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Background Context fear memory dysregulation is a hallmark symptom of several neuropsychiatric disorders, including generalized anxiety disorder and posttraumatic stress disorder. The hippocampus (HC) and prelimbic (PrL) subregion of the medial prefrontal cortex have been linked with context fear memory retrieval in rodents, but the mechanisms by which HC-PrL circuitry regulates this process remain poorly understood. Methods Spatial and genetic targeting of HC-PrL circuitry was used for RNA sequencing (n = 31), chemogenetic stimulation (n = 44), in vivo calcium imaging (n = 20), ex vivo electrophysiology (n = 8), and molecular regulation of plasticity cascades during fear behavior (context fear retrieval) (n = 16). Results We showed that ventral HC (vHC) neurons with projections to the PrL cortex (vHC-PrL projectors) are a transcriptomically distinct subpopulation compared with adjacent nonprojecting neurons, and we showed complementary enrichment for diverse neuronal processes and central nervous system–related clinical gene sets. We further showed that stimulation of this population of vHC-PrL projectors suppresses context fear memory retrieval and impairs the ability of PrL neurons to dynamically distinguish between distinct phases of fear learning. Using transgenic and circuit-specific molecular targeting approaches, we demonstrated that unique patterns of activity-dependent gene transcription associated with brain-derived neurotrophic factor signaling within vHC-PrL projectors causally regulated activity in excitatory and inhibitory PrL neurons during context fear memory retrieval. Conclusions Together, our data show that activity-dependent brain-derived neurotrophic factor release from molecularly distinct vHC-PrL projection neurons modulates postsynaptic signaling in both inhibitory and excitatory PrL neurons, modifying activity in discrete populations of PrL neurons to suppress freezing during context fear memory retrieval.

Flow boiling in a microchannel with a pin fin was experimentally studied. Micro resistance temperature detectors (RTD) array was integrated inside a microchannel to enable local transient temperature measurement. The temperature measurements were synchronized with high-speed images to analyze boiling event and the corresponding transient temperature characteristics. Three distinct two-phase flow regimes were observed: bubbly flow, slug flow, and attached vapor cavity. Cyclic temperature fluctuations were observed during slug flow and it was related to local periodic vapor slug activities. In a single cycle, three distinct stages were observed: liquid wetting, film evaporation, and local dry out. These three processes were decomposed to calculate local heat transfer coefficient based on the experimental observation, as h x , y = τ l h l + τ film h film + τ v h v and the result was compared with available models in the literature.

Background Previous findings suggest that differences in brain expression of a human-specific long intergenic noncoding RNA (LINC01268; GRCh37/hg19: LOC285758) may be linked to suicide by violent methods. We sought to replicate and extend these findings in a new sample and translate the results to the behavioral level in living healthy subjects. Methods We examined RNA sequencing data in human brains to confirm the prior postmortem association of the long intergenic noncoding RNA specifically with suicide by violent means. In addition, we used a genetic variant associated with LINC01268 expression to detect association in healthy subjects with trait aggression and with in vivo prefrontal physiology related to behavioral control. Finally, we performed weighted gene coexpression network analysis and gene ontology analysis to identify biological processes associated with a LINC01268 coexpression network. Results In the replication sample, prefrontal expression of LINC01268 was again higher in suicides by violent means (n = 65) than in both nonsuicides (n = 78; p = 1.29 × 10−6) and suicides by nonviolent means (n = 46; p = 1.4 × 10−6). In the living cohort, carriers of the minor allele of a single nucleotide polymorphism associated with increased LINC01268 expression in brain scored higher on a lifetime aggression questionnaire and show diminished engagement of prefrontal cortex (Brodmann area 10) when viewing angry faces during functional magnetic resonance imaging. Weighted gene coexpression network analysis highlighted the immune response. Conclusions These results suggest that LINC01268 influences emotional regulation, aggressive behavior, and suicide by violent means; the underlying biological dynamics may include modulation of genes potentially engaged in the immune response.

Previous studies showed that Echinococcus granulosus infection reduces allergic airway inflammation in experimentally infected hosts and the cystic fluid of E. granulosus is known to activate regulatory T (CD4+CD25+Foxp3+T, Treg) cells. To evaluate the effects of cystic fluid of E. granulosus on allergic airway inflammation, we investigated the regulation of the inflammatory reaction by cystic fluid using an allergic airway inflammation animal model. Cystic fluid was administered to C57BL/6 mice seven times every other day, after which allergic airway inflammation was induced using ovalbumin and aluminum. The airway resistance, number of eosinophils and other immune cells in the bronchoalveolar lavage fluid, and levels of Th2 and Th17-related cytokines were significantly reduced by cystic fluid pre-treatment in allergic airway inflammation-induced mice. The number IL-4+CD4+ T cells decreased, the number of Treg cells increased in the lung-draining lymph nodes and spleen of cystic fluid pre-treated mice. In conclusion, E. granulosus-derived cystic fluid may alleviate the Th2 allergic airway inflammatory response via Treg cells. Further studies of the immune regulation of cystic fluid may lead to the development of therapeutic agents for immune disorders.

Transition metal dichalcogenides (TMDs) possess great potential for use in gas sensing applications because, in contrast to conventional metal oxides, they have unique semiconducting properties with band gaps that can be tuned by adjusting thickness and composition. However, one issue is that their recovery time at room temperature is too long for them to be used practically in sustainable sensing applications. We found that incorporating Se atoms weaken interactions with gas molecules compared to when S atoms are used alone, therefore, the responsivity, as well as the recovery properties, of MoSxSe2-x sensors were significantly enhanced by increasing the ratio of Se to S. Herein, we demonstrate high-performance gas sensors that are based on reduced graphene oxide (rGO) fibers coated with MoSxSe2-x, the fabricated sensor could efficiently refresh its surface to allow fast, complete recovery at room temperature. Furthermore, it was shown that the porosity of rGO fibers with their large surface-to-volume ratio leads to enhanced sensing at room temperature.

Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis. Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited. O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP). Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells. This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes. Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1). Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA. TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA. These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis.

Local single-phase flow heat transfer downstream a single pin fin in a microchannel was experimentally and numerically studied. Three distinct flow regimes, depending on the Reynolds number, were characterized, namely: laminar flow with steady wake, laminar flow with unsteady wake, and turbulent flow. Local temperature measurements with high spatial resolution were obtained by incorporating an array of micro resistance temperature detectors (RTDs) (∼55 µm × 55 µm) on the internal microchannel surface. Local surface temperatures were related to the flow structures under different flow regimes. An enhanced local heat transfer coefficient at the trailing edge of the wake region downstream the pillar was observed. It is believed to be a result of vortex shedding and large-scale flow mixing triggered by flow instability at high Reynolds number. The numerical model enabled a full conduction/convection conjugate analysis of the entire system including heat conduction within the solid substrates and heat losses to the surrounding environment. Local heat transfer coefficient downstream the pin fin at each Reynolds number was obtained.

Local temperature measurements were made in a microchannel jet impingement cooling system with a single slot jet (Dh = 68 µm and standoff distance of 210 µm). A 40%/60% solution of propylene glycol in deionized water was used as the working fluid. Resistance temperature detectors (RTDs) were fabricated over a rectangular heater of size 1500 µm × 400 µm allowing local temperature measurements. Nominal heat fluxes ranged between 50 W/cm2 and 150 W/cm2, and jet Reynolds numbers were in the range of 122–435. A three-dimensional conduction/convection conjugated numerical model with laminar and turbulent variants was developed to predict the jet hydrodynamics and heat transfer process. Good agreement was achieved between the model and the experimental data in terms of flow coefficients and local wall temperatures. Furthermore, a generalized Nusselt number dependence on Reynolds number was formulated, taking into account the temperature-dependent viscosity of the working fluid. The results provide valuable information about local and surface-averaged heat transfer due to a flow field generated by an impinging micro slot jet.

An experimental study of hydrodynamic cavitation was conducted in a rectangular microchannel with a pillar. Distilled water was used as working fluid in an open fluid loop, and cavitation was obtained by applying a range of pressure differences between inlet and outlet tanks. High speed camera captured the flow patterns from inception to fully developed cavitating flow. A minimum delay of 10 min in the formation of cavitation was recorded in all experiments, which is due to the stochastic nature of phenomenon. Cavitation inception conditions were obtained in terms of the cavitation numbers, and a flow map was developed for subsequent cavitation flow. By analyzing time series of gray scale intensity of pixels inside the cavity, dominant frequencies were identified. Transient single phase numerical simulations were performed to gain a better understanding of the flow field in the microchannel, verify pressure measurements, and to relate the separation angle to the attached cavitation angle around the pillar. Emphasis was placed on characterizing the wake region downstream the pillar as it is closely related to the occurrence of the cavitation phenomena.

Local heat transfer downstream a single pin fin in a microchannel was experimentally studied by incorporating an array of micro resistance temperature detectors (RTD) (∼55 μm × 55 μm) on the internal microchannel surface. Local temperature distribution with spatial resolution as high as 150 μm was obtained and was superimposed onto the velocity field to reveal the interaction between the flow structure and the local heat transfer at different regions downstream the pin fin. Initial result in which the surface temperature inside the steady wake region was lower than in the regions outside the recirculation zone was explained and linked to an interplay of fluid convection and solid substrate conduction. Ignoring this local interplay and processing the data without careful consideration to the conduction process resulted in misinterpretation of the heat transfer processes. To address this issue numerical thermal and fluid model of the entire device was simulated to provide local heat flux distribution. This in turn allowed to resolve the local heat transfer coefficient in the vicinity, and outside the region, of the pin fin.

trans-BMPyP induced the B-Z transition for alternated AT oligonucleotides as it was evident by inversed CD spectrum. The transition occurred simultaneously with appearance of the extensive stacking of porphyrin. Complete B-Z transition required at least 14 base-pairs long. Insertion of one or two GC base pairs prevented the B-Z transition.

In this paper, we have fabricated and characterized In 0.7 Ga 0.3 As quantum-well (QW) metal-oxide-semiconductor field-effect-transistors (MOSFETs). We have employed the gate dielectric of the Al 2 O 3 /HfO 2 (0.6/2 nm) bi-layer stack by ALD. The fabricated device with L g = 4 μm exhibits a record maximum transconductance ( g m_max ) in excess of 520 μS/μm at >1 μm region, and reasonably good electrostatic integrity, such as SS = 110 mV/decade and DIBL = 43 mV/V. Also, we have investigated the gate length scaling behavior in terms of output, transconductance, and transfer characteristics. In particular, our devices feature very uniform values of the electrostatic integrity, such as SS = 100–110 mV/decade, V T = −0.25 V to −0.2 V and DIBL = 40–50 mV/V, as L g decreases from 10 μm to 4 μm. Furthermore, we have explored the impact of source resistance ( R S ) onto the device characteristics of the InGaAs QW MOSFETs. In doing so, we have modeled both measured extrinsic transconductance ( g m_ext ) and intrinsic transconductance ( g m_int ) as a function of L g .

Stem cell fate is largely determined by cellular signaling networks and is heavily dependent on the supplementation of exogenous recombinant proteins into culture media; however, uneven distribution and inconsistent stability of recombinant proteins are closely associated with the spontaneous differentiation of pluripotent stem cells (PSCs) and result in significant costs in large-scale manufacturing. Here, we report a novel PSC culture system via wirelessly controllable optical activation of the fibroblast growth factor (FGF) signaling pathway without the need for supplementation of recombinant FGF2 protein, a key molecule for maintaining pluripotency of PSCs. Using a fusion protein between the cytoplasmic region of the FGF receptor-1 and a light-oxygen-voltage domain, we achieved tunable, blue light-dependent activation of FGF signaling in human and porcine PSCs. Our data demonstrate that a highly controllable optical stimulation of the FGF signaling pathway is sufficient for long-term maintenance of PSCs, without the loss of differentiation potential into three germ layers. This culture system will be a cost-effective platform for a large-scale stem cell culture.

Experiments were conducted in an effort to investigate the thermal and hydraulic performance capabilities of a designed and manufactured printed circuit heat exchanger (PCHE). The core of the PCHE was made of stainless steel 316 L plates, and two different types of channels on the plates were prepared: ‘straight’ and ‘N’-shaped types. In total, 40 etched plates were stacked and diffusion-bonded in a vacuum chamber, and the diameter of the semi-circle channels was verified to be 884 μm using a scanning electron microscope (SEM). In experiments using the PCHE, the flow rate of the cold side remained at approximately 300 kg/h (ranging from 303.5 kg/h ~ 315.3 kg/h), while the inlet temperature and pressure were about −170 °C and 0.77 MPa, respectively. On the hot side, the flow rates were varied from 531 to 1002 kg/h and the corresponding inlet conditions were approximately 30 °C and 0.82 MPa. Numerical simulation using ANSYS fluent was also performed for a single channel to calculate the hot side heat transfer coefficient. And the result was used to estimate the averaged heat transfer coefficient for the two- and single-phases transition with experimental results. In order to explain the averaged two- and single-phases heat transfer coefficient, an empirical equation, θ = C(Reh/Rec)a Bob was developed by modifying an existing correlation, and it showed good agreement with R2 = 0.98. In addition, from the pressure drop result on the hot side, the sum of the pressure drop coefficients in the inlet/outlet headers and the minor losses is suggested to be 29.9 with R2 = 0.93.

We outline an ambitious project to characterize the genetic and epigenetic regulation of multiple facets of transcription in distinct brain regions across the human lifespan in samples of major neuropsychiatric disorders and controls. Initially focused on schizophrenia and mood disorders, the goal of this consortium is to elucidate the underlying molecular mechanisms of genetic associations with the goal of identifying novel therapeutic targets. The consortium currently consists of seven pharmaceutical companies and a not-for-profit medical research institution working as a precompetitive team to generate and analyze publicly available archival brain genomic data related to neuropsychiatric illness.

Background Schizophrenia polygenic risk is plausibly manifested by complex transcriptional dysregulation in the brain, involving networks of co-expressed and functionally related genes. Methods 1. Samples: DLPFC gene expression (RNA-Seq) abundance was quantified (RPKM) in postmortem human brains from the LIBD Postmortem Human Brain Repository (90 controls- CTRL, 76 schizophrenia- SCZ, Caucasians, age: 16–80, RIN≥7). Common Mind Consortium (CMC) RNA-Seq postmortem DLPFC (125 CTRL, 109 SCZ, Caucasians, age, RIN as above) was used for replication of LIBD co-expression networks. 2. Expression measures/ quality control: only genes with median RPKM≥0.1 (N=23132 genes; LIBD samples) were used. Expression data was normalized by log2 transformation and adjusted for RNA quality measures (RIN, PMI, total gene assignment, proportion of mitochondrial RNA) by empirical Bayesian models. 3. Data analysis: WGCNA was applied to the adjusted expression data to construct co-expression networks, separately for LIBD- CTRL and LIBD- SCZ. Modules of co-expressed genes were detected by dynamic tree cutting method and summarized as “module eigengenes” for further analyses. 4. Modules of LIBD (CTRL; SCZ) were tested for enrichment in PGC2 genes within the 108 loci associated with the schizophrenia risk in the latest GWAS. 5. Composite module preservation statistics- median rank and Zsummary was used for assessing the preservation of LIBD SCZ modules in LIBD CTRL network and for replication of LIBD co-expression modules in the CMC independent data sets. Gene enrichment analyses for testing modules’ enrichment in Gene Ontology (GO) biological processes (BP) was performed with AmiGO/ PANTHER. Results 17 co-expression modules were identified in each LIBD group. Module preservation analysis showed a good preservation of co-expression modules between LIBD CTRL and SCZ networks, with all but one SCZ module showing evidence for strong preservation (Zsummary≥10). PGC2 genes were overrepresented in two CTRL modules (p=0.001973, p=0.028297) enriched for GO-BP such as translation, ATP synthesis, oxidative phosphorylation, homophilic cell adhesion via plasma membrane adhesion molecules, chemical synaptic transmission, axonogenesis, and in one SCZ module (p=0.000519) enriched for RNA processing, nervous system development and modulation of synaptic transmission. 58 PGC2 genes overlapped with the SCZ module (e.g., DRD2, FURIN, TSNARE1), whereas 48 + 17 PGC2 genes were overrepresented in the two CTRL modules (e.g., CACNA1C, CHRM4, CACNA1I, TCF20). Of note, only 9 overrepresented PGC2 genes were shared by CTRL and SCZ: AMBRA1, ANKRD63, HSPA9, LRP1, PRR12, PTPRF, RERE, TOM1L2, ZDHHC5. Replication of co-expression LIBD networks in CMC data set showed evidence of weak to strong preservation (Zsummary>2, respectively ≥10) for 16/ 17 modules for each LIBD group. Discussion Our results illustrate the complexity of SCZ risk distribution within the DLPFC co-expression networks in postmortem brains of affected and unaffected individuals. Importantly, not the same PGC2 genes are members of co-expression modules in CTRL and SCZ, nor do they aggregate in similar modules. These observations may be explained by differential transcriptional regulation due to pleiotropy, epistasis, epigenetic dysregulation, or even hidden RNA quality artifacts. Future studies are necessary to elucidate the participation of SCZ risk genes in brain co-expression networks.

Background Genome-Wide Association Studies (GWAS) have identified many genomic loci associated with risk for schizophrenia, but unambiguous identification of specific risk genes has proved difficult. We investigated the 2 megabase genomic region flanking index SNP rs10791097, the 16th ranked SNP in the 2014 publication from the Psychiatric Genomics Consortium (PGC) GWAS for schizophrenia. Methods We performed RNA sequencing (RNAseq) on samples from human postmortem DLPFC, hippocampus, and caudate from the Lieber Institute Human Brain Repository (N=~495, of which 175 were patients diagnosed with schizophrenia). To detect expression quantitative trait loci (eQTLs), we tested for association between genotypes at regional GWAS schizophrenia risk variants and expressed features at the gene, exon, and junction levels under a simple additive genetic model. Results Dozens of PGC GWAS-significant markers in the region were strongly associated with expressed features in SNX19, with eQTL p values ranging from 3.06E-07 to 1.58E-44. In contrast, eleven other genes in the region produced much weaker results. A junction between exons 8 and 9 defined a canonical class of “full length” SNX19 transcripts (junc8.9 at hg19 position chr11:130750702-130773149) which was only weakly associated with genetic risk. In contrast, the PGC index SNP rs10791097 was associated with expression of a rarer class of transcripts, defined by a junction between exons 8 and 10 (junc8.10, chr11:130749607-130773149), in DLPFC (eQTL p= 5.98E-26), hippocampus (p=1.04E-19), and caudate (p=6.87E-19), with the clinical risk allele (T) predicting greater expression. Many of the junc8.10 eQTLs were confirmed in both GTEx (multiple brain regions) and in the CommonMind Consortium (DLPFC) datasets. Of note, only 46% of the 495 postmortem DLPFC samples had junc8.10 read counts > 0. Discussion In addition, we found highly significant eQTLs across multiple brain regions involving 4 other expressed features: 1) a novel junction at position chr11:130765052-130773149, 2) a novel junction at chr11:130750702-130764497), 3) a known exon at chr11:130762646-130762954, and 4) a known exon at chr11:130763659-130763769. These 4 features defined 4 more independent classes of transcripts, each with the clinical risk alleles predicting greater expression. Across 3 different brain regions, PGC GWAS risk genotypes were associated with expression levels of 5 classes of SNX19 protein coding transcripts. We suggest that a critical element of the molecular mechanism(s) of schizophrenia risk from this GWAS locus is likely to be over-expression in multiple brain regions of multiple SNX19 transcripts and proteins of diverse structure and function.

SummaryDefects in brain development are believed to contribute toward the onset of neuropsychiatric disorders, but identifying specific underlying mechanisms has proven difficult. Here, we took a multifaceted approach to investigate why 15q11.2 copy number variants are prominent risk factors for schizophrenia and autism. First, we show that human iPSC-derived neural progenitors carrying 15q11.2 microdeletion exhibit deficits in adherens junctions and apical polarity. This results from haploinsufficiency of CYFIP1, a gene within 15q11.2 that encodes a subunit of the WAVE complex, which regulates cytoskeletal dynamics. In developing mouse cortex, deficiency in CYFIP1 and WAVE signaling similarly affects radial glial cells, leading to their ectopic localization outside of the ventricular zone. Finally, targeted human genetic association analyses revealed an epistatic interaction between CYFIP1 and WAVE signaling mediator ACTR2 and risk for schizophrenia. Our findings provide insight into how CYFIP1 regulates neural stem cell function and may contribute to the susceptibility of neuropsychiatric disorders.

An experimental and numerical study was conducted to elucidate local heat transfer processes under multiple microscale jet impingements using a dielectric coolant, HFE-7000. The micro device used in this experiment was made of a 400-μm thick silicon wafer, a 210-μm thick vinyl sticker, and a 1-mm thick Pyrex substrate. Fourteen jet orifices were etched using deep reactive ion etching (DRIE) on the silicon wafer, and four 100-nm thick resistance temperature detectors (RTDs) and a heater were fabricated from titanium on the Pyrex substrate. The double-sided vinyl sticker was used to bond the layers and to form a micro fluidic channel having dimensions of 1.9 mm × 14.8 mm × 210 μm. Jet Reynolds numbers in the experimental study ranged from 162 to 4057 and nominal heat fluxes ranged from 10 W/cm2 to 80 W/cm2. A three-dimensional numerical model was developed to predict the jets hydrodynamics and the convection heat transfer coefficients using a turbulent flow model for the turbulent range of the flow. Good agreement was found between the numerical predictions and experiments. The numerical results also provided valuable insight into the flow patterns formed due to multiple jet interactions. Average Nusselt number and pressure drop coefficient values found in the present study correspond well with the existing correlations pertinent to jet array impingement.

We have investigated the effects of Ti doping on the structural, optical, and electrical properties of indium tin oxide (ITO) thin films prepared by direct-current (DC) sputtering at room temperature. It is observed that the Ti doping changes the microstructure of the ITO films from amorphous to polycrystalline improving the electrical properties. The optimized ITO:Ti thin film after annealing shows a carrier concentration of 6.24 × 1020 cm−3, a mobility of 34 cm2/V s, and a resistivity of 2.3 × 10−4 Ω cm. The ITO:Ti film also shows a better thermal stability up to 450 °C.

Trichomonas vaginalis is a protozoan parasite that causes acute tissue inflammation in vaginal trichomoniasis. In this study, we investigated the signaling mechanisms through which T. vaginalis-derived secretory products (TvSP) induce chemokine IL-8 production in human mast cells. Stimulation with TvSP induced up-regulation of IL-8 protein secretion in HMC-1 cells. In addition, TvSP induced phosphorylation of transcription factors NF-κB and CREB in HMC-1 cells. Pretreatment of TvSP with lipase, but not heat or proteinase K strongly abolished the stimulatory effect on IL-8 production. Moreover, TvSP-induced IL-8 production and phosphorylation of NF-κB or CREB were inhibited when HMC-1 cells were stimulated with modified TvSP collected from 5-lipooxygenase inhibitor-treated trichomonads. Indeed, T. vaginalis-secreted lipid mediator LTB(4) (700pg/ml) from 1×10(7) trichomonads. Furthermore, pretreatment of HMC-1 cells with antagonists for LTB(4) receptors BLT1 or BLT2 abolished the stimulatory effects of TvSP. Finally, TvSP-induced IL-8 production was inhibited by pretreatment with IκB or CREB inhibitors. These results suggest that T. vaginalis-derived secretory lipid mediator LTB(4) induces IL-8 production in mast cells via BLT-dependent activation of NF-κB and CREB.

Nano-silver is used for its anti-bacterial, anti-viral and anti-fungal properties. The aim of this study was to investigate the potential clinical efficacy of nano-silver for its anti-inflammatory effect on respiratory epithelial cell inflammation. Primary nasal polyp epithelial cells (NPECs) were exposed to Alternaria alternata, Der P1, and staphylococcal enterotoxin B for 48 h with or without various concentration of nano-silver, then the supernatants were collected. Cell cytotoxicities were measured using a CellTiter-96® aqueous cell proliferation assay kit. The interleukin (IL)-6, IL-8 and granulocyte-macrophage colony stimulating factor were measured to evaluate the inflammatory effects on the epithelial cells. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) were analyzed using western blot and ELISA method. Cell survival was found to be significantly decreased at nano-silver concentrations exceeding 10 ppm. Alternaria, Der P1 and SEB activated NPECs with increased cytokine production. Alternaria induced NPECs not inhibited by nano-silver. However, Der P1 and SEB induced cytokine production was significantly affected by concentrations over 1 ppm. Alternaria, Der P1 and SEB enhanced nuclear NF-κB expression and nano-silver inhibited NF-κB expression in SEB and Der P1 treated group. Although nano-silver is cytotoxic at higher concentrations, at safe concentrations it can inhibit the activation of NPECs. This finding suggests a novel pharmacological rationale for the treatment of airway inflammation and/or immunological disease.

InP-based high electron mobility transistors (HEMTs) were fabricated by depositing Pt-based multilayer metallization on top of a 6-nm-thick InP etch stop layer and then applying a post-annealing process. The performances of the fabricated 55-nm-gate HEMTs before and after the post-annealing were characterized and were compared to investigate the effect of the penetration of Pt through the very thin InP etch stop layer. After annealing at 250 °C for 5 min, the extrinsic transconductance ( G m ) was increased from 1.05 to 1.17 S/mm and Schottky barrier height was increased from 0.63 to 0.66 eV. The unity current gain cutoff frequency ( f T ) was increased from 351 to 408 GHz, and the maximum oscillation frequency ( f max ) was increased from 225 to 260 GHz. These performance improvements can be attributed to penetration of the Pt through the 6-nm thick InP layer, and making contact on the InAlAs layer. The STEM image of the annealed device clearly shows that the Pt atoms contacted the InAlAs layer after penetrating through the InP layer.

Transforming growth factor beta 1-induced (TGFBI) protein is an extracellular matrix (ECM) protein that is associated with other ECM proteins and functions as a ligand for various types of integrins. In this study, we investigated how human TGFBI expression is regulated in lung and breast cancer cells. We observed that the TGFBI promoter in A549 and MBA-MD-231 cells, which constitutively express TGFBI, existed in an open chromatin conformation associated with transcriptionally permissive histone modifications. Moreover, we found that TGFBI expression required Sp1 transcription elements that can bind transcription factors Sp1 and Sp3 in vitro. Occupancy of the TGFBI promoter by Sp1 and Sp3 in vivo was only observed in TGFBI-expressing cells, indicating that open chromatin conformation might facilitate the binding of Sp1 and Sp3 to the TGFBI promoter region. TGFBI promoter activity was impaired when Sp1 elements were mutated, but was increased when Sp1 or Sp3 factors was overexpressed. Furthermore, Sp1 inhibition in vivo by mithramycin A, as well as knockdown of Sp1 and/or Sp3 expression by short interfering RNA, significantly reduced TGFBI mRNA and protein levels. Thus, our data demonstrated that the expression of TGFBI is well correlated with chromatin conformation at the TGFBI promoter, and that factors Sp1 and Sp3 are the primary determinants for the control of constitutive expression of TGFBI gene.

The nuances of small non-coding RNA biology continue to be discovered. The most characterized species of non-coding RNAs are microRNA (miRNA). miRNA largely function to modulate gene expression by repressing the translation of mRNA into protein. It is now known that miRNA participate in regulating nearly every type of cellular process and their importance in brain development, function, and disease continues to be uncovered. Recently RNA sequencing revealed that miRNA are often produced in detectable levels with slight sequence variations. Several steps are involved in the biogenesis of miRNA and slight changes in these processes can lead to a variety of extensions, deletions, or alterations in the final mature sequence. The name isomiR for these isoforms of canonically described miRNA sequences was coined in 2008. Research demonstrates that these miRNA variants have altered stability and in some cases distinct functions from their close sequence relatives. Recent findings also indicate that altered isomiR expression is associated with disease states. To date little research has characterized the expression of isomiRs in the brain, however alterations in canonical miRNA expression and miRNA biogenesis have been reproducibly associated with schizophrenia, suggesting that the biogenesis of isomiRs may also be altered. Therefore, we characterized isomiR expression in 92 postmortem dorsolateral prefrontal cortex (DLPFC) human brain samples, including 30 samples from patients with schizophrenia and 62 from healthy controls. Using small RNA sequencing, we profiled the expression of both canonical miRNAs and isomiRs. We utilized the BIOO Scientific NextFlex small RNA sequencing kit, with 500 ng of starting total RNA and ran 50 base pair sequencing on the HiSeq 3000. We achieved a sequencing depth of over 20 million reads per sample. Reads were aligned to miRNA and isomiR sequences using miRge. First, we assessed the overall magnitude and diversity of isomiR expression, however no differences were found between cases and controls. We then assessed the influence of diagnosis on the expression of individual miRNAs and isomiRs. Seven canonical miRNAs and 52 isomiRs, derived from 22 canonically described miRNA sequences, were identified to be differentially expressed between cases and controls. Importantly many of these isomiRs had alterations in the 5 prime portion of their sequence. Such alterations have been shown to shift the repertoire of binding partners to be distinct from that of the canonical sequence. Therefore, altered expression of these isomiRs may especially indicate modifications in gene expression regulation in schizophrenia. More research is necessary to decipher the role of these miRNA variants in schizophrenia and the brain. However, our study suggests that such variation should not be ignored.

Field-effect graphene biosensors have in general relied on irreversible surface modification for the detection of biological entities. However, restoring a sensor to a pre-sensing-event state is highly desirable in securing sensor data integrity, especially in the case of an electrolyte-gated graphene FET which is prone to drift and degradation. We present a graphene FET biosensor array that mimics an SPR(surface plasmon resonance) system in its use of a microfluidic channel for restoration of the sensor equilibrium. A steady flow of PBS through a 20-micron wide channel provides calibration for FET conductance before and after introducing human Thrombin to the base flow, successfully isolating the protein-induced field-effect from permanent changes made to the graphene device. Graphene conductance shows exponential saturation and de-saturation curves as governed by the the Nernst Equation. The sensors show a sub-microMolar limit-of-detection which can be dynamically tuned by the flow rate. Sensor specificity is provided by electrophoretic functionalization of DNA aptamers onto the graphene surface. We confirm successful aptamer functionalization with fluorescence microscopy, amperometry, and scanning electron microscopy. The current method of sensor state restoration adds reliability to biosensor data without the necessity of a matching-device control group and also maximizes manufacturing efficiency through device recycling.

Silver could prove to be a valuable alternative raw material for antibiotics and disinfectants as it is relatively free of adverse effects. Nano-silver is now been put to practical use in commonly used items, such as, clothes, electric home appliances, and electronic industry, but has not been widely applied in the medical or pharmacological fields. This study was designed to investigate the effects of nano-silver on the production of cytokines by and on the proliferation of peripheral blood mononuclear cells (PBMCs). In addition, we investigated the potential cytotoxic effects of nano-silver on PBMCs. PBMCs from healthy human volunteers were stimulated with 5 mug/ml phytohaemagglutinin (PHA) in the presence of varying concentrations of nano-silver. PBMC proliferations were measured using an aqueous cell proliferation assay kit and supernatants were analyzed using enzyme-linked immunosorbent assays. Interleukin-5 (IL-5), interferon-gamma (INF-gamma), and tumor necrosis factor-alpha (TNF-alpha) protein levels were measured to determine the activation state of PBMCs. At levels of over 15 ppm, nano-silver was found to have a significant cytotoxic effect on PBMCs, and PHA-induced cytokine productions were significantly inhibited by nano-silver (IL-5: at 10 ppm, INF-gamma and TNF-alpha at 3 ppm). Although nano-silver had a cytotoxic effect at high concentration, nano-silver modulated cytokine production in a concentration-dependent manner. These experimental data suggest that nano-silver could be used to treat immunologic and inflammatory diseases.

Intracranial vascular malformations can be classified as telangiectasis, varices, cavernous malformations, venous malformations (VMs), or arteriovenous malformations. VMs are congenital vascular malformations of the brain thought to be anomalies of the normal venous drainage. VMs are the most common intracranial vascular malformations documented by brain imaging and by autopsy series. However, vascular lesions of the internal auditory canal (IAC) are extremely rare. We report here a case of a VM arising within the IAC and expanding to the brainstem, causing a unilateral profound sensorineural hearing loss (SNHL). To the best of our knowledge, this is the first documented case of a VM as a rare cause of a unilateral SNHL in a child.

In nasal septal deviation, the deviated narrow side is more frequently combined with sinusitis due to the mechanical obstruction of ostiomeatal unit. The purpose of this study was to determine whether reduced airflow has a harmful effect on nasal inflammation and the development of rhinosinusitis. Twenty-three healthy New Zealand white rabbit were used. One side of the nostril was closed in 15 rabbits and 5 rabbits served as control. Rabbits were sacrificed at 4, 8 and 12 weeks. The anterior maxillary and septal mucosa were obtained for EM and LM study. Mucociliary clearance rate was measured using the India ink method. At 4 weeks, the opened side mucosa showed ciliary losses and ulcerations in the mucosa, but at 8 and 12 weeks, the closed side showed more severe ulceration and ciliary loss than open side. The mucociliary clearance rate was 12.3 mm/min in the control group, but the open side was 8.7 and 7.1 mm/min and the closed side was 4.7 and 6.4 mm/min at 4 and 8 weeks, respectively. Electron microscopy showed many abnormal cilia at 8 weeks in both sides. These observations suggest that inadequate airflow is an important causative factor of nasal and sinus infection, and that patients with septal deviation have a similar chance of developing sinusitis in either side.