion battery was detected. It showed that the carbon spheres maintain a specific capacity of 513 mAh/g after 50 cycles.

The metal powder direct and rapid prototyping technology is one of the most developing methods in the laser rapid prototyping technique. The coaxial powder delivery system is the key technique. The purpose of this paper is to introduce a new type of coaxial powder delivery system and simulate the metal powder and shield gas flow in the powder nozzle. 2-D and 3-D model of the new coaxial powder delivery system are established. Then gas-solid two-phase flow model and the k-ɛ turbulent model are selected to simulate the flow of metal powder in powder nozzle. The Euler-Lagrange method is used in the simulating computation. The results show that the new coaxial powder delivery system has stable performance, uniform powder flux, high cooling efficiency, and long useful life.

Biofouling and virus penetration are two significant obstacles in water treatment membrane filtration. Biofouling reduces membrane permeability, increases energy costs, and decreases the lifetime of membranes. In order to effectively remove viruses, nanofiltration or reverse osmosis (both high energy filtration schemes) must be used. Thus, there is an urgent demand for low pressure membranes with anti-biofouling and antiviral properties. The antibacterial properties of silver are well known, and silver nanoparticles (nAg) are now incorporated into a wide variety of consumer products for microbial control. In this study, nAg incorporated into polysulfone ultrafiltration membranes (nAg-PSf) exhibited antimicrobial properties towards a variety of bacteria, including Escherichia coli K12 and Pseudomonas mendocina KR1, and the MS2 bacteriophage. Nanosilver incorporation also increased membrane hydrophilicity, reducing the potential for other types of membrane fouling. XPS analysis indicated a significant loss of silver from the membrane surface after a relatively short filtration period (0.4 L/cm2) even though ICP analysis of digested membrane material showed that 90% of the added silver remained in the membrane. This silver loss resulted in a significant loss of antibacterial and antiviral activity. Thus, successful fabrication of nAg-impregnated membranes needs to allow for the release of sufficient silver ions for microbial control while preventing a rapid depletion of silver.

We present here the complete genome sequences of nine phages that infect Paenibacillus larvae , the causative agent of American foulbrood disease in honeybees. The phages were isolated from soil, propolis, and infected bees from three U.S. states. This is the largest number of P. larvae phage genomes sequenced in a single publication to date.

Introduction: Many missense variants in G protein-coupled receptors (GPCRs) involved in the neuroendocrine regulation of reproduction have been identified by phenotype-driven or large-scale exome sequencing. Computational functional prediction analysis is commonly performed to evaluate their impact on receptor function. Methods: To assess the performance and outcome of functional prediction analyses for these GPCRs, we performed a statistical analysis of the prediction performance of SIFT and PolyPhen-2 for variants with documented biological function as well as variants retrieved from Ensembl. We obtained missense variants with documented biological function testing from patients with reproductive disorders from a comprehensive literature search. Missense variants from individuals with known reproductive disorders were retrieved from the Human Gene Mutation Database. Missense variants from the general population were retrieved from the Ensembl genome database. Results: The accuracies of SIFT and PolyPhen-2 were 83 and 85%, respectively. The performance of both prediction tools was greater in predicting loss-of-function variants (SIFT: 92%; PolyPhen-2: 95%) than in predicting variants that did not affect function (SIFT: 54%; PolyPhen-2: 57%). Concordance between SIFT and PolyPhen-2 did not improve accuracy. Surprisingly, approximately half of the variants retrieved from Ensembl were predicted as loss-of-function variants by SIFT (47%) and PolyPhen-2 (54%). Conclusion: Our findings provide new guidance for interpreting the results and limitations of computational functional prediction analyses for GPCRs and will help to determine which variants require biological function testing. In addition, our findings raise important questions regarding the link between genotype and phenotype in the general population.

Abnormalities of a key repolarizing cardiac potassium current, the fast transient outward potassium current, I to,f , are associated with both heart failure and congenital arrhythmia syndromes. However, the precise role of I to,f in shaping action potential waveforms remains unclear. This study was designed to define the functional role of the fast transient outward potassium current, I to,f , in shaping action potentials in human iPSC-derived cardiomyocytes (iPSC-CMs). Most iPSC-CMs (29 of 43 cells) demonstrated spontaneous electrical activity, slow upstroke velocity (63±71 V/s), a wide range of action potential durations (APD90 = 860±722 ms) and heterogeneous action potential waveforms. Using dynamic current clamp, a modeled human ventricular inwardly rectifying K + current, I K1 , was introduced into iPSC-CMs, resulting in silencing of spontaneous activity, hyperpolarization of the resting membrane potential (RMP = -90±3 mV), increased peak upstroke velocity (dV/dt = 346±71 V/s) and decreased APD90 (420±211 ms) to values similar to those recorded in isolated adult human ventricular myocytes (RMP = -84±3 mV, dV/dt = 348±101 V/s and APD90 = 468±133 ms, all p>0.05). Importantly, a ventricular-like action potential waveform was observed in 25 of the 26 cells studied following the dynamic clamp addition of I K1 . Using these cells as a model of human ventricular myocytes, further dynamic current clamp experiments introduced a modeled human fast transient outward K + current, I to,f , and revealed that increasing in the amplitude of I to,f results in an increase in the phase 1 notch and a progressive shortening of the action potential duration in iPSC-CMs. Together, the experiments here demonstrate that combining human iPSC-CMs with the power of the dynamic current clamp technique to modulate directly and precisely the “expression” of individual ionic currents provides a novel and quantitative approach to defining the roles of specific ionic conductances in regulating the excitability of human cardiomyocytes.

Objective To analyze the GNRHR in patients with normosmic isolated hypogonadotropic hypogonadism (IHH) and constitutional delay of growth and puberty (CDGP). Design Molecular analysis and in vitro experiments correlated with phenotype. Setting Academic medical center. Patient(s) A total of 110 individuals with normosmic IHH (74 male patients) and 50 with CDGP. Intervention(s) GNRHR coding region was amplified and sequenced. Main Outcome Measure(s) Novel variants were submitted to in vitro analysis. Frequency of mutations and genotype-phenotype correlation were analyzed. Microsatellite markers flanking GNRHR were examined in patients carrying the same mutation to investigate a possible founder effect. Result(s) Eleven IHH patients (10%) carried biallelic GNRHR mutations. In vitro analysis of novel variants (p.Y283H and p.V134G) demonstrated complete inactivation. The founder effect study revealed that Brazilian patients carrying the p.R139H mutation shared the same haplotype. Phenotypic spectrum in patients with GNRHR mutations varied from complete GnRH deficiency to partial and reversible IHH, with a relatively good genotype-phenotype correlation. One boy with CDGP was heterozygous for the p.Q106R variant, which was not considered to be pathogenic. Conclusion(s) GNRHR mutations are a frequent cause of congenital normosmic IHH and should be the first candidate gene for genetic screening in this condition, especially in autosomal recessive familial cases. The founder effect study suggested that the p.R139H mutation arises from a common ancestor in the Brazilian population. Finally, mutations in GNRHR do not appear to be involved in the pathogenesis of CDGP.

Irregular porous carbon spheres were successfully prepared from Na 2 SnO 3 coated corn porous starch by carbonization. The product was characterized with X-ray diffraction and scanning electron microscope (SEM). It is verified that the irregular porous carbon spheres are composed of disordered carbon, and the skeleton and pores of the corn porous starch was well preserved after carbonization. The pore size of the irregular porous carbon spheres is almost the same, which is similar to that of the porous starch. And the pore size decreases from about 0.91 μm to 0.53 μm measured from the SEM pictures. The texture of the irregular porous carbon spheres is mainly determined by that of porous starch.

We propose to monitor the liquid-solid and gas-liquid phase transition of water based on FBG sensors. The naked FBGs and the packaged FBG temperature sensors are used to monitoring the liquid-solid phase transition of water at the same time in order to find its characteristics, including the supercooling state and the strain and pressure change introduced by the phase transition. Fourteen FBGs are packaged and arranged in a steam boiler in order to monitor the gas-liquid phase transition, including the temperature and pressure change inside the steam boiler and the strain of the boiler wall. The preliminary experimental results are demonstrated here.

A C 2 H 5 OH gas sensor based on a LPFG coated with the T i O 2 nano-film is presented.Based on LPmodes,the four-layer model is studied the change of the effective refractive indics and the resonance wavelength of cladding modes as the thickness of overlay increased.The elementary experimental results show that the wavelength of the LPFG loss peak is shifted by ~1.7nm for the case of the T i O 2 nano-film of ~80nm in thickness when the concentration of surrounding C 2 H 5 OH gas is 1000ppm. And the sensitivity is 1.7 10 -3 nm/ppm. The results indicate that the LPFG sensor is highly sensitive to C 2 H 5 OH gas and the sensing scheme is feasible.

We study a novel multi-parameter sensing device based on writing Bragg grating in the multimode fiber of single-multi-single mode fiber structure. The theoretical analysis of the novel device is given based on a compound coupled mode theory. The simulation results of strain and temperature sensing simultaneous are demonstrated, and the elementary results of the refractive index sensing with temperature-compensation are also given.

Hedge fund investors' tendency to focus on long-term performance strengthens hedge fund stability, according to this issue of the Economic Letter.