Although capacity credits for wind power have been embodied in power systems in the U.S. and Europe, the current planning framework for electricity in China continues to treat wind power as a non-dispatchable source with zero contribution to firm capacity. This study presents a rigorous reliability model for the electric power system evaluating capacity credits that could be recognized for offshore wind resources supplying power for Jiangsu, China, which accounts for 10% of the total electricity consumed in China. Demand for electricity in Jiangsu is projected to increase from 331 TWh in 2009 to 800 TWh by 2030. Given a wind penetration level of 60% for the future additional Jiangsu power supply, wind resources distributed along the offshore region of five coastal provinces in China (Shandong, Jiangsu, Shanghai, Zhejiang and Fujian) could earn a capacity credit of 12.9%, the fraction of installed wind capacity that should be recognized to displace coal-fired systems without violating reliability standards. In the high-coal-price scenario, with 60% wind penetration, reductions in CO2 emissions relative to a business as usual reference could be as large as 200.3 million tons of CO2 or 51.8% of the potential addition, with a cost for emissions avoided of $29.0 per ton.
The temporal resolution of current computed tomography (CT) systems is limited by the rotation speed of their gantries.OBJECTIVE: A helical interlaced source detector array (HISDA) CT, which is a stationary CT system with distributed X-ray sources and detectors, is presented in this paper to overcome the aforementioned limitation and achieve high temporal resolution.METHODS: Projection data can be obtained from different angles in a short time and do not require source, detector, or object motion. Axial coverage speed is increased further by employing a parallel scan scheme. Interpolation is employed to approximate the missing data in the gaps, and then a Katsevich-type reconstruction algorithm is applied to enable an approximate reconstruction.RESULTS: The proposed algorithm suppressed the cone beam and gap-induced artifacts in HISDA CT. The results also suggest that gap-induced artifacts can be reduced by employing a large helical pitch for a fixed gap height.CONCLUSIONS: HISDA CT is a promising 3D dynamic imaging architecture given its good temporal resolution and stationary advantage.
Human connectomes constructed via neuroimaging data offer a comprehensive description of the macro-scale structural connectivity within the brain. Thus quantitative assessment of connectome-scale structural and functional connectivities will not only fundamentally advance our understanding of normal brain organization and function, but also have significant importance to systematically and comprehensively characterize many devastating brain conditions. In recognition of the importance of connectome and connectomics, in this paper, we develop and evaluate a novel computational framework to construct structural connectomes from diffusion tensor imaging (DTI) data and assess connectome-scale functional connectivity alterations in mild cognitive impairment (MCI) and schizophrenia (SZ) from concurrent resting state fMRI (R-fMRI) data, in comparison with their healthy controls. By applying effective feature selection approaches, we discovered informative and robust functional connectomics signatures that can distinctively characterize and successfully differentiate the two brain conditions of MCI and SZ from their healthy controls (classification accuracies are 96% and 100%, respectively). Our results suggest that connectomics signatures could be a general, powerful methodology for characterization and classification of many brain conditions in the future.
Tulane virus (TV), the prototype of the Recovirus genus in the calicivirus family, was isolated in the stools of rhesus monkeys and can be cultivated in vitro in monkey kidney cells. TV is genetically closely related to the Norovirus genus and recognizes the histo-blood group antigens (HBGAs) like human noroviruses (NoVs), making it a valuable surrogate for human NoVs. However, the precise structures of HBGAs recognized by TV remain elusive. In this study, we performed binding and blocking experiments on TV with extended HBGA types and showed that, while TV binds all four types (types 1 to 4) of the B antigens, it recognizes only the A-type 3 antigen among four types of A antigens tested. The requirements of HBGAs in TV replication were demonstrated by blocking of TV replication in cell culture using the A-type 3/4 and B saliva samples. Similar results were also observed in oligosaccharide-based blocking assays. Importantly, the previously reported, unexplained increase of TV replication by oligosaccharide in cell-based blocking assays has been clarified, which will facilitate the application of TV as a surrogate for human NoVs.
The binding profiles of many human noroviruses (huNoVs) for human histo-blood group antigens have been characterized. However, quantitative-binding data for these important virus-host interactions are lacking. Here, we report on the intrinsic (per binding site) affinities of HBGA oligosaccharides for the huNoV VA387 virus-like particles (VLPs) and the associated subviral P particles measured using electrospray ionization mass spectrometry. The affinities of 13 HBGA oligosaccharides, containing A, B and H epitopes, with variable sizes (disaccharide to tetrasaccharide) and different precursor chain types (types 1, 2, 3, 5 and 6), were measured for the P particle, while the affinities of the A and B trisaccharides and A and B type 6 tetrasaccharides for the VLP were determined. The intrinsic affinities of the HBGA oligosaccharides for the P particle range from 500 to 2300 M(-1), while those of the A and B trisaccharides and the A and B type 6 tetrasaccharides for the VLP range from 1000 to 4000 M(-1). Comparison of these binding data with those measured previously for the corresponding P dimer reveals that the HBGA oligosaccharides tested exhibit similar intrinsic affinities for the P dimer and P particle. The intrinsic affinities for the VLP are consistently higher than those measured for the P particle, but within a factor of three. While the cause of the subtle differences in HBGA oligosaccharide affinities for the P dimer and P particle and those for the VLP remains unknown, the present data support the use of P dimers or P particles as surrogates to the VLP for huNoV-receptor-binding studies.
In a long-term large cohort study, we introduced an electronic money system for remuneration of research participants. In comparison with the delivery of cash vouchers, the operation and mailing cost, and the processing time were significantly reduced. The workers were also able to save the time and effort they spent on the inventory management of cash vouchers. In addition, risk management was improved, as demonstrated by the reduction of complaints and associated problems such as nonarrival or content differences of cash vouchers. This is because only card points as additional money need to be added once the electronic money card has been distributed to the recipients. Furthermore, the psychological stress of workers associated with inventory management and ensuring cash voucher enclosure was also reduced.
Newborn neurons migrate along the processes of radial glial cells (RGCs) to reach their final positions in the cortex. Here, we visualized individual migrating neurons and RGCs using in utero electroporation. We show that branching of migrating neurons and RGCs is closely correlated spatiotemporally with the distribution of Reelin. Time-lapse imaging revealed that the leading processes of migrating neurons gave rise to increasingly more branches once their growth cones contacted the Reelin-containing marginal zone. This was accompanied by translocation of the nucleus and gradual shortening of the leading process. Absence of Reelin in reeler mice altered these processes resulting in misorientation, loss of bipolarity, and aberrant migration of cortical neurons. Moreover, in reeler, the branching of the basal processes of RGCs in the marginal zone was severely disrupted. Consistent with previous reports, we show that in dissociated reeler cortical cultures, exposure to recombinant Reelin enhanced dendritic complexity and glial branching. Our results suggest that Reelin induces branching of the leading processes of migrating neurons and that of basal processes of RGCs when they arrive at the Reelin-containing marginal zone. Branching of these processes may be crucial for the termination of nuclear translocation during the migratory process and for correct neuronal positioning.
Knölker's iron complex is a "green" catalyst that exhibits low toxicity and is abundant in nature. Density functional theory (DFT) was used to explore the highly chemoselective nature of the catalytic hydrogenation of CH2?CHCH2CHO. An outer-sphere concerted hydrogen transfer was found to be the most reasonable kinetic route for the hydrogenation of the olefin. However, the C?C hydrogenation reaction has a high free energy barrier of 28.1 kcal/mol, requiring a high temperature to overcome. By comparison, the CH?O bond concerted hydrogen-transfer reaction catalyzed using Knölker's iron catalyst has an energy barrier of only 14.0 kcal/mol. Therefore, only the CH?O of CH2?CHCH2CHO can be hydrogenated in the presence of Knölker's catalyst at room temperature, due to kinetic domination. All computational results were in good agreement with experimental results.
A novel method for the synthesis of non-natural L- and D-amino acids by a Ni-catalyzed reductive cross-coupling reaction is described. This strategy enables the racemization-free cross-coupling of serine/homoserine- derived iodides with aryl/acyl/alkyl halides. It provides convenient access to varieties of enantiopure and functionalized amino acids, which are important building blocks in bioactive compounds and pharmaceuticals.
A copper-catalyzed reductive cross-coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost-effective construction of aryl-alkyl and alkyl-alkyl C?C bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo- or heterocycles, such as 2,3-dihydrobenzofuran and benzochromene derivatives.
Human noroviruses (NoVs) are known to recognize histo-blood group antigens (HBGAs) as attachment factors. We report the first experimental evidence that sialic acid-containing glycosphingolipids (gangliosides) are also ligands for human NoVs. Electrospray ionization mass spectrometry-based carbohydrate binding measurements performed on assemblies (P dimer, P particle, and virus-like particle) of recombinant viral capsid proteins of two NoV strains, VA387 (GII.4) and VA115 (GI.3), identified binding to the oligosaccharides of mono-, di-, and trisialylated gangliosides. The intrinsic (per binding site) affinities measured for these ligands are similar in magnitude (10(2)-10(3) M(-1)) to those of human HBGAs. Binding of NoV VLPs, P particles, and glutathione S-transferase (GST)-P domain fusion proteins to sialic acid-containing glycoconjugates, observed in enzyme-linked immunosorbent assays, provided additional confirmation of the NoV-ganglioside interactions.
The use of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) for study and treatment of bone diseases or traumatic bone injuries requires efficient protocols to differentiate hESCs/iPSCs into cells with osteogenic potential and the ability to isolate differentiated osteoblasts for analysis. We have used zinc finger nuclease technology to deliver a construct containing the Col2.3 promoter driving GFPemerald to the AAVS1 site (referred to as a "safe harbor" site), in human embryonic stem cells (H9Zn2.3GFP), with the goal of marking the cells that have become differentiated osteoblasts. In teratomas formed using these cells, we identified green fluorescent protein (GFP)-positive cells specifically associated with in vivo bone formation. We also differentiated the cells into a mesenchymal stem cell population with osteogenic potential and implanted them into a mouse calvarial defect model. We observed GFP-positive cells associated with alizarin complexone-labeled newly formed bone surfaces. The cells were alkaline phosphatase-positive, and immunohistochemistry with human specific bone sialoprotein (BSP) antibody indicates that the GFP-positive cells are also associated with the human BSP-containing matrix, demonstrating that the Col2.3GFP construct marks cells in the osteoblast lineage. Single-cell cloning generated a 100% Col2.3GFP-positive cell population, as demonstrated by fluorescence in situ hybridization using a GFP probe. The karyotype was normal, and pluripotency was demonstrated by Tra1-60 immunostaining, pluripotent low density reverse transcription-polymerase chain reaction array and embryoid body formation. These cells will be useful to develop optimal osteogenic differentiation protocols and to isolate osteoblasts from normal and diseased iPSCs for analysis.
A copper-catalyzed Suzuki-Miyaura coupling of benzyl halides with arylboronates is described. Varieties of primary benzyl halides as well as more challenging secondary benzyl halides with ? hydrogens or steric hindrance could be successfully converted into the corresponding products. Thus it provides access to diarylmethanes, diarylethanes and triarylmethanes.
Abstract Alzheimer's disease (AD) is the most common type of dementia (accounting for 60% to 80%) and is the fifth leading cause of death for those people who are 65 or older. By 2050, one new case of AD in United States is expected to develop every 33?sec. Unfortunately, there is no available effective treatment that can stop or slow the death of neurons that causes AD symptoms. On the other hand, it is widely believed that AD starts before development of the associated symptoms, so its prestages, including mild cognitive impairment (MCI) or even significant memory concern (SMC), have received increasing attention, not only because of their potential as a precursor of AD, but also as a possible predictor of conversion to other neurodegenerative diseases. Although these prestages have been defined clinically, accurate/efficient diagnosis is still challenging. Moreover, brain functional abnormalities behind those alterations and conversions are still unclear. In this article, by developing novel sparse representations of whole-brain resting-state functional magnetic resonance imaging signals and by using the most updated Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we successfully identified multiple functional components simultaneously, and which potentially represent those intrinsic functional networks involved in the resting-state activities. Interestingly, these identified functional components contain all the resting-state networks obtained from traditional independent-component analysis. Moreover, by using the features derived from those functional components, it yields high classification accuracy for both AD (94%) and MCI (92%) versus normal controls. Even for SMC we can still have 92% accuracy.
Spectral computed tomography (CT) has attracted considerable attention because of its energy-resolving capability in identifying and discriminating materials. The use of a narrow energy bin can improve energy resolution. However, a narrow energy bin has high noise ratio, which degrades the imaging quality of spectral CT. To address this problem, this study exploits the structure correlations of images in the energy domain and proposed two types of united iterative reconstruction (UIR) algorithms. One type uses the well-reconstructed broad-spectrum image, with all available photons, as a constraint, whereas the other type uses a pseudo narrow-energy image, which is estimated with the use of our proposed structure-coupling (SC) method, as a constraint. The SC method utilizes local structures to connect images that are reconstructed with broad-spectrum and narrow-energy CT datasets. Given a broad-spectrum image, the SC method can accurately estimate its corresponding narrow-energy image. Results show that UIR algorithms significantly outperform conventional iterative reconstruction algorithms for narrow-energy image reconstruction in spectral CT. Among the UIR algorithms, SC-UIR yields the best results.
A series of microgel particles composed of a polystyrene (PS) core and a thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) shell with different shell thicknesses were investigated to elucidate the effect of microgel softness on its shear thickening behavior. Since the softness of the microgels increases with decreasing temperature through the volume phase transition effect of PNIPAM shell, the measured softness parameter, n, which is derived from the Zwanzig-Mountain equation, was used to measure and describe the combined influences of temperature and shell thickness. Confocal microscopy is used to investigate the interaction potential between microgel particles with different softness parameters. According to the obtained results, the softness parameter can provide an estimate for the shear thickening behavior of microgel suspensions, at least semi-quantitatively.
The detection of single amino-acid variants (SAVs) usually depends on single-nucleotide polymorphisms (SNPs) database. Here, we describe a novel method that discovers SAVs at proteome level independent of SNPs data. Using mass spectrometry-based de novo sequencing algorithm, peptide-candidates are identified and compared with theoretical protein database to generate SAVs under pairing strategy, which is followed by database re-searching to control false discovery rate. In human brain tissues, we can confidently identify known and novel protein variants with diverse origins. Combined with DNA/RNA sequencing, we verify SAVs derived from DNA mutations, RNA alternative splicing, and unknown post-transcriptional mechanisms. Furthermore, quantitative analysis in human brain tissues reveals several tissue-specific differential expressions of SAVs. This approach provides a novel access to high-throughput detection of protein variants, which may offer the potential for clinical biomarker discovery and mechanistic research.
We investigated the specificity and structures of job-related stress in psychiatric dementia nurses (PDNs) caring for elderly patients with serious behavioral and psychological symptoms of dementia who required substantial assistance with activities of daily living, in order to obtain fundamental knowledge toward providing mental health care for these nurses.
Stem cell-based tissue engineering for large bone defect healing has attracted enormous attention in regenerative medicine. However, sufficient osseointegration of the grafts combined with exogenous stem cells still remains a major challenge. Here we developed a material approach to modulate the integration of the grafts to the host tissue when exogenous bone marrow stromal cells (BMSCs) were used as donor cells. Distinctive osseointegration of bone grafts was observed as we varied the content of hydroxyapatite (HA) in the tissue scaffolds implanted in a mouse femur model. More than 80% of new bone was formed in the first two weeks of implantation in high HA content scaffold but lack of host integration while only less than 5% of the new bone was formed during this time period in the no HA group but with much stronger host integration. Cell origin analysis leveraging GFP reporter indicates new bone in HA containing groups was mainly derived from donor BMSCs. In comparison, both host and donor cells were found on new bone surface in the no HA groups which led to seamless bridging between host tissue and the scaffold. Most importantly, host integration during bone formation is closely dictated to the content of HA present in the scaffolds. Taken together, we demonstrate a material approach to modulate the osseointegration of bone grafts in the context of exogenous stem cell-based bone healing strategy which might lead to fully functional bone tissue regeneration.
The study aims to provide a theoretical guidance of postmaxillary implant in the augmented sinus without grafting materials by establishing a three-dimensional model of this new implant restorative technique, evaluating failure risk of sinus augmentation without grafting materials of different alveolar ridge heights, and analyzing stress distribution of different healing stage.
We have investigated the clinical characteristics and prognostic factors of squamous cell carcinoma (SCC) of the tongue after definitive radiotherapy for nasopharyngeal carcinoma, and evaluated the effect of common therapeutic regimens for these patients. We retrospectively reviewed follow-up data for patients whose nasopharyngeal carcinoma had been treated by radiotherapy, and selected the 68 who had then developed SCC of the tongue, in the border of the tongue in half, and in the dorsum in 25 (37%). Eight of the 68 patients had clinical lymph node metastasis (12%), and 45 presented with stage I-II disease at the time of the diagnosis of the SCC (66%). Resection or radiotherapy alone was an effective treatment for patients with stage I-II SCC of the tongue, but patients with stage III-IV disease had a poor prognosis, despite being given multidisciplinary treatment. Multivariate analysis showed that the risk factors that independently influenced the survival of these patients were use of alcohol, recurrence of their nasopharyngeal carcinoma, the latency period, and the clinical TNM stage. Tongue SCC after radiotherapy was generally at an early stage and commonly occurred on the border or the dorsum of the tongue, with few lymph node metastases. Resection or radiotherapy is an effective treatment, and the risk factors that independently influenced the survival of patients indicate that improving the technique of radiotherapy and close follow-up after nasopharyngeal cancer are vitally important.
A solid-phase extraction (SPE) method using multi-walled carbon nanotubes as adsorbent coupled with high-performance liquid chromatography was developed for the determination of four pyrazole and pyrrole pesticides (fenpyroximate, chlorfenapyr, fipronil and flusilazole) in environmental water samples. Several parameters, such as extraction adsorbent, elution solvent and volume and sample loading flow rate were optimized to obtain high SPE recoveries and extraction efficiency. The calibration curves for the pesticides extracted were linear in the range of 0.05-10 ?g L(-1) for chlorfenapyr and fenpyroximate and 0.05-20 ?g L(-1) for fipronil and flusilazole, with the correlation coefficients (r(2)) between 0.9966 and 0.9990. The method gave good precisions (relative standard deviation %) from 2.9 to 10.1% for real spiked samples from reservoir water and seawater; method recoveries ranged 92.2-105.9 and 98.5-103.9% for real spiked samples from reservoir water and seawater, respectively. Limits of detection (S/N = 3) for the method were determined to be 8-19 ng L(-1). The optimized method was successfully applied to the determination of four pesticides of pyrazoles and pyrroles in real environmental water samples.
Human norovirus infection is the most common cause of viral gastroenteritis worldwide. Development of an effective vaccine is required for reducing norovirus outbreaks. The inability to grow human norovirus in cell culture has hindered the development of live-attenuated vaccines. To overcome this obstacle, we generated a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We compared two different NDV vectors, a conventional rNDV vector and a modified rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed that the modified vector replicated to higher titers and expressed higher levels of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs than did the conventional vector. We further demonstrated that the VP1 protein produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that are morphologically similar to baculovirus-expressed VLPs. Evaluation of their immunogenicity in mice showed that the modified rNDV vector induced a higher level of IgG response than those induced by the conventional vector and by the baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass antibody for the Th1 response, and specifically, high levels of gamma interferon (IFN-?), tumor necrosis factor alpha (TNF-?), and interleukin-2 (IL-2) were detected in splenocytes. In addition, the modified rNDV vector induced a higher level of fecal IgA response in mice than did baculovirus-expressed VLPs. Our findings suggest that the rNDV vector is an efficient system to produce cost-effective VLPs in embryonated chicken eggs and has the potential to be used as a live-attenuated vaccine in humans.
Noroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis worldwide in people of all ages. The P particle is a novel vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. This study utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies of primary infection, P particles, and virus-like particles (VLPs) against NoV infection and disease and the T cell responses to these treatments. Pigs either were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b variant and monitored for diarrhea and virus shedding for 7 days. The T cell responses in intestinal and systemic lymphoid tissues were examined. Primary NoV infection provided 83% homologous protection against diarrhea and 49% homologous protection against virus shedding, while the P particle and VLP vaccines provided cross-variant protection (47% and 60%, respectively) against diarrhea. The protection rates against diarrhea are significantly inversely correlated with T cell expansion in the duodenum and are positively correlated with T cell expansion in the ileum and spleen. The P particle vaccine primed for stronger immune responses than VLPs, including significantly higher numbers of activated CD4+ T cells in all tissues, gamma interferon-producing (IFN-?+) CD8+ T cells in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth factor ? (TGF-?)-producing CD4+ CD25- FoxP3+ Tregs in the spleen postchallenge, indicating that P particles are more immunogenic than VLPs at the same dose. In conclusion, the P particle vaccine is a promising vaccine candidate worthy of further development.
Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of Src family kinase, plays an important role in neuronal migration by binding to its myriad substrates. However, the role of Src homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for action of Fyn on neuronal migration and cortical lamination. Point mutation of Fyn SH2 domain (FynR176A) impaires neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.
Knölker's iron catalyst is characterized by low toxicity and relatively low price in comparison with precious metal catalysts. Density functional theory was used to explore improvements to this catalyst. It was found that electron-withdrawing substituents on the CpOH ring are favorable for improving the efficiency of iron catalysts. Increasing the acidity of CpOH is also an available means of improving the catalytic efficiency. However, replacing the hydroxyl of CpOH with the amino group is not a valid choice for improvement. In contrast, substituting phosphine ligands for carbonyls is the most effective method for improving the catalytic activity of the iron catalyst. But the PR3 ligand must have electron-donating groups and its steric effect should be controlled in a suitable range. Replacing carbonyl groups by PH3 and PPhH2 ligands can effectually improve the catalytic activity for hydrogenation of ketones.
The concentrations and size distributions of organic carbon (OC) and elemental carbon (EC) in particles collected in Nanjing Normal University representing urban area and in Nanjing College of Chemical Technology standing for industrial area were analyzed using Model 2001A Thermal Optical Carbon Analyzer. The mass concentrations were the highest with the size below 0.43 microm in urban and industrial area. OC accounted for 20.9%, 21.9%, 29.6%, 27.9% respectively and those were 24.0%, 23.5%, 31.4%, 22.6% respectively for EC in the four seasons in urban area. In the industrial area, OC accounted for 18.6%, 45.8%, 26.6%, 25.9% respectively and the proportions of EC were 16.7%, 60.9%, 26.3%, 24.3% respectively. Overall, OC and EC were enriched in fine particles below 2.1 microm and they accounted for the highest proportion in summer in urban area while it did not show significant seasonal variation for industrial area. SOC in fine particles achieved high values in summer while the unobvious seasonal variation in coarse particles might be attributed to the contribution of different pollution sources and meteorological factors. Correlations and OC/EC ratio method implied that OC and EC mainly came from vehicles exhaust and coal combustion in fine particles while they were also related to biomass combustion and cooking in coarse particles.
Decision-making, as a way to discover the preference of ranking, has been used in various fields. However, owing to the uncertainty in group decision-making, how to rank alternatives by incomplete pairwise comparisons has become an open issue. In this paper, an improved method is proposed for ranking of alternatives by incomplete pairwise comparisons using Dempster-Shafer evidence theory and information entropy. Firstly, taking the probability assignment of the chosen preference into consideration, the comparison of alternatives to each group is addressed. Experiments verified that the information entropy of the data itself can determine the different weight of each group's choices objectively. Numerical examples in group decision-making environments are used to test the effectiveness of the proposed method. Moreover, the divergence of ranking mechanism is analyzed briefly in conclusion section.
The mammalian cerebral cortex develops through the coordinated migration of postmitotic neurons. Fyn, a member of the Src tyrosine kinase family (SFKs), is involved in the neuronal migration and the absence of Fyn leads to abnormal migration. However, the molecular mechanism whereby Fyn acts on migrating neurons has remained unclear. Here, we employed two Fyn mutants (Fyn259T and FynD390A) to investigate the function of Fyn kinase domain in neuronal migration. Using in utero electroporation, we co-transfected the migrating neurons in embryonic cortex with these mutants combined with plasmid expressing GFP. Interestingly, although both of them impaired neuronal migration, FynD390A, rather than Fyn259T, induced remarkable morphology change. Our work provides in vivo and in vitro evidence that the aspartic acid of Fyn at 390 is indispensable for the radial migration, and it is required for precise cooperation with focal adhesion kinase.
Noroviruses (NoVs) are important pathogens causing epidemic acute gastroenteritis affecting millions of people worldwide. Due to the inability to cultivate NoVs, current NoV vaccine development relies on bioengineering technologies to produce virus-like particles (VLPs) and other subviral particles of NoVs as subunit vaccines. The first VLP vaccine has reached phase II clinical trials and several others are under development in pre-clinical research. Several subviral complexes made from the protruding (P) domains of NoV capsid share common features of easy production, high stability and high immunogenicity and thus are candidates for low cost vaccines. These P domain complexes can also be used as vaccine platforms to present foreign antigens for potential dual vaccines against NoVs and other pathogens. Development of NoV vaccines also faces other challenges, including genetic diversity of NoVs, limit understanding of NoV immunology and evolution, and lack of an efficient NoV animal model for vaccine assessment, which are discussed in this article.
6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment.
To evaluate the applicability, accuracy and clinical outcome of the computer assisted design and computer assisted manufacture (CAD & CAM) tooth-supported implant surgical guide in the mandibular free-end partially edentulous patients with insufficient vertical bone height.
Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies (i.e., protein complexes and viruses). Although single particle cryo-EM requires less concentrated and smaller amounts of samples than X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques can potentially further extend single particle cryo-EM to these challenging samples by combining sample purification and cryo-EM grid preparation into a single step. Here we report a new design of affinity cryo-EM approach, cryo-SPIEM, that applies a traditional pathogen diagnosis tool Solid Phase Immune Electron Microscopy (SPIEM) to the single particle cryo-EM method. This approach provides an alternative, largely simplified and easier to use affinity grid that directly works with most native macromolecular complexes with established antibodies, and enables cryo-EM studies of native samples directly from cell cultures. In the present work, we extensively tested the feasibility of cryo-SPIEM with multiple samples including those of high or low molecular weight, macromolecules with low or high symmetry, His-tagged or native particles, and high- or low-yield macromolecules. Results for all these samples (non-purified His-tagged bacteriophage T7, His-tagged Escherichiacoli ribosomes, native Sindbis virus, and purified but low-concentration native Tulane virus) demonstrated the capability of cryo-SPIEM approach in specifically trapping and concentrating target particles on TEM grids with minimal view constraints for cryo-EM imaging and determination of 3D structures.
Many pathogens produce the ?-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from different serogroups expressed PNAG. Vaccine-induced antibody mediated in vitro killing of STEC and neutralization of both Stx1 and Stx2. Passive administration of antibody to the conjugate showed protection requiring immunity to both PNAG and Stx for O157 strains, although for an O104 strain, antibody to PNAG alone was protective. Immunity to PNAG may contribute to protection against STEC infections.
Many viral structural proteins and their truncated domains share a common feature of homotypic interaction forming dimers, trimers, and/or oligomers with various valences. We reported previously a simple strategy for construction of linear and network polymers through the dimerization feature of viral proteins for vaccine development. In this study, technologies were developed to produce more sophisticated polyvalent complexes through both the dimerization and oligomerization natures of viral antigens. As proof of concept, branched-linear and agglomerate polymers were made via fusions of the dimeric glutathione-s-transferase (GST) with either a tetrameric hepatitis E virus (HEV) protruding protein or a 24-meric norovirus (NoV) protruding protein. Furthermore, a monomeric antigen, either the M2e epitope of influenza A virus or the VP8* antigen of rotavirus, was inserted and displayed by the polymer platform. All resulting polymers were easily produced in Escherichia coli at high yields. Immunization of mice showed that the polymer vaccines induced significantly higher specific humoral and T cell responses than those induced by the dimeric antigens. Additional evidence in supporting use of polymer vaccines included the significantly higher neutralization activity and protective immunity of the polymer vaccines against the corresponding viruses than those of the dimer vaccines. Thus, our technology for production of polymers containing different viral antigens offers a strategy for vaccine development against infectious pathogens and their associated diseases.
Noroviruses (NoVs) and rotaviruses (RVs), the two most important causes of viral acute gastroenteritis, are found to recognise histo-blood group antigens (HBGAs) as receptors or ligands for attachment. Human HBGAs are highly polymorphic containing ABO, secretor and Lewis antigens. In addition, both NoVs and RVs are highly diverse in how they recognise these HBGAs. Structural analysis of the HBGA-binding interfaces of NoVs revealed a conserved central binding pocket (CBP) interacting with a common major binding saccharide (MaBS) of HBGAs and a variable surrounding region interacting with additional minor binding saccharides. The conserved CBP indicates a strong selection of NoVs by the host HBGAs, whereas the variable surrounding region explains the diverse recognition patterns of different HBGAs by NoVs and RVs as functional adaptations of the viruses to human HBGAs. Diverse recognition of HBGAs has also been found in bacterial pathogen Helicobacter pylori. Thus, exploratory research into whether such diverse recognitions also occur for other viral and bacterial pathogens that recognise HBGAs is warranted.
Radial spoke protein 3 (RSP3) was first identified in Chlamydomonas as a component of the radial spoke. The mammalian homologue of the Chlamydomonas RSP3 gene is mainly expressed in testis and developing central nervous system (CNS). However, the subcellular localization and function of mammalian RSP3 in the developing brain and mammalian cells remain poorly understood. Here we show that the mouse RSP3 accumulates at the perinuclear region of Chinese hamster ovary (CHO) and 293T cells. Detailed analysis shows that the mouse RSP3 is not co-localized with the endoplasmic reticulum or Golgi apparatus markers in CHO cells. Using in utero electroporation, we found that over-expression of mammalian RSP3 increases the percentage of neurons reaching the upper cortical plate. In vivo analysis shows that the mouse RSP3 mainly accumulates in the proximal cytoplasmic dilation of the leading process of the migrating cortical neurons. Furthermore, we find that the mammalian RSP3 concentrates in the ependymal cilia as a component of the cilia. Thus, our data provide the first evidence for the subcellular localization and function of mammalian RSP3 in mammalian cells and developing CNS.
Poly(ethylene oxide) (PEO) single crystals were grown from dilute solution using a self-seeding method. The PEO single crystals with uniform dimensions, homogeneous chemical and physical properties were used as a simplified ultrathin film system to probe the interfacial properties of different substrates. In situ studying the annealing and melting behavior of PEO single crystals on the PAA, amorphous PEO and PVA substrates were carried out using an atomic force microscope (AFM) equipped with a hot stage. The interaction force between the PEO modified probe and various substrates was measured at different temperatures, and the universal dependence of the interaction force between the probe and polymer substrate on the temperature was demonstrated. The wetting and dewetting behavior of PEO melt on the PAA and amorphous PEO and PVA substrates were observed and the spreading coefficient (S) was proposed to prejudge the spreading behavior of a polymer ultra-thin film on a solid substrate according to the interaction force. Different melting points were found and the initial melting of the PEO single crystals occurred at 51, 54 and 61 °C on the PAA, PEO and PVA substrates, respectively. How the interfacial energy affects the melting point of single crystals was demonstrated, and the theoretical prediction agrees well with the experimental results.
Although Neanderthals are extinct, fragments of their genomes persist in contemporary humans. Here we show that while the genome-wide frequency of Neanderthal-like sites is approximately constant across all contemporary out-of-Africa populations, genes involved in lipid catabolism contain more than threefold excess of such sites in contemporary humans of European descent. Evolutionally, these genes show significant association with signatures of recent positive selection in the contemporary European, but not Asian or African populations. Functionally, the excess of Neanderthal-like sites in lipid catabolism genes can be linked with a greater divergence of lipid concentrations and enzyme expression levels within this pathway, seen in contemporary Europeans, but not in the other populations. We conclude that sequence variants that evolved in Neanderthals may have given a selective advantage to anatomically modern humans that settled in the same geographical areas.
The constrained shortest path (CSP) problem has been widely used in transportation optimization, crew scheduling, network routing and so on. It is an open issue since it is a NP-hard problem. In this paper, we propose an innovative method which is based on the internal mechanism of the adaptive amoeba algorithm. The proposed method is divided into two parts. In the first part, we employ the original amoeba algorithm to solve the shortest path problem in directed networks. In the second part, we combine the Physarum algorithm with a bio-inspired rule to deal with the CSP. Finally, by comparing the results with other method using an examples in DCLC problem, we demonstrate the accuracy of the proposed method.
Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues.
Sacral plexus avulsions lead to severe disability in patients and remain a thorny clinical problem due to the lack of anatomical, experimental and clinical studies. Attempts have been made to treat lumbosacral plexus injuries with such operations as direct anastomosis of the ends of injured sacral plexuses, and certain therapeutic effects were achieved. To further explore the degeneration pattern of anterior cornual motoneurons and determine the best time for treatment, we carried out this study.
Text messaging may be excessive and young people may be dependent on it. We distributed the Self-perception of Text-message Dependency Scale (STDS), Hospital Anxiety and Depression Scale (HADS), Temperament and Character Inventory (TCI), and Relationship Questionnaire (RQ) to 223 Japanese university students in a two-wave study, separated by a 5-month interval. The STDS yielded a three-factor structure. The STDS scores across the two measurement occasions were stable across time (except for the Relationship Maintenance subscale). A hierarchical cluster analysis suggested a three-class structure interpreted as Normal Users, Excessive Users, and Dependent Users. Excessive Users and Dependent Users were characterized by a young age at initial mobile phone use, more frequent use of text messaging, higher Novelty Seeking, and better Other-Model patterns of adult attachment. Unlike Excessive Users, Dependent Users were characterized by lower Self-directedness, poorer Self-Model of adult attachment, and higher anxiety and depression. The Excessive Users, but not the Dependent Users, were characterized by high Reward Dependence and Co-operativeness. The present study demonstrated that the STDS has a robust factor structure, good construct validity, and temporal stability (except for Relationship Maintenance subscale); students could be classified into normal, excessive, and Dependent Users of the text messaging; and Dependent Users were characterized by Excessive Use and personality immaturity.
The incidence of Alzheimer's disease (AD) has been increasing in the recent years but the underlying mechanisms remain uncertain. This study aimed to analyze the differentially expressed genes (DEGs) in entorhinal cortex with AD and identify featured genes related to AD. Gene expression profile GSE5281 was downloaded from Gene Expression Omnibus, including 10 AD and 13 control samples. Differentially expressed genes were identified by Student t test including 119 upregulated and 591 downregulated DEGs. Then, we obtained 14 enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways among which 11 pathways were significantly enriched (adjusted P value < .05). The KEGG pathway network which was constructed by 14 KEGG pathways showed that 6-phosphofructokinase, muscle type, phosphoglucomutase 1, aldolase A, and adolase C had high degree. Glycometabolism pathways network which was constructed by 4 glycometabolism pathways showed that adenosine triphosphate (ATP) synthase, H+transporting, mitochondrial F1 complex ATP5B, ATP5C1, ATP5D, and ATP5G1 had high degree related to ATP metabolism. These findings suggested that these genes with high degree may be the underlying potential therapeutic targets for AD.
An important application of resting state fMRI data has been to identify resting state networks (RSN). The conventional RSN studies attempted to discover consistent networks through functional connectivity analysis over the whole scan time, which implicitly assumes that RSNs are static. However, the brain undergoes dynamic functional state changes and the functional connectome patterns vary along with time, even in resting state. Hence, this study aims to characterize temporal brain dynamics in resting state. It utilizes the temporally dynamic functional connectome patterns to extract a set of resting state clusters and their corresponding RSNs based on the large-scale consistent, reproducible and predictable whole-brain reference system of dense individualized and common connectivity-based cortical landmarks (DICCCOL). Especially, an effective multi-view spectral clustering method was performed by treating each dynamic functional connectome pattern as one view, and this procedure was also applied on static multi-subject functional connectomes to obtain the static clusters for comparison. It turns out that some dynamic clusters exhibit high similarity with static clusters, suggesting the stability of those RSNs including the visual network and the default mode network. Moreover, two motor-related dynamic clusters show correspondence with one static cluster, which implies substantially more temporal variability of the motor resting network. Particularly, four dynamic clusters exhibited large differences in comparison with their corresponding static networks. Thus it is suggested that these four networks might play critically important roles in functional brain dynamics and interactions during resting state, offering novel insights into the brain function and its dynamics.
Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.
The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies showed regulation of ?1-adrenergic receptor function by D1-like dopamine receptors in vascular smooth muscle cells. Because renalase could regulate circulating epinephrine levels and dopamine production in renal proximal tubules (RPTs), we tested the hypothesis that D1-like receptors regulate renalase expression in kidney. The effect of D1-like receptor stimulation on renalase expression and function was measured in immortalized RPT cells from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). We found that the D1-like receptor agonist fenoldopam (10(-7)-10(-5) mol/l) increased renalase protein expression and function in WKY RPT cells but decreased them in SHR cells. Fenoldopam also increased renalase mRNA levels in WKY but not in SHR cells. In contrast, fenoldopam increased the degradation of renalase protein in SHR cells but not in WKY cells. The regulation of renalase by the D1-like receptor was mainly via the D5 receptor because silencing of the D5 but not D1 receptor by antisense oligonucleotides blocked the stimulatory effect of the D1-like receptor on renalase expression in WKY cells. Moreover, inhibition of PKC, by the PKC inhibitor 19-31, blocked the stimulatory effect of fenoldopam on renalase expression while stimulation of PKC, by a PKC agonist (PMA), increased renalase expression, indicating that PKC is involved in the process. Our studies suggest that the D5 receptor positively regulates renalase expression in WKY but not SHR RPT cells; aberrant regulation of renalase by the D5 receptor may be involved in the pathogenesis of hypertension.
Cardiovascular disease is the leading cause of mortality worldwide. Stem cell transplantation has become a new treatment option for cardiovascular disease because the stem cells are able to migrate to damaged cardiac tissue, repair the myocardial infarction area and ultimately reduce the role of the infarct-related mortality. Cardiac magnetic resonance imaging (MRI) is a new robust non-invasive imaging technique that can detect anatomical information and myocardial dysfunction, study the mechanism of stem cells therapy with superb spatial/temporal resolution, relatively safe contrast material and lack of radiation. This review describes the advantages and disadvantages of cardiac MRI applied in stem cells transplantation and discusses how to translate this technique into clinical therapy. Sources of Data/Study Selection: Data from cross-sectional and prospective studies published between the years 2001-2013 on the topic were included. Data searches included both human and animal studies.
Coevolution of beneficial microorganisms with the mammalian intestine fundamentally shapes mammalian physiology. Here, we report that the intestinal microbe Bacteroides fragilis modifies the homeostasis of host invariant natural killer T (iNKT) cells by supplementing the host's endogenous lipid antigen milieu with unique inhibitory sphingolipids. The process occurs early in life and effectively impedes iNKT cell proliferation during neonatal development. Consequently, total colonic iNKT cell numbers are restricted into adulthood, and hosts are protected against experimental iNKT cell-mediated, oxazolone-induced colitis. In studies with neonatal mice lacking access to bacterial sphingolipids, we found that treatment with B. fragilis glycosphingolipids-exemplified by an isolated peak (MW = 717.6) called GSL-Bf717-reduces colonic iNKT cell numbers and confers protection against oxazolone-induced colitis in adulthood. Our results suggest that the distinctive inhibitory capacity of GSL-Bf717 and similar molecules may prove useful in the treatment of autoimmune and allergic disorders in which iNKT cell activation is destructive.
Curcumin (CUR), a non-toxic polyphenol from Curcuma longa, has been investigated as a potential therapy with anti-inflammatory and anti-oxidative effects for Alzheimer's disease (AD), which depicts features of chronic inflammatory environment resulting in cellular death. However, it remains largely unknown whether the anti-inflammatory effect of CUR in AD is associated with its property of CpG demethylation, which is another function of CUR with the most research interest during recent years. Neprilysin (NEP, EP24.11), a zinc-dependent metallopeptidase expressed relatively low in the brain, is emerging as a potent inhibitor of AKT/Protein Kinase B. In addition, hypermethylated promoter of NEP has been reported to be associated with decreases in NEP expression. In the present study, using bisulfite-sequencing PCR (BSP) assay, we showed that the CpG sites in NEP gene were hypermethylated both in wild-type mouse neuroblastoma N2a cells (N2a/wt) and N2a cells stably expressing human Swedish mutant amyloid precursor protein (APP) (N2a/APPswe) associated with familial early onset AD. CUR treatment induced restoration of NEP gene via CpG demethylation. This CUR-mediated upregulation of NEP expression was also concomitant with the inhibition of AKT, subsequent suppression of nuclear transcription factor-?B (NF-?B) and its downstream pro-inflammatory targets including COX-2, iNOS in N2a/APPswe cells. This study represents the first evidence on a link between CpG demethylation effect on NEP and anti-inflammation ability of CUR that may provide a novel mechanistic insight into the anti-inflammatory actions of CUR as well as new basis for using CUR as a therapeutic intervention for AD.
The objective of this work is to quantitatively investigate the dripping-burning and flowing fire of thermoplastics. A new experimental setup is developed with a heating vessel and a T-trough. Hot thermoplastic liquids are generated in the vessel by electric heating. N2 gas is continuously injected into the vessel to avoid a sudden ignition of fuel in it. The detailed flowing burning behaviors of pool fire in the T-trough are analyzed through the measurements of the mass, heat flux and temperatures etc. The experimental results suggest that a continuous dripping of melted thermoplastic liquids in a nearly constant mass rate can be successfully made in the new setup. It also shows that the mass dripping rate of melted PS liquid is smaller than PP and PE since its large viscosity. In addition, the flame spread velocities of hot liquids of PS in the T-trough are also smaller than that of PP and PE because of its large viscosity. The mass burning rate of the PP and PE pool fire in T-trough are smaller than PS. Finally, considering the heating, melting, dripping and flowing burning behaviors of these polymers, it is suggested that the fire hazard of PE and PP are obviously higher than PS for their faster flowing burning.
Demands for electricity and energy to supply heat are expected to expand by 71% and 47%, respectively, for Beijing in 2020 relative to 2009. If the additional electricity and heat are supplied solely by coal as is the current situation, annual emissions of CO2 may be expected to increase by 59.6% or 99 million tons over this interval. Assessed against this business as usual (BAU) background, the present study indicates that significant reductions in emissions could be realized using wind-generated electricity to provide a source of heat, employed either with heat pumps or with electric thermal storage (ETS) devices. Relative to BAU, reductions in CO2 with heat pumps assuming 20% wind penetration could be as large as 48.5% and could be obtained at a cost for abatement of as little as $15.6 per ton of avoided CO2. Even greater reductions, 64.5%, could be realized at a wind penetration level of 40% but at a higher cost, $29.4 per ton. Costs for reduction of CO2 using ETS systems are significantly higher, reflecting the relatively low efficiency for conversion of coal to power to heat.
Curcumin is known to have neuroprotective properties in cerebral ischemia reperfusion (I/R) injury. However, the underlying molecular mechanisms remain largely unknown. Recently, emerging evidences suggested that increased mitochondrial biogenesis enabled preventing I/R injury. Here, we sought to determinate whether curcumin alleviates I/R damage through regulation of mitochondrial biogenesis. Sprague-Dawley rats were subjected to a 2-h period of right middle cerebral artery occlusion followed by 24 h of reperfusion. Prior to onset of occlusion, rats had been pretreated with either low (50 mg/kg, intraperitoneal injection) or high (100 mg/kg, intraperitoneal injection) dose of curcumin for 5 days. Consequently, we found that curcumin pretreatment enabled improving neurological deficit, diminishing infarct volume and increasing the number of NeuN-labeled neurons in the I/R rats. Accordingly, the index of mitochondrial biogenesis including nuclear respiratory factor-1, mitochondrial transcription factor A and mitochondrial number significantly down-regulated in I/R rats were reversed by curcumin pretreatment in a dose-dependent manner, and the mitochondrial uncoupling protein 2 presented the similar change. Taken together, our findings provided novel evidence that curcumin may exert neuroprotective effects by increasing mitochondrial biogenesis.
MRX-I is a potent oxazolidinone antibiotic against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), penicillin-intermediate S. pneumoniae (PISP), and vancomycin-resistant enterococci (VRE). In this study, the in vivo efficacy of orally administered MRX-I was evaluated using linezolid as a comparator. MRX-I showed the same or better efficacy than linezolid in both systemic and local infection models against the tested strains.
Epigenetic modifications, particularly histone acetylation, have been implicated in Alzheimer's disease (AD). While previous studies have suggested that histone hypoacetylation may regulate the expression of genes associated with memory and learning in AD, little is known about histone regulation of AD-related genes such as Presenilin 1(PS1) and beta-site amyloid precursor protein cleaving enzyme 1(BACE1). By utilizing neuroblastoma N2a cells transfected with Swedish mutated human amyloid precursor protein (APP) (N2a/APPswe) and wild-type APP (N2a/APPwt) as cellular models of AD, we examined the alterations of histone acetylation at the promoter regions of PS1 and BACE1 in these cells. Our results revealed that histone H3 acetylation in PS1 and BACE1 promoters is markedly increased in N2a/APPswe cells when compared to N2a/APPwt cells and control cells (vector-transfected), respectively, causing the elevated expression of PS1 and BACE1. In addition, expression of histone acetyltransferase (HAT) adenoviral E1A-associated 300-kDa protein (p300) is dramatically enhanced in N2a/APPswe cells compared to N2a/APPwt and control cells. We have further demonstrated the direct binding of p300 protein to the PS1 and BACE1 promoters in N2a/APPswe cells. The expression levels of H3 acetylation of the PS1 and BACE1 promoters and p300 protein, however, were found to be not significantly different in N2a/APPwt cells when compared to controls in our studies. Furthermore, curcumin, a natural selective inhibitor of p300 in HATs, significantly suppressed the expression of PS1 and BACE1 through inhibition of H3 acetylation in their promoter regions in N2a/APPswe cells. These findings indicated that histone acetyltransferase p300 plays a critical role in controlling the expression of AD-related genes through regulating the acetylation of their promoter regions, suggesting that p300 may represent a novel potential therapeutic target for AD.
Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.
Due to the difficulties in establishing correspondences between functional regions across individuals and populations, systematic elucidation of functional connectivity alterations in mild cognitive impairment (MCI) in comparison with normal controls (NC) is still a challenging problem. In this paper, we assessed the functional connectivity alterations in MCI via novel, alternative predictive models of resting state networks (RSNs) learned from multimodal resting state fMRI (R-fMRI) and diffusion tensor imaging (DTI) data. First, ICA-clustering was used to construct RSNs from R-fMRI data in NC group. Second, since the RSNs in MCI are already altered and can hardly be constructed directly from R-fMRI data, structural landmarks derived from DTI data were employed as the predictive models of RSNs for MCI. Third, given that the landmarks are structurally consistent and correspondent across NC and MCI, functional connectivities in MCI were assessed based on the predicted RSNs and compared with those in NC. Experimental results demonstrated that the predictive models of RSNs based on multimodal R-fMRI and DTI data systematically and comprehensively revealed widespread functional connectivity alterations in MCI in comparison with NC.
An important question regarding the biologic implications of antibiotic-resistant microbes is how resistance impacts the organisms overall fitness and virulence. Currently it is generally thought that antibiotic resistance carries a fitness cost and reduces virulence. For the human pathogen Pseudomonas aeruginosa, treatment with carbapenem antibiotics is a mainstay of therapy that can lead to the emergence of resistance, often through the loss of the carbapenem entry channel OprD. Transposon insertion-site sequencing was used to analyze the fitness of 300,000 mutants of P. aeruginosa strain PA14 in a mouse model for gut colonization and systemic dissemination after induction of neutropenia. Transposon insertions in the oprD gene led not only to carbapenem resistance but also to a dramatic increase in mucosal colonization and dissemination to the spleen. These findings were confirmed in vivo with different oprD mutants of PA14 as well as with related pairs of carbapenem-susceptible and -resistant clinical isolates. Compared with OprD(+) strains, those lacking OprD were more resistant to killing by acidic pH or normal human serum and had increased cytotoxicity against murine macrophages. RNA-sequencing analysis revealed that an oprD mutant showed dramatic changes in the transcription of genes that may contribute to the various phenotypic changes observed. The association between carbapenem resistance and enhanced survival of P. aeruginosa in infected murine hosts suggests that either drug resistance or host colonization can cause the emergence of more pathogenic, drug-resistant P. aeruginosa clones in a single genetic event.
The aim of the present study was to investigate the effects of prenatal alcohol exposure (PAE) on the development and cell differentiation of retina in offspring. The mouse model of PAE was made. HE staining and immunofluorescent labeling were carried out to visualize the structure, development and cell differentiation of the retina from postnatal day 0 (P0)-P30 offspring. The results showed that PAE can lead to the retardation of retinal development, the reduction of number of bipolar cells and horizontal cells, the disorder of horizontal cells polarity, as well as the retinal thickening in a dose-dependent manner. The data suggest that alcohol exposure during pregnancy can lead to the developmental retardation of retina and decreased number of bipolar cells and horizontal cells in the retina of offspring.
As an imaging technique with low radiation dose and improved contrast, digital x-ray tomosynthesis is widely used in clinical diagnoses. Based on the superior capability of x-ray phase-contrast imaging (PCI) techniques for imaging low density materials, the combination of X-ray tomosynthesis and PCI can potentially provide higher efficiency in the detection of soft tissues. The goal of this work was to develop a fast imaging method for phase-contrast tomosynthesis, called fast grating-based phase-contrast tomosynthesis (GPC-Tomo), which integrates tomosynthesis with a grating-based PCI technique. Following the interlaced phase-stepping (PS) data collection method, which is much faster than conventional PS method, we propose a novel image reconstruction method called inner-focusing (IF) reconstruction for the fast GPC-Tomo. The proposed IF reconstruction method was validated by real experiments and the results suggested its effectiveness in achieving a fast GPC-Tomo.
The in vivo osteogenesis potential of mesenchymal-like cells derived from human embryonic stem cells (hESC-MCs) was evaluated in vivo by implantation on collagen/hydroxyapatite scaffolds into calvarial defects in immunodeficient mice. This study is novel because no osteogenic or chondrogenic differentiation protocols were applied to the cells prior to implantation. After 6 weeks, X-ray, microCT, and histological analysis showed that the hESC-MCs had consistently formed a highly vascularized new bone that bridged the bone defect and seamlessly integrated with host bone. The implanted hESC-MCs differentiated in situ to functional hypertrophic chondrocytes, osteoblasts, and osteocytes forming new bone tissue via an endochondral ossification pathway. Evidence for the direct participation of the human cells in bone morphogenesis was verified by two separate assays: with Alu and by human mitochondrial antigen positive staining in conjunction with co-localized expression of human bone sialoprotein in histologically verified regions of new bone. The large volume of new bone in a calvarial defect and the direct participation of the hESC-MCs far exceeds that of previous studies and that of the control adult hMSCs. This study represents a key step forward for bone tissue engineering because of the large volume, vascularity, and reproducibility of new bone formation and the discovery that it is advantageous to not over-commit these progenitor cells to a particular lineage prior to implantation. The hESC-MCs were able to recapitulate the mesenchymal developmental pathway and were able to repair the bone defect semi-autonomously without preimplantation differentiation to osteo- or chondroprogenitors.
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