Neuronal surface antigen antibodies in limbic encephalitis

PubMed Central

Graus, F; Saiz, A; Lai, M; Bruna, J; López, F; Sabater, L; Blanco, Y; Rey, M J.; Ribalta, T; Dalmau, J

2008-01-01

Objective: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE). Methods: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. Results: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04). Conclusions: In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies. GLOSSARY GAD = glutamic acid decarboxylase; LE = limbic encephalitis; NMDAR = N-methyl-D-aspartate receptor; NSA = neuronal surface antigens; nNSA = novel NSA; SCLC = small-cell lung cancer; VGKC = voltage-gated potassium channels; WBC = white blood cells. PMID:18794496

Studies of guinea pig immunoglobulin isotype, idiotype and antiidiotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tirrell, S.M.

1988-01-01

Immunization of Guinea pigs with diphtheria toxoid generated antibodies of the IgG class that were capable of neutralizing native toxin in vivo. Sera from these animals were used to affinity purify idiotypic antibodies (AB1). AB1 vaccines derived from the IgG1 class and from F(ab{prime}){sub 2} of IgG1 + IgG2 (IgG1/2) classes were effective in inducing a syngeneic anti-idiotype (AB2) response. Animals immunized with AB1 consisting of both IgG1/2 did not elicit a detectable AB2 response. Binding of homologous {sup 125}I-F(ab{prime}){sub 2} (AB1) to the antiidiotype was inhibited 90% in the presence of DT.F(ab{prime}){sub 2} derived from preimmune serum or hadmore » no inhibitory effects on the idiotype-antiidiotype interactions. Two groups of outbred guinea pigs were vaccinated with alum absorbed F(ab{prime}){sub 2} of anti-idiotype IgG1/2 (AB2). Of the ten animals inoculated with AB2, three tested positive by RIA against {sup 125}I-DT. Two of the RIA positive sera contained antibodies that neutralized diphtheria toxin in a rabbit intracutaneous assay. Purification of guinea pig IgG by protein A-Sepharose affinity chromatography resulted in the separation of three distinct IgG populations.« less

IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies.

PubMed

Klang, Andrea; Schmidt, Peter; Kneissl, Sibylle; Bagó, Zoltán; Vincent, Angela; Lang, Bethan; Moloney, Teresa; Bien, Christian G; Halász, Péter; Bauer, Jan; Pákozdy, Akos

2014-05-01

Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

46 CFR 111.12-7 - Voltage regulation and parallel operation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Generator Construction and Circuits § 111.12-7 Voltage regulation and... reference; see 46 CFR 110.10-1); (b) For DC systems: section 4-8-3/3.13.3(c) of the ABS Steel Vessel Rules...

Comparative Assessment of Anti-HLA Antibodies Using Two Commercially Available Luminex-Based Assays.

PubMed

Clerkin, Kevin J; See, Sarah B; Farr, Maryjane A; Restaino, Susan W; Serban, Geo; Latif, Farhana; Li, Lingzhi; Colombo, Paolo C; Vlad, George; Ray, Bryan; Vasilescu, Elena R; Zorn, Emmanuel

2017-11-01

Allospecific anti-HLA antibodies (Abs) are associated with rejection of solid organ grafts. The 2 main kits to detect anti-HLA Ab in patient serum are commercialized by Immucor and One Lambda/ThermoFisher. We sought to compare the performance of both platforms. Background-adjusted mean fluorescence intensity (MFI) values were used from both platforms to compare sera collected from 125 pretransplant and posttransplant heart and lung transplant recipients. Most HLA class I (94.5%) and HLA class II (89%) Abs with moderate to high MFI titer (≥4000) were detected by both assays. A modest correlation was observed between MFI values obtained from the 2 assays for both class I ( r = 0.3, r 2 = 0.09, P < 0.0001) and class II Ab ( r = 0.707, r 2 = 0.5, P < 0.0001). Both assays detected anti-class I and II Ab that the other did not; however, no specific HLA allele was detected preferentially by either of the 2 assays. For a limited number of discrepant sera, dilution resulted in comparable reactivity profiles between the 2 platforms. Immucor and One Lambda/ThermoFisher assays have a similar, albeit nonidentical, ability to detect anti-HLA Ab. Although the correlation between the assays was present, significant variances exist, some of which can be explained by a dilution-sensitive "prozone" effect.

Comparative Assessment of Anti-HLA Antibodies Using Two Commercially Available Luminex-Based Assays

PubMed Central

Clerkin, Kevin J.; See, Sarah B.; Farr, Maryjane A.; Restaino, Susan W.; Serban, Geo; Latif, Farhana; Li, Lingzhi; Colombo, Paolo C.; Vlad, George; Ray, Bryan; Vasilescu, Elena R.; Zorn, Emmanuel

2017-01-01

Background Allospecific anti-HLA antibodies (Abs) are associated with rejection of solid organ grafts. The 2 main kits to detect anti-HLA Ab in patient serum are commercialized by Immucor and One Lambda/ThermoFisher. We sought to compare the performance of both platforms. Methods Background-adjusted mean fluorescence intensity (MFI) values were used from both platforms to compare sera collected from 125 pretransplant and posttransplant heart and lung transplant recipients. Results Most HLA class I (94.5%) and HLA class II (89%) Abs with moderate to high MFI titer (≥4000) were detected by both assays. A modest correlation was observed between MFI values obtained from the 2 assays for both class I (r = 0.3, r2 = 0.09, P < 0.0001) and class II Ab (r = 0.707, r2 = 0.5, P < 0.0001). Both assays detected anti–class I and II Ab that the other did not; however, no specific HLA allele was detected preferentially by either of the 2 assays. For a limited number of discrepant sera, dilution resulted in comparable reactivity profiles between the 2 platforms. Conclusions Immucor and One Lambda/ThermoFisher assays have a similar, albeit nonidentical, ability to detect anti-HLA Ab. Although the correlation between the assays was present, significant variances exist, some of which can be explained by a dilution-sensitive “prozone” effect. PMID:29184907

Uncoupling the widespread occurrence of anti-NMDAR1 autoantibodies from neuropsychiatric disease in a novel autoimmune model.

PubMed

Pan, Hong; Oliveira, Bárbara; Saher, Gesine; Dere, Ekrem; Tapken, Daniel; Mitjans, Marina; Seidel, Jan; Wesolowski, Janina; Wakhloo, Debia; Klein-Schmidt, Christina; Ronnenberg, Anja; Schwabe, Kerstin; Trippe, Ralf; Mätz-Rensing, Kerstin; Berghoff, Stefan; Al-Krinawe, Yazeed; Martens, Henrik; Begemann, Martin; Stöcker, Winfried; Kaup, Franz-Josef; Mischke, Reinhard; Boretius, Susann; Nave, Klaus-Armin; Krauss, Joachim K; Hollmann, Michael; Lühder, Fred; Ehrenreich, Hannelore

2018-02-09

Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons. The age dependence of seroprevalence is lost in nonhuman primates in captivity and in human migrants, raising the intriguing possibility that chronic life stress may be related to NMDAR1-AB formation, predominantly of the IgA class. Active immunization of ApoE -/- and ApoE +/+ mice against four peptides of the extracellular NMDAR1 domain or ovalbumin (control) leads to high circulating levels of specific AB. After 4 weeks, the endogenously formed NMDAR1-AB (IgG) induce psychosis-like symptoms upon MK-801 challenge in ApoE -/- mice, characterized by an open blood-brain barrier, but not in their ApoE +/+ littermates, which are indistinguishable from ovalbumin controls. Importantly, NMDAR1-AB do not induce any sign of inflammation in the brain. Immunohistochemical staining for microglial activation markers and T lymphocytes in the hippocampus yields comparable results in ApoE -/- and ApoE +/+ mice, irrespective of immunization against NMDAR1 or ovalbumin. These data suggest that NMDAR1-AB of the IgG class shape behavioral phenotypes upon access to the brain but do not cause brain inflammation on their own.

mAbs

PubMed Central

2009-01-01

The twenty two monoclonal antibodies (mAbs) currently marketed in the U.S. have captured almost half of the top-20 U.S. therapeutic biotechnology sales for 2007. Eight of these products have annual sales each of more than $1 B, were developed in the relatively short average period of six years, qualified for FDA programs designed to accelerate drug approval, and their cost has been reimbursed liberally by payers. With growth of the product class driven primarily by advancements in protein engineering and the low probability of generic threats, mAbs are now the largest class of biological therapies under development. The high cost of these drugs and the lack of generic competition conflict with a financially stressed health system, setting reimbursement by payers as the major limiting factor to growth. Advances in mAb engineering are likely to result in more effective mAb drugs and an expansion of the therapeutic indications covered by the class. The parallel development of biomarkers for identifying the patient subpopulations most likely to respond to treatment may lead to a more cost-effective use of these drugs. To achieve the success of the current top-tier mAbs, companies developing new mAb products must adapt to a significantly more challenging commercial environment. PMID:20061824

Voltage-Gated Na+ Channel Isoforms and Their mRNA Expression Levels and Protein Abundance in Three Electric Organs and the Skeletal Muscle of the Electric Eel Electrophorus electricus

PubMed Central

Hiong, Kum C.; Boo, Mel V.; Wong, Wai P.; Chew, Shit F.

2016-01-01

This study aimed to obtain the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter’s EO, Sach’s EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus, which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna (scn4aa and scn4ab) and three scnb (scn1b, scn2b and scn4b) were identified for the first time (except scn4aa) in E. electricus. In adult fish, the scn4aa transcript level was the highest in the main EO and the lowest in the Sach’s EO, indicating that it might play an important role in generating high voltage EODs. For scn4ab/Scn4ab, the transcript and protein levels were unexpectedly high in the EOs, with expression levels in the main EO and the Hunter’s EO comparable to those of scn4aa. As the key domains affecting the properties of the channel were mostly conserved between Scn4aa and Scn4ab, Scn4ab might play a role in electrogenesis. Concerning scnb, the transcript level of scn4b was much higher than those of scn1b and scn2b in the EOs and the SM. While the transcript level of scn4b was the highest in the main EO, protein abundance of Scn4b was the highest in the SM. Taken together, it is unlikely that Scna could function independently to generate EODs in the EOs as previously suggested. It is probable that different combinations of Scn4aa/Scn4ab and various Scnb isoforms in the three EOs account for the differences in EODs produced in E. electricus. In general, the transcript levels of various scn isoforms in the EOs and the SM were much higher in adult than in juvenile, and the three EOs of the juvenile fish could be functionally indistinct. PMID:27907137

Design and test of a tip-tilt driver for an image stabilization system

NASA Astrophysics Data System (ADS)

Casas, Albert; Gómez, José María.; Roma, David; Carmona, Manuel; López, Manel; Bosch, José; Herms, Atilù; Sabater, Josep; Volkmer, Reiner; Heidecke, Frank; Maue, Thorsten; Nakai, Eiji; Baumgartner, Jörg; Schmidt, Wolfgang

2016-08-01

The tip/tilt driver is part of the Polarimetric and Helioseismic Imager (PHI) instrument for the ESA Solar Orbiter (SO), which is scheduled to launch in 2017. PPHI captures polarimetric images from the Sun to better understand our nearest star, the Sun. The paper covers an analog amplifier design to drive capacitive solid state actuator such ass piezoelectric actuator. Due to their static and continuous operation, the actuator needs to be supplied by high-quality, low-frequency, high-voltage sinusoidal signals. The described circuit is an efficiency-improved Class-AB amplifier capable of recovering up to 60% of the charge stored in the actuator. The results obtained after the qualification model test demonstrate the feasibility of the circuit with the accomplishment of the requirements fixed by the scientific team.

75 FR 20918 - High-Voltage Continuous Mining Machine Standard for Underground Coal Mines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... DEPARTMENT OF LABOR Mine Safety and Health Administration 30 CFR Parts 18 and 75 RIN 1219-AB34 High-Voltage Continuous Mining Machine Standard for Underground Coal Mines Correction In rule document 2010-7309 beginning on page 17529 in the issue of Tuesday, April 6, 2010, make the following correction...

Comparative influence study of gate-formation structuring on Al0.22Ga0.78As/In0.16Ga0.84As/Al0.22Ga0.78As double heterojunction high electron mobility transistors

NASA Astrophysics Data System (ADS)

Hsu, M. K.; Chiu, S. Y.; Wu, C. H.; Guo, D. F.; Lour, W. S.

2008-12-01

Pseudomorphic Al0.22Ga0.78As/In0.16Ga0.84As/Al0.22Ga0.78As double heterojunction high electron mobility transistors (DH-HEMTs) fabricated with different gate-formation structures of a single-recess gate (SRG), a double-recess gate (DRG) and a field-plate gate (FPG) were comparatively investigated. FPG devices show the best breakdown characteristics among these devices due to great reduction in the peak electric field between the drain and gate electrodes. The measured gate-drain breakdown voltages defined at a 1 mA mm-1 reverse gate-drain current density were -15.3, -19.1 and -26.0 V for SRG, DRG and FPG devices, respectively. No significant differences in their room-temperature common-source current-voltage characteristics were observed. However, FPG devices exhibit threshold voltages being the least sensitive to temperature. Threshold voltages as a function of temperature indicate a threshold-voltage variation as low as -0.97 mV K-1 for FPG devices. According to the 2.4 GHz load-pull power measurement at VDS = 3.0 V and VGS = -0.5 V, the saturated output power (POUT), power gain (GP) and maximum power-added efficiency (PAE) were 10.3 dBm/13.2 dB/36.6%, 11.2 dBm/13.1 dB/39.7% and 13.06 dBm/12.8 dB/47.3%, respectively, for SRG, DRG and FPG devices with a pi-gate in class AB operation. When the FPG device is biased at a VDS of 10 V, the saturated power density is more than 600 mW mm-1.

Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

PubMed Central

Ganesan, Subramanian; Beri, Sushil; Khan, Beri; Hussain, Nahin

2013-01-01

Autoimmune limbic encephalitis (LE) associated with voltage gated potassium channel antibodies (VGKC-Abs) in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management. PMID:24339586

An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA.

PubMed

Thomas, K A; Valenzuela, N M; Gjertson, D; Mulder, A; Fishbein, M C; Parry, G C; Panicker, S; Reed, E F

2015-08-01

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab')2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro. © 2015 The Authors. American Journal of Transplantation Published by Wiley Periodicals, Inc.

Autoantibody Profiles in Collagen Disease Patients with Interstitial Lung Disease (ILD): Antibodies to Major Histocompatibility Complex Class I-Related Chain A (MICA) as Markers of ILD

PubMed Central

Furukawa, Hiroshi; Oka, Shomi; Shimada, Kota; Masuo, Kiyoe; Nakajima, Fumiaki; Funano, Shunichi; Tanaka, Yuki; Komiya, Akiko; Fukui, Naoshi; Sawasaki, Tatsuya; Tadokoro, Kenji; Nose, Masato; Tsuchiya, Naoyuki; Tohma, Shigeto

2015-01-01

Interstitial lung disease (ILD) is frequently associated with collagen disease. It is then designated as collagen vascular disease-associated ILD (CVD-ILD), and influences patients’ prognosis. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in patients with collagen disease is quite poor. Here, we report our investigation of auto-antibody (Ab) profiles to determine whether they may be useful in diagnosing CVD-ILD or AoDILD in collagen disease. Auto-Ab profiles were analyzed using the Lambda Array Beads Multi-Analyte System, granulocyte immunofluorescence test, Proto-Array Human Protein Microarray, AlphaScreen assay, and glutathione S-transferase capture enzyme-linked immunosorbent assay in 34 patients with rheumatoid arthritis (RA) with or without CVD-ILD and in 15 patients with collagen disease with AoDILD. The average anti-major histocompatibility complex class I-related chain A (MICA) Ab levels were higher in RA patients with CVD-ILD than in those without (P = 0.0013). The ratio of the average anti-MICA Ab level to the average anti-human leukocyte antigen class I Ab level (ie, MICA/Class I) was significantly higher in RA patients with CVD-ILD compared with those without (P = 4.47 × 10−5). To the best of our knowledge, this is the first report of auto-Ab profiles in CVD-ILD. The MICA/Class I ratio could be a better marker for diagnosing CVD-ILD than KL-6 (Krebs von den lungen-6). PMID:26327779

mAbs: a business perspective.

PubMed

Scolnik, Pablo A

2009-01-01

The twenty two monoclonal antibodies (mAbs) currently marketed in the U.S. have captured almost half of the top-20 U.S. therapeutic biotechnology sales for 2007. Eight of these products have annual sales each of more than $1 B, were developed in the relatively short average period of six years, qualified for FDA programs designed to accelerate drug approval, and their cost has been reimbursed liberally by payers. With growth of the product class driven primarily by advancements in protein engineering and the low probability of generic threats, mAbs are now the largest class of biological therapies under development. The high cost of these drugs and the lack of generic competition conflict with a financially stressed health system, setting reimbursement by payers as the major limiting factor to growth. Advances in mAb engineering are likely to result in more effective mAb drugs and an expansion of the therapeutic indications covered by the class. The parallel development of biomarkers for identifying the patient subpopulations most likely to respond to treatment may lead to a more cost-effective use of these drugs. To achieve the success of the current top-tier mAbs, companies developing new mAb products must adapt to a significantly more challenging commercial environment.

Lithium Cell Reactions.

DTIC Science & Technology

1983-12-01

Li/SOCL, cells in- dicate that up to PPM water can be added to the electrolyte without detrimental effects. At water levels ab 100 PPM voltage delay...48 2.3 THE EFFECT OF WATER AND HYDROLYSIS PRODUCTS ON PERFORMANCE ........ 51 2.4 THE...Li/SOCI, Cells with 0, 20 and 100 PPM Water added to the Electrolyte.* ..................................................... 52 51. Voltage Delay for

Touch responsiveness in zebrafish requires voltage-gated calcium channel 2.1b

PubMed Central

Low, Sean E.; Woods, Ian G.; Lachance, Mathieu; Ryan, Joel; Saint-Amant, Louis

2012-01-01

The molecular and physiological basis of the touch-unresponsive zebrafish mutant fakir has remained elusive. Here we report that the fakir phenotype is caused by a missense mutation in the gene encoding voltage-gated calcium channel 2.1b (CACNA1Ab). Injection of RNA encoding wild-type CaV2.1 restores touch responsiveness in fakir mutants, whereas knockdown of CACNA1Ab via morpholino oligonucleotides recapitulates the fakir mutant phenotype. Fakir mutants display normal current-evoked synaptic communication at the neuromuscular junction but have attenuated touch-evoked activation of motor neurons. NMDA-evoked fictive swimming is not affected by the loss of CaV2.1b, suggesting that this channel is not required for motor pattern generation. These results, coupled with the expression of CACNA1Ab by sensory neurons, suggest that CaV2.1b channel activity is necessary for touch-evoked activation of the locomotor network in zebrafish. PMID:22490555

First-Principles Characterization of the Unknown Crystal Structure and Ionic Conductivity of Li7P2S8I as a Solid Electrolyte for High-Voltage Li Ion Batteries.

PubMed

Kang, Joonhee; Han, Byungchan

2016-07-21

Using first-principles density functional theory calculations and ab initio molecular dynamics (AIMD) simulations, we demonstrate the crystal structure of the Li7P2S8I (LPSI) and Li ionic conductivity at room temperature with its atomic-level mechanism. By successively applying three rigorous conceptual approaches, we identify that the LPSI has a similar symmetry class as Li10GeP2S12 (LGPS) material and estimate the Li ionic conductivity to be 0.3 mS cm(-1) with an activation energy of 0.20 eV, similar to the experimental value of 0.63 mS cm(-1). Iodine ions provide an additional path for Li ion diffusion, but a strong Li-I attractive interaction degrades the Li ionic transport. Calculated density of states (DOS) for LPSI indicate that electrochemical instability can be substantially improved by incorporating iodine at the Li metallic anode via forming a LiI compound. Our methods propose the computational design concept for a sulfide-based solid electrolyte with heteroatom doping for high-voltage Li ion batteries.

An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA

PubMed Central

Thomas, K A; Valenzuela, N M; Gjertson, D; Mulder, A; Fishbein, M C; Parry, G C; Panicker, S; Reed, E F

2015-01-01

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab′)2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro. PMID:25904443

Clinical relevance of voltage-gated potassium channel–complex antibodies in children.

PubMed

Hacohen, Yael; Singh, Rahul; Rossi, Meghan; Lang, Bethan; Hemingway, Cheryl; Lim, Ming; Vincent, Angela

2015-09-15

To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients’ condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.

Clinical relevance of voltage-gated potassium channel–complex antibodies in children

PubMed Central

Hacohen, Yael; Singh, Rahul; Rossi, Meghan; Lang, Bethan; Hemingway, Cheryl; Lim, Ming

2015-01-01

Objective: To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Methods: Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (>100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients' condition was independently classified as inflammatory (n = 159) or noninflammatory (n = 204). Positive sera (>100 pM) were tested/retested for the VGKC-complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (>400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. Results: VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p = 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers >400 pM (n = 12) were found only in inflammatory diseases (p < 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 >400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Conclusion: Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined. PMID:26296514

Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies.

PubMed

Eijsink, Chantal; Kester, Michel G D; Franke, Marry E I; Franken, Kees L M C; Heemskerk, Mirjam H M; Claas, Frans H J; Mulder, Arend

2006-08-31

The ability of tetrameric major histocompatibility complex (MHC) class I-peptide complexes (tetramers) to detect antigen-specific T lymphocyte responses has yielded significant information about the generation of in vivo immunity in numerous antigenic systems. Here we present a novel method for rapid validation of tetrameric HLA molecules based on the presence of allodeterminants. Human monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I were immobilized on polystyrene microparticles and used to probe the structural integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22 tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their counterpart mAbs, thus confirming their antigenic integrity. A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays.

Mussel-inspired one-pot synthesis of transition metal and nitrogen co-doped carbon (M/N-C) as efficient oxygen catalysts for Zn-air batteries

NASA Astrophysics Data System (ADS)

Li, Bing; Chen, Ye; Ge, Xiaoming; Chai, Jianwei; Zhang, Xiao; Hor, T. S. Andy; Du, Guojun; Liu, Zhaolin; Zhang, Hua; Zong, Yun

2016-02-01

Transition metal and nitrogen co-doping into carbon is an effective approach to promote the catalytic activities towards the oxygen reduction reaction (ORR) and/or oxygen evolution reaction (OER) in the resultant electrocatalysts, M/N-C. The preparation of such catalysts, however, is often complicated and in low yield. Herein we report a robust approach for easy synthesis of M/N-C hybrids in high yield, which includes a mussel-inspired polymerization reaction at room temperature and a subsequent carbonization process. With the introduction of selected transition metal salts into an aqueous solution of dopamine (DA), the obtained mixture self-polymerizes to form metal-containing polydopamine (M-PDA) composites, e.g. Co-PDA, Ni-PDA and Fe-PDA. Upon carbonization at elevated temperatures, these metal-containing composites were converted into M/N-C, i.e. Co-PDA-C, Ni-PDA-C and Fe-PDA-C, respectively, whose morphologies, chemical compositions, and electrochemical performances were fully studied. Enhanced ORR activities were found in all the obtained hybrids, with Co-PDA-C standing out as the most promising catalyst with excellent stability and catalytic activities towards both ORR and OER. This was further proven in Zn-air batteries (ZnABs) in terms of discharge voltage stability and cycling performance. At a discharge-charge current density of 2 mA cm-2 and 1 h per cycle, the Co-PDA-C based ZnABs were able to steadily cycle up to 500 cycles with only a small increase in the discharge-charge voltage gap which notably outperformed Pt/C; at a discharge current density of 5 mA cm-2, the battery continuously discharged for more than 540 h with the discharge voltage above 1 V and a voltage drop rate of merely 0.37 mV h-1. With the simplicity and scalability of the synthetic approach and remarkable battery performances, the Co-PDA-C hybrid catalyst is anticipated to play an important role in practical ZnABs.Transition metal and nitrogen co-doping into carbon is an effective approach to promote the catalytic activities towards the oxygen reduction reaction (ORR) and/or oxygen evolution reaction (OER) in the resultant electrocatalysts, M/N-C. The preparation of such catalysts, however, is often complicated and in low yield. Herein we report a robust approach for easy synthesis of M/N-C hybrids in high yield, which includes a mussel-inspired polymerization reaction at room temperature and a subsequent carbonization process. With the introduction of selected transition metal salts into an aqueous solution of dopamine (DA), the obtained mixture self-polymerizes to form metal-containing polydopamine (M-PDA) composites, e.g. Co-PDA, Ni-PDA and Fe-PDA. Upon carbonization at elevated temperatures, these metal-containing composites were converted into M/N-C, i.e. Co-PDA-C, Ni-PDA-C and Fe-PDA-C, respectively, whose morphologies, chemical compositions, and electrochemical performances were fully studied. Enhanced ORR activities were found in all the obtained hybrids, with Co-PDA-C standing out as the most promising catalyst with excellent stability and catalytic activities towards both ORR and OER. This was further proven in Zn-air batteries (ZnABs) in terms of discharge voltage stability and cycling performance. At a discharge-charge current density of 2 mA cm-2 and 1 h per cycle, the Co-PDA-C based ZnABs were able to steadily cycle up to 500 cycles with only a small increase in the discharge-charge voltage gap which notably outperformed Pt/C; at a discharge current density of 5 mA cm-2, the battery continuously discharged for more than 540 h with the discharge voltage above 1 V and a voltage drop rate of merely 0.37 mV h-1. With the simplicity and scalability of the synthetic approach and remarkable battery performances, the Co-PDA-C hybrid catalyst is anticipated to play an important role in practical ZnABs. Electronic supplementary information (ESI) available: Schematic structure of ZnAB; photos of home-made ZnABs; EDX spectra and elemental mapping of M-PDA-C; N2 adsorption/desorption isotherms, high magnification TEM images of M-PDA-C, and RDE data of M-PDA-C, etc. See DOI: 10.1039/c5nr06538k

MHC class I–specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice

PubMed Central

Strait, Richard T.; Hicks, Wyenona; Barasa, Nathaniel; Mahler, Ashley; Khodoun, Marat; Köhl, Jörg; Stringer, Keith; Witte, David; Van Rooijen, Nico; Susskind, Brian M.

2011-01-01

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic pulmonary edema that develops during or within 6 h after a blood transfusion, is the most frequent cause of transfusion-associated death in the United States. Because development of TRALI is associated with donor antibodies (Abs) reactive with recipient major histocompatibility complex (MHC), a mouse model has been studied in which TRALI-like disease is caused by injecting mice with anti–MHC class I monoclonal Ab (mAb). Previous publications with this model have concluded that disease is caused by FcR-dependent activation of neutrophils and platelets, with production of reactive oxygen species that damage pulmonary vascular endothelium. In this study, we confirm the role of reactive oxygen species in the pathogenesis of this mouse model of TRALI and show ultrastructural evidence of pulmonary vascular injury within 5 min of anti–MHC class I mAb injection. However, we demonstrate that disease induction in this model involves macrophages rather than neutrophils or platelets, activation of complement and production of C5a rather than activation of FcγRI, FcγRIII, or FcγRIV, and binding of anti–MHC class I mAb to non-BM–derived cells such as pulmonary vascular endothelium. These observations have important implications for the prevention and treatment of TRALI. PMID:22025304

Generation of immunosuppressive mesenchymal stem cells in allogeneic human serum.

PubMed

Le Blanc, Katarina; Samuelsson, Håkan; Lönnies, Lena; Sundin, Mikael; Ringdén, Olle

2007-10-27

Mesenchymal stem cells (MSC) may be used to treat acute graft-versus-host disease and for tissue repair. In vitro expansion of MSC has been achieved in the presence of fetal calf serum (FCS). For safety and regulatory reasons, we explored if FCS could be replaced by human blood group AB serum. Proliferation and fold increase of MSC was higher in the presence of AB-serum, compared to FCS. Similar to cells generated in FCS media, MSC from AB-serum media were more than 95% positive for CD90, CD105 and human leukocyte antigen (HLA) class I, and negative for hematopoietic and endothelial markers CD14, CD31, CD34, CD45, and CD80. HLA class II expression was higher in MSC generated in AB-serum, but decreased with higher passage numbers. MSC generated in AB-serum suppressed lymphocyte proliferation in mixed lymphocyte cultures and after stimulation with phytohemagglutinin. MSC expanded in AB-serum and FCS have similar in vitro properties.

Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tsuji, Sadatoshi; Nishizawa, Shigeru

2014-06-01

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

Characterization of Na+ and Ca2+ Channels in Zebrafish Dorsal Root Ganglion Neurons

PubMed Central

Won, Yu-Jin; Ono, Fumihito; Ikeda, Stephen R.

2012-01-01

Background Dorsal root ganglia (DRG) somata from rodents have provided an excellent model system to study ion channel properties and modulation using electrophysiological investigation. As in other vertebrates, zebrafish (Danio rerio) DRG are organized segmentally and possess peripheral axons that bifurcate into each body segment. However, the electrical properties of zebrafish DRG sensory neurons, as compared with their mammalian counterparts, are relatively unexplored because a preparation suitable for electrophysiological studies has not been available. Methodology/Principal Findings We show enzymatically dissociated DRG neurons from juvenile zebrafish expressing Isl2b-promoter driven EGFP were easily identified with fluorescence microscopy and amenable to conventional whole-cell patch-clamp studies. Two kinetically distinct TTX-sensitive Na+ currents (rapidly- and slowly-inactivating) were discovered. Rapidly-inactivating INa were preferentially expressed in relatively large neurons, while slowly-inactivating INa was more prevalent in smaller DRG neurons. RT-PCR analysis suggests zscn1aa/ab, zscn8aa/ab, zscn4ab and zscn5Laa are possible candidates for these INa components. Voltage-gated Ca2+ currents (ICa) were primarily (87%) comprised of a high-voltage activated component arising from ω-conotoxin GVIA-sensitive CaV2.2 (N-type) Ca2+ channels. A few DRG neurons (8%) displayed a miniscule low-voltage-activated component. ICa in zebrafish DRG neurons were modulated by neurotransmitters via either voltage-dependent or -independent G-protein signaling pathway with large cell-to-cell response variability. Conclusions/Significance Our present results indicate that, as in higher vertebrates, zebrafish DRG neurons are heterogeneous being composed of functionally distinct subpopulations that may correlate with different sensory modalities. These findings provide the first comparison of zebrafish and rodent DRG neuron electrical properties and thus provide a basis for future studies. PMID:22880050

Bifunctional cis-Abienol Synthase from Abies balsamea Discovered by Transcriptome Sequencing and Its Implications for Diterpenoid Fragrance Production*

PubMed Central

Zerbe, Philipp; Chiang, Angela; Yuen, Macaire; Hamberger, Björn; Hamberger, Britta; Draper, Jason A.; Britton, Robert; Bohlmann, Jörg

2012-01-01

The labdanoid diterpene alcohol cis-abienol is a major component of the aromatic oleoresin of balsam fir (Abies balsamea) and serves as a valuable bioproduct material for the fragrance industry. Using high-throughput 454 transcriptome sequencing and metabolite profiling of balsam fir bark tissue, we identified candidate diterpene synthase sequences for full-length cDNA cloning and functional characterization. We discovered a bifunctional class I/II cis-abienol synthase (AbCAS), along with the paralogous levopimaradiene/abietadiene synthase and isopimaradiene synthase, all of which are members of the gymnosperm-specific TPS-d subfamily. The AbCAS-catalyzed formation of cis-abienol proceeds via cyclization and hydroxylation at carbon C-8 of a postulated carbocation intermediate in the class II active site, followed by cleavage of the diphosphate group and termination of the reaction sequence without further cyclization in the class I active site. This reaction mechanism is distinct from that of synthases of the isopimaradiene- or levopimaradiene/abietadiene synthase type, which employ deprotonation reactions in the class II active site and secondary cyclizations in the class I active site, leading to tricyclic diterpenes. Comparative homology modeling suggested the active site residues Asp-348, Leu-617, Phe-696, and Gly-723 as potentially important for the specificity of AbCAS. As a class I/II bifunctional enzyme, AbCAS is a promising target for metabolic engineering of cis-abienol production. PMID:22337889

[Specificity and sensitivity of immunological diagnosis of congenital neonatal syphilis by the 19S(IgM)-FTA-ABS test (author's transl)].

PubMed

Müller, F; Sinzig, G

1982-07-01

Reports on the significance in the demonstration of IgM class antibodies in congenital syphilis are contradictory. The reason for discrepant observations are of technical or biological source. In order to explain the several uncertainties, serum samples from 1031 newborns and infants of syphilitic mothers were investigated quantitatively with the IgM-FTA-ABS, the 19S (IgM)-FTA-ABS and cardiolipin CF test. If serum specimens of the mothers were available they were investigated in the same tests for treponema-specific 19S(IgM) class and antilipoidal antibodies. In the evaluation of the results, the history of infection and treatment of the mothers as well as clinical observations in the infants were considered. In 26 children a congenital acquired syphilis was strongly indicated by demonstration of treponema-specific 19S(IgM) class antibodies by the 19S(IgM)-FTA-ABS-Test and tae good agreement with the history of untreated mothers. In another 1005 infants a congenital infection by T. pallidum could be excluded by the non-reactive 19S(IgM)-FTA-ABS as well as clinical observations. Furthermore, immunological findings of three children who had acquired syphilis after birth are demonstrated before and after specific treatment. It could be shown that the 19S(IgM)-FTA-ABS is much more infaillable than the IgM-FTA-ABS as far as technical and biological uncertainties are concerned. Considering all possible errors and the results of re-investigations of IgM non-reactive infants of syphilitic mothers (up to one year after birth) it is demonstrated that congenital syphilis can be differentiated from passively transmitted 7S(IgG) class antibodies (of the mother) or 19S(IgM) class anti-antibodies (of the child) with a significance of about 99%. It is finally concluded that serological diagnosis of congenital syphilis should be started in the pregnant women. By making the diagnosis in pregnancy followed by adequate treatment, irreversible damages as well as so-called serological scars can be avoided in the children.

Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes—A Recursive Partitioning Analysis

PubMed Central

Krischer, Jeffrey P.

2016-01-01

OBJECTIVE To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clinical characteristics, including genotype, antibody titers, and metabolic markers were analyzed. RESULTS Age and GAD65 autoantibody (GAD65Ab) titers defined three risk classes for progression from single to multiple autoantibodies. The 5-year risk was 11% for those subjects >16 years of age with low GAD65Ab titers, 29% for those ≤16 years of age with low GAD65Ab titers, and 45% for those subjects with high GAD65Ab titers regardless of age. Progression to dysglycemia was associated with islet antigen 2 Ab titers, and 2-h glucose and fasting C-peptide levels. The 5-year risk is 28%, 39%, and 51% for respective risk classes defined by the three predictors. Progression to type 1 diabetes was associated with the number of positive autoantibodies, peak C-peptide level, HbA1c level, and age. Four risk classes defined by RPA had a 5-year risk of 9%, 33%, 62%, and 80%, respectively. CONCLUSIONS The use of RPA offered a new classification approach that could predict the timing of transitions from one preclinical stage to the next in the development of type 1 diabetes. Using these RPA classes, new prevention techniques can be tailored based on the individual prognostic risk characteristics at different preclinical stages. PMID:27208341

Morvan syndrome: a rare cause of syndrome of inappropriate antidiuretic hormone secretion

PubMed Central

DEMIRBAS, SEREF; AYKAN, MUSA BARIS; ZENGIN, HAYDAR; MAZMAN, SEMIR; SAGLAM, KENAN

2017-01-01

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for an important part of hyponatremia cases. The causes of SIADH can be detected almost always. As a rare disorder, Morvan Syndrome can be defined by the sum of peripheral nerve hyperexcitability, autonomic instability and neuropsychiatric features. Antibodies to voltage-gated potassium channels (Anti – VGKC-Ab) including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab) were previously known for the potential association with this condition. We present a Morvan Syndrome in a patient who presented with various neuropsychiatric symptoms and SIADH. PMID:28781533

Morvan syndrome: a rare cause of syndrome of inappropriate antidiuretic hormone secretion.

PubMed

Demirbas, Seref; Aykan, Musa Baris; Zengin, Haydar; Mazman, Semir; Saglam, Kenan

2017-01-01

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for an important part of hyponatremia cases. The causes of SIADH can be detected almost always. As a rare disorder, Morvan Syndrome can be defined by the sum of peripheral nerve hyperexcitability, autonomic instability and neuropsychiatric features. Antibodies to voltage-gated potassium channels (Anti - VGKC-Ab) including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab) were previously known for the potential association with this condition. We present a Morvan Syndrome in a patient who presented with various neuropsychiatric symptoms and SIADH.

Class E/F switching power amplifiers

NASA Technical Reports Server (NTRS)

Hajimiri, Seyed-Ali (Inventor); Aoki, Ichiro (Inventor); Rutledge, David B. (Inventor); Kee, Scott David (Inventor)

2004-01-01

The present invention discloses a new family of switching amplifier classes called class E/F amplifiers. These amplifiers are generally characterized by their use of the zero-voltage-switching (ZVS) phase correction technique to eliminate of the loss normally associated with the inherent capacitance of the switching device as utilized in class-E amplifiers, together with a load network for improved voltage and current wave-shaping by presenting class-F.sup.-1 impedances at selected overtones and class-E impedances at the remaining overtones. The present invention discloses a several topologies and specific circuit implementations for achieving such performance.

More than Memory Impairment in Voltage-Gated Potassium Channel Complex Encephalopathy

PubMed Central

Bettcher, Brianne M.; Gelfand, Jeffrey M.; Irani, Sarosh R.; Neuhaus, John; Forner, Sven; Hess, Christopher P.; Geschwind, Michael D.

2014-01-01

Objective Autoimmune encephalopathies (AE) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AE inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC-Abs) in order to delineate cognitive strengths and weaknesses. Methods We assessed serial VGKCC-Abs AE subjects (n=12) with a comprehensive evaluation of memory, executive functions, visuospatial skills, and language. Clinical MRI (n=10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change. Results Subjects demonstrated mild to moderate impairment in memory (mean Z=−1.9) and executive functions (mean Z=−1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients. Conclusions This study augments prior neuropsychological analyses in VGKCC-Ab AE by identifying not only memory and executive function deficits, but also language impairments, with preservation of visuospatial functioning. This study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC-Ab AE. PMID:24981998

Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies*

PubMed Central

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; Goger, Michael; Wang, Xiaobo; Fries, Bettina C.

2015-01-01

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

Mechanisms mediating enhanced neutralization efficacy of Staphylococcal enterotoxin B by combinations of monoclonal antibodies

DOE PAGES

Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; ...

2015-01-08

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used tomore » validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Lastly structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.« less

Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

PubMed Central

Hildebrandt, Tom; Epstein, Elizabeth E.; Sysko, Robyn; Bux, Donald A.

2017-01-01

Background The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. Method We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. Results Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. Conclusions The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs. PMID:28247423

The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

PubMed Central

Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

2016-01-01

Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations.

PubMed

Graus, F; Saiz, A; Lai, M; Bruna, J; López, F; Sabater, L; Blanco, Y; Rey, M J; Ribalta, T; Dalmau, J

2008-09-16

To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE). Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04). In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies.

QT Interval Prolongation and QRS Voltage Reduction in Patients with Liver Cirrhosis.

PubMed

Cichoż-Lach, Halina; Tomaszewski, Michał; Kowalik, Agnieszka; Lis, Emilia; Tomaszewski, Andrzej; Lach, Tomasz; Boczkowska, Sylwia; Celiński, Krzysztof

2015-01-01

Liver cirrhosis is associated with functional abnormalities of the cardiovascular system with co-existing electrocardiographic (ECG) abnormalities. The aim was to analyze ECG changes in patients with cirrhosis, to evaluate whether alcoholic etiology of cirrhosis and ascites has an impact on ECG changes. The study involved 81 patients with previously untreated alcoholic cirrhosis (64 patients with ascites, classes B and C according to the Child-Pugh classification; and 17 without ascites, categorized as class A); 41 patients with previously untreated cirrhosis due to chronic hepatitis C (HCV--30 patients with ascites, classes B and C; and 11 without ascites, class A); 42 with alcoholic steatohepatitis and 46 with alcoholic steatosis. The control group consisted of 32 healthy volunteers. Twelve-lead ECG recordings were performed and selected parameters were measured. Significantly longer QT and QTc intervals and lower QRS voltage were found in patients with alcoholic and HCV cirrhosis compared to the controls. Significantly lower QRS voltage was found in subjects with ascites than in those without ascites. Removal of ascites significantly increased QRS voltage. In cirrhosis, irrespective of etiology, ECG changes involved prolonged QT and QTc intervals and reduced QRS voltage. Prolonged QT and QTc intervals were not related to the severity of cirrhosis or to the presence of ascites. However, low QRS voltage was associated with the presence of ascites. Removal of ascites reverses low QRS voltage.

Design and analysis of optimised class E power amplifier using shunt capacitance in the output structure

NASA Astrophysics Data System (ADS)

Hayati, Mohsen; Roshani, Sobhan; Zirak, Ali Reza

2017-05-01

In this paper, a class E power amplifier (PA) with operating frequency of 1 MHz is presented. MOSFET non-linear drain-to-source parasitic capacitance, linear external capacitance at drain-to-source port and linear shunt capacitance in the output structure are considered in design theory. One degree of freedom is added to the design of class E PA, by assuming the shunt capacitance in the output structure in the analysis. With this added design degree of freedom it is possible to achieve desired values for several parameters, such as output voltage, load resistance and operating frequency, while both zero voltage and zero derivative switching (ZVS and ZDS) conditions are satisfied. In the conventional class E PA, high value of peak switch voltage results in limitations for the design of amplifier, while in the presented structure desired specifications could be achieved with the safe margin of peak switch voltage. The results show that higher operating frequency and output voltage can also be achieved, compared to the conventional structure. PSpice software is used in order to simulate the designed circuit. The presented class E PA is designed, fabricated and measured. The measured results are in good agreement with simulation and theory results.

Mechanism for Si–Si Bond Rupture in Single Molecule Junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Haixing; Kim, Nathaniel T.; Su, Timothy A.

The stability of chemical bonds can be studied experimentally by rupturing single molecule junctions under applied voltage. Here, we compare voltage-induced bond rupture in two Si–Si backbones: one has no alternate conductive pathway whereas the other contains an additional naphthyl pathway in parallel to the Si–Si bond. We show that in contrast to the first system, the second can conduct through the naphthyl group when the Si–Si bond is ruptured using an applied voltage. We investigate this voltage induced Si–Si bond rupture by ab initio density functional theory calculations and molecular dynamics simulations that ultimately demonstrate that the excitation ofmore » molecular vibrational modes by tunneling electrons leads to homolytic Si–Si bond rupture.« less

Mechanism for Si-Si Bond Rupture in Single Molecule Junctions.

PubMed

Li, Haixing; Kim, Nathaniel T; Su, Timothy A; Steigerwald, Michael L; Nuckolls, Colin; Darancet, Pierre; Leighton, James L; Venkataraman, Latha

2016-12-14

The stability of chemical bonds can be studied experimentally by rupturing single molecule junctions under applied voltage. Here, we compare voltage-induced bond rupture in two Si-Si backbones: one has no alternate conductive pathway whereas the other contains an additional naphthyl pathway in parallel to the Si-Si bond. We show that in contrast to the first system, the second can conduct through the naphthyl group when the Si-Si bond is ruptured using an applied voltage. We investigate this voltage induced Si-Si bond rupture by ab initio density functional theory calculations and molecular dynamics simulations that ultimately demonstrate that the excitation of molecular vibrational modes by tunneling electrons leads to homolytic Si-Si bond rupture.

Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits

PubMed Central

Nishimichi, Norihisa; Kawashima, Nagako; Yokosaki, Yasuyuki

2015-01-01

Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face of the β-propeller. Loop-tips sufficiently close to W2:41 (<25 Å) contained within a footprint of the mAbs were mutated, and the loop W3:34 on the bottom face was identified as an additional component of the epitope of one antibody, clone YZ5. Binding sequences on the two loops were conserved in virtually all mammals, and that on W3:34 was also conserved in chickens. These indicate 1) YZ5 binds both top and bottom loops, and the binding to W3:34 is by interactions to conserved residues between immunogen and host species, 2) five other blocking mAbs solely bind to W2:41 and 3) the α8 mAbs would cross-react with most mammals. Comparing with the mAbs against the other α-subunits of RGD-integrins, two classes were delineated; those binding to “W3:34 and an top-loop”, and “solely W2:41”, accounting for 82% of published RGD-integrin-mAbs. PMID:26349930

Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits.

PubMed

Nishimichi, Norihisa; Kawashima, Nagako; Yokosaki, Yasuyuki

2015-09-09

Identification of epitopes for integrin-blocking monoclonal antibodies (mAbs) has aided our understanding of structure-function relationship of integrins. We mapped epitopes of chicken anti-integrin-α8-subunit-blocking mAbs by mutational analyses, examining regions that harboured all mapped epitopes recognized by mAbs against other α-subunits in the RGD-binding-integrin subfamily. Six mAbs exhibited blocking function, and these mAbs recognized residues on the same W2:41-loop on the top-face of the β-propeller. Loop-tips sufficiently close to W2:41 (<25 Å) contained within a footprint of the mAbs were mutated, and the loop W3:34 on the bottom face was identified as an additional component of the epitope of one antibody, clone YZ5. Binding sequences on the two loops were conserved in virtually all mammals, and that on W3:34 was also conserved in chickens. These indicate 1) YZ5 binds both top and bottom loops, and the binding to W3:34 is by interactions to conserved residues between immunogen and host species, 2) five other blocking mAbs solely bind to W2:41 and 3) the α8 mAbs would cross-react with most mammals. Comparing with the mAbs against the other α-subunits of RGD-integrins, two classes were delineated; those binding to "W3:34 and an top-loop", and "solely W2:41", accounting for 82% of published RGD-integrin-mAbs.

A low power on-chip class-E power amplifier for remotely powered implantable sensor systems

NASA Astrophysics Data System (ADS)

Ture, Kerim; Kilinc, Enver G.; Dehollain, Catherine

2015-06-01

This paper presents a low power fully integrated class-E power amplifier and its integration with remotely powered sensor system. The class-E power amplifier is suitable solution for low-power applications due to its high power efficiency. However, the required high inductance values which make the on-chip integration of the power amplifier difficult. The designed power amplifier is fully integrated in the remotely powered sensor system and fabricated in 0.18 μm CMOS process. The power is transferred to the implantable sensor system at 13.56 MHz by using an inductively coupled remote powering link. The induced AC voltage on the implant coil is converted into a DC voltage by a passive full-wave rectifier. A voltage regulator is used to suppress the ripples and create a clean and stable 1.8 V supply voltage for the sensor and communication blocks. The data collected from the sensors is transmitted by on-off keying modulated low-power transmitter at 1.2 GHz frequency. The transmitter is composed of a LC tank oscillator and a fully on-chip class-E power amplifier. An additional output network is used for the power amplifier which makes the integration of the power amplifier fully on-chip. The integrated power amplifier with 0.2 V supply voltage has a drain efficiency of 31.5% at -10 dBm output power for 50 Ω load. The measurement results verify the functionality of the power amplifier and the remotely powered implantable sensor system. The data communication is also verified by using a commercial 50 Ω chip antenna and has 600 kbps data rate at 1 m communication distance.

Common lines modeling for reference free Ab-initio reconstruction in cryo-EM.

PubMed

Greenberg, Ido; Shkolnisky, Yoel

2017-11-01

We consider the problem of estimating an unbiased and reference-free ab initio model for non-symmetric molecules from images generated by single-particle cryo-electron microscopy. The proposed algorithm finds the globally optimal assignment of orientations that simultaneously respects all common lines between all images. The contribution of each common line to the estimated orientations is weighted according to a statistical model for common lines' detection errors. The key property of the proposed algorithm is that it finds the global optimum for the orientations given the common lines. In particular, any local optima in the common lines energy landscape do not affect the proposed algorithm. As a result, it is applicable to thousands of images at once, very robust to noise, completely reference free, and not biased towards any initial model. A byproduct of the algorithm is a set of measures that allow to asses the reliability of the obtained ab initio model. We demonstrate the algorithm using class averages from two experimental data sets, resulting in ab initio models with resolutions of 20Å or better, even from class averages consisting of as few as three raw images per class. Copyright © 2017 Elsevier Inc. All rights reserved.

Gerstmann-Straüssler-Scheinker disease: novel PRNP mutation and VGKC-complex antibodies.

PubMed

Jones, Matthew; Odunsi, Sola; du Plessis, Daniel; Vincent, Angela; Bishop, Matthew; Head, Mark W; Ironside, James W; Gow, David

2014-06-10

To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene. The patient was diagnosed in life with VGKC-complex Ab-associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found. VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease. © 2014 American Academy of Neurology.

Three dimensional reliability analyses of currently used methods for assessment of sagittal jaw discrepancy

PubMed Central

Almaqrami, Bushra-Sufyan; Alhammadi, Maged-Sultan

2018-01-01

Background The objective of this study was to analyse three dimensionally the reliability and correlation of angular and linear measurements in assessment of anteroposterior skeletal discrepancy. Material and Methods In this retrospective cross sectional study, a sample of 213 subjects were three-dimensionally analysed from cone-beam computed tomography scans. The sample was divided according to three dimensional measurement of anteroposterior relation (ANB angle) into three groups (skeletal Class I, Class II and Class III). The anterior-posterior cephalometric indicators were measured on volumetric images using Anatomage software (InVivo5.2). These measurements included three angular and seven linear measurements. Cross tabulations were performed to correlate the ANB angle with each method. Intra-class Correlation Coefficient (ICC) test was applied for the difference between the two reliability measurements. P value of < 0.05 was considered significant. Results There was a statistically significant (P<0.05) agreement between all methods used with variability in assessment of different anteroposterior relations. The highest correlation was between ANB and DSOJ (0.913), strong correlation with AB/FH, AB/SN/, MM bisector, AB/PP, Wits appraisal (0.896, 0.890, 0.878, 0.867,and 0.858, respectively), moderate with AD/SN and Beta angle (0.787 and 0.760), and weak correlation with corrected ANB angle (0.550). Conclusions Conjunctive usage of ANB angle with DSOJ, AB/FH, AB/SN/, MM bisector, AB/PP and Wits appraisal in 3D cephalometric analysis provide a more reliable and valid indicator of the skeletal anteroposterior relationship. Clinical relevance: Most of orthodontic literature depends on single method (ANB) with its drawbacks in assessment of skeletal discrepancy which is a cardinal factors for proper treatment planning, this study assessed three dimensionally the degree of correlation between all available methods to make clinical judgement more accurate based on more than one method of assessment. Key words:Anteroposterior relationships, ANB angle, Three-dimension, CBCT. PMID:29750096

Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes-A Recursive Partitioning Analysis.

PubMed

Xu, Ping; Krischer, Jeffrey P

2016-06-01

To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clinical characteristics, including genotype, antibody titers, and metabolic markers were analyzed. Age and GAD65 autoantibody (GAD65Ab) titers defined three risk classes for progression from single to multiple autoantibodies. The 5-year risk was 11% for those subjects >16 years of age with low GAD65Ab titers, 29% for those ≤16 years of age with low GAD65Ab titers, and 45% for those subjects with high GAD65Ab titers regardless of age. Progression to dysglycemia was associated with islet antigen 2 Ab titers, and 2-h glucose and fasting C-peptide levels. The 5-year risk is 28%, 39%, and 51% for respective risk classes defined by the three predictors. Progression to type 1 diabetes was associated with the number of positive autoantibodies, peak C-peptide level, HbA1c level, and age. Four risk classes defined by RPA had a 5-year risk of 9%, 33%, 62%, and 80%, respectively. The use of RPA offered a new classification approach that could predict the timing of transitions from one preclinical stage to the next in the development of type 1 diabetes. Using these RPA classes, new prevention techniques can be tailored based on the individual prognostic risk characteristics at different preclinical stages. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies

PubMed Central

Hwang, Joyce K.; Wang, Chong; Du, Zhou; Meyers, Robin M.; Kepler, Thomas B.; Neuberg, Donna; Kwong, Peter D.; Mascola, John R.; Joyce, M. Gordon; Bonsignori, Mattia; Haynes, Barton F.; Yeap, Leng-Siew; Alt, Frederick W.

2017-01-01

Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase antigen-binding affinity. Some HIV-1–infected human subjects develop broadly neutralizing antibodies (bnAbs), such as the potent VRC01-class bnAbs, that neutralize diverse HIV-1 strains. Mature VRC01-class bnAbs, including VRC-PG04, accumulate very high SHM levels, a property that hinders development of vaccine strategies to elicit them. Because many VRC01-class bnAb SHMs are not required for broad neutralization, high overall SHM may be required to achieve certain functional SHMs. To elucidate such requirements, we used a V(D)J passenger allele system to assay, in mouse GC B cells, sequence-intrinsic SHM-targeting rates of nucleotides across substrates representing maturation stages of human VRC-PG04. We identify rate-limiting SHM positions for VRC-PG04 maturation, as well as SHM hotspots and intrinsically frequent deletions associated with SHM. We find that mature VRC-PG04 has low SHM capability due to hotspot saturation but also demonstrate that generation of new SHM hotspots and saturation of existing hotspot regions (e.g., CDR3) does not majorly influence intrinsic SHM in unmutated portions of VRC-PG04 progenitor sequences. We discuss implications of our findings for bnAb affinity maturation mechanisms. PMID:28747530

Relativity and the lead-acid battery.

PubMed

Ahuja, Rajeev; Blomqvist, Andreas; Larsson, Peter; Pyykkö, Pekka; Zaleski-Ejgierd, Patryk

2011-01-07

The energies of the solid reactants in the lead-acid battery are calculated ab initio using two different basis sets at nonrelativistic, scalar-relativistic, and fully relativistic levels, and using several exchange-correlation potentials. The average calculated standard voltage is 2.13 V, compared with the experimental value of 2.11 V. All calculations agree in that 1.7-1.8 V of this standard voltage arise from relativistic effects, mainly from PbO2 but also from PbSO4.

The Cellular Bases of Antibody Responses during Dengue Virus Infection

PubMed Central

Yam-Puc, Juan Carlos; Cedillo-Barrón, Leticia; Aguilar-Medina, Elsa Maribel; Ramos-Payán, Rosalío; Escobar-Gutiérrez, Alejandro; Flores-Romo, Leopoldo

2016-01-01

Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell-dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated. PMID:27375618

Tandem-ESQ for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreiner, A. J.; Escuela de Ciencia y Tecnologia, Universidad de Gral San Martin; CONICET,

2007-02-12

A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed as a machine for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT). The machine is shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep seated tumors in less than an hour.

A look-up-table digital predistortion technique for high-voltage power amplifiers in ultrasonic applications.

PubMed

Gao, Zheng; Gui, Ping

2012-07-01

In this paper, we present a digital predistortion technique to improve the linearity and power efficiency of a high-voltage class-AB power amplifier (PA) for ultrasound transmitters. The system is composed of a digital-to-analog converter (DAC), an analog-to-digital converter (ADC), and a field-programmable gate array (FPGA) in which the digital predistortion (DPD) algorithm is implemented. The DPD algorithm updates the error, which is the difference between the ideal signal and the attenuated distorted output signal, in the look-up table (LUT) memory during each cycle of a sinusoidal signal using the least-mean-square (LMS) algorithm. On the next signal cycle, the error data are used to equalize the signal with negative harmonic components to cancel the amplifier's nonlinear response. The algorithm also includes a linear interpolation method applied to the windowed sinusoidal signals for the B-mode and Doppler modes. The measurement test bench uses an arbitrary function generator as the DAC to generate the input signal, an oscilloscope as the ADC to capture the output waveform, and software to implement the DPD algorithm. The measurement results show that the proposed system is able to reduce the second-order harmonic distortion (HD2) by 20 dB and the third-order harmonic distortion (HD3) by 14.5 dB, while at the same time improving the power efficiency by 18%.

A Triad of Molecular Regions Contribute to the Formation of Two Distinct MHC Class II Conformers

PubMed Central

Drake, Lisa A.; Drake, James R.

2016-01-01

MHC class II molecules present antigen-derived peptides to CD4 T cells to drive the adaptive immune response. Previous work has established that class II αβ dimers can adopt two distinct conformations, driven by the differential pairing of transmembrane domain GxxxG dimerization motifs. These class II conformers differ in their ability to be loaded with antigen-derived peptide and to effectively engage CD4 T cells. Motif 1 (M1) paired I-Ak class II molecules are efficiently loaded with peptides derived from the processing of B cell receptor-bound antigen, have unique B cell signaling properties and high T cell stimulation activity. The 11-5.2 mAb selectively binds M1 paired I-Ak class II molecules. However, the molecular determinants of 11-5.2 binding are currently unclear. Here, we report the ability of a human class II transmembrane domain to drive both M1 and M2 class II conformer formation. Protease sensitivity analysis further strengthens the idea that there are conformational differences between the extracellular domains of M1 and M2 paired class II. Finally, MHC class II chain alignments and site directed mutagenesis reveals a triad of molecular regions that contributes to 11-5.2 mAb binding. In addition to transmembrane GxxxG motif domain pairing, 11-5.2 binding is influenced directly by α chain residue Glu-71 and indirectly by the region around the inter-chain salt bridge formed by α chain Arg-52 and β chain Glu-86. These findings provide insight into the complexity of 11-5.2 mAb recognition of the M1 paired I-Ak class II conformer and further highlight the molecular heterogeneity of peptide-MHC class II complexes that drive T cell antigen recognition. PMID:27148821

Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report.

PubMed

Savard, Martin; Irani, Sarosh R; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H; Gould, Peter V; Laforce, Robert

2016-02-01

Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.

Electrical Characterization Laboratory | Energy Systems Integration

Science.gov Websites

the ability of electrical equipment to withstand high-voltage surges and high-current faults. A capability. High-Voltage Characterization The high-voltage characterization hub offers a Class 1, Div 2 lab

A novel impedance-based cellular assay for the detection of anti-calcium channel autoantibodies in type 1 diabetes.

PubMed

Jackson, Michael W; Gordon, Tom P

2010-09-30

We have recently postulated that functional autoantibodies (Abs) against L-type voltage-gated calcium channels (VGCCs) contribute to autonomic dysfunction in type 1 diabetes (T1D). Previous studies based on whole-organ assays have proven valuable in establishing the mechanism of anti-VGCC Ab activity, but are complex and unsuitable for screening large patient cohorts. In the current study, we used real-time dynamic monitoring of cell impedance to demonstrate that anti-VGCC Abs from patients with T1D inhibit the adherence of Rin A12 cells. The functional effect of the anti-VGCC Abs was mimicked by the dihydropyridine agonist, Bay K8644, and reversed by the antagonist, nicardipine, providing a pharmacological link to the whole-organ studies. IVIg neutralized the effect on cell adhesion of the anti-VGCC Abs, consistent with the presence of anti-idiotypic Abs in IVIg that may prevent the emergence of pathogenic Abs in healthy individuals. The cell impedance assay can be performed in a 96 well plate format, and represents a simple method for detecting the presence of anti-VGCC activity in patient immunoglobulin (IgG). The new cell assay should prove useful for further studies to determine the prevalence of the Ab and its association with symptoms of autonomic dysfunction in patients with T1D. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

The Design and Characterization of a Prototype Wideband Voltage Sensor Based on a Resistive Divider

PubMed Central

Garnacho, Fernando; Khamlichi, Abderrahim; Rovira, Jorge

2017-01-01

The most important advantage of voltage dividers over traditional voltage transformers is that voltage dividers do not have an iron core with non-linear hysteresis characteristics. The voltage dividers have a linear behavior with respect to over-voltages and a flat frequency response larger frequency range. The weak point of a voltage divider is the influence of external high-voltage (HV) and earth parts in its vicinity. Electrical fields arising from high voltages in neighboring phases and from ground conductors and structures are one of their main sources for systematic measurement errors. This paper describes a shielding voltage divider for a 24 kV medium voltage network insulated in SF6 composed of two resistive-capacitive dividers, one integrated within the other, achieving a flat frequency response up to 10 kHz for ratio error and up to 5 kHz for phase displacement error. The metal shielding improves its immunity against electric and magnetic fields. The characterization performed on the built-in voltage sensor shows an accuracy class of 0.2 for a frequency range from 20 Hz to 5 kHz and a class of 0.5 for 1 Hz up to 20 Hz. A low temperature effect is also achieved for operation conditions of MV power grids. PMID:29149085

The Design and Characterization of a Prototype Wideband Voltage Sensor Based on a Resistive Divider.

PubMed

Garnacho, Fernando; Khamlichi, Abderrahim; Rovira, Jorge

2017-11-17

The most important advantage of voltage dividers over traditional voltage transformers is that voltage dividers do not have an iron core with non-linear hysteresis characteristics. The voltage dividers have a linear behavior with respect to over-voltages and a flat frequency response larger frequency range. The weak point of a voltage divider is the influence of external high-voltage (HV) and earth parts in its vicinity. Electrical fields arising from high voltages in neighboring phases and from ground conductors and structures are one of their main sources for systematic measurement errors. This paper describes a shielding voltage divider for a 24 kV medium voltage network insulated in SF6 composed of two resistive-capacitive dividers, one integrated within the other, achieving a flat frequency response up to 10 kHz for ratio error and up to 5 kHz for phase displacement error. The metal shielding improves its immunity against electric and magnetic fields. The characterization performed on the built-in voltage sensor shows an accuracy class of 0.2 for a frequency range from 20 Hz to 5 kHz and a class of 0.5 for 1 Hz up to 20 Hz. A low temperature effect is also achieved for operation conditions of MV power grids.

Gerstmann-Straüssler-Scheinker disease

PubMed Central

Jones, Matthew; Odunsi, Sola; du Plessis, Daniel; Vincent, Angela; Bishop, Matthew; Head, Mark W.; Ironside, James W.

2014-01-01

Objective: To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Methods: Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene. Results: The patient was diagnosed in life with VGKC-complex Ab–associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found. Conclusion: VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease. PMID:24814844

Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

PubMed

Malter, M P; Frisch, C; Schoene-Bake, J C; Helmstaedter, C; Wandinger, K P; Stoecker, W; Urbach, H; Surges, R; Elger, C E; Vincent, A V; Bien, C G

2014-09-01

In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE.

75 FR 17511 - Coal Mine Dust Sampling Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... Part III Department of Labor Mine Safety and Health Adminisration 30 CFR Parts 18, 74, and 75 Coal Mine Dust Sampling Devices; High-Voltage Continuous Mining Machine Standard for Underground Coal Mines...-AB61 Coal Mine Dust Sampling Devices AGENCY: Mine Safety and Health Administration, Labor. ACTION...

Frequency and severity of transfusion-related acute lung injury--German haemovigilance data (2006-2007).

PubMed

Keller-Stanislawski, B; Reil, A; Günay, S; Funk, M B

2010-01-01

In an observational cohort study (2006-2007) the Paul-Ehrlich-Institut collected epidemiological data to investigate the frequency and causes of TRALI. Diagnosis of TRALI was confirmed according to criteria of the European Haemovigilance Network. Subsequent testing of white blood cell antibodies (WBC-Ab) against HLA or human neutrophil alloantigens was performed. Of a total of 187 reported TRALI cases, 44 could be confirmed consisting of 35 cases of antibody-mediated TRALI and nine cases of non-immune-mediated TRALI. Eight of 44 affected patients (18%) had a fatal outcome, seven cases with WBC-Ab positive plasma donors and one case with red blood cell donors. WBC antibodies were found in one male and 39 female donors. In 34 female donors, a history of pregnancy was confirmed. WBC-Ab positive donors presented four HLA class I antibodies, 15 HLA class II antibodies, 13 HLA class I and class II antibodies, one HNA-2a, and seven HNA-3a antibodies. WBC antibodies matching with recipient antigens were found exclusively in 28 female donors; 26 FFP donors, one platelet donor and one red blood cell donor. Reporting frequency of immune-mediated TRALI was 1:66,000 for fresh frozen plasma, 1:2.86 million for red blood cell concentrates and 1:420,000 for platelet concentrates. Reporting frequency of TRALI-related fatalities was 1:285,000 for FFP. Haemovigilance data show the significance of female donors with a history of pregnancy for the development of antibody-mediated TRALI. Manufacturing of FFP from male plasma and female donor screening for WBC-Ab could represent preventive measures.

Hierarchical mutational events compensate for glutamate auxotrophy of a Bacillus subtilis gltC mutant.

PubMed

Dormeyer, Miriam; Lübke, Anastasia L; Müller, Peter; Lentes, Sabine; Reuß, Daniel R; Thürmer, Andrea; Stülke, Jörg; Daniel, Rolf; Brantl, Sabine; Commichau, Fabian M

2017-06-01

Glutamate is the major donor of nitrogen for anabolic reactions. The Gram-positive soil bacterium Bacillus subtilis either utilizes exogenously provided glutamate or synthesizes it using the gltAB-encoded glutamate synthase (GOGAT). In the absence of glutamate, the transcription factor GltC activates expression of the GOGAT genes for glutamate production. Consequently, a gltC mutant strain is auxotrophic for glutamate. Using a genetic selection and screening system, we could isolate and differentiate between gltC suppressor mutants in one step. All mutants had acquired the ability to synthesize glutamate, independent of GltC. We identified (i) gain-of-function mutations in the gltR gene, encoding the transcription factor GltR, (ii) mutations in the promoter of the gltAB operon and (iii) massive amplification of the genomic locus containing the gltAB operon. The mutants belonging to the first two classes constitutively expressed the gltAB genes and produced sufficient glutamate for growth. By contrast, mutants that belong to the third class appeared most frequently and solved glutamate limitation by increasing the copy number of the poorly expressed gltAB genes. Thus, glutamate auxotrophy of a B. subtilis gltC mutant can be relieved in multiple ways. Moreover, recombination-dependent amplification of the gltAB genes is the predominant mutational event indicating a hierarchy of mutations. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

LOW VOLTAGE 14 Mev NEUTRON SOURCE

DOEpatents

Little, R.N. Jr.; Graves, E.R.

1959-09-29

An apparatus yielding high-energy neutrons at the rate of 10/sup 8/ or more per second by the D,T or D,D reactions is described. The deuterium gas filling is ionized by electrons emitted from a filament, and the resulting ions are focused into a beam and accelerated against a fixed target. The apparatus is built in accordance with the relationship V/sub s/ = A--B log pd, where V/sub s/ is the sparking voltage, p the gas pressure, and d the gap length between the high voltage electrodes. Typical parameters to obtain the high neutron yields are 55 to 80 kv, 0.5 to 7.0 ma beam current, 5 to 12 microns D/sub 2/, and a gap length of 1 centimeter.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

PubMed Central

Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

2012-01-01

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

Extension of E7024 Electrode Applications in Shipbuilding

DTIC Science & Technology

1980-08-01

E7028, or ABS Grades 2, 2Y electrodes. A class of E7024 electrodes meeting elongation and Charpy V-notch requirements equivalent to ABS Grades 2 and...that adequate weld quality is maintained. The ABS limitations on E7024 electrodes are associated with the absence of a Charpy impact requirement and...fillet welds 1/2” base plate was used were made with each brand of E7024 electrodes; for tension tests; 1“ plate was used for Charpy . tests to provide

Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated p21 expression in papillary thyroid carcinoma.

PubMed

Gou, Qiheng; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian-Kang; Gong, Yanqiu; He, Juan; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yu-Quan; Zhang, Lin; Peng, Yong

2018-05-07

Long noncoding RNAs (lncRNAs) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Copyright ©2018, American Association for Cancer Research.

Applicability of Type A/B alcohol dependence in the general population.

PubMed

Tam, Tammy W; Mulia, Nina; Schmidt, Laura A

2014-05-01

This study examined the concurrent and predictive validity of Type A/B alcohol dependence in the general population-a typology developed in clinical populations to gauge severity of dependence. Data were drawn from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The sample included 1,172 alcohol-dependent drinkers at baseline who were reinterviewed three years later. Latent class analysis was used to derive Type A/B classification using variables replicating the original Type A/B typology. Predictive validity of the Type A/B classification was assessed by multivariable linear and logistic regressions. A two-class solution consistent with Babor's original Type A/B typology adequately fit the data. Type B alcoholics in the general population, compared to Type As, had higher alcohol severity and more co-occurring drug, mental, and physical health problems. In the absence of treatment services utilization, Type B drinkers had two times the odds of being alcohol dependent three years later. Among those who utilized alcohol treatment services, Type B membership was predictive of heavy drinking and drug dependence, but not alcohol dependence, three years later. Findings suggest that Type A/B classification is both generalizable to, and valid within, the US general population of alcohol dependent drinkers. Results highlight the value of treatment for mitigating the persistence of dependence among Type B alcoholics in the general population. Screening for markers of vulnerability to Type B dependence could be of clinical value for health care providers to determine appropriate intervention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Bacillus subtilis ywjI (glpX) gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the class III Fbp enzyme.

PubMed

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-05-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions.

The Bacillus subtilis ywjI (glpX) Gene Encodes a Class II Fructose-1,6-Bisphosphatase, Functionally Equivalent to the Class III Fbp Enzyme▿

PubMed Central

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-01-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions. PMID:19270101

Ligand-induced Epitope Masking

PubMed Central

Mould, A. Paul; Askari, Janet A.; Byron, Adam; Takada, Yoshikazu; Jowitt, Thomas A.; Humphries, Martin J.

2016-01-01

We previously demonstrated that Arg-Gly-Asp (RGD)-containing ligand-mimetic inhibitors of integrins are unable to dissociate pre-formed integrin-fibronectin complexes (IFCs). These observations suggested that amino acid residues involved in integrin-fibronectin binding become obscured in the ligand-occupied state. Because the epitopes of some function-blocking anti-integrin monoclonal antibodies (mAbs) lie near the ligand-binding pocket, it follows that the epitopes of these mAbs may become shielded in the ligand-occupied state. Here, we tested whether function-blocking mAbs directed against α5β1 can interact with the integrin after it forms a complex with an RGD-containing fragment of fibronectin. We showed that the anti-α5 subunit mAbs JBS5, SNAKA52, 16, and P1D6 failed to disrupt IFCs and hence appeared unable to bind to the ligand-occupied state. In contrast, the allosteric anti-β1 subunit mAbs 13, 4B4, and AIIB2 could dissociate IFCs and therefore were able to interact with the ligand-bound state. However, another class of function-blocking anti-β1 mAbs, exemplified by Lia1/2, could not disrupt IFCs. This second class of mAbs was also distinguished from 13, 4B4, and AIIB2 by their ability to induce homotypic cell aggregation. Although the epitope of Lia1/2 was closely overlapping with those of 13, 4B4, and AIIB2, it appeared to lie closer to the ligand-binding pocket. A new model of the α5β1-fibronectin complex supports our hypothesis that the epitopes of mAbs that fail to bind to the ligand-occupied state lie within, or very close to, the integrin-fibronectin interface. Importantly, our findings imply that the efficacy of some therapeutic anti-integrin mAbs could be limited by epitope masking. PMID:27484800

Aqueous biphasic systems in the separation of food colorants.

PubMed

Santos, João H P M; Capela, Emanuel V; Boal-Palheiros, Isabel; Coutinho, João A P; Freire, Mara G; Ventura, Sónia P M

2018-04-25

Aqueous biphasic systems (ABS) composed of polypropylene glycol and carbohydrates, two benign substances are proposed to separate two food colorants (E122 and E133). ABS are promising extractive platforms, particularly for biomolecules, due to their aqueous and mild nature (pH and temperature), reduced environmental impact and processing costs. Another major aspect considered, particularly useful in downstream processing, is the "tuning" ability for the extraction and purification of these systems by a proper choice of the ABS components. In this work, our intention is to show the concept of ABS as an alternative and volatile organic solvent-free tool to separate two different biomolecules in a simple way, so simple that teachers can effectively adopt it in their classes to explain the concept of bioseparation processes. Informative documents and general information about the preparation of binodal curves and their use in the partition of biomolecules is available in this work to be used by teachers in their classes. In this sense, the students use different carbohydrates to build ABS, then study the partition of two food color dyes (synthetic origin), thus evaluating their ability on the separation of both food colorants. Through these experiments, the students get acquainted with ABS, learn how to determine solubility curves and perform extraction procedures using colorant food additives, that can also be applied in the extraction of various (bio)molecules. © 2018 by The International Union of Biochemistry and Molecular Biology, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

Equivalence-Equivalence: Matching Stimuli with Same Discriminative Functions

ERIC Educational Resources Information Center

Carpentier, Franck; Smeets, Paul M.; Barnes-Holmes, Dermot

2004-01-01

Previous studies have shown that after being trained on A-B and A-C match-to-sample tasks, adults match not only same-class B and C stimuli (equivalence) but also BC compounds with same-class elements and with different-class elements (BC-BC). The assumption was that the BC-BC performances are based on matching equivalence and nonequivalence…

Promoting Teacher Adoption of Physical Activity Breaks in the Classroom: Findings of the Central Texas Catch Middle School Project

ERIC Educational Resources Information Center

Delk, Joanne; Springer, Andrew E.; Kelder, Steven H.; Grayless, Megan

2014-01-01

Background: Research suggests that physical activity breaks (ABs) during class increase students' physical activity levels and provide an academic benefit. This study evaluates a 3-year intervention aimed at encouraging teacher AB use. Methods: Thirty central Texas middle schools were assigned to 1 of 3 conditions: training-only…

Ab initio modeling of steady-state and time-dependent charge transport in hole-only α-NPD devices

NASA Astrophysics Data System (ADS)

Liu, Feilong; Massé, Andrea; Friederich, Pascal; Symalla, Franz; Nitsche, Robert; Wenzel, Wolfgang; Coehoorn, Reinder; Bobbert, Peter A.

2016-12-01

We present an ab initio modeling study of steady-state and time-dependent charge transport in hole-only devices of the amorphous molecular semiconductor α-NPD [N ,N'-Di(1 -naphthyl)-N ,N'-diphenyl-(1 ,1'-biphenyl)-4 ,4'-diamine] . The study is based on the microscopic information obtained from atomistic simulations of the morphology and density functional theory calculations of the molecular hole energies, reorganization energies, and transfer integrals. Using stochastic approaches, the microscopic information obtained in simulation boxes at a length scale of ˜10 nm is expanded and employed in one-dimensional (1D) and three-dimensional (3D) master-equation modeling of the charge transport at the device scale of ˜100 nm. Without any fit parameter, predicted current density-voltage and impedance spectroscopy data obtained with the 3D modeling are in very good agreement with measured data on devices with different α-NPD layer thicknesses in a wide range of temperatures, bias voltages, and frequencies. Similarly good results are obtained with the computationally much more efficient 1D modeling after optimizing a hopping prefactor.

Hypothermia in VGKC antibody-associated limbic encephalitis.

PubMed

Jacob, S; Irani, S R; Rajabally, Y A; Grubneac, A; Walters, R J; Yazaki, M; Clover, L; Vincent, A

2008-02-01

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.

Analysis and design of continuous class-E power amplifier at sub-nominal condition

NASA Astrophysics Data System (ADS)

Chen, Peng; Yang, Kai; Zhang, Tianliang

2017-12-01

The continuous class-E power amplifier at sub-nominal condition is proposed in this paper. The class-E power amplifier at continuous mode means it can be high efficient on a series matching networks while at sub-nominal condition means it only requires the zero-voltage-switching condition. Comparing with the classical class-E power amplifier, the proposed design method releases two additional design freedoms, which increase the class-E power amplifier's design flexibility. Also, the proposed continuous class-E power amplifier at sub-nominal condition can perform high efficiency over a broad bandwidth. The performance study of the continuous class-E power amplifier at sub-nominal condition is derived and the design procedure is summarised. The normalised switch voltage and current waveforms are investigated. Furthermore, the influences of different sub-nominal conditions on the power losses of the switch-on resistor and the output power capability are also discussed. A broadband continuous class-E power amplifier based on a Gallium Nitride (GaN) transistor is designed and testified to verify the proposed design methodology. The measurement results show, it can deliver 10-15 W output power with 64-73% power-added efficiency over 1.4-2.8 GHz.

Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial cell-monocyte interactions via mTOR in transplant antibody-mediated rejection.

PubMed

Salehi, Sahar; Sosa, Rebecca A; Jin, Yi-Ping; Kageyama, Shoichi; Fishbein, Michael C; Rozengurt, Enrique; Kupiec-Weglinski, Jerzy W; Reed, Elaine F

2018-05-01

Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA, which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment. We used an in vitro model to assess monocyte binding to HLA I Ab-activated endothelial cells and found mTOR inhibition reduced ezrin/radixin/moesin (ERM) phosphorylation, intercellular adhesion molecule 1 (ICAM-1) clustering, and monocyte firm adhesion to HLA I Ab-activated endothelium. Further, in a mouse model of AMR, in which C57BL/6. RAG1 -/- recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies, mTOR inhibition significantly reduced vascular injury, ERM phosphorylation, and macrophage infiltration of the allograft. Taken together, these studies indicate mTOR inhibition suppresses ERM phosphorylation in endothelial cells, which impedes ICAM-1 clustering in response to HLA class I Ab and prevents macrophage infiltration into cardiac allografts. These findings indicate a novel therapeutic application for mTOR inhibitors to disrupt endothelial cell-monocyte interactions during AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Analysis of the binding loops configuration and surface adaptation of different crystallized single-domain antibodies in response to various antigens.

PubMed

Al Qaraghuli, Mohammed M; Ferro, Valerie A

2017-04-01

Monoclonal antibodies have revolutionized the biomedical field through their ubiquitous utilization in different diagnostics and therapeutic applications. Despite this widespread use, their large size and structural complexity have limited their versatility in specific applications. The antibody variable region that is responsible for binding antigen is embodied within domains that can be rescued individually as single-domain antibody (sdAb) fragments. Because of the unique characteristics of sdAbs, such as low molecular weight, high physicochemical stability, and the ability to bind antigens inaccessible to conventional antibodies, they represent a viable alternative to full-length antibodies. Consequently, 149 crystal structures of sdAbs, originating from human (VH), camelids (VHH), or sharks (VNAR), were retrieved from the Protein Data Bank, and their structures were compared. The 3 types of sdAbs displayed complementarity determining regions (CDRs) with different lengths and configurations. CDR3 of the VHH and VNAR domains were dominated by pleated and extended orientations, respectively. Although VNAR showed the smallest average molecular weight and molecular surface area compared with VHH and VH antibodies. However, the solvent accessible surface area measurements of the 3 tested sdAbs types were very similar. All the antihapten VHH antibodies showed pleated CDR3, which were sufficient to create a binding pocket to accommodate haptens (methotrexate and azo dyes) in terms of shape and electrostatic potential. The sdAbs that recognized lysozyme showed more diversity in their CDR3 orientation to enable them to recognize various topographies of lysozyme. Subsequently, the three sdAb classes were different in size and surface area and have shown distinguishable ability to optimize their CDR length and orientation to recognize different antigen classes. Copyright © 2016 John Wiley & Sons, Ltd.

50 KW Class Krypton Hall Thruster Performance

NASA Technical Reports Server (NTRS)

Jacobson, David T.; Manzella, David H.

2003-01-01

The performance of a 50-kilowatt-class Hall thruster designed for operation on xenon propellant was measured using kryton propellant. The thruster was operated at discharge power levels ranging from 6.4 to 72.5 kilowatts. The device produced thrust ranging from 0.3 to 2.5 newtons. The thruster was operated at discharge voltages between 250 and 1000 volts. At the highest anode mass flow rate and discharge voltage and assuming a 100 percent singly charged condition, the discharge specific impulse approached the theoretical value. Discharge specific impulse of 4500 seconds was demonstrated at a discharge voltage of 1000 volts. The peak discharge efficiency was 64 percent at 650 volts.

METHOD OF LOCATING GROUNDS

DOEpatents

Macleish, K.G.

1958-02-11

ABS>This patent presents a method for locating a ground in a d-c circult having a number of parallel branches connected across a d-c source or generator. The complete method comprises the steps of locating the ground with reference to the mildpoint of the parallel branches by connecting a potentiometer across the terminals of the circuit and connecting the slider of the potentiometer to ground through a current indicating instrument, adjusting the slider to right or left of the mildpoint so as to cause the instrument to indicate zero, connecting the terminal of the network which is farthest from the ground as thus indicated by the potentiometer to ground through a condenser, impressing a ripple voltage on the circuit, and then measuring the ripple voltage at the midpoint of each parallel branch to find the branch in which is the lowest value of ripple voltage, and then measuring the distribution of the ripple voltage along this branch to determine the point at which the ripple voltage drops off to zero or substantially zero due to the existence of a ground. The invention has particular application where a circuit ground is present which will disappear if the normal circuit voltage is removed.

Simplified Design Equations for Class-E Neural Prosthesis Transmitters

PubMed Central

Troyk, Philip; Hu, Zhe

2013-01-01

Extreme miniaturization of implantable electronic devices is recognized as essential for the next generation of neural prostheses, owing to the need for minimizing the damage and disruption of the surrounding neural tissue. Transcutaneous power and data transmission via a magnetic link remains the most effective means of powering and controlling implanted neural prostheses. Reduction in the size of the coil, within the neural prosthesis, demands the generation of a high-intensity radio frequency magnetic field from the extracoporeal transmitter. The Class-E power amplifier circuit topology has been recognized as a highly effective means of producing large radio frequency currents within the transmitter coil. Unfortunately, design of a Class-E circuit is most often fraught by the need to solve a complex set of equations so as to implement both the zero-voltage-switching and zero-voltage-derivative-switching conditions that are required for efficient operation. This paper presents simple explicit design equations for designing the Class-E circuit topology. Numerical design examples are presented to illustrate the design procedure. PMID:23292784

Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies.

PubMed

Cernea, Simona; Herold, Kevan C

2010-02-01

The way in which anti-CD3 monoclonal antibodies (mAbs) modify human immune responses in type 1 diabetes (T1DM) is not known. We prepared a panel of Class I HLA-A2.1 tetramers with peptides from diabetes-associated antigens and studied the frequency and phenotype of the cells in patients with T1DM and blood donors and in patients treated with anti-CD3 mAb (Teplizumab). More patients with T1DM showed positive staining for at least 1 tetramer using frozen and fresh samples (p<0.05). Three months following treatment with anti-CD3 mAb, the proportion of GAD65- and InsB-peptide reactive CD8+ T cells increased (p<0.05). The phenotype of these cells was modulated from naïve to effector memoryRA+. We concludethat Class I MHC tetramers can identify antigen specific CD8+ T cells in patients with T1DM. The frequency of certain specificities increases after treatment with anti-CD3 mAb. Their modulated phenotype may have functional consequences for their pathogenicity. Copyright 2009 Elsevier Inc. All rights reserved.

Low Wind Speed Turbine Project Phase II: The Application of Medium-Voltage Electrical Apparatus to the Class of Variable Speed Multi-Megawatt Low Wind Speed Turbines; 15 June 2004--30 April 2005

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erdman, W.; Behnke, M.

2005-11-01

Kilowatt ratings of modern wind turbines have progressed rapidly from 50 kW to 1,800 kW over the past 25 years, with 3.0- to 7.5-MW turbines expected in the next 5 years. The premise of this study is simple: The rapid growth of wind turbine power ratings and the corresponding growth in turbine electrical generation systems and associated controls are quickly making low-voltage (LV) electrical design approaches cost-ineffective. This report provides design detail and compares the cost of energy (COE) between commercial LV-class wind power machines and emerging medium-voltage (MV)-class multi-megawatt wind technology. The key finding is that a 2.5% reductionmore » in the COE can be achieved by moving from LV to MV systems. This is a conservative estimate, with a 3% to 3.5% reduction believed to be attainable once purchase orders to support a 250-turbine/year production level are placed. This evaluation considers capital costs as well as installation, maintenance, and training requirements for wind turbine maintenance personnel. Subsystems investigated include the generator, pendant cables, variable-speed converter, and padmount transformer with switchgear. Both current-source and voltage-source converter/inverter MV topologies are compared against their low-voltage, voltage-source counterparts at the 3.0-, 5.0-, and 7.5-MW levels.« less

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs.

PubMed

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-06-15

Ab-mediated rejection (AMR) of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor-specific Ab binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the Ab. We investigated the mechanisms underlying monocyte recruitment by HLA class I (HLA I) Ab-activated endothelium. We used a panel of murine mAbs of different subclasses to crosslink HLA I on human aortic, venous, and microvascular endothelial cells and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine (m)IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. mIgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during AMR. We confirmed these observations using human HLA allele-specific mAbs and IgG purified from transplant patient sera. HLA I Abs universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during AMR. Importantly, the subclass of donor-specific Ab may influence its pathogenesis. These results imply that human IgG1 and human IgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions.

IB-12LUNG MASS AND IMMUNOSUPPRESSANT RESPONSIVE SEIZURES: VGKC AUTOIMMUNITY MASQUERADING AS ETIOLOGY OR ACTING AS REACTIVE MARKER?

PubMed Central

Umemura, Yoshie; Bujarski, Krzysztof; Ronan, Lara

2014-01-01

Voltage gated potassium channel complex antibody (VGKC Ab) has been associated with many neurological illnesses including seizures. VGKC Ab related seizures are less responsive to antiepileptic drugs alone, and often require immunosuppression to achieve seizure freedom. Recently, specific antigenic targets such as LGI1 and CASPR2 within VGKC have been found and have been associated with specific syndromes. It has also been noted that the term "VGKC Ab" itself is problematic because it groups LGI1 and CASPR2 mediated disorders with other illnesses with unknown antigenic specificity. We describe a case of faciobrachial dystonia seizures refractory to multiple antiepileptic agents. Video EEG monitoring revealed mesial frontal epileptic discharges and serum test was positive for VGKC Ab. Patient's seizures were controlled after intravenous corticosteroid then oral mycophenolate maintenance, however, seizures returned with immunotherapy taper and cessation. When the seizures recurred, serum VGKC Ab, CSF CASPR 2 and LGI1 Abs were negative. Interestingly, she was subsequently found to have a lung mass consistent with sarcoidosis. Seizure control was achieved again with restarting of mycophenolate. Most VGKC Ab related illnesses are autoimmune even though it is a part of readily available commercial paraneoplastic testing panels. There has been no previously reported VGKC Ab related seizures associated with sarcoidosis. Although sarcoidosis is also an autoimmune entity, it is of T-cell mediated condition. It has been proposed that VGKC Ab may be a part of normal autoantibodies found in otherwise healthy individuals, which can rise to detectable levels under some circumstances. This patient suffered recurrent seizures responsive to immunotherapy even though VGKC, LGI1, and CASPR2 Abs were negative, suggesting another underlying autoimmune pathogenesis and VGKC Ab may have been a mere reactive marker of such underlying process. This raises the question of clinical significance of these antibodies and whether they are causative or reactive of the pathology.

Computation of Propagation Speed and Reflection of Axially Symmetric Waves in Composite Cylinders, with Application to Impedance Tube and Calibrator.

DTIC Science & Technology

1982-08-25

where w is the angular frequency and k the wave number; the phase speed c is related by W - kc. Because of the geometry, it is assumed that the field...PSA Phase of sample PST Phase of standard STEP Step size TEMP Temperature (C) THICK Length of sample (cm) VSA Voltage of sample VST Voltage of standard...VSA/ VST 0)027 W=4001.*RS69+.8*(TEMP-24 .0)- .037*( TEMFP-24 .0) **2.*0 00o29 E=(PSA-PST)/57.2958 0030 G=E-O 0031 IF (ABS(G)-2*3.14159 *LE. 0) GO TO 50

‘In-Format’ screening of a novel bispecific antibody format reveals significant potency improvements relative to unformatted molecules

PubMed Central

Scott, Martin J.; Lee, Jennifer A.; Wake, Matthew S.; Batt, Kelly V.; Wattam, Trevor A.; Hiles, Ian D.; Batuwangala, Thil D.; Ashman, Claire I.; Steward, Michael

2017-01-01

ABSTRACT Bispecific antibodies (BsAbs) are emerging as an important class of biopharmaceutical. The majority of BsAbs are created from conventional antibodies or fragments engineered into more complex configurations. A recurring challenge in their development, however, is the identification of components that are optimised for inclusion in the final format in order to deliver both efficacy and robust biophysical properties. Using a modular BsAb format, the mAb-dAb, we assessed whether an ‘in-format’ screening approach, designed to select format-compatible domain antibodies, could expedite lead discovery. Human nerve growth factor (NGF) was selected as an antigen to validate the approach; domain antibody (dAb) libraries were screened, panels of binders identified, and binding affinities and potencies compared for selected dAbs and corresponding mAb-dAbs. A number of dAbs that exhibited high potency (IC50) when assessed in-format were identified. In contrast, the corresponding dAb monomers had ∼1000-fold lower potency than the formatted dAbs; such dAb monomers would therefore have been omitted from further characterization. Subsequent stoichiometric analyses of mAb-dAbs bound to NGF, or an additional target antigen (vascular endothelial growth factor), suggested different target binding modes; this indicates that the observed potency improvements cannot be attributed simply to an avidity effect offered by the mAb-dAb format. We conclude that, for certain antigens, screening naïve selection outputs directly in-format enables the identification of a subset of format-compatible dAbs, and that this offers substantial benefits in terms of molecular properties and development time. PMID:27786601

Harnessing the Flow of Excitation: TRP, Voltage-Gated Na(+), and Voltage-Gated Ca(2+) Channels in Contemporary Medicine.

PubMed

Frolov, Roman V; Weckström, Matti

2016-01-01

Cellular signaling in both excitable and nonexcitable cells involves several classes of ion channels. Some of them are of minor importance, with very specialized roles in physiology, but here we concentrate on three major channel classes: TRP (transient receptor potential channels), voltage-gated sodium channels (Nav), and voltage-gated calcium channels (Cav). Here, we first propose a conceptual framework binding together all three classes of ion channels, a "flow-of-excitation model" that takes into account the inputs mediated by TRP and other similar channels, the outputs invariably provided by Cav channels, and the regenerative transmission of signals in the neural networks, for which Nav channels are responsible. We use this framework to examine the function, structure, and pharmacology of these channel classes both at cellular and also at whole-body physiological level. Building on that basis we go through the pathologies arising from the direct or indirect malfunction of the channels, utilizing ion channel defects, the channelopathies. The pharmacological interventions affecting these channels are numerous. Part of those are well-established treatments, like treatment of hypertension or some forms of epilepsy, but many other are deeply problematic due to poor drug specificity, ion channel diversity, and widespread expression of the channels in tissues other than those actually targeted. © 2016 Elsevier Inc. All rights reserved.

Detection of gamma-irradiation effect on DNA and protein using magnetic sensor and cyclic voltammetry.

PubMed

Park, Duck-Gun; Song, Hoon; Kishore, M B; Vértesy, G; Lee, Duk-Hyun

2013-11-01

In this study, a magnetic sensor utilizing Planar Hall Resistance (PHR) and cyclic Voltammetry (CV) for detecting the radiation effect was fabricated. Specifically, we applied in parallel a PHR sensor and CV device to monitor the irradiation effect on DNA and protein respectively. Through parallel measurements, we demonstrated that the PHR sensor and CV are sensitive enough to measure irradiation effect. The PHR voltage decreased by magnetic nanobead labeled DNA was slightly recovered after gamma ray irradiation. The behavior of cdk inhibitor protein p21 having a sandwich structure of Au/protein G/Ab/Ag/Ab was checked by monitoring the cyclic Voltammetry signal in analyzing the gamma ray irradiation effect.

Structural analysis of an intact monoclonal antibody by online electrochemical reduction of disulfide bonds and Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Nicolardi, Simone; Deelder, André M; Palmblad, Magnus; van der Burgt, Yuri E M

2014-06-03

Structural confirmation and quality control of recombinant monoclonal antibodies (mAbs) by top-down mass spectrometry is still challenging due to the size of the proteins, disulfide content, and post-translational modifications such as glycosylation. In this study we have applied electrochemistry (EC) to overcome disulfide bridge complexity in top-down analysis of mAbs. To this end, an electrochemical cell was coupled directly to an electrospray ionization (ESI) source and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer (MS) equipped with a 15 T magnet. By performing online EC-assisted reduction of interchain disulfide bonds in an intact mAb, the released light chains could be selected for tandem mass spectrometry (MS/MS) analysis without interference from heavy-chain fragments. Moreover, the acquisition of full MS scans under denaturing conditions allowed profiling of all abundant mAb glycoforms. Ultrahigh-resolution FTICR-MS measurements provided fully resolved isotopic distributions of intact mAb and enabled the identification of the most abundant adducts and other interfering species. Furthermore, it was found that reduction of interchain disulfide bonds occurs in the ESI source dependent on capillary voltage and solvent composition. This phenomenon was systematically evaluated and compared with the results obtained from reduction in the electrochemical cell.

A Qualitative Study to Understand Nativity Differences in Breastfeeding Behaviors Among Middle-Class African American and African-Born Women.

PubMed

Fabiyi, Camille; Peacock, Nadine; Hebert-Beirne, Jennifer; Handler, Arden

2016-10-01

Objective To explore nativity differences and the role of attitudes, social norms, and behavioral control perceptions surrounding breastfeeding initiation and duration among middle-class African-American (AA) and African-born (AB) mothers in the US. Methods Semi-structured individual interviews were conducted with 20 middle-class AA and AB mothers in central Ohio from December 2012 to February 2013. Interview questions were developed based on the Theory of Planned Behavior (TPB). Interviews were analyzed for salient themes by TPB constructs. Differences in themes were examined by nativity status. Results All study participants had initiated breastfeeding or bottle-feeding with expressed breast milk, noting the benefits it conferred as well as the persuasive encouragement they received from others. Persistent encouragement was often cited as a factor for sustaining breastfeeding. More AA mothers had discontinued breastfeeding by the time of the interview, which was often attributed to health, lactation, and work challenges. Inconsistent support from health providers, dissuasive remarks from others, ambivalent breastfeeding attitudes, and diminished family support led some mothers to begin formula supplementation. Analysis of maternal narratives revealed nativity differences across sources of encouragement. Specifically, important sources of encouragement were health providers for AA mothers and family, friends, partners and culture for AB mothers. Only AB mothers expressed concerns about difficulty they encountered with breastfeeding due to the lack of proximal family support. Conclusions Findings reveal that both groups of mothers may be susceptible to unsupportive breastfeeding norms in the US and also highlight the need for intervention in health care settings and workplaces to improve AA women's breastfeeding rates.

HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases.

PubMed

Swets, Marloes; König, Marion H; Zaalberg, Anniek; Dekker-Ensink, Neeltje G; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K

2016-09-01

De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Ligand-induced Epitope Masking: DISSOCIATION OF INTEGRIN α5β1-FIBRONECTIN COMPLEXES ONLY BY MONOCLONAL ANTIBODIES WITH AN ALLOSTERIC MODE OF ACTION.

PubMed

Mould, A Paul; Askari, Janet A; Byron, Adam; Takada, Yoshikazu; Jowitt, Thomas A; Humphries, Martin J

2016-09-30

We previously demonstrated that Arg-Gly-Asp (RGD)-containing ligand-mimetic inhibitors of integrins are unable to dissociate pre-formed integrin-fibronectin complexes (IFCs). These observations suggested that amino acid residues involved in integrin-fibronectin binding become obscured in the ligand-occupied state. Because the epitopes of some function-blocking anti-integrin monoclonal antibodies (mAbs) lie near the ligand-binding pocket, it follows that the epitopes of these mAbs may become shielded in the ligand-occupied state. Here, we tested whether function-blocking mAbs directed against α5β1 can interact with the integrin after it forms a complex with an RGD-containing fragment of fibronectin. We showed that the anti-α5 subunit mAbs JBS5, SNAKA52, 16, and P1D6 failed to disrupt IFCs and hence appeared unable to bind to the ligand-occupied state. In contrast, the allosteric anti-β1 subunit mAbs 13, 4B4, and AIIB2 could dissociate IFCs and therefore were able to interact with the ligand-bound state. However, another class of function-blocking anti-β1 mAbs, exemplified by Lia1/2, could not disrupt IFCs. This second class of mAbs was also distinguished from 13, 4B4, and AIIB2 by their ability to induce homotypic cell aggregation. Although the epitope of Lia1/2 was closely overlapping with those of 13, 4B4, and AIIB2, it appeared to lie closer to the ligand-binding pocket. A new model of the α5β1-fibronectin complex supports our hypothesis that the epitopes of mAbs that fail to bind to the ligand-occupied state lie within, or very close to, the integrin-fibronectin interface. Importantly, our findings imply that the efficacy of some therapeutic anti-integrin mAbs could be limited by epitope masking. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovchinnikov, Victor; Louveau, Joy E.; Barton, John P.

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutationsmore » increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed.« less

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

DOE PAGES

Ovchinnikov, Victor; Louveau, Joy E.; Barton, John P.; ...

2018-02-14

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutationsmore » increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed.« less

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

PubMed Central

2018-01-01

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutations increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed. PMID:29442996

HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.

PubMed

Landais, Elise; Murrell, Ben; Briney, Bryan; Murrell, Sasha; Rantalainen, Kimmo; Berndsen, Zachary T; Ramos, Alejandra; Wickramasinghe, Lalinda; Smith, Melissa Laird; Eren, Kemal; de Val, Natalia; Wu, Mengyu; Cappelletti, Audrey; Umotoy, Jeffrey; Lie, Yolanda; Wrin, Terri; Algate, Paul; Chan-Hui, Po-Ying; Karita, Etienne; Ward, Andrew B; Wilson, Ian A; Burton, Dennis R; Smith, Davey; Pond, Sergei L Kosakovsky; Poignard, Pascal

2017-11-21

Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Voltage-step pulsed electromembrane as a novel view of electrical field-induced liquid-phase microextraction.

PubMed

Rezazadeh, Maryam; Yamini, Yadollah; Seidi, Shahram; Arjomandi-Behzad, Leila

2014-01-10

In the present work, the effect of application of voltage steps on extraction efficiency of pulsed electromembrane extraction (PEME) was investigated for the first time. The effects of voltage variations including initial and final voltages, number of steps between the initial and final voltages as well as their time durations were studied on the extraction efficiencies of three different classes of analytes. These classes include amitriptyline (AMI) and nortriptyline (NOR) as more hydrophobic analytes, diclofenac (DIC) and mefenamic acid (MEF) as acidic drugs and salbutamol (SB) and terbutaline (TB) as hydrophilic compounds. It was anticipated that the application of high voltages is not necessary at the beginning of the extraction, since large amounts of target analytes exist around the supported liquid membrane (SLM)/sample solution interface. So, they could be easily transferred into the acceptor phase utilizing lower voltages. Results showed that the benefits of voltage-step PEME (VS-PEME) are more obvious in systems with low electrical resistance (regarding the SLM composition). Efficiencies of VS-PEME for extraction of AMI and NOR (96% and 89% for AMI and NOR, respectively) were comparable with those achieved from applying a constant voltage (95% for AMI and 83% for NOR). However, recoveries from the VS-PEME of DIC and MEF (53% and 44% for DIC and MEF, respectively) were significantly higher than those from the application of a constant voltage (33% for DIC and 31% for MEF). Also, recoveries obtained from the VS-PEME for SB and TB were approximately 3 orders of magnitude greater than those from a constant voltage. Moreover, it was demonstrated that in all cases analytes could effectively be extracted at the beginning of extraction by applying low voltages. Copyright © 2013 Elsevier B.V. All rights reserved.

Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

PubMed

Yearley, Eric J; Godfrin, Paul D; Perevozchikova, Tatiana; Zhang, Hailiang; Falus, Peter; Porcar, Lionel; Nagao, Michihiro; Curtis, Joseph E; Gawande, Pradad; Taing, Rosalynn; Zarraga, Isidro E; Wagner, Norman J; Liu, Yun

2014-04-15

Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Design of two-photon molecular tandem architectures for solar cells by ab initio theory

DOE PAGES

Ornso, Kristian B.; Garcia-Lastra, Juan M.; De La Torre, Gema; ...

2015-03-04

An extensive database of spectroscopic properties of molecules from ab initio calculations is used to design molecular complexes for use in tandem solar cells that convert two photons into a single electron–hole pair, thereby increasing the output voltage while covering a wider spectral range. Three different architectures are considered: the first two involve a complex consisting of two dye molecules with appropriately matched frontier orbitals, connected by a molecular diode. Optimized combinations of dye molecules are determined by taking advantage of our computational database of the structural and energetic properties of several thousand porphyrin dyes. The third design is amore » molecular analogy of the intermediate band solar cell, and involves a single dye molecule with strong intersystem crossing to ensure a long lifetime of the intermediate state. Based on the calculated energy levels and molecular orbitals, energy diagrams are presented for the individual steps in the operation of such tandem solar cells. We find that theoretical open circuit voltages of up to 1.8 V can be achieved using these tandem designs. Questions about the practical implementation of prototypical devices, such as the synthesis of the tandem molecules and potential loss mechanisms, are addressed.« less

Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies.

PubMed

Krumm, Stefanie A; Mohammed, Hajer; Le, Khoa M; Crispin, Max; Wrin, Terri; Poignard, Pascal; Burton, Dennis R; Doores, Katie J

2016-02-02

Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch.

Design of an improved RCD buffer circuit for full bridge circuit

NASA Astrophysics Data System (ADS)

Yang, Wenyan; Wei, Xueye; Du, Yongbo; Hu, Liang; Zhang, Liwei; Zhang, Ou

2017-05-01

In the full bridge inverter circuit, when the switch tube suddenly opened or closed, the inductor current changes rapidly. Due to the existence of parasitic inductance of the main circuit. Therefore, the surge voltage between drain and source of the switch tube can be generated, which will have an impact on the switch and the output voltage. In order to ab sorb the surge voltage. An improve RCD buffer circuit is proposed in the paper. The peak energy will be absorbed through the buffer capacitor of the circuit. The part energy feedback to the power supply, another part release through the resistor in the form of heat, and the circuit can absorb the voltage spikes. This paper analyzes the process of the improved RCD snubber circuit, According to the specific parameters of the main circuit, a reasonable formula for calculating the resistance capacitance is given. A simulation model will be modulated in Multisim, which compared the waveform of tube voltage and the output waveform of the circuit without snubber circuit with the improved RCD snubber circuit. By comparing and analyzing, it is proved that the improved buffer circuit can absorb surge voltage. Finally, experiments are demonstrated to validate that the correctness of the RC formula and the improved RCD snubber circuit.

Establishing Auditory-Tactile-Visual Equivalence Classes in Children with Autism and Developmental Delays

ERIC Educational Resources Information Center

Mullen, Stuart; Dixon, Mark R.; Belisle, Jordan; Stanley, Caleb

2017-01-01

The current study sought to evaluate the efficacy of a stimulus equivalence training procedure in establishing auditory-tactile-visual stimulus classes with 2 children with autism and developmental delays. Participants were exposed to vocal-tactile (A-B) and tactile-picture (B-C) conditional discrimination training and were tested for the…

Identification of Bacillus thuringiensis Cry1AbMod binding-proteins from Spodoptera frugiperda.

PubMed

Martínez de Castro, Diana L; García-Gómez, Blanca I; Gómez, Isabel; Bravo, Alejandra; Soberón, Mario

2017-12-01

Bacillus thuringiensis Cry toxins are currently used for pest control in transgenic crops but evolution of resistance by the insect pests threatens the use of this technology. The Cry1AbMod toxin was engineered to lack the alpha helix-1 of the parental Cry1Ab toxin and was shown to counter resistance to Cry1Ab and Cry1Ac toxins in different insect species including the fall armyworm Spodoptera frugiperda. In addition, Cry1AbMod showed enhanced toxicity to Cry1Ab-susceptible S. frugiperda populations. To gain insights into the mechanisms of this Cry1AbMod-enhanced toxicity, we isolated the Cry1AbMod toxin binding proteins from S. frugiperda brush border membrane vesicles (BBMV), which were identified by pull-down assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS results indicated that Cry1AbMod toxin could bind to four classes of aminopeptidase (N1, N3, N4 y N5) and actin, with the highest amino acid sequence coverage acquired for APN 1 and APN4. In addition to these proteins, we found other proteins not previously described as Cry toxin binding proteins. This is the first report that suggests the interaction between Cry1AbMod and APN in S. frugiperda. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology.

PubMed

Dubey, Divyanshu; Alqallaf, Abdulradha; Hays, Ryan; Freeman, Matthew; Chen, Kevin; Ding, Kan; Agostini, Mark; Vernino, Steven

2017-04-01

Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016. Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom. Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an autoimmune cause of epilepsy were seen in 23 patients (20.5%). Certain clinical features, such as autonomic dysfunction, neuropsychiatric changes, viral prodrome, faciobrachial dystonic spells or facial dyskinesias, and mesial temporal sclerosis abnormality on magnetic resonance imaging, correlated with seropositivity. The APE score was a useful tool in predicting positive serologic findings. Patients who were Ab positive were more likely to have good seizure outcome than were patients with epilepsy of unknown etiology (15 of 23 [65.2%] vs 24 of 89 [27.0%]; odds ratio, 4.8; 95% CI, 1.8-12.9; P = .002). In patients who were seropositive, reduction in seizure frequency was associated with use of immunomodulatory therapy. Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs suggesting an autoimmune etiology. Certain clinical features (encoded in the APE score) could be used to identify patients with the highest probability of harboring neurological Abs.

Unusual amnesia in a patient with VGKC-Ab limbic encephalitis: a case study.

PubMed

Kartsounis, Luke D; de Silva, Rajith

2011-04-01

We describe the case of a patient with confirmed voltage-gated potassium channel antibody-associated encephalitis (VGKC-Ab). MRI studies revealed bilateral hyper-intensity in the hippocampi, with their volumes preserved. At presentation, the patient's anterograde and retrograde memory skills were found to be impaired and he showed fluctuation in his ability to recall familiar information. Following treatment with immunotherapy, his condition improved considerably and, in a series of follow up assessments, he performed satisfactorily (i.e., within the average range or above) on formal tests of memory, as well as on a range of other cognitive tests, including tests of executive function. By contrast, in the context of contemporaneous unstructured interviews, he showed a strong tendency to confabulate. We argue that the reported case broadens the phenomenology of VGKC-Ab limbic encephalitis and raises important theoretical questions about the aetiology of this patient's most unusual memory disorder. Copyright © 2010 Elsevier Srl. All rights reserved.

Multiscale modeling of current-induced switching in magnetic tunnel junctions using ab initio spin-transfer torques

NASA Astrophysics Data System (ADS)

Ellis, Matthew O. A.; Stamenova, Maria; Sanvito, Stefano

2017-12-01

There exists a significant challenge in developing efficient magnetic tunnel junctions with low write currents for nonvolatile memory devices. With the aim of analyzing potential materials for efficient current-operated magnetic junctions, we have developed a multi-scale methodology combining ab initio calculations of spin-transfer torque with large-scale time-dependent simulations using atomistic spin dynamics. In this work we introduce our multiscale approach, including a discussion on a number of possible schemes for mapping the ab initio spin torques into the spin dynamics. We demonstrate this methodology on a prototype Co/MgO/Co/Cu tunnel junction showing that the spin torques are primarily acting at the interface between the Co free layer and MgO. Using spin dynamics we then calculate the reversal switching times for the free layer and the critical voltages and currents required for such switching. Our work provides an efficient, accurate, and versatile framework for designing novel current-operated magnetic devices, where all the materials details are taken into account.

Reorganization of equivalence classes: effects of preliminary training and meaningful stimuli.

PubMed

Arntzen, Erik; Nartey, Richard K; Fields, Lanny

2018-05-01

In Condition 1, adults learned the baseline relations for the three equivalence classes A1-B1-C1-D1-E1, A2-B2-C2-D2-E2, and A3-B3-C3-D3-E3. Classes contained abstract shapes in the ABS and four preliminary training groups. Each class in the PIC group contained one picture and four abstract shapes. Before class formation for four other groups, preliminary training involved establishing identity (CC) or arbitrary (CX) relations either with or without a delay. Without preliminary training, classes formed with low and high likelihoods in the ABS and PIC groups, respectively. Preliminary training with no delay produced modest increases in class formation, while preliminary training with delay produced large increases in class formation. Condition 2 replicated Condition 1 but with training of reassigned BC and CD relations that linked C from one class to B and D from another class: B1-C2, B2-C3, B3-C1, C2-D1, C3-D2, and C1-D3. Subsequent tests assessed the emergence of the reorganized classes A1-B1-C2-D1-E1, A2-B2-C3-D2-E2, and A3-B3-C1-D3-E3. All preliminary training procedures increased likelihood of forming the reorganized classes to the level seen in the PIC group. Greater gains were produced by preliminary training with no delays than with delays. Test performances also showed how preliminary training influenced baseline acquisition speed and participant-defined relations. © 2018 Society for the Experimental Analysis of Behavior.

Research and development of therapeutic mAbs: An analysis based on pipeline projects.

PubMed

Geng, Xiaomei; Kong, Xiangjun; Hu, Hao; Chen, Jiayu; Yang, Fengqing; Liang, Hongyu; Chen, Xin; Hu, Yuanjia

2015-01-01

As the subject of active research and development (R&D) in recent decades, monoclonal antibodies have emerged among the major classes of therapeutic agents for treatment of many human diseases, especially cancers, infections, and immunological disorders. This article surveys the landscape of R&D projects of therapeutic monoclonal antibodies (mAbs), which are mostly used for disease immunotherapy, from a number of perspectives, including therapeutic indications, development phases, participants, and citation of related patents. The results of this research can be used as a reference resource for pharmaceutical researchers, investors, and policymakers in the field of therapeutic mAbs.

Research and development of therapeutic mAbs: An analysis based on pipeline projects

PubMed Central

Geng, Xiaomei; Kong, Xiangjun; Hu, Hao; Chen, Jiayu; Yang, Fengqing; Liang, Hongyu; Chen, Xin; Hu, Yuanjia

2015-01-01

As the subject of active research and development (R&D) in recent decades, monoclonal antibodies have emerged among the major classes of therapeutic agents for treatment of many human diseases, especially cancers, infections, and immunological disorders. This article surveys the landscape of R&D projects of therapeutic monoclonal antibodies (mAbs), which are mostly used for disease immunotherapy, from a number of perspectives, including therapeutic indications, development phases, participants, and citation of related patents. The results of this research can be used as a reference resource for pharmaceutical researchers, investors, and policymakers in the field of therapeutic mAbs PMID:26211701

Functional Characterization of Two scFv-Fc Antibodies from an HIV Controller Selected on Soluble HIV-1 Env Complexes: A Neutralizing V3- and a Trimer-Specific gp41 Antibody

PubMed Central

Trott, Maria; Weiß, Svenja; Antoni, Sascha; Koch, Joachim; von Briesen, Hagen; Hust, Michael; Dietrich, Ursula

2014-01-01

HIV neutralizing antibodies (nAbs) represent an important tool in view of prophylactic and therapeutic applications for HIV-1 infection. Patients chronically infected by HIV-1 represent a valuable source for nAbs. HIV controllers, including long-term non-progressors (LTNP) and elite controllers (EC), represent an interesting subgroup in this regard, as here nAbs can develop over time in a rather healthy immune system and in the absence of any therapeutic selection pressure. In this study, we characterized two particular antibodies that were selected as scFv antibody fragments from a phage immune library generated from an LTNP with HIV neutralizing antibodies in his plasma. The phage library was screened on recombinant soluble gp140 envelope (Env) proteins. Sequencing the selected peptide inserts revealed two major classes of antibody sequences. Binding analysis of the corresponding scFv-Fc derivatives to various trimeric and monomeric Env constructs as well as to peptide arrays showed that one class, represented by monoclonal antibody (mAb) A2, specifically recognizes an epitope localized in the pocket binding domain of the C heptad repeat (CHR) in the ectodomain of gp41, but only in the trimeric context. Thus, this antibody represents an interesting tool for trimer identification. MAb A7, representing the second class, binds to structural elements of the third variable loop V3 and neutralizes tier 1 and tier 2 HIV-1 isolates of different subtypes with matching critical amino acids in the linear epitope sequence. In conclusion, HIV controllers are a valuable source for the selection of functionally interesting antibodies that can be selected on soluble gp140 proteins with properties from the native envelope spike. PMID:24828352

2005 NDIA Combat Vehicles Conference. Volume 2- Thursday Presentations and Videos

DTIC Science & Technology

2005-09-22

Mounted Combat System MULE: (Countermine) MULE: (Transport) Class II Class III Class IV Armed Robotic Vehicle ARV RSTA ARV Assault FCS Recovery and...Vehicles – Infantry Carrier Vehicle (ICV) – Armed Robotic Vehicle - Assault (ARV (A)) – Recon & Surveillance Vehicle (RSV)  Training Ammo for AP & AB...Holtz and Mr. Dick Williams, Boeing Mr. Dean Vanderstelt, General Dynamics Land Systems ( GDLS ) Mr. Mike Zoltoski, TARDEC Mr. Peter DeMasi, Program

Cytokine/Antibody complexes: an emerging class of immunostimulants.

PubMed

Mostböck, Sven

2009-01-01

In recent years, complexes formed from a cytokine and antibodies against that respective cytokine (cytokine/Ab complex) have been shown to induce remarkable powerful changes in the immune system. Strong interest exists especially for complexes formed with Interleukin (IL)-2 and anti-IL-2-antibody (IL-2/Ab complex). IL-2/Ab complex activates maturation and proliferation in CD8(+) T cells and natural killer (NK) cells to a much higher degree than conventional IL-2 therapy. In addition, IL-2/Ab complex does not stimulate regulatory T cells as much as IL-2 alone. This suggests the possibility to replace the conventional IL-2 therapy with a therapy using low-dose IL-2/Ab complex. Further synthetic cytokine/Ab complexes are studied currently, including IL-3/Ab complex for its effects on the mast cell population, and IL-4/Ab complex and IL-7/Ab complex for inducing B and T cell expansion and maturation. Cytokine complexes can also be made from a cytokine and its soluble receptor. Pre-association of IL-15 with soluble IL-15 receptor alpha produces a complex with strong agonistic functions that lead to an expansion of CD8(+) T cells and NK cells. However, cytokine/Ab complexes also occur naturally in humans. A multitude of auto-antibodies to cytokines are found in human sera, and many of these auto-antibodies build cytokine/Ab complexes. This review presents naturally occurring auto-antibodies to cytokines and cytokine/Ab complexes in health and disease. It further summarizes recent research on synthetic cytokine/Ab complexes with a focus on the basic mechanisms behind the function of cytokine/Ab complexes.

Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine.

PubMed

Fairstein, Moran; Swissa, Rotem; Dahan, Arik

2013-04-01

Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (P(eff)) class boundary, pseudoephedrine was provisionally classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F(abs)) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized P(eff)-F(abs) correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine's BCS classification. Pseudoephedrine's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine's permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine's complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between P(eff) and F(abs) is involved in its absorption. Rather, it reflects the complexity behind P(eff) when considering the whole of the intestine. We propose to allow high-permeability classification to drugs with P(eff) that matches/exceeds the low/high class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

The Effect of a Constant Level Lighting Control System on Small Offices With Windows

DTIC Science & Technology

1992-01-01

Scientific 2101 Digital Power Analyzer. The power factor was calculated by dividing the real power by the apparent power (current multiplied by voltage...CBNSC-TT-P 22060 INSODM - Cb. huad. Div. Delace Tockslcol to. C 2M30 US Arm Bo~kuau Disvriaw Pt Dalvoir VA 22M6 AWN: DTIC-AB (2) ATTN: Libary (41) ATmN

Critical Problems in Very Large Scale Computer Systems

DTIC Science & Technology

1989-09-30

N Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Anant Agarwal (617) 253-1448 William J. Dally (617) 253-6043 Srinivas Devadas ...rapidly switched between the ports. Labelling the terminal voltages ab.c. d. this attempts to enforce a constraint a - b = c - d. This is a reciprocal...Srinivas Devadas and his students have been focusing on the optimization ofcomibinational and sequen- tial circuits specified at the register

Quasiparticle conductance-voltage characteristics for break junctions involving d-wave superconductors: charge-density-wave effects.

PubMed

Ekino, T; Gabovich, A M; Suan Li, Mai; Szymczak, H; Voitenko, A I

2017-12-20

Quasiparticle tunnel conductance-voltage characteristics (CVCs), [Formula: see text], were calculated for break junctions (BJs) made up of layered d-wave superconductors partially gapped by charge-density waves (CDWs). The current is assumed to flow in the ab-plane of electrodes. The influence of CDWs is analyzed by comparing the resulting CVCs with CVCs calculated for BJs made up of pure d-wave superconductors with relevant parameters. The main CDW-effects were found to be the appearance of new CVC peculiarities and the loss of CVC symmetry with respect to the V-sign. Tunnel directionality was shown to be one of the key factors in the formation of [Formula: see text] dependences. In particular, the orientation of electrodes with respect to the current channel becomes very important. As a result, [Formula: see text] can acquire a large variety of forms similar to those for tunnel junctions between superconductors with s-wave, d-wave, and mixed symmetry of their order parameters. The diversity of peculiarities is especially striking at finite temperatures. In the case of BJs made up of pure d-wave superconductors, the resulting CVC can include a two-peak gap-driven structure. The results were compared with the experimental BJ data for a number of high-T c oxides. It was shown that the large variety of the observed current-voltage characteristics can be interpreted in the framework of our approach. Thus, quasiparticle tunnel currents in the ab-plane can be used as an additional mean to detect CDWs competing with superconductivity in cuprates or other layered superconductors.

Quasiparticle conductance-voltage characteristics for break junctions involving d-wave superconductors: charge-density-wave effects

NASA Astrophysics Data System (ADS)

Ekino, T.; Gabovich, A. M.; Li, Mai Suan; Szymczak, H.; Voitenko, A. I.

2017-12-01

Quasiparticle tunnel conductance-voltage characteristics (CVCs), G(V) , were calculated for break junctions (BJs) made up of layered d-wave superconductors partially gapped by charge-density waves (CDWs). The current is assumed to flow in the ab-plane of electrodes. The influence of CDWs is analyzed by comparing the resulting CVCs with CVCs calculated for BJs made up of pure d-wave superconductors with relevant parameters. The main CDW-effects were found to be the appearance of new CVC peculiarities and the loss of CVC symmetry with respect to the V-sign. Tunnel directionality was shown to be one of the key factors in the formation of G(V) dependences. In particular, the orientation of electrodes with respect to the current channel becomes very important. As a result, G(V) can acquire a large variety of forms similar to those for tunnel junctions between superconductors with s-wave, d-wave, and mixed symmetry of their order parameters. The diversity of peculiarities is especially striking at finite temperatures. In the case of BJs made up of pure d-wave superconductors, the resulting CVC can include a two-peak gap-driven structure. The results were compared with the experimental BJ data for a number of high-T c oxides. It was shown that the large variety of the observed current-voltage characteristics can be interpreted in the framework of our approach. Thus, quasiparticle tunnel currents in the ab-plane can be used as an additional mean to detect CDWs competing with superconductivity in cuprates or other layered superconductors.

Probing α-3(10) transitions in a voltage-sensing S4 helix.

PubMed

Kubota, Tomoya; Lacroix, Jérôme J; Bezanilla, Francisco; Correa, Ana M

2014-09-02

The S4 helix of voltage sensor domains (VSDs) transfers its gating charges across the membrane electrical field in response to changes of the membrane potential. Recent studies suggest that this process may occur via the helical conversion of the entire S4 between α and 310 conformations. Here, using LRET and FRET, we tested this hypothesis by measuring dynamic changes in the transmembrane length of S4 from engineered VSDs expressed in Xenopus oocytes. Our results suggest that the native S4 from the Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP) does not exhibit extended and long-lived 310 conformations and remains mostly α-helical. Although the S4 of NavAb displays a fully extended 310 conformation in x-ray structures, its transplantation in the Ci-VSP VSD scaffold yielded similar results as the native Ci-VSP S4. Taken together, our study does not support the presence of long-lived extended α-to-310 helical conversions of the S4 in Ci-VSP associated with voltage activation. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Development of immunoglobulin class-specific enzyme-linked immunosorbent assays for measuring antibodies against avian rotavirus.

PubMed

Myers, T J; Schat, K A; Mockett, A P

1989-01-01

Immunoglobulin class-specific enzyme-linked immunosorbent assays were developed for detecting antibodies against avian rotavirus in serum, intestinal contents, and bile from experimentally infected specific-pathogen-free (SPF) chickens. Both indirect and antibody-capture (AbC) assays were developed based on monoclonal antibodies specific for chicken IgG, IgM, and IgA. Treatment of purified rotavirus with sodium thiocyanate before coating the plate improved the rotavirus-specific reading in the indirect assay. Use of Immunolon 2 plates facilitated attachment of monoclonal antibodies to the plate in the AbC assay. Addition of 5% powdered skim milk to the diluent buffer reduced nonspecific background readings. The indirect assay was superior for detecting rotavirus-specific IgG, whereas the AbC assay was better for detecting rotavirus-specific IgM and IgA. The presence of intestinal contents in the assay wells did not reduce the measurable titers of IgG, IgM, or IgA. These assays showed that SPF chickens produced systemic and mucosal antibodies against avian rotavirus.

Evidence for three-dimensional XY critical properties in underdoped YBa2Cu3O7-δ

NASA Astrophysics Data System (ADS)

Schneider, T.

2007-05-01

We perform a detailed analysis of the reversible magnetization data of Salem-Sugui and Babíc of underdoped and optimally doped YBa2Cu3O7-δ single crystals. Near the zero field transition temperature we observe extended consistency with the properties of the three-dimensional XY universality class, even though the attained critical regime is limited by an inhomogeneity induced finite size effect. Nevertheless, as Tc falls from 93.5to41.5K , the critical amplitude of the in-plane correlation length ξab0 , the anisotropy γ=ξab0/ξc0 and the critical amplitude of the in-plane penetration depth λab0 increase substantially, while the critical amplitude of the c -axis correlation length ξc0 does not change much. As a consequence, the correlation volume Vcorr- increases and the critical amplitude of the specific heat singularity A- decreases dramatically, while the rise of λab0 reflects the behavior of the zero temperature counterpart. Conversely, although ξab0 and λab0 increase with reduced Tc , the ratio λab0/ξab0- , corresponding to the Ginzburg-Landau parameter κab , decreases substantially and YBa2Cu3O7-δ crosses over from an extreme to a weak type-II superconductor.

Investigating the Outcomes and Perceptions of an Inclusive Aquatic Exercise Class for University Students with Physical Disabilities

ERIC Educational Resources Information Center

Dysterheft, Jennifer; Chaparro, Gioella; Rice, Laura; Rice, Ian

2018-01-01

The purpose of this study was to determine whether university students with physical disabilities (SWD) gained similar benefits from recreational physical activity participation as able-bodied (AB) university students as reported in the literature. Researchers designed an inclusive, university-offered aquatic exercise class for SWD. Six SWD…

Online Hydrophobic Interaction Chromatography-Mass Spectrometry for the Analysis of Intact Monoclonal Antibodies.

PubMed

Chen, Bifan; Lin, Ziqing; Alpert, Andrew J; Fu, Cexiong; Zhang, Qunying; Pritts, Wayne A; Ge, Ying

2018-06-19

Therapeutic monoclonal antibodies (mAbs) are an important class of drugs for a wide spectrum of human diseases. Liquid chromatography (LC) coupled to mass spectrometry (MS) is one of the techniques in the forefront for comprehensive characterization of analytical attributes of mAbs. Among various protein chromatography modes, hydrophobic interaction chromatography (HIC) is a popular offline nondenaturing separation technique utilized to purify and analyze mAbs, typically with the use of non-MS-compatible mobile phases. Herein we demonstrate for the first time, the application of direct HIC-MS and HIC-tandem MS (MS/MS) with electron capture dissociation (ECD) for analyzing intact mAbs on quadrupole-time-of-flight (Q-TOF) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, respectively. Our method allows for rapid determination of relative hydrophobicity, intact masses, and glycosylation profiles of mAbs as well as sequence and structural characterization of the complementarity-determining regions in an online configuration.

[Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome].

PubMed

Misawa, Tamako; Mizusawa, Hidehiro

2010-04-01

Anti-voltage-gated potassium channel antibodies (anti-VGKC-Ab) cause hyperexcitability of the peripheral nerve and central nervous system. Peripheral nerve hyperexcitability is the chief manifestation of Issacs syndrome and cramp-fasciculation syndrome. Morvan syndrome is characterized by neuromyotonia with autonomic and CNS involvement. Manifestations involving the CNS without peripheral involvement are characteristic of limbic encephalitis and epilepsy. The clinical features of anti-VGKC-Ab-associated limbic encephalitis are subacute onset of episodic memory impairment, disorientation and agitation. Hyponatremia is also noted in most patients. Cortico-steroid therapy, plasma exchange and intravenous immunoglobulin are effective in treating to not only the clinical symptoms but also hyponatremia. Unlike other anti-VGKC-Ab-associated neurological disorders, paraneoplastic cases are rare. Thus, anti-VGKC-Ab-associated limbic encephalopathy is considered to be an autoimmune, non-paraneoplastic, potentially treatable encephalitis. Morvan syndrome is characterized by widespread neurological symptoms involving the peripheral nervous system (neuromyotonia), autonomic system (hyperhidrosis, severe constipation, urinary incontinence, and cardiac arrhythmia) and the CNS (severe insomnia, hallucinations, impairment of short-term memory and epilepsy). Many patients have an underlying tumor, for example thymoma, lung cancer, testicular cancer and lymphoma; this indicates the paraneoplastic nature of the disease. Needle electro-myography reveals myokimic discharge. In nerve conduction study, stimulus-induced repetitive descharges are frequently demonstrated in involved muscles. Plasma exchange is an effective treatment approach, and tumor resection also improves symptoms. Both VGKC-Ab-associated limbic encephalitis and Morvan syndrome can be successfully treated. Therefore, when these diseases are suspected, it's important to measure the anti-VGKC-Ab level.

Discriminative functions and over-training as class-enhancing determinants of meaningful stimuli.

PubMed

Travis, Robert W; Fields, Lanny; Arntzen, Erik

2014-07-01

Likelihood of equivalence class formation (yield) was influenced by pre-class formation of simultaneous and successive discriminations, their mastery criteria, and overtraining of the successive discriminations. Each undergraduate in seven groups attempted to form two 3-node, 5-member equivalence classes (ABCDE). In the pictorial (PIC) group, meaningless nonsense syllables were used as the A, B, D, and E stimuli and meaningful pictures as the C stimuli. Nonsense syllables only were used in the other groups. The abstract (ABS) or 0-0-0 group involved no pre-class training. In the 84-0-0, 84-5-0 and 84-20-0 groups, simultaneous discriminations were trained among C stimuli to a mastery criterion of 84 trials, followed by successive discriminations trained to mastery criteria of 0, 5, and 20 trials, respectively. In the 84-20-0, 84-20-100, and 84-20-500 groups, simultaneous and successive discriminations were trained as noted, followed by overtraining with 0, 100, 500 successive-discrimination trials, respectively. The ABS group produced a 6% yield with the 84-0-0, 84-5-0, and 84-20-0 groups producing further modest increments. Overtraining produced a linear increase in yield, reaching 85% after 500 overtraining trials, a yield matching that produced by classes containing pictures as C stimuli (PIC). Thus, acquired discriminative functions and the overtraining of at least one function can account for class enhancement by meaningful stimuli. © Society for the Experimental Analysis of Behavior.

Enhancement of equivalence class formation by pretraining discriminative functions.

PubMed

Nartey, Richard K; Arntzen, Erik; Fields, Lanny

2015-03-01

The present experiment showed that a simple discriminative function acquired by an abstract stimulus through simultaneous and/or successive discrimination training enhanced the formation of an equivalence class of which that stimulus was a member. College students attempted to form three equivalence classes composed of three nodes and five members (A→B→C→D→E), using the simultaneous protocol. In the PIC group, the C stimuli were pictures and the A, B, D, and E stimuli were abstract shapes. In the ABS group, all of the stimuli were abstract shapes. In the SIM + SUCC (simultaneous and successive) group, simple discriminations were formed with the C stimuli through both simultaneous and successive discrimination training before class formation. Finally, in the SIM-only and SUCC-only groups, prior to class formation, simple discriminations were established for the C stimuli with a simultaneous procedure and a successive procedure, respectively. Equivalence classes were formed by 80% and 70% of the participants in the PIC and SIM + SUCC groups respectively, by 30% in the SUCC-only group, and by 10% apiece in the ABS and SIM-only groups. Thus, pretraining of combined simultaneous and successive discriminations enhanced class formation, as did the inclusion of a meaningful stimulus in a class. The isolated effect of forming successive discriminations was more influential than that of forming simultaneous discriminations. The establishment of both discriminations together produced an enhancement greater than the sum of the two procedures alone. Finally, a sorting test documented the maintenance of the classes formed during the simultaneous protocol. These results also provide a stimulus control-function account of the class-enhancing effects of meaningful stimuli.

Approaches to ab initio molecular replacement of α-helical transmembrane proteins.

PubMed

Thomas, Jens M H; Simkovic, Felix; Keegan, Ronan; Mayans, Olga; Zhang, Chengxin; Zhang, Yang; Rigden, Daniel J

2017-12-01

α-Helical transmembrane proteins are a ubiquitous and important class of proteins, but present difficulties for crystallographic structure solution. Here, the effectiveness of the AMPLE molecular replacement pipeline in solving α-helical transmembrane-protein structures is assessed using a small library of eight ideal helices, as well as search models derived from ab initio models generated both with and without evolutionary contact information. The ideal helices prove to be surprisingly effective at solving higher resolution structures, but ab initio-derived search models are able to solve structures that could not be solved with the ideal helices. The addition of evolutionary contact information results in a marked improvement in the modelling and makes additional solutions possible.

Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing.

PubMed

Numata, Tomohiro; Tsumoto, Kunichika; Yamada, Kazunori; Kurokawa, Tatsuki; Hirose, Shinichi; Nomura, Hideki; Kawano, Mitsuhiro; Kurachi, Yoshihisa; Inoue, Ryuji; Mori, Yasuo

2017-08-29

Numerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (P open )-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, G max . Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of G max in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and Na V Ab structures suggest that such voltage dependence of P open and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties.

Molecular and Physiological Logics of the Pyruvate-Induced Response of a Novel Transporter in Bacillus subtilis.

PubMed

Charbonnier, Teddy; Le Coq, Dominique; McGovern, Stephen; Calabre, Magali; Delumeau, Olivier; Aymerich, Stéphane; Jules, Matthieu

2017-10-03

At the heart of central carbon metabolism, pyruvate is a pivotal metabolite in all living cells. Bacillus subtilis is able to excrete pyruvate as well as to use it as the sole carbon source. We herein reveal that ysbAB (renamed pftAB ), the only operon specifically induced in pyruvate-grown B. subtilis cells, encodes a hetero-oligomeric membrane complex which operates as a facilitated transport system specific for pyruvate, thereby defining a novel class of transporter. We demonstrate that the LytST two-component system is responsible for the induction of pftAB in the presence of pyruvate by binding of the LytT response regulator to a palindromic region upstream of pftAB We show that both glucose and malate, the preferred carbon sources for B. subtilis , trigger the binding of CcpA upstream of pftAB , which results in its catabolite repression. However, an additional CcpA-independent mechanism represses pftAB in the presence of malate. Screening a genome-wide transposon mutant library, we find that an active malic enzyme replenishing the pyruvate pool is required for this repression. We next reveal that the higher the influx of pyruvate, the stronger the CcpA-independent repression of pftAB , which suggests that intracellular pyruvate retroinhibits pftAB induction via LytST. Such a retroinhibition challenges the rational design of novel nature-inspired sensors and synthetic switches but undoubtedly offers new possibilities for the development of integrated sensor/controller circuitry. Overall, we provide evidence for a complete system of sensors, feed-forward and feedback controllers that play a major role in environmental growth of B. subtilis IMPORTANCE Pyruvate is a small-molecule metabolite ubiquitous in living cells. Several species also use it as a carbon source as well as excrete it into the environment. The bacterial systems for pyruvate import/export have yet to be discovered. Here, we identified in the model bacterium Bacillus subtilis the first import/export system specific for pyruvate, PftAB, which defines a novel class of transporter. In this bacterium, extracellular pyruvate acts as the signal molecule for the LytST two-component system (TCS), which in turn induces expression of PftAB. However, when the pyruvate influx is high, LytST activity is drastically retroinhibited. Such a retroinhibition challenges the rational design of novel nature-inspired sensors and synthetic switches but undoubtedly offers new possibilities for the development of integrated sensor/controller circuitry. Copyright © 2017 Charbonnier et al.

Effects of a Meaningful, a Discriminative, and a Meaningless Stimulus on Equivalence Class Formation

ERIC Educational Resources Information Center

Fields, Lanny; Arntzen, Erik; Nartey, Richard; Eilifsen, Christoffer

2012-01-01

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A-E stimuli were all abstract…

Controlling the thermoelectric effect by mechanical manipulation of the electron's quantum phase in atomic junctions.

PubMed

Aiba, Akira; Demir, Firuz; Kaneko, Satoshi; Fujii, Shintaro; Nishino, Tomoaki; Tsukagoshi, Kazuhito; Saffarzadeh, Alireza; Kirczenow, George; Kiguchi, Manabu

2017-08-11

The thermoelectric voltage developed across an atomic metal junction (i.e., a nanostructure in which one or a few atoms connect two metal electrodes) in response to a temperature difference between the electrodes, results from the quantum interference of electrons that pass through the junction multiple times after being scattered by the surrounding defects. Here we report successfully tuning this quantum interference and thus controlling the magnitude and sign of the thermoelectric voltage by applying a mechanical force that deforms the junction. The observed switching of the thermoelectric voltage is reversible and can be cycled many times. Our ab initio and semi-empirical calculations elucidate the detailed mechanism by which the quantum interference is tuned. We show that the applied strain alters the quantum phases of electrons passing through the narrowest part of the junction and hence modifies the electronic quantum interference in the device. Tuning the quantum interference causes the energies of electronic transport resonances to shift, which affects the thermoelectric voltage. These experimental and theoretical studies reveal that Au atomic junctions can be made to exhibit both positive and negative thermoelectric voltages on demand, and demonstrate the importance and tunability of the quantum interference effect in the atomic-scale metal nanostructures.

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

PubMed Central

Rasmussen, Mark; Zhu, Jieqing; Aster, Richard H.

2012-01-01

Arginine-glycine-aspartic acid (RGD)–mimetic platelet inhibitors act by occupying the RGD recognition site of αIIb/β3 integrin (GPIIb/IIIa), thereby preventing the activated integrin from reacting with fibrinogen. Thrombocytopenia is a well-known side effect of treatment with this class of drugs and is caused by Abs, often naturally occurring, that recognize αIIb/β3 in a complex with the drug being administered. RGD peptide and RGD-mimetic drugs are known to induce epitopes (ligand-induced binding sites [LIBS]) in αIIb/β3 that are recognized by certain mAbs. It has been speculated, but not shown experimentally, that Abs from patients who develop thrombocytopenia when treated with an RGD-mimetic inhibitor similarly recognize LIBS determinants. We addressed this question by comparing the reactions of patient Abs and LIBS-specific mAbs against αIIb/β3 in a complex with RGD and RGD-mimetic drugs, and by examining the ability of selected non-LIBS mAbs to block binding of patient Abs to the liganded integrin. Findings made provide evidence that the patient Abs recognize subtle, drug-induced structural changes in the integrin head region that are clustered about the RGD recognition site. The target epitopes differ from classic LIBS determinants, however, both in their location and by virtue of being largely drug-specific. PMID:22490676

VGKC antibodies in pediatric encephalitis presenting with status epilepticus.

PubMed

Suleiman, J; Brenner, T; Gill, D; Brilot, F; Antony, J; Vincent, A; Lang, B; Dale, R C

2011-04-05

Voltage-gated potassium channel antibodies (VGKC Ab) are associated with limbic encephalitis and neuromyotonia in adults. There have been no systematic investigations in children to date. We looked for antibodies that are associated with CNS syndromes in adults including antibodies to VGKCs, NMDARs, glutamic acid decarboxylase (GAD), and glycine receptor (GlyR) in the stored acute serum from 10 children with unexplained encephalitis presenting with encephalopathy and status epilepticus. We also looked for antibodies to leucine-rich glioma-inactivated 1 (Lgi1) and contactin-associated protein-like 2 (Caspr2), which are now known to be tightly complexed with VGKCs in vivo. Sixty-nine pediatric controls were used for comparison. An elevated VGKC Ab (>100 pM) was detected in 4/10 patients with encephalitis compared to only 1/69 controls (p < 0.001). The outcome in the 4 VGKC Ab-positive patients with encephalitis was variable including good recovery (n = 1), cognitive impairment (n = 3), temporal lobe epilepsy (n = 2), and mesial temporal sclerosis (n = 1). No other antibodies were detected, including those to Lgi1 and Caspr2. Encephalitis associated with VGKC Ab occurs in children and presents with status epilepticus and focal epilepsy. These antibodies are not directed against Lgi1 or Caspr2.

Enterocin B3A-B3B produced by LAB collected from infant faeces: potential utilization in the food industry for Listeria monocytogenes biofilm management.

PubMed

Al-Seraih, Alaa; Belguesmia, Yanath; Baah, John; Szunerits, Sabine; Boukherroub, Rabah; Drider, Djamel

2017-02-01

Enterococcus faecalis B3A-B3B produces the bacteriocin B3A-B3B with activity against Listeria monocytogenes, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens, but apparently not against fungi or Gram-negative bacteria, except for Salmonella Newport. B3A-B3B enterocin has two different nucleotides but similar amino acid composition to the class IIb MR10A-MR10B enterocin. B3A-B3B consists of two peptides of predicted molecular mass of 5176.31 Da (B3A) and 5182.21 Da (B3B). Importantly, B3A-B3B impeded biofilm formation of the foodborne pathogen L. monocytogenes 162 grown on stainless steel. The antimicrobial treatment of stainless steel with nisin (1 or 16 mg ml -1 ) decreased the cell numbers by about 2 log CFU ml -1 , thereby impeding the biofilm formation by L. monocytogenes 162 or its nisin-resistant derivative strain L. monocytogenes 162R. Furthermore, the combination of nisin and B3A-B3B enterocin reduced the MIC required to inhibit this pathogen grown in planktonic or biofilm cultures.

Prospective iterative trial of proteasome inhibitor-based desensitization.

PubMed

Woodle, E S; Shields, A R; Ejaz, N S; Sadaka, B; Girnita, A; Walsh, R C; Alloway, R R; Brailey, P; Cardi, M A; Abu Jawdeh, B G; Roy-Chaudhury, P; Govil, A; Mogilishetty, G

2015-01-01

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

PubMed Central

Nunes, A.D.C.; Souza, A.P.S.; Macedo, L.M.; Alves, P.H.; Pedrino, G.R.; Colugnati, D.B.; Mendes, E.P.; Santos, R.A.S.; Castro, C.H.

2017-01-01

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases. PMID:28355350

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.

PubMed

Nunes, A D C; Souza, A P S; Macedo, L M; Alves, P H; Pedrino, G R; Colugnati, D B; Mendes, E P; Santos, R A S; Castro, C H

2017-03-23

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Modeling and Optimization of Class-E Amplifier at Subnominal Condition in a Wireless Power Transfer System for Biomedical Implants.

PubMed

Liu, Hao; Shao, Qi; Fang, Xuelin

2017-02-01

For the class-E amplifier in a wireless power transfer (WPT) system, the design parameters are always determined by the nominal model. However, this model neglects the conduction loss and voltage stress of MOSFET and cannot guarantee the highest efficiency in the WPT system for biomedical implants. To solve this problem, this paper proposes a novel circuit model of the subnominal class-E amplifier. On a WPT platform for capsule endoscope, the proposed model was validated to be effective and the relationship between the amplifier's design parameters and its characteristics was analyzed. At a given duty ratio, the design parameters with the highest efficiency and safe voltage stress are derived and the condition is called 'optimal subnominal condition.' The amplifier's efficiency can reach the highest of 99.3% at the 0.097 duty ratio. Furthermore, at the 0.5 duty ratio, the measured efficiency of the optimal subnominal condition can reach 90.8%, which is 15.2% higher than that of the nominal condition. Then, a WPT experiment with a receiving unit was carried out to validate the feasibility of the optimized amplifier. In general, the design parameters of class-E amplifier in a WPT system for biomedical implants can be determined with the proposed optimization method in this paper.

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

PubMed

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Specificity and biologic activities of novel anti-membrane IgM antibodies

PubMed Central

Welt, Rachel S.; Welt, Jonathan A.; Kostyal, David; Gangadharan, Yamuna D; Raymond, Virginia; Welt, Sydney

2016-01-01

The concept that the B-cell Receptor (BCR) initiates a driver pathway in lymphoma-leukemia has been clinically validated. Previously described unique BCR Ig-class-specific sequences (proximal domains (PDs)), are not expressed in serum Ig (sIg). As a consequence of sequence and structural differences in the membrane IgM (mIgM) μ-Constant Domain 4, additional epitopes distinguish mIgM from sIgM. mAbs generated to linear and conformational epitopes, restricted to mIgM and not reacting with sIgM, were generated despite the relative hydrophobicity of the PDm sequence. Anti-PD mAbs (mAb1, mAb2, and mAb3) internalize mIgM. Anti-mIgM mAb4, which recognizes a distinct non-ligand binding site epitope, mediates mIgM internalization, and in low-density cultures, growth inhibition, anti-clonogenic activity, and apoptosis. We show that mAb-mediated mIgM internalization generally does not interrupt BCR-directed cell growth, however, mAb4 binding to a non-ligand binding site in the mIgM PDm-μC4 domain induces both mIgM internalization and anti-tumor effects. BCR micro-clustering in many B-cell leukemia and lymphoma lines is demonstrated by SEM micrographs using these new mAb reagents. mAb4 is a clinical candidate as a mediator of inhibition of the BCR signaling pathway. As these agents do not bind to non-mIgM B-cells, nor cross-react to non-lymphatic tissues, they may spare B-cell/normal tissue destruction as mAb-drug conjugates. PMID:27732950

Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of monoclonal antibodies in children.

PubMed

Edlund, Helena; Melin, Johanna; Parra-Guillen, Zinnia P; Kloft, Charlotte

2015-01-01

Monoclonal antibodies (mAbs) constitute a therapeutically and economically important drug class with increasing use in both adult and paediatric patients. The rather complex pharmacokinetic and pharmacodynamic properties of mAbs have been extensively reviewed in adults. In children, however, limited information is currently available. This paper aims to comprehensively review published pharmacokinetic and pharmacokinetic-pharmacodynamic studies of mAbs in children. The current status of mAbs in the USA and in Europe is outlined, including a critical discussion of the dosing strategies of approved mAbs. The pharmacokinetic properties of mAbs in children are exhaustively summarised along with comparisons to reports in adults: for each pharmacokinetic process, we discuss the general principles and mechanisms of the pharmacokinetic/pharmacodynamic characteristics of mAbs, as well as key growth and maturational processes in children that might impact these characteristics. Throughout this review, considerable knowledge gaps are identified, especially regarding children-specific properties that influence pharmacokinetics, pharmacodynamics and immunogenicity. Furthermore, the large heterogeneity in the presentation of pharmacokinetic/pharmacodynamic data limited clinical inferences in many aspects of paediatric mAb therapy. Overall, further studies are needed to fully understand the impact of body size and maturational changes on drug exposure and response. To maximise future knowledge gain, we propose a 'Guideline for Best Practice' on how to report pharmacokinetic and pharmacokinetic-pharmacodynamic results from mAb studies in children which also facilitates comparisons. Finally, we advocate the use of more sophisticated modelling strategies (population analysis, physiology-based approaches) to appropriately characterise pharmacokinetic-pharmacodynamic relationships of mAbs and, thus, allow for a more rational use of mAb in the paediatric population.

Specificity and biologic activities of novel anti-membrane IgM antibodies.

PubMed

Welt, Rachel S; Welt, Jonathan A; Kostyal, David; Gangadharan, Yamuna D; Raymond, Virginia; Welt, Sydney

2016-11-15

The concept that the B-cell Receptor (BCR) initiates a driver pathway in lymphoma-leukemia has been clinically validated. Previously described unique BCR Ig-class-specific sequences (proximal domains (PDs)), are not expressed in serum Ig (sIg). As a consequence of sequence and structural differences in the membrane IgM (mIgM) µ-Constant Domain 4, additional epitopes distinguish mIgM from sIgM. mAbs generated to linear and conformational epitopes, restricted to mIgM and not reacting with sIgM, were generated despite the relative hydrophobicity of the PDm sequence. Anti-PD mAbs (mAb1, mAb2, and mAb3) internalize mIgM. Anti-mIgM mAb4, which recognizes a distinct non-ligand binding site epitope, mediates mIgM internalization, and in low-density cultures, growth inhibition, anti-clonogenic activity, and apoptosis. We show that mAb-mediated mIgM internalization generally does not interrupt BCR-directed cell growth, however, mAb4 binding to a non-ligand binding site in the mIgM PDm-μC4 domain induces both mIgM internalization and anti-tumor effects. BCR micro-clustering in many B-cell leukemia and lymphoma lines is demonstrated by SEM micrographs using these new mAb reagents. mAb4 is a clinical candidate as a mediator of inhibition of the BCR signaling pathway. As these agents do not bind to non-mIgM B-cells, nor cross-react to non-lymphatic tissues, they may spare B-cell/normal tissue destruction as mAb-drug conjugates.

A dual-mode highly efficient class-E stimulator controlled by a low-Q class-E power amplifier through duty cycle.

PubMed

Chiu, Hung-Wei; Lu, Chien-Chi; Chuang, Jia-min; Lin, Wei-Tso; Lin, Chii-Wann; Kao, Ming-Chien; Lin, Mu-Lien

2013-06-01

This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

An Inexpensive Source of High Voltage

ERIC Educational Resources Information Center

Saraiva, Carlos

2012-01-01

As a physics teacher I like recycling old apparatus and using them for demonstrations in my classes. In physics laboratories in schools, sources of high voltage include induction coils or electronic systems that can be bought from companies that sell lab equipment. But these sources can be very expensive. In this article, I will explain how you…

Functionalized Fullerene Targeting Human Voltage-Gated Sodium Channel, hNav1.7.

PubMed

Hilder, Tamsyn A; Robinson, Anna; Chung, Shin-Ho

2017-08-16

Mutations of hNa v 1.7 that cause its activities to be enhanced contribute to severe neuropathic pain. Only a small number of hNa v 1.7 specific inhibitors have been identified, most of which interact with the voltage-sensing domain of the voltage-activated sodium ion channel. In our previous computational study, we demonstrated that a [Lys 6 ]-C 84 fullerene binds tightly (affinity of 46 nM) to Na v Ab, the voltage-gated sodium channel from the bacterium Arcobacter butzleri. Here, we extend this work and, using molecular dynamics simulations, demonstrate that the same [Lys 6 ]-C 84 fullerene binds strongly (2.7 nM) to the pore of a modeled human sodium ion channel hNa v 1.7. In contrast, the fullerene binds only weakly to a mutated model of hNa v 1.7 (I1399D) (14.5 mM) and a model of the skeletal muscle hNa v 1.4 (3.7 mM). Comparison of one representative sequence from each of the nine human sodium channel isoforms shows that only hNa v 1.7 possesses residues that are critical for binding the fullerene derivative and blocking the channel pore.

Improvements to a five-phase ABS algorithm for experimental validation

NASA Astrophysics Data System (ADS)

Gerard, Mathieu; Pasillas-Lépine, William; de Vries, Edwin; Verhaegen, Michel

2012-10-01

The anti-lock braking system (ABS) is the most important active safety system for passenger cars. Unfortunately, the literature is not really precise about its description, stability and performance. This research improves a five-phase hybrid ABS control algorithm based on wheel deceleration [W. Pasillas-Lépine, Hybrid modeling and limit cycle analysis for a class of five-phase anti-lock brake algorithms, Veh. Syst. Dyn. 44 (2006), pp. 173-188] and validates it on a tyre-in-the-loop laboratory facility. Five relevant effects are modelled so that the simulation matches the reality: oscillations in measurements, wheel acceleration reconstruction, brake pressure dynamics, brake efficiency changes and tyre relaxation. The time delays in measurement and actuation have been identified as the main difficulty for the initial algorithm to work in practice. Three methods are proposed in order to deal with these delays. It is verified that the ABS limit cycles encircle the optimal braking point, without assuming any tyre parameter being a priori known. The ABS algorithm is compared with the commercial algorithm developed by Bosch.

A Comparative Analysis between GaN-Based Current and Voltage Mode Class-D and E PAs for Communications

DTIC Science & Technology

2017-03-01

power level (5-10W) transmitters. The designs are analyzed and compared with respect to non-idealities such as bondwire effects and input signal duty...Hence, sub-optimum class- E/inverse class-E designs were implemented in this work and compared with respect to reduced duty cycle performance...inverse class E PA achieves 61.5% efficiency for medium power levels (37.7dBm) at 880MHz. The three designed PAs have been compared with respect to

Evaluation of masonry coatings.

DOT National Transportation Integrated Search

1969-08-01

This report describes the evaluation of five coating systems to replace the conventional Class 2 rubbed finish now required on concrete structures. The evaluation consisted of preparing test specimens with each of the five coatings and conducting abs...

Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles

PubMed Central

1994-01-01

GL183 or EB6 (p58) molecules have been shown to function as receptors for different HLA-C alleles and to deliver an inhibitory signal to natural killer (NK) cells, thus preventing lysis of target cells. In this study, we analyzed a subset of NK cells characterized by a p58- negative surface phenotype. We show that p58-negative clones, although specific for class I molecules do not recognize HLA-C alleles. In addition, by the use of appropriate target cells transfected with different HLA-class I alleles we identified HLA-B7 as the protective element recognized by a fraction of p58-negative clones. In an attempt to identify the receptor molecules expressed by HLA-B7-specific clones, monoclonal antibodies (mAbs) were selected after mice immunization with such clones. Two of these mAbs, termed XA-88 and XA-185, and their F(ab')2 fragments, were found to reconstitute lysis of B7+ target cells by B7-specific NK clones. Both mAbs were shown to be directed against the recently clustered Kp43 molecule (CD94). Thus, mAb-mediated masking of Kp43 molecules interferes with recognition of HLA-B7 and results in target cell lysis. Moreover, in a redirected killing assay, the cross- linking of Kp43 molecules mediated by the XA185 mAb strongly inhibited the cytolytic activity of HLA-B7-specific NK clones, thus mimicking the functional effect of B7 molecules. Taken together, these data strongly suggest that Kp43 molecules function as receptors for HLA-B7 and that this receptor/ligand interaction results in inhibition of the NK- mediated cytolytic activity. Indirect immunofluorescence and FACS analysis of a large number of random NK clones showed that Kp43 molecules (a) were brightly expressed on a subset of p58-negative clones, corresponding to those specific for HLA-B7; (b) displayed a medium/low fluorescence in the p58-negative clones that are not B7- specific as well as in most p58+ NK clones; and (c) were brightly expressed as in the p58+ clone ET34 (GL183-/EB6+, Cw4-specific). Functional analysis revealed that Kp43 functioned as an inhibitory receptor only in NK clones displaying bright fluorescence. These studies also indicate that some NK clones (e.g., the ET34) can coexpress two distinct receptors (p58 and Kp43) for different class I alleles (Cw4 and B7). Finally, we show that Kp43 molecules function as receptors only for some HLA-B alleles and that still undefined receptor(s) must exist for other HLA-B alleles including B27. PMID:8046333

LONGITUDINAL TRAJECTORIES OF GESTATIONAL THYROID FUNCTION: A NEW APPROACH TO BETTER UNDERSTAND CHANGES IN THYROID FUNCTION.

PubMed

Pop, Victor; Broeren, Maarten; Wijnen, Hennie; Endendijk, Joyce; van Baar, Anneloes; Wiersinga, Wilmar; Williams, Graham R

2018-05-28

Most studies of thyroid function changes during pregnancy use a cross-sectional design comparing means between groups rather than similarities within groups. Latent class growth analysis (LCGA) is a novel approach to investigate longitudinal changes that provide dynamic understanding of the relationship between thyroid status and advancing pregnancy. Prospective observational study with repeated assessments. General community. 1100 healthy pregnant women who were included at their first antenatal visit at 12 weeks gestation. Statistically defined distinct groups based on determined specific changing trajectories by LCGA of both fT4 and TSH at each trimester. LCGA revealed three trajectory classes. Class 1 (n = 1019, 92.4%), a 'Low increasing TSH' reference group, had a gradual increase in TSH throughout gestation (from 1.1 to 1.3 IU/l). Class 2 (n = 30, 2.8%), 'High increasing TSH'', displayed the largest increase in TSH (from 1.9 to 3.3 IU/l); Class 3 (n = 51, 4.6%), 'Decreasing TSH', had the largest fall in TSH (from 3.2 to 2.4 IU/l). (Sub)clinical hypothyroidism at 12 weeks occurred in up to 60% of class 3 women and was accompanied by elevated TPO-Ab titres (50%) and a parental history of thyroid dysfunction (23%). 70% of class 2 women were nulliparous compared to 46% and 49% in classes 1 and 3. LCGA revealed distinct trajectories of longitudinal changes of fT4 and TSH levels during pregnancy in 7.4% of women. These trajectories were correlated with parity and TPO-Ab status and followed patterns that might reflect differences in pregnancy-specific immune tolerance between nulliparous and multiparous women.

PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma

PubMed Central

Sabbatino, Francesco; Villani, Vincenzo; Yearley, Jennifer H.; Deshpande, Vikram; Cai, Lei; Konstantinidis, Ioannis T.; Moon, Christina; Nota, Sjoerd; Wang, Yangyang; Al-Sukaini, Ahmad; Zhu, Andrew X.; Goyal, Lipika; Ting, David T.; Bardeesy, Nabeel; Hong, Theodore S.; Castillo, Carlos Fernandez-del; Tanabe, Kenneth K.; Lillemoe, Keith D.; Ferrone, Soldano; Ferrone, Cristina R.

2017-01-01

Purpose More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Experimental Design Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Results Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8+ T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. Conclusions ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression. PMID:26373575

Fast Mg2+ diffusion in Mo3(PO4)3O for Mg batteries.

PubMed

Rong, Ziqin; Xiao, Penghao; Liu, Miao; Huang, Wenxuan; Hannah, Daniel C; Scullin, William; Persson, Kristin A; Ceder, Gerbrand

2017-07-13

In this work, we identify a new potential Mg battery cathode structure Mo 3 (PO 4 ) 3 O, which is predicted to exhibit ultra-fast Mg 2+ diffusion and relatively high voltage based on first-principles density functional theory calculations. Nudged elastic band calculations reveal that the migration barrier of the percolation channel is only ∼80 meV, which is remarkably low, and comparable to the best Li-ion conductors. This low barrier is verified by ab initio molecular dynamics and kinetic Monte Carlo simulations. The voltage and specific energy are predicted to be ∼1.98 V and ∼173 W h kg -1 , respectively. If confirmed by experiments, this material would have the highest known Mg mobility among inorganic compounds.

An ab initio study on the effect of iron atom junction on transport characteristics of carbon-silicon mixed chain

NASA Astrophysics Data System (ADS)

Hu, Wei; Zhou, Qinghua; Liu, Wenhua; Liang, Yan; Wang, Tao; Wan, Haiqing

2018-04-01

The effect of iron atom junction on transport characteristics of carbon-silicon mixed chain has been studied from an ab initio study. At zero bias, the Fe(CSi)n system appears to be the decrease of the conductance as the number of the Si-C pairs in the chain increases (n changes). When n > 5, the conductance tends to zero. These changes are independent of the transferring charge of the system, depending on the coupling of the electrodes and the central region. Under bias, the higher the bias voltage, the bigger the transmission coefficient of the system, and the transmission peak moves closer to the Fermi level. The I-V curves of Fe(CSi)2 and Fe (CSi)3 are linear, showing the behavior of metal resistance.

Identification and grafting of a unique peptide-binding site in the Fab framework of monoclonal antibodies

DOE PAGES

Donaldson, Joshua M.; Zer, Cindy; Avery, Kendra N.; ...

2013-10-07

Capitalizing on their extraordinary specificity, monoclonal antibodies (mAbs) have become one of the most reengineered classes of biological molecules. A major goal in many of these engineering efforts is to add new functionality to the parental mAb, including the addition of cytotoxins and imaging agents for medical applications. Herein, we present a unique peptide-binding site within the central cavity of the fragment antigen binding framework region of the chimeric, anti-epidermal growth factor receptor mAb cetuximab. We demonstrate through diffraction methods, biophysical studies, and sequence analysis that this peptide, a meditope, has moderate affinity for the Fab, is specific to cetuximabmore » (i.e., does not bind to human IgGs), and has no significant effect on antigen binding. We further demonstrate by diffraction studies and biophysical methods that the meditope binding site can be grafted onto the anti-human epidermal growth factor receptor 2 mAb trastuzumab, and that the antigen binding affinity of the grafted trastuzumab is indistinguishable from the parental mAb. Lastly, we demonstrate a bivalent meditope variant binds specifically and stably to antigen-bearing cells only in the presence of the meditope-enabled mAbs. Collectively, this finding and the subsequent characterization and engineering efforts indicate that this unique interface could serve as a noncovalent “linker” for any meditope-enabled mAb with applications in multiple mAb-based technologies including diagnostics, imaging, and therapeutic delivery.« less

Marker of cemento-periodontal ligament junction associated with periodontal regeneration.

PubMed

Hara, Ryohko; Wato, Masahiro; Tanaka, Akio

2005-06-01

The purpose of this study was to identify factors promoting formation of the cemento-periodontal ligament junction. Regeneration of the cemento-periodontal ligament junction is an important factor in recovery of the connective tissue attachment to the cementum and it is important to identify all specific substances that promote its formation. To clarify the substances involved in cemento-periodontal ligament junction formation, we produced a monoclonal antibody (mAb) to human cemento-periodontal ligament junction (designated as the anti-TAP mAb) and examined its immunostaining properties and reactive antigen. Hybridomas producing monoclonal antibody against human cemento-periodontal ligament junction antigens were established by fusing P3U1 mouse myeloma cells with spleen cells from BALB/c mice immunized with homogenized human cemento-periodontal ligament junction. The mAb, the anti-TAP mAb for cemento-periodontal ligament junction, was then isolated. The immunoglobulin class and light chain of the mAb were examined using an isotyping kit. Before immunostaining, antigen determination using an enzymatic method or heating was conducted. Human teeth, hard tissue-forming lesions, and animal tissues were immunostained by the anti-TAP mAb. The anti-TAP mAb was positive in human cemento-periodontal ligament junction and predentin but negative in all other human and animal tissues examined. In the cemento-osseous lesions, the anti-TAP mAb was positive in the peripheral area of the cementum and cementum-like hard tissues and not in the bone and bone-like tissues. The anti-TAP mAb showed IgM (kappa) and recognized phosphoprotein. The anti-TAP mAb is potentially useful for developing new agents promoting cementogenesis and periodontal regeneration.

The sandwich-type electrochemiluminescence immunosensor for α-fetoprotein based on enrichment by Fe3O4-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP.

PubMed

Zhou, Hankun; Gan, Ning; Li, Tianhua; Cao, Yuting; Zeng, Saolin; Zheng, Lei; Guo, Zhiyong

2012-10-09

A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of α-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe(3)O(4)-Au nanoparticles, which was first employed to capture AFP antigens to form Fe(3)O(4)-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe(3)O(4)-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe(3)O(4)-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL(-1) with a detection limit of 0.2 pg mL(-1). The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the amplification of the signal tag, the immunosensor is highly sensitive, which can offer great promise for rapid, simple, selective and cost-effective detection of effective biomonitoring for clinical application. Copyright © 2012 Elsevier B.V. All rights reserved.

Broadband linearisation of high-efficiency power amplifiers

NASA Technical Reports Server (NTRS)

Kenington, Peter B.; Parsons, Kieran J.; Bennett, David W.

1993-01-01

A feedforward-based amplifier linearization technique is presented which is capable of yielding significant improvements in both linearity and power efficiency over conventional amplifier classes (e.g. class-A or class-AB). Theoretical and practical results are presented showing that class-C stages may be used for both the main and error amplifiers yielding practical efficiencies well in excess of 30 percent, with theoretical efficiencies of much greater than 40 percent being possible. The levels of linearity which may be achieved are required for most satellite systems, however if greater linearity is required, the technique may be used in addition to conventional pre-distortion techniques.

Design of two-photon molecular tandem architectures for solar cells by ab initio theory† †Electronic supplementary information (ESI) available: Visualizations of molecular orbitals, one-particle mechanisms and a table with Kohn–Sham eigenvalues. See DOI: 10.1039/c4sc03835e

PubMed Central

Garcia-Lastra, Juan M.; De La Torre, Gema; Himpsel, F. J.; Rubio, Angel

2015-01-01

An extensive database of spectroscopic properties of molecules from ab initio calculations is used to design molecular complexes for use in tandem solar cells that convert two photons into a single electron–hole pair, thereby increasing the output voltage while covering a wider spectral range. Three different architectures are considered: the first two involve a complex consisting of two dye molecules with appropriately matched frontier orbitals, connected by a molecular diode. Optimized combinations of dye molecules are determined by taking advantage of our computational database of the structural and energetic properties of several thousand porphyrin dyes. The third design is a molecular analogy of the intermediate band solar cell, and involves a single dye molecule with strong intersystem crossing to ensure a long lifetime of the intermediate state. Based on the calculated energy levels and molecular orbitals, energy diagrams are presented for the individual steps in the operation of such tandem solar cells. We find that theoretical open circuit voltages of up to 1.8 V can be achieved using these tandem designs. Questions about the practical implementation of prototypical devices, such as the synthesis of the tandem molecules and potential loss mechanisms, are addressed. PMID:29142685

Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.

PubMed

Alaimo, Alessandro; Alberdi, Araitz; Gomis-Perez, Carolina; Fernández-Orth, Juncal; Bernardo-Seisdedos, Ganeko; Malo, Covadonga; Millet, Oscar; Areso, Pilar; Villarroel, Alvaro

2014-01-01

Kv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca(2+). First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using (15)N-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca(2+) the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca(2+) makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca(2+).

Monoclonal antibodies to the light-harvesting chlorophyll a/b protein complex of photosystem II

PubMed Central

1986-01-01

A collection of 17 monoclonal antibodies elicited against the light- harvesting chlorophyll a/b protein complex which serves photosystem II (LHC-II) of Pisum sativum shows six classes of binding specificity. Antibodies of two of the classes recognize a single polypeptide (the 28- or the 26- kD polypeptides), thereby suggesting that the two proteins are not derived from a common precursor. Other classes of antibodies cross-react with several polypeptides of LHC-II or with polypeptides of both LHC-II and the light-harvesting chlorophyll a/b polypeptides of photosystem I (LHC-I), indicating that there are structural similarities among the polypeptides of LHC-II and LHC-I. The evidence for protein processing by which the 26-, 25.5-, and 24.5-kD polypeptides are derived from a common precursor polypeptide is discussed. Binding studies using antibodies specific for individual LHC- II polypeptides were used to quantify the number of antigenic polypeptides in the thylakoid membrane. 27 copies of the 26-kD polypeptide and two copies of the 28-kD polypeptide were found per 400 chlorophylls. In the chlorina f2 mutant of barley, and in intermittent light-treated barley seedlings, the amount of the 26-kD polypeptide in the thylakoid membranes was greatly reduced, while the amount of 28-kD polypeptide was apparently not affected. We propose that stable insertion and assembly of the 28-kD polypeptide, unlike the 26-kD polypeptide, is not regulated by the presence of chlorophyll b. PMID:3528171

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2013-11-27

systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush approved four decommissioned Kidd-class destroyers for sale as Excess Defense...239 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon Coproduce Patriot,” Defense News, February 22-28...340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with 176 AESA radars

Potential involvement of rainbow trout thrombocytes in immune functions: a study using a panel of monoclonal antibodies and RT-PCR

USGS Publications Warehouse

Kollner, B.; Fisher, U.; Rombout, J.H.W.M.; Taverne-Thiele, J.J.; Hansen, J.D.

2004-01-01

The functional relationship between fish and mammalian thrombocytes is relatively unknown. In this study, a panel of monoclonal antibodies (mAbs) was used to investigate the functional properties of rainbow trout thrombocytes. The mAbs recognize cell-surface molecules on thrombocytes with molecular weights ranging from 17 to 160 kDa. Flow cytometric and immuno-electron microscopic analyses demonstrate that these molecules are expressed at different levels and that surface expression increased upon activation with bovine collagen. Two of these cell-surface molecules (17 and 21 kDa) were directly involved in collagen-induced aggregation of thrombocytes since aggregation was blocked upon pre-treatment with mAbs that recognize the two surface markers. Interestingly, the percentage of thrombocytes in blood increased after stimulation using different antigens. The transcriptional profile of trout thrombocytes was then examined after immuno-magnetic enrichment using the described mAbs to assess potential roles of trout thrombocytes in immune functions. Trout thrombocytes express components of the MHC class Ia pathway, IL1β, TNFα, TGFβ, the interleukin receptor common γ chain as well as CXC and CC chemokines. MHC class IIB and TNFα were expressed at low levels in resting thrombocytes. No evidence was found for the expression of TCRαβ, Ig heavy chain, CD8α or CK1 mRNA. Taken together, these results suggest that rainbow trout thrombocytes express molecules involved in activation, aggregation and genes encoding proteins, that are involved in antigen presentation and immune regulation.

Load insensitive electrical device. [power converters for supplying direct current at one voltage from a source at another voltage

NASA Technical Reports Server (NTRS)

Schwarz, F. C. (Inventor)

1974-01-01

A class of power converters is described for supplying direct current at one voltage from a source at another voltage. It includes a simple passive circuit arrangement of solid-state switches, inductors, and capacitors by which the output voltage of the converter tends to remain constant in spite of changes in load. The switches are sensitive to the current flowing in the circuit and are employed to permit the charging of capacitance devices in accordance with the load requirements. Because solid-state switches (such as SCR's) may be used with relatively high voltage and because of the inherent efficiency of the invention that permits relatively high switching frequencies, power supplies built in accordance with the invention, together with their associated cabling, can be substantially lighter in weight for a given output power level and efficiency of operation than systems of the prior art.

Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes

PubMed Central

1988-01-01

T cells primed specifically for the envelope glycoprotein of Friend murine leukemia helper virus (F-MuLV) were prepared by immunizing mice with a recombinant vaccinia virus that expressed the entire env gene of F-MuLV. Significant proliferative responses of F-MuLV envelope- specific, H-2a/b T cells were observed when the T cells were stimulated with antigen-pulsed peritoneal exudate cells (PEC) having the b allele at the K, A beta, A alpha, and E beta loci of the H-2. On the other hand, PEC having only the kappa allele at these loci did not induce the envelope-specific T cell proliferation, even when the PEC had the b allele at the E alpha, S, or D loci. F-MuLV envelope-specific proliferation of H-2a/b T cells under the stimulation of antigen- pulsed, H-2a/b PEC was specifically blocked with anti-I-Ab and anti-I- Ek mAbs but not with anti-Kb, anti-Kk, or anti-I-Ak mAbs. Moreover, (B10.MBR x A/WySn)F1 mice that have the b allele only at the K locus but not in I-A subregion were nonresponders to the envelope glycoprotein, and the bm12 mutation at the A beta locus completely abolished the T cell responsiveness to this antigen. These results indicate that proliferative T cells recognize a limited number of epitopes on F-MuLV envelope protein in the context of I-Ab, hybrid I- Ak/b, and/or hybrid I-Ek/b class II MHC molecules but fail to recognize the same envelope protein in the context of I-Ak or I-Ek molecules. This influence of the H-2I region on T cell recognition of the envelope glycoprotein appeared to control in vivo induction of protective immunity against Friend virus complex after immunization with the vaccinia-F-MuLV env vaccine. Thus, these results provide, for the first time, direct evidence for Ir gene-controlled responder/nonresponder phenotypes influencing the immune response to a pathogenic virus of mice. PMID:3141552

Harnessing Solar Energy Using Photosynthetic and Organic Pigments

NASA Astrophysics Data System (ADS)

Fitzsimons, Toby Ryan

Fossil fuels are a finite energy resource that must be supplemented or replaced by more stable forms of electrical energy. Solar technology research strives to supplement and provide eventual replacement for fossil fuel technology. This experiment focused on the use of natural pigments as photo-sensitizers in the current generation of solar cells called dye sensitized solar cells (DSSCs). Pigments from purified chlorophyll a, chlorophyll b, chlorophyll a/b, crude spinach (Spinacia oleracea) extract, phycocyanin, and chlorophyllin were used to construct DSSCs and evaluated, along with a control containing no pigment, for solar energy conversion. The anode of the solar cells consisted of titanium dioxide (TiO2) plates soaked in pigment solutions for twenty-four hours. The plates were assembled, along with an electrolyte sandwiched between cells, and a platinum-coated counter plate that functioned as the cathode. A gasket seal was placed between the plates and held together with rubber bands. The DSSCs were each tested for a maximum power (Pmax) point and a resistor was selected that corresponded to the resistance at that point. The cells were randomly placed into a power block assembly located in an environmental chamber with lighting that provided an average of 27,590 lumens at the surface of DSSCs. With appropriate resistors in place, the cells were subjected to twelve-hour days and twelve-hour nights for ten days, and measurements were recorded every ten minutes. Data were collected to obtain values for voltage in millivolts (mV), current in microamps (microA), and power in microwatts (microW), as well as beginning and ending efficiencies in converting light to usable energy. Voltages were substantially higher during the day than at night for all pigments, except for the control, indicating that the pigments functioned as DSSCs. Hence, only daytime values were used for data analysis. Voltage during the ten-day experiment ranged from 3.99 to 274 mV; current ranged from 0.0180 to 41.9 microA, and power ranged from 0.00 to 11.3 microW. Chlorophyllin had the highest peak and least voltage (274 and 161 mV), highest peak and least current (41.9 and 21.8 microA), and highest peak and least power (11.3 and 4.84 microW). The ranking of the pigments for peak voltage was: Chlorophyllin = Crude Extract ≥ Chlorophyll a = Chlorophyll a/b ≥ Phycocyanin = Chlorophyll b > Control. The ranking for least voltage was: Chlorophyllin > Phycocyanin ≥ Chlorophyll a/b ≥ Crude Extract ≥ Chlorophyll b ≥ Chlorophyll a ≥ Control. Ranking for peak and least values were similar for current and power. Solar energy conversion (efficiency in converting light energy to usable energy in watts per square meter) for all treatments ranged from 0.000595 to 0.0217% at the beginning of the experiment, and was highest in cells constructed with chlorophyllin. Based on rankings from peak and ending voltage values, as well as other measurements, it was concluded that DSSCs constructed with chlorophyllin performed the best and lasted the longest as photo-sensitizers, compared to other pigments used in this investigation. The DSSCs constructed with crude extract performed almost as well as those constructed with chlorophyllin at the beginning of the experiment, but degradation of this naturally-made pigment may have prevented these cells from sustaining solar energy conversion for more than a few days. Other pigments demonstrated conversion values higher than those of control DSSCs which contained no pigments. The results from this project provide evidence that DSSCs can produce useable energy. More research is needed to enhance and prolong the efficiency of DSSCs in solar energy conversion.

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

PubMed Central

2017-01-01

The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies. A mAb that could mimic IVIg in lowering Abs, with defined mechanism of action, would be highly beneficial for patients. Demonstrably, the anti-HLA-E mAbs mimicked several functions of IVIg relevant to suppressing the antiallograft Abs. The mAbs suppressed activated T cells and anti-HLA antibody production by activated B cells, which were dose-wise superior to IVIg. The anti-HLA-E mAb expanded CD4+, CD25+, and Foxp3+ Tregs, which are known to suppress T and B cells involved in antibody production. These defined functions of the anti-HLA-E IgG2a mAbs at a level superior to IVIg encourage developing their humanized version to lower antibodies in allograft recipients, to promote graft survival, and to control autoimmune diseases. PMID:28634589

Physiologically Based Pharmacokinetic Modeling of Therapeutic Proteins.

PubMed

Wong, Harvey; Chow, Timothy W

2017-09-01

Biologics or therapeutic proteins are becoming increasingly important as treatments for disease. The most common class of biologics are monoclonal antibodies (mAbs). Recently, there has been an increase in the use of physiologically based pharmacokinetic (PBPK) modeling in the pharmaceutical industry in drug development. We review PBPK models for therapeutic proteins with an emphasis on mAbs. Due to their size and similarity to endogenous antibodies, there are distinct differences between PBPK models for small molecules and mAbs. The high-level organization of a typical mAb PBPK model consists of a whole-body PBPK model with organ compartments interconnected by both blood and lymph flows. The whole-body PBPK model is coupled with tissue-level submodels used to describe key mechanisms governing mAb disposition including tissue efflux via the lymphatic system, elimination by catabolism, protection from catabolism binding to the neonatal Fc (FcRn) receptor, and nonlinear binding to specific pharmacological targets of interest. The use of PBPK modeling in the development of therapeutic proteins is still in its infancy. Further application of PBPK modeling for therapeutic proteins will help to define its developing role in drug discovery and development. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Ab-initio study of structural, electronic, and transport properties of zigzag GaP nanotubes.

PubMed

Srivastava, Anurag; Jain, Sumit Kumar; Khare, Purnima Swarup

2014-03-01

Stability and electronic properties of zigzag (3 ≤ n ≤ 16) gallium phosphide nanotubes (GaP NTs) have been analyzed by employing a systematic ab-intio approach based on density functional theory using generalized gradient approximation with revised Perdew Burke Ernzerhoff type parameterization. Diameter dependence of bond length, buckling, binding energy, and band gap has been investigated and the analysis shows that the bond length and buckling decreases with increasing diameter of the tube, highest binding energy of (16, 0) confirms this as the most stable amongst all the NTs taken into consideration. The present GaP NTs shows direct band gap and it increases with diameter of the tubes. Using a two probe model for (4, 0) NT the I-V relationship shows an exponential increase in current on applying bias voltage beyond 1.73 volt.

The electromigration force in metallic bulk

NASA Astrophysics Data System (ADS)

Lodder, A.; Dekker, J. P.

1998-01-01

The voltage induced driving force on a migrating atom in a metallic system is discussed in the perspective of the Hellmann-Feynman force concept, local screening concepts and the linear-response approach. Since the force operator is well defined in quantum mechanics it appears to be only confusing to refer to the Hellmann-Feynman theorem in the context of electromigration. Local screening concepts are shown to be mainly of historical value. The physics involved is completely represented in ab initio local density treatments of dilute alloys and the implementation does not require additional precautions about screening, being typical for jellium treatments. The linear-response approach is shown to be a reliable guide in deciding about the two contributions to the driving force, the direct force and the wind force. Results are given for the wind valence for electromigration in a number of FCC and BCC metals, calculated using an ab initio KKR-Green's function description of a dilute alloy.

TOPICAL REVIEW: First principles studies of multiferroic materials

NASA Astrophysics Data System (ADS)

Picozzi, Silvia; Ederer, Claude

2009-07-01

Multiferroics, materials where spontaneous long-range magnetic and dipolar orders coexist, represent an attractive class of compounds, which combine rich and fascinating fundamental physics with a technologically appealing potential for applications in the general area of spintronics. Ab initio calculations have significantly contributed to recent progress in this area, by elucidating different mechanisms for multiferroicity and providing essential information on various compounds where these effects are manifestly at play. In particular, here we present examples of density-functional theory investigations for two main classes of materials: (a) multiferroics where ferroelectricity is driven by hybridization or purely structural effects, with BiFeO3 as the prototype material, and (b) multiferroics where ferroelectricity is driven by correlation effects and is strongly linked to electronic degrees of freedom such as spin-, charge-, or orbital-ordering, with rare-earth manganites as prototypes. As for the first class of multiferroics, first principles calculations are shown to provide an accurate qualitative and quantitative description of the physics in BiFeO3, ranging from the prediction of large ferroelectric polarization and weak ferromagnetism, over the effect of epitaxial strain, to the identification of possible scenarios for coupling between ferroelectric and magnetic order. For the second class of multiferroics, ab initio calculations have shown that, in those cases where spin-ordering breaks inversion symmetry (e.g. in antiferromagnetic E-type HoMnO3), the magnetically induced ferroelectric polarization can be as large as a few µC cm-2. The examples presented point the way to several possible avenues for future research: on the technological side, first principles simulations can contribute to a rational materials design, aimed at identifying spintronic materials that exhibit ferromagnetism and ferroelectricity at or above room temperature. On the fundamental side, ab initio approaches can be used to explore new mechanisms for ferroelectricity by exploiting electronic correlations that are at play in transition metal oxides, and by suggesting ways to maximize the strength of these effects as well as the corresponding ordering temperatures.

VGKC complex antibodies in epilepsy: diagnostic yield and therapeutic implications.

PubMed

Lilleker, James B; Jones, Matthew S; Mohanraj, Rajiv

2013-11-01

In a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. We reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. We identified 6 (4.2%) patients who had titres of >400 pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. Patients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells.

PubMed

Lee, Jun Sik; Lee, Je Chul; Lee, Chang-Min; Jung, In Duk; Jeong, Young-Il; Seong, Eun-Young; Chung, Hae-Young; Park, Yeong-Min

2007-06-30

Acinetobacter baumannii is an increasing hospital-acquired pathogen that causes a various type of infections, but little is known about the protective immune response to this microorganism. Outer membrane protein A of A. baumannii (AbOmpA) is a major porin protein and plays an important role in pathogenesis. We analyzed interaction between AbOmpA and dendritic cells (DCs) to characterize the role of this protein in promoting innate and adaptive immune responses. AbOmpA functionally activates bone marrow-derived DCs by augmenting expression of the surface markers, CD40, CD54, B7 family (CD80 and CD86) and major histocompatibility complex class I and II. AbOmpA induces production of Th1-promoting interleukin-12 from DCs and augments the syngeneic and allogeneic immunostimulatory capacity of DCs. AbOmpA stimulates production of interferon-gamma from T cells in mixed lymphocyte reactions, which suggesting Th1-polarizing capacity. CD4(+) T cells stimulated by AbOmpA-stimulated DCs show a Th1-polarizing cytokine profile. The expression of surface markers on DCs is mediated by both mitogen-activated protein kinases and NF-kappaB pathways. Our findings suggest that AbOmpA induces maturation of DCs and drives Th1 polarization, which are important properties for determining the nature of immune response against A. baumannii.

Importance of Control Groups When Delineating Antibiotic Use as Risk Factors for Carbapenem-Resistance, Extreme-Drug and Pan-Drug Resistance in Acinetobacter baumannii and Pseudomonas aeruginosa: A Systematic Review and Meta-Analysis.

PubMed

Lim, Cheryl Li Ling; Chua, Alvin Qijia; Teo, Jocelyn Qi Min; Cai, Yiying; Lee, Winnie; Kwa, Andrea Lay-Hoon

2018-06-02

Carbapenem-resistant (CR), extreme-drug-resistant (XDR) & pan-drug-resistant (PDR) AB and PA (AB-PA) pose a huge clinical threat. This study reviews the impact of control groups on association of antecedent antibiotic use & acquisition of CR/XDR/PDR AB-PA. Studies investigating the role of antibiotics as risk factor for CR/XDR/PDR AB-PA acquisition in adult hospitalized patients from 1950 to 2016 were identified with databases. These were divided into 2 groups: antibiotic-resistant versus antibiotic-sensitive pathogens (Group I); versus no infection (Group II). A random effects model was performed. Eighty-five studies (46 AB, 38 PA, 1 both) with 22,396 patients were included. CR, XDR & PDR was investigated in 60, 20 and 2 studies respectively. Prior antibiotic exposure was associated with significant acquisition of CR/XDR/PDR AB-PA in both Groups I and II (p <0.05). Antibiotic classes implicated in both groups include aminoglycosides, carbapenems, glycopeptides and penicillins. Cephalosporin use was not associated with resistance in either group. Fluoroquinolones exposure was only associated with resistance in Group I but not Group II. Control groups play an important role in determining magnitudes of risk estimates for risk factor studies, hence careful selection is necessary. Antibiotic exposure increases acquisition of highly-resistant AB-PA, thus appropriate antibiotic use is imperative. Copyright © 2018. Published by Elsevier Ltd.

Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

PubMed

Cindolo, Luca; Pirozzi, Luisella; Sountoulides, Petros; Fanizza, Caterina; Romero, Marilena; Castellan, Pietro; Antonelli, Alessandro; Simeone, Claudio; Tubaro, Andrea; de Nunzio, Cosimo; Schips, Luigi

2015-09-21

Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p < 0.0001). Moreover, CT was associated with a reduced risk of hospitalization for BPH-related surgery (HR 0.94; p < 0.0001) compared to AB monotherapy. Adherence to pharmacological therapy of BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression.

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2012-05-17

countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush approved four decommissioned Kidd-class destroyers for sale as...Section 36(b) of the AECA. See CRS Report RL31675, Arms Sales: Congressional Review Process, by Richard F. Grimmett. 250 Commercial sale. Opall Barbara...340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with 176 AESA radars

A Study of the Invertebrates and Fishes of Salt Marshes in Two Oregon Estuaries.

DTIC Science & Technology

1981-06-01

TAXON Level Level Debris TAXON Level Level Debris Marsh Marsh Line Marsh Marsh Line Cnidaria Coleopr era Halaoampa s? p. A Carabidae A A A Turbellaria A...HAB ITAT H fAB ITAT TAXON Tidal Tidal Flat Tidal Tidal Flat Lan Creek Sandy Mudd TAXON PA Creek SandyMdd Cnidaria A A Tanaidacea Nemertea A A Pancolus...INVERTEBRATES Phylum Protozoa Subphylum Sarcomastigophora Class Rhizopodea Order Foraminifera Phylum Cnidaria Class Anthozoa Subclass Zoantharia Order

Improvement of electricity generating performance and life expectancy of MCFC stack by applying Li/Na carbonate electrolyte. Test results and analysis of 0.44 m 2/10 kW- and 1.03 m 2/10 kW-class stack

NASA Astrophysics Data System (ADS)

Yoshiba, Fumihiko; Morita, Hiroshi; Yoshikawa, Masahiro; Mugikura, Yoshihiro; Izaki, Yoshiyuki; Watanabe, Takao; Komoda, Mineo; Masuda, Yuji; Zaima, Nobuyuki

Following the development of a 10 kW-class MCFC stack with a reactive area of 0.44 and 1.03 m 2, which applies a Li/Na carbonate electrolyte and a press stamping separator, many tests have now been carried out. In the installation tests, the observed cell voltages of the 0.44 m 2/10 kW-class stack agreed with the voltage predicted from the test results of the 100 cm 2 bench scale cell. This agreement proves that the installing procedure of the bench scale cell can be applied to the 0.44 m 2/10 kW-class stacks. The temperature distribution analysis model applied to the 100 kW-class stack was modified to calculate the temperature distribution of the 0.44 m 2/10 kW-class stack. Taking the heat loss and the heat transfer effect of the stack holder into account, the calculated temperature was close to the measured temperature; this result proves that the modification was adequate for the temperature analysis model. In the high current density operating tests on the 0.44 m 2/10 kW-class stack, an electrical power density of 2.46 kW/m 2 was recorded at an operating current density of 3000 A/m 2. In the endurance test on the 0.44 m 2/10 kW-class stack, however, unexpected Ni shortening occurred during the operating period 2500-4500 h, which had been caused by a defective formation of the electrolyte matrix. The shortening seems to have been caused by the crack, which appeared in the electrolyte matrix. The voltage degradation rate of the 0.44 m 2/10 kW-class stack was 0.52% over 1000 h, which proves that the matrix was inadequate for a long life expectancy of the MCFC stack. A final endurance test was carried out on the 1.03 m 2/10 kW-class stack, of which the matrix had been revised. The fuel utilisation and the leakage of anode gas never changed during the 10,000 h operating test. This result suggests that no shortening occurred during the 10,000 h endurance test. The cell voltage degradation rate was around 0.2-0.3% over 1000 h in the 1.03 m 2/10 kW-class stack. According to a comparison of the stack electricity generating performance of the 0.44 m 2 and the 1.03 m 2/10 kW-class stack under the same operating conditions, the performance of the 1.03 m 2 stack was lower at the beginning of the endurance test, however, its performance exceeded the performance of the 0.44 m 2/10 kW-class stack during the 10,000 h operating test. By carrying out the high current density operating test and the 10,000-hour endurance test using commercial sized 10 kW-class stacks, the stability of the MCFC stack with a Li/Na carbonate electrolyte and a press stamping separator has been proven.

Contemporary Trends in Land Surface Phenologies from the Aral Basin Suggest Weather- or Irrigation-Driven Changes in GPP not Land Cover Change

NASA Astrophysics Data System (ADS)

Wright, C. K.; de Beurs, K.; Henebry, G. M.

2009-12-01

The transformation of the Aral Sea into the Aral Lakes is a startling example of anthropogenic environmental degradation. However, ongoing impacts of hydrologic modification and climatic change are occurring throughout the nearly 2 million km2 Aral Basin (AB), thus requiring synoptic, basin-wide monitoring of environmental trends. The MODIS 500m global land cover (LC) product is a potential source of such information in a data-sparse region like the AB. However, we find that it is particularly unstable in this arid/semi-arid region. For example, 25% of AB pixels change LC class between 2001 and 2005 versions of the global LC using the IGBP LC scheme. Here we present an alternate analysis of environmental trends in the AB using MODIS data at the same spatial resolution, but incorporating temporal information embedded within contemporary land surface phenologies (LSPs), in contrast to temporally delimited LC. NDVI time series from 2001-2008 were derived from 500m MODIS NBAR data (16-d composites every 8 d; MCD43A4). Focusing on the period from 1 March to 1 October, each pixel time series was comprised of 27 NDVI values per year (or 216 composites in total). Trend analysis using the nonparametric Seasonal Kendall test revealed a number of spatially coherent hotspots of highly significant (p<0.01) positive and negative trends in NDVI dynamics over the 2001-2008 interval. Relative to the 2001 and 2005 LC classifications, positive trends tended to coincide with the following transitions between IGBP classes: open shrub → closed shrub; grassland → {open shrub, cropland}; {open shrub, cropland/natural vegetation mix} → cropland. These findings suggest that apparent LC change events might be false-positives caused by weather-driven increases in GPP. In turn, negative trends were largely coincident with putative LC change to grassland from mostly woody classes: {closed shrub, open shrub, woody savanna, savanna, snow/ice, barren} → grassland. Here, potential false-positives may reflect effects of regional drought on woody classes, declining mountain snowpack, or original misclassification of grassland as barren, i.e., we would expect declining NDVI in drought-affected grassland, with limited sensitivity to NDVI trends in the barren class. In the intensively irrigated subregion of Karakalpakstan, the MODIS LC product indicates an elevated rate of change from natural vegetation to cropland and vice versa. These transitions tend to coincide with highly significant (p<0.01) negative or positive NDVI trends. However, visual inspection of 2001 and 2005 Landsat imagery from Karakalpakstan did not indicate extensive LC change. Here we interpret apparent false-positives in the global LC product as arising from localized changes in irrigation or cropping practices. Overall, this work demonstrates the utility of temporally dense LSPs for large-area monitoring of environmental change, as opposed to occasional LC classifications which, in arid regions like the AB, may exhibit instability and sensitivity with respect to a region’s normal range of interannual spectral variability.

Focused Mission High Speed Combatant

DTIC Science & Technology

2003-05-09

Landing and airborne autonomous vehicle ( AAV ) operations. AMW 6.7 Serve as a helo haven. AMW 14.6 Conduct spotting for Naval gunfire and artillery...for Building and Classing High Speed Naval Craft 2002, Houston, Texas: ABS, 2002. 13 International Maritime Organization. 2000 HSC Code

In vitro phase I metabolism of gamabufotalin and arenobufagin: Reveal the effect of substituent group on metabolic stability.

PubMed

Feng, Yujie; Wang, Chao; Tian, Xiangge; Huo, Xiaokui; Feng, Lei; Sun, Chengpeng; Ge, Guangbo; Yang, Ling; Ning, Jing; Ma, Xiaochi

2017-09-01

Bufadienolides are a major class of bioactive compounds derived from amphibian skin secretion. Gamabufotalin (GB) and arenobufagin (AB) are among the top of the intensively investigated natural bufadienolides for their outstanding biological activities. This study aimed to characterize the phase I metabolism of GB and AB with respect to the metabolic profiles, enzymes involved, and catalytic efficacy, thereafter tried to reveal substituent effects on metabolism. Two mono-hydroxylated products of GB and AB were detected in the incubation mixtures, and they were accurately identified as 1- and 5-hydroxylated bufadienolides by NMR and HPLC-MS techniques. Reaction phenotyping studies demonstrated that CYP3A mediated the metabolism of the two bufadienolides with a high specific selectivity. Further kinetic evaluation demonstrated that the metabolism stability of GB and AB were better than other reported bufadienolides. Additionally, the CYP3A5 preference for hydroxylation of AB was observed, which was different to the selectivity of CYP3As for bufadienolides suggested by our previous report. This study can provide important data for elucidating the phase I metabolism of GB and AB and can lead to a better understanding of the bufadienolide-CYP3A interaction which is helpful for preclinical development and rational use of bufadienolides. Copyright © 2017 Elsevier B.V. All rights reserved.

A high-efficiency low-voltage class-E PA for IoT applications in sub-1 GHz frequency range

NASA Astrophysics Data System (ADS)

Zhou, Chenyi; Lu, Zhenghao; Gu, Jiangmin; Yu, Xiaopeng

2017-10-01

We present and propose a complete and iterative integrated-circuit and electro-magnetic (EM) co-design methodology and procedure for a low-voltage sub-1 GHz class-E PA. The presented class-E PA consists of the on-chip power transistor, the on-chip gate driving circuits, the off-chip tunable LC load network and the off-chip LC ladder low pass filter. The design methodology includes an explicit design equation based circuit components values' analysis and numerical derivation, output power targeted transistor size and low pass filter design, and power efficiency oriented design optimization. The proposed design procedure includes the power efficiency oriented LC network tuning, the detailed circuit/EM co-simulation plan on integrated circuit level, package level and PCB level to ensure an accurate simulation to measurement match and first pass design success. The proposed PA is targeted to achieve more than 15 dBm output power delivery and 40% power efficiency at 433 MHz frequency band with 1.5 V low voltage supply. The LC load network is designed to be off-chip for the purpose of easy tuning and optimization. The same circuit can be extended to all sub-1 GHz applications with the same tuning and optimization on the load network at different frequencies. The amplifier is implemented in 0.13 μm CMOS technology with a core area occupation of 400 μm by 300 μm. Measurement results showed that it provided power delivery of 16.42 dBm at antenna with efficiency of 40.6%. A harmonics suppression of 44 dBc is achieved, making it suitable for massive deployment of IoT devices. Project supported by the National Natural Science Foundation of China (No. 61574125) and the Industry Innovation Project of Suzhou City of China (No. SYG201641).

[Design of next generation antibody drug conjugates].

PubMed

Zhu, Gui-Dong; Fu, Yang-Xin

2013-07-01

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.

Solar array experiments on the SPHINX satellite. [Space Plasma High voltage INteraction eXperiment satellite

NASA Technical Reports Server (NTRS)

Stevens, N. J.

1974-01-01

The Space Plasma, High Voltage Interaction Experiment (SPHINX) is the name given to an auxiliary payload satellite scheduled to be launched in January 1974. The principal experiments carried on this satellite are specifically designed to obtain the engineering data on the interaction of high voltage systems with the space plasma. The classes of experiments are solar array segments, insulators, insulators with pin holes and conductors. The satellite is also carrying experiments to obtain flight data on three new solar array configurations: the edge illuminated-multijunction cells, the teflon encased cells, and the violet cells.

Topological Quantum Phase Transitions in Two-Dimensional Hexagonal Lattice Bilayers

NASA Astrophysics Data System (ADS)

Zhai, Xuechao; Jin, Guojun

2013-09-01

Since the successful fabrication of graphene, two-dimensional hexagonal lattice structures have become a research hotspot in condensed matter physics. In this short review, we theoretically focus on discussing the possible realization of a topological insulator (TI) phase in systems of graphene bilayer (GBL) and boron nitride bilayer (BNBL), whose band structures can be experimentally modulated by an interlayer bias voltage. Under the bias, a band gap can be opened in AB-stacked GBL but is still closed in AA-stacked GBL and significantly reduced in AA- or AB-stacked BNBL. In the presence of spin-orbit couplings (SOCs), further demonstrations indicate whether the topological quantum phase transition can be realized strongly depends on the stacking orders and symmetries of structures. It is observed that a bulk band gap can be first closed and then reopened when the Rashba SOC increases for gated AB-stacked GBL or when the intrinsic SOC increases for gated AA-stacked BNBL. This gives a distinct signal for a topological quantum phase transition, which is further characterized by a jump of the ℤ2 topological invariant. At fixed SOCs, the TI phase can be well switched by the interlayer bias and the phase boundaries are precisely determined. For AA-stacked GBL and AB-stacked BNBL, no strong TI phase exists, regardless of the strength of the intrinsic or Rashba SOCs. At last, a brief overview is given on other two-dimensional hexagonal materials including silicene and molybdenum disulfide bilayers.

Molecular and Physiological Logics of the Pyruvate-Induced Response of a Novel Transporter in Bacillus subtilis

PubMed Central

Charbonnier, Teddy; Le Coq, Dominique; McGovern, Stephen; Calabre, Magali; Delumeau, Olivier; Aymerich, Stéphane

2017-01-01

ABSTRACT At the heart of central carbon metabolism, pyruvate is a pivotal metabolite in all living cells. Bacillus subtilis is able to excrete pyruvate as well as to use it as the sole carbon source. We herein reveal that ysbAB (renamed pftAB), the only operon specifically induced in pyruvate-grown B. subtilis cells, encodes a hetero-oligomeric membrane complex which operates as a facilitated transport system specific for pyruvate, thereby defining a novel class of transporter. We demonstrate that the LytST two-component system is responsible for the induction of pftAB in the presence of pyruvate by binding of the LytT response regulator to a palindromic region upstream of pftAB. We show that both glucose and malate, the preferred carbon sources for B. subtilis, trigger the binding of CcpA upstream of pftAB, which results in its catabolite repression. However, an additional CcpA-independent mechanism represses pftAB in the presence of malate. Screening a genome-wide transposon mutant library, we find that an active malic enzyme replenishing the pyruvate pool is required for this repression. We next reveal that the higher the influx of pyruvate, the stronger the CcpA-independent repression of pftAB, which suggests that intracellular pyruvate retroinhibits pftAB induction via LytST. Such a retroinhibition challenges the rational design of novel nature-inspired sensors and synthetic switches but undoubtedly offers new possibilities for the development of integrated sensor/controller circuitry. Overall, we provide evidence for a complete system of sensors, feed-forward and feedback controllers that play a major role in environmental growth of B. subtilis. PMID:28974613

Antibodies to Both Terminal and Internal B-Cell Epitopes of Francisella tularensis O-Polysaccharide Produced by Patients with Tularemia

PubMed Central

Lu, Zhaohua; Perkins, Hillary M.

2014-01-01

Francisella tularensis, the Gram-negative bacterium that causes tularemia, is considered a potential bioterrorism threat due to its low infectivity dose and the high morbidity and mortality from respiratory disease. We previously characterized two mouse monoclonal antibodies (MAbs) specific for the O-polysaccharide (O antigen [OAg]) of F. tularensis lipopolysaccharide (LPS): Ab63, which targets a terminal epitope at the nonreducing end of OAg, and Ab52, which targets a repeating internal OAg epitope. These two MAbs were protective in a mouse model of respiratory tularemia. To determine whether these epitope types are also targeted by humans, we tested the ability of each of 18 blood serum samples from 11 tularemia patients to inhibit the binding of Ab63 or Ab52 to F. tularensis LPS in a competition enzyme-linked immunosorbent assay (ELISA). Although all serum samples had Ab63- and Ab52-inhibitory activities, the ratios of Ab63 to Ab52 inhibitory potencies varied 75-fold. However, the variation was only 2.3-fold for sequential serum samples from the same patient, indicating different distributions of terminal- versus internal-binding antibodies in different individuals. Western blot analysis using class-specific anti-human Ig secondary antibodies showed that both terminal- and internal-binding OAg antibodies were of the IgG, IgM, and IgA isotypes. These results support the use of a mouse model to discover protective B-cell epitopes for tularemia vaccines or prophylactic/therapeutic antibodies, and they present a general strategy for interrogating the antibody responses of patients and vaccinees to microbial carbohydrate epitopes that have been characterized in experimental animals. PMID:24351753

Genotypic and Antimicrobial Susceptibility of Carbapenem-resistant Acinetobacter baumannii: Analysis of ISAba Elements and blaOXA-23-like Genes Including a New Variant

PubMed Central

Bahador, Abbas; Raoofian, Reza; Pourakbari, Babak; Taheri, Mohammad; Hashemizadeh, Zahra; Hashemi, Farhad B.

2015-01-01

Carbapenem-resistant Acinetobacter baumannii (CR-AB) causes serious nosocomial infections, especially in ICU wards of hospitals, worldwide. Expression of blaOXA genes is the chief mechanism of conferring carbapenem resistance among CR-AB. Although some blaOXA genes have been studied among CR-AB isolates from Iran, their blaOXA-23-like genes have not been investigated. We used a multiplex-PCR to detect Ambler class A, B, and D carbapenemases of 85 isolates, and determined that 34 harbored blaOXA-23-like genes. Amplified fragment length polymorphism (AFLP) genotyping, followed by DNA sequencing of blaOXA-23-like amplicons of CR-AB from each AFLP group was used to characterize their blaOXA-23-like genes. We also assessed the antimicrobial susceptibility pattern of CR-AB isolates, and tested whether they harbored insertion sequences ISAba1 and ISAba4. Sequence comparison with reference strain A. baumannii (NCTC12156) revealed five types of mutations in blaOXA-23-like genes; including one novel variant and four mutants that were already reported from China and the USA. All of the blaOXA-23-like genes mutations were associated with increased minimum inhibitory concentrations (MICs) against imipenem. ISAba1 and ISAba4 sequences were detected upstream of blaOXA-23 genes in 19 and 7% of isolates, respectively. The isolation of CR-AB with new blaOXA-23 mutations including some that have been reported from the USA and China highlights CR-AB pervasive distribution, which underscores the importance of concerted national and global efforts to control the spread of CR-AB isolates worldwide. PMID:26617588

SFG experiment and ab initio study of the chemisorption of CN - on low-index platinum surfaces

NASA Astrophysics Data System (ADS)

Tadjeddine, M.; Flament, J.-P.; Le Rille, A.; Tadjeddine, A.

2006-05-01

A dual analysis is proposed in order to have a better understanding of the adsorption of the cyanide ions on a platinum electrode. The SFG (Sum Frequency Generation) spectroscopy allows the in situ vibrational study and the SFG spectra of the CN - species adsorbed on single crystal Pt electrode allow a systematic study of the low-index platinum surfaces. This experimental work is supported by ab initio calculations using density functional theory and cluster models. For each surface orientation and each geometry, a cluster model of 20-30 Pt atoms has been built in order to interpret the chemisorption of the CN - ions through four kinds of adsorption geometry: on-top or bridge site, bonding via C or N atoms. Geometries have been optimized and adsorption energies, electronic properties and vibrational frequencies have been computed. From the electronic properties, we can propose an analysis of the bonding mechanism for each studied kind of adsorption. The SFG spectra of the CN -/Pt(1 1 1) system present an unique resonance owing to the top C adsorption. It is mainly the same for the CN -/Pt(1 0 0) system. It is also the case for the SFG spectra of the CN -/Pt(1 1 0) system recorded at negative electrochemical voltage; at more positive voltage, a second resonance appears at a lower frequency, owing to the top N adsorption. Experimental and theoretical values of the C-N stretching frequencies are in excellent agreement.

Tuning spin transport properties and molecular magnetoresistance through contact geometry

NASA Astrophysics Data System (ADS)

Ulman, Kanchan; Narasimhan, Shobhana; Delin, Anna

2014-01-01

Molecular spintronics seeks to unite the advantages of using organic molecules as nanoelectronic components, with the benefits of using spin as an additional degree of freedom. For technological applications, an important quantity is the molecular magnetoresistance. In this work, we show that this parameter is very sensitive to the contact geometry. To demonstrate this, we perform ab initio calculations, combining the non-equilibrium Green's function method with density functional theory, on a dithienylethene molecule placed between spin-polarized nickel leads of varying geometries. We find that, in general, the magnetoresistance is significantly higher when the contact is made to sharp tips than to flat surfaces. Interestingly, this holds true for both resonant and tunneling conduction regimes, i.e., when the molecule is in its "closed" and "open" conformations, respectively. We find that changing the lead geometry can increase the magnetoresistance by up to a factor of ˜5. We also introduce a simple model that, despite requiring minimal computational time, can recapture our ab initio results for the behavior of magnetoresistance as a function of bias voltage. This model requires as its input only the density of states on the anchoring atoms, at zero bias voltage. We also find that the non-resonant conductance in the open conformation of the molecule is significantly impacted by the lead geometry. As a result, the ratio of the current in the closed and open conformations can also be tuned by varying the geometry of the leads, and increased by ˜400%.

46 CFR 110.10-1 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Classing Mobile Offshore Drilling Units, Part 4 Machinery and Systems, 2001 (“ABS MODU Rules”), IBR... Hazardous (Classified) Locations: Type of Protection—Encapsulation “m”, approved July 31, 2009 (“ANSI/ISA... Practice for Classification of Locations for Electrical Installations at Petroleum Facilities Classified as...

49 CFR 1150.32 - Procedures and relevant dates-transactions that involve creation of Class III carriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... given to shippers. (c) If the notice contains false or misleading information, the exemption is void ab initio. A petition to revoke under 49 U.S.C. 10502(d) does not automatically stay the exemption. Stay...

Log-Gamma Polymer Free Energy Fluctuations via a Fredholm Determinant Identity

NASA Astrophysics Data System (ADS)

Borodin, Alexei; Corwin, Ivan; Remenik, Daniel

2013-11-01

We prove that under n 1/3 scaling, the limiting distribution as n → ∞ of the free energy of Seppäläinen’s log-Gamma discrete directed polymer is GUE Tracy-Widom. The main technical innovation we provide is a general identity between a class of n-fold contour integrals and a class of Fredholm determinants. Applying this identity to the integral formula proved in Corwin et al. (Tropical combinatorics and Whittaker functions. http://arxiv.org/abs/1110.3489v3 [math.PR], 2012) for the Laplace transform of the log-Gamma polymer partition function, we arrive at a Fredholm determinant which lends itself to asymptotic analysis (and thus yields the free energy limit theorem). The Fredholm determinant was anticipated in Borodin and Corwin (Macdonald processes. http://arxiv.org/abs/1111.4408v3 [math.PR], 2012) via the formalism of Macdonald processes yet its rigorous proof was so far lacking because of the nontriviality of certain decay estimates required by that approach.

Fuel Injection Strategy for a Next Generation Pulse Detonation Engine

DTIC Science & Technology

2006-06-01

at 45°C CE Approved EMC EMC Directive 89/336/EEC; EN 61326-1 Emissions and Immunity Safety Low Voltage Directive 73/23/EEC; EN 61010 -1...Operating Humidity 0–90% Nonoperating Humidity 0–100% CDRH Class IIIb IEC Class 3B From www.mellesgriot.com 47 SILICON OPTICAL SENSOR Model

The electron-optical system of the LIU-2 induction accelerator

NASA Astrophysics Data System (ADS)

Kuznetsov, G. I.; Batazova, M. A.

2014-09-01

The electron-optical system (EOS) of an induction accelerator for generation of an electron beam with an energy of 2 MeV, a current of 2 kA, an impulse duration of 2 × 10-7 s, and a geometric output emittance not exceeding the thermal value of it is described. The EOS consists of two parts. The first part is a diode gun with a perveance of 2 × 10-6 A/B3/2 and a cathode-anode voltage of 1 MeV. The second part is an accelerating tube with uniform distribution of the same accelerating voltage. A beam is transported at a distance of about 4 m from the cathode and focused on a spot with a diameter of about 1 mm. The compliance tests results of the linear-induction accelerator precisely conform to the calculated design parameters.

Electronic structure and transport properties of zigzag MoS2 nanoribbons

NASA Astrophysics Data System (ADS)

Sharma, Uma Shankar; Shah, Rashmi; Mishra, Pankaj Kumar

2018-05-01

In present study, electronic and transport properties of the 8zigzag MoS2 nanoribbons (8ZMoS2NRs) are investigated using ab-initio density functional theory [DFT]. The calculations were performed using nonequilibrium Green's function (NEGF) formalism based on DFT as implemented in the TranSiesta code. Results show that the defect can introduces few extra states into the energy gap, which lead nanoribbons to reveal a metallic characteristic. The voltage-current (VI) graph of 8ZMoS2NRs show a threshold current increases after introducing Mo defect in the devices. when introducing a Mo vacancy under low biases, the current will be suppressed—whereas under high biases, the current through the defected 8ZMoS2NRs will increases rapidly, due to the other channel being opened, that make possibility of 8ZMoS2NRs application in electronic devices such as voltage regulation.

The Effect of Voltage Charging on the Transport Properties of Gold Nanotube Membranes.

PubMed

Experton, Juliette; Martin, Charles R

2018-05-01

Porous membranes are used in chemical separations and in many electrochemical processes and devices. Research on the transport properties of a unique class of porous membranes that contain monodisperse gold nanotubes traversing the entire membrane thickness is reviewed here. These gold nanotubes can act as conduits for ionic and molecular transports through the membrane. Because the tubes are electronically conductive, they can be electrochemically charged by applying a voltage to the membrane. How this "voltage charging" affects the transport properties of gold nanotube membranes is the subject of this Review. Experiments showing that voltage charging can be used to reversibly switch the membrane between ideally cation- and anion-transporting states are reviewed. Voltage charging can also be used to enhance the ionic conductivity of gold nanotube membranes. Finally, voltage charging to accomplish electroporation of living bacteria as they pass through gold nanotube membranes is reviewed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic variation of the MHC class II DRB genes in the Japanese weasel, Mustela itatsi, endemic to Japan, compared with the Siberian weasel, Mustela sibirica.

PubMed

Nishita, Y; Abramov, A V; Kosintsev, P A; Lin, L-K; Watanabe, S; Yamazaki, K; Kaneko, Y; Masuda, R

2015-12-01

Major histocompatibility complex (MHC) genes encode proteins that play a critical role in vertebrate immune system and are highly polymorphic. To further understand the molecular evolution of the MHC genes, we compared MHC class II DRB genes between the Japanese weasel (Mustela itatsi), a species endemic to Japan, and the Siberian weasel (Mustela sibirica), a closely related species on the continent. We sequenced a 242-bp region of DRB exon 2, which encodes antigen-binding sites (ABS), and found 24 alleles from 31 M. itatsi individuals and 17 alleles from 21 M. sibirica individuals, including broadly distributed, species-specific and/or geographically restricted alleles. Our results suggest that pathogen-driven balancing selection have acted to maintain the diversity in the DRB genes. For predicted ABS, nonsynonymous substitutions exceeded synonymous substitutions, also indicating positive selection, which was not seen at non-ABS. In a Bayesian phylogenetic tree, two M. sibirica DRB alleles were basal to the rest of the sequences from mustelid species and may represent ancestral alleles. Trans-species polymorphism was evident between many mustelid DRB alleles, especially between M. itatsi and M. sibirica. These two Mustela species divided about 1.7 million years ago, but still share many MHC alleles, indicative of their close phylogenetic relationship. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular interfaces for plasmonic hot electron photovoltaics

NASA Astrophysics Data System (ADS)

Pelayo García de Arquer, F.; Mihi, Agustín; Konstantatos, Gerasimos

2015-01-01

The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices.The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices. Electronic supplementary information (ESI) available: Contact-potential differentiometry measurements, FTIR characterization, performance statistics and gold devices. See DOI: 10.1039/c4nr06356b

In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa

NASA Astrophysics Data System (ADS)

Verchère, Alice; Dezi, Manuela; Adrien, Vladimir; Broutin, Isabelle; Picard, Martin

2015-04-01

Antibiotic resistance is a major public health issue and many bacteria responsible for human infections have now developed a variety of antibiotic resistance mechanisms. For instance, Pseudomonas aeruginosa, a disease-causing Gram-negative bacteria, is now resistant to almost every class of antibiotics. Much of this resistance is attributable to multidrug efflux pumps, which are tripartite membrane protein complexes that span both membranes and actively expel antibiotics. Here we report an in vitro procedure to monitor transport by the tripartite MexAB-OprM pump. By combining proteoliposomes containing the MexAB and OprM portions of the complex, we are able to assay energy-dependent substrate translocation in a system that mimics the dual-membrane architecture of Gram-negative bacteria. This assay facilitates the study of pump transport dynamics and could be used to screen pump inhibitors with potential clinical use in restoring therapeutic activity of old antibiotics.

Antibodies to watch in 2010

PubMed Central

2010-01-01

Monoclonal antibodies (mAbs) are a burgeoning class of therapeutics, with more than 25 approved in countries worldwide. Novel molecules are entering clinical study at a rate of nearly 40 per year, and the commercial pipeline includes approximately 240 mAb therapeutics in clinical studies that have not yet progressed to regulatory approval or been approved. Of particular interest are the 26 mAbs that are currently at Phase 3, when safety and efficacy data critical to approval is established. Phase 3 study lengths are typically two to four years, so results for some studies might be announced in 2010, but data from others might not be presented until 2014. This overview of the 26 candidates provides a brief description of the background and the on-going Phase 3 studies of each mAb. Additional mAbs that have progressed to regulatory review or been approved may also be in Phase 3 studies, but these, as well as Fc fusion proteins, have been excluded. Due to the large body of primary literature about the 26 candidates, only selected references are given, with a focus on recent publications and articles that were relevant to Phase 3 studies. Current as of October 2009, the results presented here will serve as a baseline against which future progress can be measured. PMID:20065640

Steel — ab Initio: Quantum Mechanics Guided Design of New Fe-Based Materials

NASA Astrophysics Data System (ADS)

Prahl, Ulrich; Bleck, Wolfgang; Saeed-Akbari, Alireza

This contribution reports the results of the collaborative research unit SFB 761 "Steel — ab initio", a cooperative project between RWTH Aachen University and the Max-Planck-Institute for Iron Research in Düsseldorf (MPIE) financed by the German Research Foundation (DFG). For the first time, it is exploited how ab initio approaches may lead to a detailed understanding and thus to a specific improvement of material development. The challenge lies in the combination of abstract natural science theories with rather engineering-like established concepts. Aiming at the technological target of the development of a new type of structural materials based on Fe-Mn-C alloys, the combination of ab initio and engineering methods is new, but could be followed quite successfully. Three major topics are treated in this research unit: a) development of a new method for material- and process-development based on ab initio calculations; b) design of a new class of structural materials with extraordinary property combinations; c) acceleration of development time and reduction of experimental efforts and complexity for material- and process-development. In the present work, an overview of the results of the first five years as well as an outlook for the upcoming three-year period is given.

Quantitative Analysis of Endocytic Recycling of Membrane Proteins by Monoclonal Antibody-Based Recycling Assays.

PubMed

Blagojević Zagorac, Gordana; Mahmutefendić, Hana; Maćešić, Senka; Karleuša, Ljerka; Lučin, Pero

2017-03-01

In this report, we present an analysis of several recycling protocols based on labeling of membrane proteins with specific monoclonal antibodies (mAbs). We analyzed recycling of membrane proteins that are internalized by clathrin-dependent endocytosis, represented by the transferrin receptor, and by clathrin-independent endocytosis, represented by the Major Histocompatibility Class I molecules. Cell surface membrane proteins were labeled with mAbs and recycling of mAb:protein complexes was determined by several approaches. Our study demonstrates that direct and indirect detection of recycled mAb:protein complexes at the cell surface underestimate the recycling pool, especially for clathrin-dependent membrane proteins that are rapidly reinternalized after recycling. Recycling protocols based on the capture of recycled mAb:protein complexes require the use of the Alexa Fluor 488 conjugated secondary antibodies or FITC-conjugated secondary antibodies in combination with inhibitors of endosomal acidification and degradation. Finally, protocols based on the capture of recycled proteins that are labeled with Alexa Fluor 488 conjugated primary antibodies and quenching of fluorescence by the anti-Alexa Fluor 488 displayed the same quantitative assessment of recycling as the antibody-capture protocols. J. Cell. Physiol. 232: 463-476, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Find a Dermatologic Surgeon

MedlinePlus

... class="button-learn-more"> State AL AK AZ AR CA CO CT DE DC FL GA HI ... 250 Miles Locality City: State: AB AK AL AR AZ BC CA CO CT DC DE FL ... clicking on the procedure name. State AK AL AR AZ CA CO CT DC DE FL GA ...

Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins.

PubMed

Liu, Liming

2015-06-01

Understanding the impact of glycosylation and keeping a close control on glycosylation of product candidates are required for both novel and biosimilar monoclonal antibodies (mAbs) and Fc-fusion protein development to ensure proper safety and efficacy profiles. Most therapeutic mAbs are of IgG class and contain a glycosylation site in the Fc region at amino acid position 297 and, in some cases, in the Fab region. For Fc-fusion proteins, glycosylation also frequently occurs in the fusion partners. Depending on the expression host, glycosylation patterns in mAb or Fc-fusions can be significantly different, thus significantly impacting the pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs. Glycans that have a major impact on PK and PD of mAb or Fc-fusion proteins include mannose, sialic acids, fucose (Fuc), and galactose (Gal). Mannosylated glycans can impact the PK of the molecule, leading to reduced exposure and potentially lower efficacy. The level of sialic acid, N-acetylneuraminic acid (NANA), can also have a significant impact on the PK of Fc-fusion molecules. Core Fuc in the glycan structure reduces IgG antibody binding to IgG Fc receptor IIIa relative to IgG lacking Fuc, resulting in decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activities. Glycoengineered Chinese hamster ovary (CHO) expression systems can produce afucosylated mAbs that have increased ADCC activities. Terminal Gal in a mAb is important in the complement-dependent cytotoxicity (CDC) in that lower levels of Gal reduce CDC activity. Glycans can also have impacts on the safety of mAb. mAbs produced in murine myeloma cells such as NS0 and SP2/0 contain glycans such as Galα1-3Galβ1-4N-acetylglucosamine-R and N-glycolylneuraminic acid (NGNA) that are not naturally present in humans and can be immunogenic when used as therapeutics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Assessment of the spatial variability in tall wheatgrass forage using LANDSAT 8 satellite imagery to delineate potential management zones.

PubMed

Cicore, Pablo; Serrano, João; Shahidian, Shakib; Sousa, Adelia; Costa, José Luis; da Silva, José Rafael Marques

2016-09-01

Little information is available on the degree of within-field variability of potential production of Tall wheatgrass (Thinopyrum ponticum) forage under unirrigated conditions. The aim of this study was to characterize the spatial variability of the accumulated biomass (AB) without nutritional limitations through vegetation indexes, and then use this information to determine potential management zones. A 27-×-27-m grid cell size was chosen and 84 biomass sampling areas (BSA), each 2 m(2) in size, were georeferenced. Nitrogen and phosphorus fertilizers were applied after an initial cut at 3 cm height. At 500 °C day, the AB from each sampling area, was collected and evaluated. The spatial variability of AB was estimated more accurately using the Normalized Difference Vegetation Index (NDVI), calculated from LANDSAT 8 images obtained on 24 November 2014 (NDVInov) and 10 December 2014 (NDVIdec) because the potential AB was highly associated with NDVInov and NDVIdec (r (2)  = 0.85 and 0.83, respectively). These models between the potential AB data and NDVI were evaluated by root mean squared error (RMSE) and relative root mean squared error (RRMSE). This last coefficient was 12 and 15 % for NDVInov and NDVIdec, respectively. Potential AB and NDVI spatial correlation were quantified with semivariograms. The spatial dependence of AB was low. Six classes of NDVI were analyzed for comparison, and two management zones (MZ) were established with them. In order to evaluate if the NDVI method allows us to delimit MZ with different attainable yields, the AB estimated for these MZ were compared through an ANOVA test. The potential AB had significant differences among MZ. Based on these findings, it can be concluded that NDVI obtained from LANDSAT 8 images can be reliably used for creating MZ in soils under permanent pastures dominated by Tall wheatgrass.

How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies

PubMed Central

Spencer, Carole; LoPresti, Jonathan; Fatemi, Shireen

2014-01-01

Purpose of review To discuss new insights regarding how sensitive (second-generation) thyroglobulin immunometric assays (Tg2GIMAs), (functional sensitivities ≤0.10 μg/L) necessitate different approaches for postoperative thyroglobulin monitoring of patients with differentiated thyroid cancer (DTC), depending on the presence of thyroglobulin autoantibodies (TgAbs). Recent findings Reliable low-range serum thyroglobulin measurement has both enhanced clinical utility and economic advantages, provided TgAb is absent (∼75% DTC patients). Basal [nonthyroid-stimulating hormone (TSH) stimulated] Tg2GIMA measurement obviates the need for recombinant human TSH stimulation because basal Tg2GIMA below 0.20 μg/L has comparable negative predictive value (>95%) to recombinant human TSH-stimulated thyroglobulin values below the cutoff of 2 μg/L. Now that radioiodine remnant ablation is no longer considered necessary to treat low-risk DTC, the trend and doubling time of low basal thyroglobulin values arising from postsurgical thyroid remnants have recognized prognostic significance. The major limitation of Tg2GIMA testing is interference by TgAb (∼25% DTC patients), causing Tg2GIMA underestimation that can mask disease. When TgAb is present, the trend in TgAb concentrations (measured by the same method) can serve as the primary (surrogate) tumor-marker and be augmented by thyroglobulin measured by a TgAb-resistant class of method (radioimmunoassay or liquid chromatography-tandem mass spectrometry). Summary The growing use of Tg2GIMA measurement is changing paradigms for postoperative DTC monitoring. When TgAb is absent, it is optimal to monitor the basal Tg2GIMA trend and doubling time (using the same method) in preference to recombinant human TSH-stimulated thyroglobulin testing. When TgAb is present, interference renders Tg2GIMA testing unreliable and the trend in serum TgAb concentrations per se (same method) can serve as a (surrogate) tumor-marker. PMID:25122493

Electrotransport-induced unmixing and decomposition of ternary oxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chun, Jakyu; Yoo, Han-Ill, E-mail: hiyoo@snu.ac.kr; Martin, Manfred

A general expectation is that in a uniform oxygen activity atmosphere, cation electrotransport induces a ternary or higher oxide, e.g., AB{sub 1+ξ}O{sub 3+δ}, to kinetically unmix unless the electrochemical mobilities of, say, A{sup 2+}and B{sup 4+} cations are identically equal, and eventually to decompose into the component oxides AO and BO{sub 2} once the extent of unmixing exceeds the stability range of its nonmolecularity ξ. It has, however, earlier been reported [Yoo et al., Appl. Phys. Lett. 92, 252103 (2008)] that even a massive cation electrotransport induces BaTiO{sub 3} to neither unmix nor decompose even at a voltage far exceedingmore » the so-called decomposition voltage U{sub d}, a measure of the standard formation free energy of the oxide (|ΔG{sub f}{sup o}| = nFU{sub d}). Here, we report that as expected, NiTiO{sub 3} unmixes at any voltage and even decomposes if the voltage applied exceeds seemingly a threshold value larger than U{sub d}. We demonstrate experimentally that the electrochemical mobilities of Ni{sup 2+} and Ti{sup 4+} should be necessarily unequal for unmixing. Also, we show theoretically that equal cation mobilities appear to be a sufficiency for BaTiO{sub 3} only for a thermodynamic reason.« less

High current nonlinear transmission line based electron beam driver

NASA Astrophysics Data System (ADS)

Hoff, B. W.; French, D. M.; Simon, D. S.; Lepell, P. D.; Montoya, T.; Heidger, S. L.

2017-10-01

A gigawatt-class nonlinear transmission line based electron beam driver is experimentally demonstrated. Four experimental series, each with a different Marx bank charge voltage (15, 20, 25, and 30 kV), were completed. Within each experimental series, shots at peak frequencies ranging from 950 MHz to 1.45 GHz were performed. Peak amplitude modulations of the NLTL output voltage signal were found to range between 18% and 35% for the lowest frequency shots and between 5% and 20% for the highest frequency shots (higher modulation at higher Marx charge voltage). Peak amplitude modulations of the electron beam current were found to range between 10% and 20% for the lowest frequency shots and between 2% and 7% for the highest frequency shots (higher modulation at higher Marx charge voltage).

Host T-cell primary allosensitization to MHC class-I- and class-II-expressing human cardiac myocytes requires the presence of a second signal.

PubMed

Ansari, A A; Wang, Y C; Kanter, K; Villinger, F; Mayne, A; Sell, K W; Herskowitz, A

1993-06-01

Normal FHCMs, or transformed cell lines derived from FHCMs, such as W1, even after induction of MHC antigens by pretreatment with IFN-gamma, failed to induce proliferation of allogeneic human PBMCs in vitro. To test the hypothesis that antigen-specific T-cell activation and proliferation require not only the binding of the TCR with its ligand, the MHC molecule, but also a second signal that involves the interaction of T-cell surface molecules with their natural ligands on the stimulating cells, a mAb against CD28 was used. Cocultures of allogeneic PBMCs with IFN-gamma-pretreated irradiated FHCMs or the W1 cell line in microtiter plates containing immobilized anti-CD28 mAb induced marked stimulator cells MHC class-II-specific proliferative responses. The W1 cell line and FHCMs failed to express detectable levels of the BB1/B7 molecule (the natural ligand for CD28) as determined by flow microfluorometry or mRNA levels coding for BB1/B7 as determined by RT-PCR. These data suggest that one of the probably reasons for the failure of MHC-expressing cardiac myocytes to induce allogeneic activation is the absence of costimulatory signals.

Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

PubMed Central

Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

2008-01-01

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287

Optically Driven Spin Based Quantum Dots for Quantum Computing

DTIC Science & Technology

2008-01-01

time . Figure 3. Demonstration of optical pumping. This shows the absorption as a function of bias voltage and laser energy. In region...319,076 319,079 0 2 0 2 0 2 0 2 0 2 R el at iv e ab so rp tio n (× 1 0– 4 ) Probe frequency (GHz) Time constant (ms) 1 1 3 10 30 c Figure 1 | Laser ...spectrum of the forward (or backward) scan. c, The probe absorption spectrum as a function of the laser scan rate, indicated by the lock-in time

The Development of a High-Power, Low-Frequency Underwater Acoustic Source for Use in a Deep-Towed Geophysical Array Section

DTIC Science & Technology

1982-11-15

Metca) for each ring 6 Aluminum orirlce end ring 15 Rubber bumpers 7 Back plate inner boot ring 16 Castor oil rill-fluid I ’)-ring %eals I ’ Nikel ...electrode .ab% with hook-up wire -ig. 6 - Sectional v-icw orf ISRI) typc (662 tran.dhcer 9 YOUNG, TIMS. AND HENRIQUFZ 0.42 m. Approximately 85% of the...electrical leads for each ring are routed to individual bulkhead connectors on the trans- ducer back plate with high-voltage silicone-jacketed hookup wire

TARDEC FMEA TRAINING: Understanding and Evaluating Failure Mode and Effects Analyses (FMEA)

DTIC Science & Technology

2012-06-07

Tip Brass 1 1.1.2.1.3 Ball Tungsten Carbide 1 1.1.2.1.4 Blue Ink Ink .1 grams 1.1.2.2 Steel 1 1.1.3 ABS/PP 1 Ink/Spring Assembly Ink Tube Spring Nib...does not meet airflow (8) voltage circuit analy sis of vehic le - New Yuma - test requirements (6 in. WCtJ.P -Blown fuse control c ircuit vehicle...1500 CFM for XXXX) - Broken wire - Compare fuse capacity to in-rush current and stall current during high ambient temperature conditions - Review

Antibodies to oxidized LDL as predictors of morbidity and mortality in patients with chronic heart failure.

PubMed

Charach, Gideon; George, Jacob; Afek, Arnon; Wexler, Dov; Sheps, David; Keren, Gad; Rubinstein, Ardon

2009-11-01

Oxidative stress appears to play a significant role in the pathogenesis of heart failure (HF). Antibodies to oxidized low-density lipoprotein (Ox LDL Abs) reflect an immune response to LDL over a prolonged period and may thus represent oxidative stress over an extended time. Ox LDL Abs have been shown to correlate with clinical control in HF patients. We evaluated the predictive power of Ox LDL Abs on the outcome in patients with HF. Baseline levels of Ox LDL Abs were determined by enzyme-linked immunosorbent assay in 284 consecutive outpatients with severe chronic HF who were being treated in the cardiology services of our medical center. Their mean New York Heart Association (NYHA) Class was 2.8. The mean follow-up for the group was 3.7 years, during which 107 (37%) died. The mean time from symptom onset to first hospital admission from HF was 25.8 months. Ox LDL Abs were found to predict morbidity and mortality as evaluated by a Cox multivariate regression analysis with a hazard ration of 1.013 (P < .013), whereas N-terminal pro-B-type natriuretic peptide (NT pro-BNP) levels achieved a HR of 1.028 (P < .099). Ox LDL Abs level maybe a useful parameter for monitoring and planning better management of patients with HF. It was superior to pro-BNP as a predictor of clinical course as expressed by time to hospitalization.

Strong and oriented immobilization of single domain antibodies from crude bacterial lysates for high-throughput compatible cost-effective antibody array generation

PubMed Central

Even-Desrumeaux, Klervi; Baty, Daniel; Chames, Patrick

2010-01-01

Antibodies microarrays are among the novel class of rapidly emerging proteomic technologies that will allow us to efficiently perform specific diagnosis and proteome analysis. Recombinant antibody fragments are especially suited for this approach but their stability is often a limiting factor. Camelids produce functional antibodies devoid of light chains (HCAbs) of which the single N-terminal domain is fully capable of antigen binding. When produced as an independent domain, these so-called single domain antibody fragments (sdAbs) have several advantages for biotechnological applications thanks to their unique properties of size (15 kDa), stability, solubility, and expression yield. These features should allow sdAbs to outperform other antibody formats in a number of applications, notably as capture molecule for antibody arrays. In this study, we have produced antibody microarrays using direct and oriented immobilization of sdAbs produced in crude bacterial lysates to generate proof-of-principle of a high-throughput compatible array design. Several sdAb immobilization strategies have been explored. Immobilization of in vivo biotinylated sdAbs by direct spotting of bacterial lysate on streptavidin and sandwich detection was developed to achieve high sensitivity and specificity, whereas immobilization of “multi-tagged” sdAbs via anti-tag antibodies and direct labeled sample detection strategy was optimized for the design of high-density antibody arrays for high-throughput proteomics and identification of potential biomarkers. PMID:20859568

Movement and fate of detergents in groundwater: a field study

USGS Publications Warehouse

Thurman, E.M.; Barber, L.B.; LeBlanc, D.

1986-01-01

The major cations, anions, and detergents in a plume of contaminated groundwater at Otis Air Base on Cape Cod (Mass., U.S.A.) have moved approximately 3.5 km down gradient from the disposal beds. We hypothesize that the detergents form two distinct plumes, which consist of alkyl benzene sulfonates (ABS) detergents and linear alkyl sulfonates (LAS) and sodium dodecyl sulfate (NaLS) detergents. The ABS detergents were deposited from approximately 1940 through 1965, when ABS detergents were banned. From 1965 to the present, LAS and NaLS detergents were in the sewage. The ABS detergents appear to be transported in the aquifer at the same rate as the specific conductance (major cations and anions) and boron, which are currently used as conservative tracers of the plume of contaminated groundwater. There appears to be little or no biological degradation of the ABS detergents in the aquifer, based on their concentration in the plume. On the other hand, the LAS and NaLS detergents have degraded rapidly and have been detected only 0.6 km down gradient. The roleof the detergents in the transport of other organic compounds in the plume is nuclear. There is a separation of the ABS detergent plume and the volatile organic compound plume; however, the time of entry of the detergents and the volatile organic compounds is unknown. Therefore, it is not possible to conclude on the interaction of these two classes of compounds. ?? 1986.

An AlGaN/GaN high-electron-mobility transistor with an AlN sub-buffer layer

NASA Astrophysics Data System (ADS)

Shealy, J. R.; Kaper, V.; Tilak, V.; Prunty, T.; Smart, J. A.; Green, B.; Eastman, L. F.

2002-04-01

The AlGaN/GaN high-electron-mobility transistor requires a thermally conducting, semi-insulating substrate to achieve the best possible microwave performance. The semi-insulating SiC substrate is currently the best choice for this device technology; however, fringing fields which penetrate the GaN buffer layer at pinch-off introduce significant substrate conduction at modest drain bias if channel electrons are not well confined to the nitride structure. The addition of an insulating AlN sub-buffer on the semi-insulating SiC substrate suppresses this parasitic conduction, which results in dramatic improvements in the AlGaN/GaN transistor performance. A pronounced reduction in both the gate-lag and the gate-leakage current are observed for structures with the AlN sub-buffer layer. These structures operate up to 50 V drain bias under drive, corresponding to a peak voltage of 80 V, for a 0.30 µm gate length device. The devices have achieved high-efficiency operation at 10 GHz (>70% power-added efficiency in class AB mode at 15 V drain bias) and the highest output power density observed thus far (11.2 W mm-1). Large-periphery devices (1.5 mm gate width) deliver 10 W (continuous wave) of maximum saturated output power at 10 GHz. The growth, processing, and performance of these devices are briefly reviewed.

The ac power line protection for an IEEE 587 Class B environment

NASA Technical Reports Server (NTRS)

Roehr, W. D.; Clark, O. M.

1984-01-01

The 587B series of protectors are unique, low clamping voltage transient suppressors to protect ac-powered equipment from the 6000V peak open-circuit voltage and 3000A short circuit current as defined in IEEE standard 587 for Category B transients. The devices, which incorporate multiple-stage solid-state protector components, were specifically designed to operate under multiple exposures to maximum threat levels in this severe environment. The output voltage peaks are limited to 350V under maximum threat conditions for a 120V ac power line, thus providing adequate protection to vulnerable electronic equipment. The principle of operation and test performance data is discussed.

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function.

PubMed

Chang, Aram; Abderemane-Ali, Fayal; Hura, Greg L; Rossen, Nathan D; Gate, Rachel E; Minor, Daniel L

2018-02-21

Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

75 FR 8431 - Carbon Dioxide Fire Suppression Systems on Commercial Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... Fire Suppression Systems on Commercial Vessels; Proposed Rule #0;#0;Federal Register / Vol. 75 , No. 36... 1625-AB44 Carbon Dioxide Fire Suppression Systems on Commercial Vessels AGENCY: Coast Guard, DHS... for fire suppression systems on several classes of commercial vessels. The amendments would clarify...

Success Stories | NCI Technology Transfer Center | TTC

Cancer.gov

NIH’s world-class facilities, resources, and discoveries. Some of our partnerships have resulted in the commercialization of therapeutics, vaccines, diagnostics, medical devices and research tools that benefit patients worldwide. TTC is proud to share a few examples of our successful partnerships. | [google6f4cd5334ac394ab.html

Modeling the Voltage Dependence of Electrochemical Reactions at Solid-Solid and Solid-Liquid Interfaces in Batteries

NASA Astrophysics Data System (ADS)

Leung, Kevin

2015-03-01

Electrochemical reactions at electrode/electrolyte interfaces are critically dependent on the total electrochemical potential or voltage. In this presentation, we briefly review ab initio molecular dynamics (AIMD)-based estimate of voltages on graphite basal and edge planes, and then apply similar concepts to solid-solid interfaces relevant to lithium ion and Li-air batteries. Thin solid films on electrode surfaces, whether naturally occuring during power cycling (e.g., undesirable lithium carbonate on Li-air cathodes) or are artificially introduced, can undergo electrochemical reactions as the applied voltage varies. Here the onset of oxidation of lithium carbonate and other oxide thin films on model gold electrode surfaces is correlated with the electronic structure in the presence/absence of solvent molecules. Our predictions help determine whether oxidation first occurs at the electrode-thin film or electrolyte-thin film interface. Finally, we will critically compare the voltage estimate methodology used in the fuel cell community with the lithium cohesive energy calibration method broadly applied in the battery community, and discuss why they may yield different predictions. This work was supported by Nanostructures for Electrical Energy Storage (NEES), an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DESC0001160. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Deparment of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Comparison between the magnetic and transport critical current densities in high critical current density melt-textured yttrium barium copper-oxide

NASA Technical Reports Server (NTRS)

Gao, L.; Meng, R. L.; Xue, Y. Y.; Hor, P. H.; Chu, C. W.

1991-01-01

Using a recently developed pulsed critical current density (Jc) measuring system, the Jc of the high-Jc melt-textured YBa2Cu3O(7-delta) (Y123) bulk samples has been determined. I-V curves with a voltage resolution of 0.5 microV were obtained, and transport Jc's along the a-b plane as high as 7.2 x 10 to the 4th A/sq cm were extracted. These results are comparable to the values obtained magnetically. On the other hand, transport Jc along the c axis were found to be two orders of magnitude smaller, even though the magnetic Jc along the c axis is only about five times smaller than Jc along the a-b plane. It is suggested that for the high-temperature superconducting materials which are highly anisotropic, caution should be taken when using the nontransport magnetic methods to determine Jc.

Magneto-electronic properties and spin-resolved I-V curves of a Co/GeSe heterojunction diode: an ab initio study

NASA Astrophysics Data System (ADS)

Makinistian, Leonardo; Albanesi, Eduardo A.

2013-06-01

We present ab initio calculations of magnetoelectronic and transport properties of the interface of hcp Cobalt (001) and the intrinsic narrow-gap semiconductor germanium selenide (GeSe). Using a norm-conserving pseudopotentials scheme within DFT, we first model the interface with a supercell approach and focus on the spin-resolved densities of states and the magnetic moment (spin and orbital components) at the different atomic layers that form the device. We also report a series of cuts (perpendicular to the plane of the heterojunction) of the electronic and spin densities showing a slight magnetization of the first layers of the semiconductor. Finally, we model the device with a different scheme: using semiinfinite electrodes connected to the heterojunction. These latter calculations are based upon a nonequilibrium Green's function approach that allows us to explore the spin-resolved electronic transport under a bias voltage (spin-resolved I-V curves), revealing features of potential applicability in spintronics.

Time resolved native ion-mobility mass spectrometry to monitor dynamics of IgG4 Fab arm exchange and "bispecific" monoclonal antibody formation.

PubMed

Debaene, François; Wagner-Rousset, Elsa; Colas, Olivier; Ayoub, Daniel; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2013-10-15

Monoclonal antibodies (mAbs) and derivatives such as antibody-drug conjugates (ADC) and bispecific antibodies (bsAb), are the fastest growing class of human therapeutics. Most of the therapeutic antibodies currently on the market and in clinical trials are chimeric, humanized, and human immunoglobulin G1 (IgG1). An increasing number of IgG2s and IgG4s that have distinct structural and functional properties are also investigated to develop products that lack or have diminished antibody effector functions compared to IgG1. Importantly, wild type IgG4 has been shown to form half molecules (one heavy chain and one light chain) that lack interheavy chain disulfide bonds and form intrachain disulfide bonds. Moreover, IgG4 undergoes a process of Fab-arm exchange (FAE) in which the heavy chains of antibodies of different specificities can dissociate and recombine in bispecific antibodies both in vitro and in vivo. Here, native mass spectrometry (MS) and time-resolved traveling wave ion mobility MS (TWIM-MS) were used for the first time for online monitoring of FAE and bsAb formation using Hz6F4-2v3 and natalizumab, two humanized IgG4s which bind to human Junctional Adhesion Molecule-A (JAM-A) and alpha4 integrin, respectively. In addition, native MS analysis of bsAb/JAM-A immune complexes revealed that bsAb can bind up to two antigen molecules, confirming that the Hz6F4 family preferentially binds dimeric JAM-A. Our results illustrate how IM-MS can rapidly assess bsAb structural heterogeneity and be easily implemented into MS workflows for bsAb production follow up and bsAb/antigen complex characterization. Altogether, these results provide new MS-based methodologies for in-depth FAE and bsAb formation monitoring. Native MS and IM-MS will play an increasing role in next generation biopharmaceutical product characterization like bsAbs, antibody mixtures, and antibody-drug conjugates (ADC) as well as for biosimilar and biobetter antibodies.

Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahama, Y.; Ono, S.; Ishihara, K.

1990-01-01

The present study has examined a functional role of Ia molecules expressed on murine B cells in polyclonal B cell differentiation induced by lipopolysaccharide (LPS). Reverse, IgM PFC responses of unprimed B cells induced by LPS in the apparent absence of T cells and adherent accessory cells were markedly inhibited in a haplotype-specific manner by Fab monomer fragment of anti-class II (Ia) but not anti-class I MHC monoclonal antibody (mAb). However, the degree of inhibition of LPS responses of H-2-heterozygous F1 B cells expressing both parental I-A products by either one of anti-I-A mAb was at best half that ofmore » the parental B cells. Interestingly, when (B10 x B10.-BR)F1 (H-2b/k) B cells were fractionated into adherent and nonadherent populations by their ability to bind to parental B10 B cell monolayers, LPS responses of F1 B cells adherent to and nonadherent to the B10 B cell monolayers were selectively inhibited by anti-I-Ab and anti-I-Ak mAb, respectively. These results suggest that LPS-responsive F1 B cells comprise at least two separate populations with restriction specificity for only one of the parental I-A products expressed on B cells. In addition, it was demonstrated that the I-A-restriction specificity of LPS-responsive B cells is plastic and determined by H-2-genotype of bone marrow cells present during B cell ontogeny but not by that of radiation-resistant host elements. Namely, the LPS responses of B10-derived B cells from (B10 + B10.BR) (H-2b x H - 2k)F1 radiation bone marrow chimeras but not from B10 (H-2b x H-2k)F1 chimeras became sensitive to the inhibition of anti-I-Ak mAb in the presence of mitomycin C-treated I-Ak-positive B cells, supporting a notion of receptor-Ia molecules interactions rather than like-like interactions.« less

Simulation of Tripod Gaits for a Hexapod Underwater Walking Machine

DTIC Science & Technology

1993-06-01

AquarobotBody class H/ Subclass of RigidBody class fl 170 #iid~dKAQUAROBOTBODY # defint HAQUAROBOTBODY #include <stdio.h> #include *Lia*1.H" #include "AbRis4H...nulU&A4g parameters enuk heme returm (arcsegmnww flag); HI smuit finction ends here i/REVISED: .... /r.71TLE: seito i/INPUT: (x~y)body coordinates of a...kttacqt - foot[1D; d - (x ._inssrq* - fbot(On’x gusrcept - focttI~); todigace= -sqr(c + Y HI orientation we and heme II lieSep=*t izusectionto ten as

Research and Experiments on a Unipolar Capacitive Voltage Sensor

PubMed Central

Zhou, Qiang; He, Wei; Li, Songnong; Hou, Xingzhe

2015-01-01

Voltage sensors are an important part of the electric system. In service, traditional voltage sensors need to directly contact a high-voltage charged body. Sensors involve a large volume, complex insulation structures, and high design costs. Typically an iron core structure is adopted. As a result, ferromagnetic resonance can occur easily during practical application. Moreover, owing to the multilevel capacitor divider, the sensor cannot reflect the changes of measured voltage in time. Based on the electric field coupling principle, this paper designs a new voltage sensor; the unipolar structure design solves many problems of traditional voltage sensors like the great insulation design difficulty and high costs caused by grounding electrodes. A differential signal input structure is adopted for the detection circuit, which effectively restrains the influence of the common-mode interference signal. Through sensor modeling, simulation and calculations, the structural design of the sensor electrode was optimized, miniaturization of the sensor was realized, the voltage division ratio of the sensor was enhanced, and the phase difference of sensor measurement was weakened. The voltage sensor is applied to a single-phase voltage class line of 10 kV for testing. According to the test results, the designed sensor is able to meet the requirements of accurate and real-time measurement for voltage of the charged conductor as well as to provide a new method for electricity larceny prevention and on-line monitoring of the power grid in an electric system. Therefore, it can satisfy the development demands of the smart power grid. PMID:26307992

Prediction of a new class of half-metallic ferromagnets from first principles [A new class of half-metallic ferromagnets from first principles

DOE PAGES

Griffin, Sinead M.; Neaton, Jeffrey B.

2017-09-12

Half-metallic ferromagnetism (HMFM) occurs rarely in materials and yet offers great potential for spintronic devices. Recent experiments suggest a class of compounds with the `ThCrmore » $$_{2}$$Si$$_{2}$$' (122) structure -- isostructural and containing elements common with Fe pnictide-based superconductors -- can exhibit HMFM. Here we use $ab$ $initio$ density-functional theory calculations to understand the onset of half-metallicity in this family of materials and explain the appearance of ferromagnetism at a quantum critical point. We also predict new candidate materials with HMFM and high Curie temperatures through A-site alloying.« less

Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

PubMed Central

Mutoh, Hiroki; Mishina, Yukiko; Gallero-Salas, Yasir; Knöpfel, Thomas

2015-01-01

Traditional small molecule voltage sensitive dye indicators have been a powerful tool for monitoring large scale dynamics of neuronal activities but have several limitations including the lack of cell class specific targeting, invasiveness and difficulties in conducting longitudinal studies. Recent advances in the development of genetically-encoded voltage indicators have successfully overcome these limitations. Genetically-encoded voltage indicators (GEVIs) provide sufficient sensitivity to map cortical representations of sensory information and spontaneous network activities across cortical areas and different brain states. In this study, we directly compared the performance of a prototypic GEVI, VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD), RH1691, in terms of their ability to resolve mesoscopic scale cortical population responses. We used three synchronized CCD cameras to simultaneously record the dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691 fluorescence. The results show that VSFP2.3 offers more stable and less invasive recording conditions, while the signal-to-noise level and the response dynamics to sensory inputs are comparable to RH1691 recordings. PMID:25964738

Conduction Mechanisms in Multiferroic Multilayer BaTiO3/NiFe2O4/BaTiO3 Memristors

NASA Astrophysics Data System (ADS)

Samardzic, N.; Bajac, B.; Srdic, V. V.; Stojanovic, G. M.

2017-10-01

Memristive devices and materials are extensively studied as they offer diverse properties and applications in digital, analog and bio-inspired circuits. In this paper, we present an important class of memristors, multiferroic memristors, which are composed of multiferroic multilayer BaTiO3/NiFe2O4/BaTiO3 thin films, fabricated by a spin-coating deposition technique on platinized Si wafers. This cost-effective device shows symmetric and reproducible current-voltage characteristics for the actuating voltage amplitude of ±10 V. The origin of the conduction mechanism was investigated by measuring the electrical response in different voltage and temperature conditions. The results indicate the existence of two mechanisms: thermionic emission and Fowler-Nordheim tunnelling, which alternate with actuating voltage amplitude and operating temperature.

Tuning spin transport properties and molecular magnetoresistance through contact geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ulman, Kanchan; Narasimhan, Shobhana; Sheikh Saqr Laboratory, ICMS, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064

2014-01-28

Molecular spintronics seeks to unite the advantages of using organic molecules as nanoelectronic components, with the benefits of using spin as an additional degree of freedom. For technological applications, an important quantity is the molecular magnetoresistance. In this work, we show that this parameter is very sensitive to the contact geometry. To demonstrate this, we perform ab initio calculations, combining the non-equilibrium Green's function method with density functional theory, on a dithienylethene molecule placed between spin-polarized nickel leads of varying geometries. We find that, in general, the magnetoresistance is significantly higher when the contact is made to sharp tips thanmore » to flat surfaces. Interestingly, this holds true for both resonant and tunneling conduction regimes, i.e., when the molecule is in its “closed” and “open” conformations, respectively. We find that changing the lead geometry can increase the magnetoresistance by up to a factor of ∼5. We also introduce a simple model that, despite requiring minimal computational time, can recapture our ab initio results for the behavior of magnetoresistance as a function of bias voltage. This model requires as its input only the density of states on the anchoring atoms, at zero bias voltage. We also find that the non-resonant conductance in the open conformation of the molecule is significantly impacted by the lead geometry. As a result, the ratio of the current in the closed and open conformations can also be tuned by varying the geometry of the leads, and increased by ∼400%.« less

Low power arcjet thruster pulse ignition

NASA Technical Reports Server (NTRS)

Sarmiento, Charles J.; Gruber, Robert P.

1987-01-01

An investigation of the pulse ignition characteristics of a 1 kW class arcjet using an inductive energy storage pulse generator with a pulse width modulated power converter identified several thruster and pulse generator parameters that influence breakdown voltage including pulse generator rate of voltage rise. This work was conducted with an arcjet tested on hydrogen-nitrogen gas mixtures to simulate fully decomposed hydrazine. Over all ranges of thruster and pulser parameters investigated, the mean breakdown voltages varied from 1.4 to 2.7 kV. Ignition tests at elevated thruster temperatures under certain conditions revealed occasional breakdowns to thruster voltages higher than the power converter output voltage. These post breakdown discharges sometimes failed to transition to the lower voltage arc discharge mode and the thruster would not ignite. Under the same conditions, a transition to the arc mode would occur for a subsequent pulse and the thruster would ignite. An automated 11 600 cycle starting and transition to steady state test demonstrated ignition on the first pulse and required application of a second pulse only two times to initiate breakdown.

Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells.

PubMed

Srikrishna, G; Panneerselvam, K; Westphal, V; Abraham, V; Varki, A; Freeze, H H

2001-04-01

We recently showed that a class of novel carboxylated N:-glycans was constitutively expressed on endothelial cells. Activated, but not resting, neutrophils expressed binding sites for the novel glycans. We also showed that a mAb against these novel glycans (mAbGB3.1) inhibited leukocyte extravasation in a murine model of peritoneal inflammation. To identify molecules that mediated these interactions, we isolated binding proteins from bovine lung by their differential affinity for carboxylated or neutralized glycans. Two leukocyte calcium-binding proteins that bound in a carboxylate-dependent manner were identified as S100A8 and annexin I. An intact N terminus of annexin I and heteromeric assembly of S100A8 with S100A9 (another member of the S100 family) appeared necessary for this interaction. A mAb to S100A9 blocked neutrophil binding to immobilized carboxylated glycans. Purified human S100A8/A9 complex and recombinant human annexin I showed carboxylate-dependent binding to immobilized bovine lung carboxylated glycans and recognized a subset of mannose-labeled endothelial glycoproteins immunoprecipitated by mAbGB3.1. Saturable binding of S100A8/A9 complex to endothelial cells was also blocked by mAbGB3.1. These results suggest that the carboxylated glycans play important roles in leukocyte trafficking by interacting with proteins known to modulate extravasation.

Differential effects of antibiotic therapy on the structure and function of human gut microbiota.

PubMed

Pérez-Cobas, Ana Elena; Artacho, Alejandro; Knecht, Henrik; Ferrús, María Loreto; Friedrichs, Anette; Ott, Stephan J; Moya, Andrés; Latorre, Amparo; Gosalbes, María José

2013-01-01

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

X-band inverse class-F GaN internally-matched power amplifier

NASA Astrophysics Data System (ADS)

Zhao, Bo-Chao; Lu, Yang; Han, Wen-Zhe; Zheng, Jia-Xin; Zhang, Heng-Shuang; Ma, Pei-jun; Ma, Xiao-Hua; Hao, Yue

2016-09-01

An X-band inverse class-F power amplifier is realized by a 1-mm AlGaN/GaN high electron mobility transistor (HEMT). The intrinsic and parasitic components inside the transistor, especially output capacitor Cds, influence the harmonic impedance heavily at the X-band, so compensation design is used for meeting the harmonic condition of inverse class-F on the current source plane. Experiment results show that, in the continuous-wave mode, the power amplifier achieves 61.7% power added efficiency (PAE), which is 16.3% higher than the class-AB power amplifier realized by the same kind of HEMT. To the best of our knowledge, this is the first inverse class-F GaN internally-matched power amplifier, and the PAE is quite high at the X-band. Project supported by the National High Technology Research and Development Program of China (Grant No. 2015AA016801).

Exploring Partonic Structure of Hadrons Using ab initio Lattice QCD Calculations.

PubMed

Ma, Yan-Qing; Qiu, Jian-Wei

2018-01-12

Following our previous proposal, we construct a class of good "lattice cross sections" (LCSs), from which we can study the partonic structure of hadrons from ab initio lattice QCD calculations. These good LCSs, on the one hand, can be calculated directly in lattice QCD, and on the other hand, can be factorized into parton distribution functions (PDFs) with calculable coefficients, in the same way as QCD factorization for factorizable hadronic cross sections. PDFs could be extracted from QCD global analysis of the lattice QCD generated data of LCSs. We also show that the proposed functions for lattice QCD calculation of PDFs in the literature are special cases of these good LCSs.

Factors Associated with Success in College Calculus II

ERIC Educational Resources Information Center

Rosasco, Margaret E.

2013-01-01

Students are entering college having earned credit for college Calculus 1 based on their scores on the College Board's Advanced Placement (AP) Calculus AB exam. Despite being granted credit for college Calculus 1, it is unclear whether these students are adequately prepared for college Calculus 2. College calculus classes are often taught from a…

Mass spectrometry-based method of detecting and distinguishing type 1 and type 2 Shiga-like toxins in human serum

USDA-ARS?s Scientific Manuscript database

Shiga-like toxins (verotoxins) are a class of AB5 holotoxins that are responsible for the virulence associated with bacterial pathogens such as Shigella dysenteriae, shigatoxigenic and enterohemorrhagic strains of Escherichia coli (STEC and EHEC), and some Enterobacter strains. The actual expression...

26 CFR 31.3121(c)-1 - Included and excluded services.

Code of Federal Regulations, 2011 CFR

2011-04-01

... enrolled and is regularly attending classes at a university, to perform domestic service for the club and to keep the club's books. The domestic services performed by D for the AB Club do not constitute employment, and his services as the club's bookkeeper constitute employment. D receives a payment at the end...

26 CFR 31.3121(c)-1 - Included and excluded services.

Code of Federal Regulations, 2013 CFR

2013-04-01

... enrolled and is regularly attending classes at a university, to perform domestic service for the club and to keep the club's books. The domestic services performed by D for the AB Club do not constitute employment, and his services as the club's bookkeeper constitute employment. D receives a payment at the end...

26 CFR 31.3121(c)-1 - Included and excluded services.

Code of Federal Regulations, 2010 CFR

2010-04-01

... enrolled and is regularly attending classes at a university, to perform domestic service for the club and to keep the club's books. The domestic services performed by D for the AB Club do not constitute employment, and his services as the club's bookkeeper constitute employment. D receives a payment at the end...

26 CFR 31.3121(c)-1 - Included and excluded services.

Code of Federal Regulations, 2014 CFR

2014-04-01

... enrolled and is regularly attending classes at a university, to perform domestic service for the club and to keep the club's books. The domestic services performed by D for the AB Club do not constitute employment, and his services as the club's bookkeeper constitute employment. D receives a payment at the end...

26 CFR 31.3121(c)-1 - Included and excluded services.

Code of Federal Regulations, 2012 CFR

2012-04-01

... enrolled and is regularly attending classes at a university, to perform domestic service for the club and to keep the club's books. The domestic services performed by D for the AB Club do not constitute employment, and his services as the club's bookkeeper constitute employment. D receives a payment at the end...

Single-molecule fluorimetry and gating currents inspire an improved optical voltage indicator

PubMed Central

Treger, Jeremy S; Priest, Michael F; Bezanilla, Francisco

2015-01-01

Voltage-sensing domains (VSDs) underlie the movement of voltage-gated ion channels, as well as the voltage-sensitive fluorescent responses observed from a common class of genetically encoded voltage indicators (GEVIs). Despite the widespread use and potential utility of these GEVIs, the biophysical underpinnings of the relationship between VSD movement and fluorophore response remain unclear. We investigated the recently developed GEVI ArcLight, and its close variant Arclight', at both the single-molecule and macroscopic levels to better understand their characteristics and mechanisms of activity. These studies revealed a number of previously unobserved features of ArcLight's behavior, including millisecond-scale fluorescence fluctuations in single molecules as well as a previously unreported delay prior to macroscopic fluorescence onset. Finally, these mechanistic insights allowed us to improve the optical response of ArcLight to fast or repetitive pulses with the development of ArcLightning, a novel GEVI with improved kinetics. DOI: http://dx.doi.org/10.7554/eLife.10482.001 PMID:26599732

Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.

PubMed

Hong, Liang; Pathak, Medha M; Kim, Iris H; Ta, Dennis; Tombola, Francesco

2013-01-23

Voltage-gated sodium, potassium, and calcium channels are made of a pore domain (PD) controlled by four voltage-sensing domains (VSDs). The PD contains the ion permeation pathway and the activation gate located on the intracellular side of the membrane. A large number of small molecules are known to inhibit the PD by acting as open channel blockers. The voltage-gated proton channel Hv1 is made of two VSDs and lacks the PD. The location of the activation gate in the VSD is unknown and open channel blockers for VSDs have not yet been identified. Here, we describe a class of small molecules which act as open channel blockers on the Hv1 VSD and find that a highly conserved phenylalanine in the charge transfer center of the VSD plays a key role in blocker binding. We then use one of the blockers to show that Hv1 contains two intracellular and allosterically coupled gates. Copyright © 2013 Elsevier Inc. All rights reserved.

Ultralow-voltage design of graphene PN junction quantum reflective switch transistor

NASA Astrophysics Data System (ADS)

Sohier, Thibault; Yu, Bin

2011-05-01

We propose the concept of a graphene-based quantum reflective switch (QRS) for low-power logic application. With the unique electronic properties of graphene, a tilted PN junction is used to implement logic switch function with 103 ON/OFF ratio. Carriers are reflected on an electrostatically induced potential step with strong incidence-angle-dependency due to the widening of classically forbidden energies. Optimized design of the device for ultralow-voltage operating has been conducted. The device is constantly ON with a turning-off gate voltage around 180 mV using thin HfO2 as the gate dielectric. The results suggest a class of logic switch devices operating with micropower dissipation.

1.8V Operation Power Amplifier IC for Bluetooth Class 1 Utilizing p+-GaAs Gate Hetero-Junction FET

NASA Astrophysics Data System (ADS)

Harima, Fumio; Bito, Yasunori; Takahashi, Hidemasa; Iwata, Naotaka

We have developed a power amplifier IC for Bluetooth Class 1 operating at single low voltage of 1.8V for both control and drain voltages. We can realize it due to fully enhancement-mode hetero-junction FETs utilizing a re-grown p+-GaAs gate technology. The power amplifier is a highly compact design as a small package of 1.5mm×1.5mm×0.4mm with fully integrated gain control and shutdown functions. An impressive power added efficiency of 52% at an output power of 20dBm is achieved with an associated gain of 22dB. Also, sufficiently low leakage current of 0.25μA at 27°C is exhibited, which is comparable to conventional HBT power amplifiers.

Site-Specific Recombination at XerC/D Sites Mediates the Formation and Resolution of Plasmid Co-integrates Carrying a blaOXA-58- and TnaphA6-Resistance Module in Acinetobacter baumannii

PubMed Central

Cameranesi, María M.; Morán-Barrio, Jorgelina; Limansky, Adriana S.; Repizo, Guillermo D.; Viale, Alejandro M.

2018-01-01

Members of the genus Acinetobacter possess distinct plasmid types which provide effective platforms for the acquisition, evolution, and dissemination of antimicrobial resistance structures. Many plasmid-borne resistance structures are bordered by short DNA sequences providing potential recognition sites for the host XerC and XerD site-specific tyrosine recombinases (XerC/D-like sites). However, whether these sites are active in recombination and how they assist the mobilization of associated resistance structures is still poorly understood. Here we characterized the plasmids carried by Acinetobacter baumannii Ab242, a multidrug-resistant clinical strain belonging to the ST104 (Oxford scheme) which produces an OXA-58 carbapenem-hydrolyzing class-D β-lactamase (CHDL). Plasmid sequencing and characterization of replication, stability, and adaptive modules revealed the presence in Ab242 of three novel plasmids lacking self-transferability functions which were designated pAb242_9, pAb242_12, and pAb242_25, respectively. Among them, only pAb242_25 was found to carry an adaptive module encompassing an ISAba825-blaOXA-58 arrangement accompanied by a TnaphA6 transposon, the whole structure conferring simultaneous resistance to carbapenems and aminoglycosides. Ab242 plasmids harbor several XerC/D-like sites, with most sites found in pAb242_25 located in the vicinity or within the adaptive module described above. Electrotransformation of susceptible A. nosocomialis cells with Ab242 plasmids followed by imipenem selection indicated that the transforming plasmid form was a co-integrate resulting from the fusion of pAb242_25 and pAb242_12. Further characterization by cloning and sequencing studies indicated that a XerC/D site in pAb242_25 and another in pAb242_12 provided the active sister pair for the inter-molecular site-specific recombination reaction mediating the fusion of these two plasmids. Moreover, the resulting co-integrate was found also to undergo intra-molecular resolution at the new pair of XerC/D sites generated during fusion thus regenerating the original pAb242_25 and pAb242_12 plasmids. These observations provide the first evidence indicating that XerC/D-like sites in A. baumannii plasmids can provide active pairs for site-specific recombination mediating inter-molecular fusions and intra-molecular resolutions. The overall results shed light on the evolutionary dynamics of A. baumannii plasmids and the underlying mechanisms of dissemination of genetic structures responsible for carbapenem and other antibiotics resistance among the Acinetobacter clinical population. PMID:29434581

Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain.

PubMed

Mishina, Yukiko; Mutoh, Hiroki; Song, Chenchen; Knöpfel, Thomas

2014-01-01

Deciphering how the brain generates cognitive function from patterns of electrical signals is one of the ultimate challenges in neuroscience. To this end, it would be highly desirable to monitor the activities of very large numbers of neurons while an animal engages in complex behaviors. Optical imaging of electrical activity using genetically encoded voltage indicators (GEVIs) has the potential to meet this challenge. Currently prevalent GEVIs are based on the voltage-sensitive fluorescent protein (VSFP) prototypical design or on the voltage-dependent state transitions of microbial opsins. We recently introduced a new VSFP design in which the voltage-sensing domain (VSD) is sandwiched between a fluorescence resonance energy transfer pair of fluorescent proteins (termed VSFP-Butterflies) and also demonstrated a series of chimeric VSD in which portions of the VSD of Ciona intestinalis voltage-sensitive phosphatase are substituted by homologous portions of a voltage-gated potassium channel subunit. These chimeric VSD had faster sensing kinetics than that of the native Ci-VSD. Here, we describe a new set of VSFPs that combine chimeric VSD with the Butterfly structure. We show that these chimeric VSFP-Butterflies can report membrane voltage oscillations of up to 200 Hz in cultured cells and report sensory evoked cortical population responses in living mice. This class of GEVIs may be suitable for imaging of brain rhythms in behaving mammalians.

Gates to Gregg High Voltage Transmission Line Study. [California

NASA Technical Reports Server (NTRS)

Bergis, V.; Maw, K.; Newland, W.; Sinnott, D.; Thornbury, G.; Easterwood, P.; Bonderud, J.

1982-01-01

The usefulness of LANDSAT data in the planning of transmission line routes was assessed. LANDSAT digital data and image processing techniques, specifically a multi-date supervised classification aproach, were used to develop a land cover map for an agricultural area near Fresno, California. Twenty-six land cover classes were identified, of which twenty classes were agricultural crops. High classification accuracies (greater than 80%) were attained for several classes, including cotton, grain, and vineyards. The primary products generated were 1:24,000, 1:100,000 and 1:250,000 scale maps of the classification and acreage summaries for all land cover classes within four alternate transmission line routes.

An update on the role of daratumumab in the treatment of multiple myeloma

PubMed Central

Costello, Caitlin

2016-01-01

Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials. The general tolerability of mAbs has allowed for widespread investigation and use of DARA among a variety of MM patients, however their use requires special consideration. Infusion-related reactions (IRRs), interference with blood compatibility assays and response assessments are all unique factors related to the use of DARA. This review provides an update of the results from the DARA clinical trials conducted to date, its future plans for investigation, and practical management considerations for the use of DARA in daily practice. PMID:28042457

Characterization of a new HLA-B allele (B{sup *}3702) generated by an intronic recombination event

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santos, S.; Vicario, J.L.; Merino, J.L.

1996-12-31

Routine serological HLA typing of s Syrian family revealed a Bw4-associated HLA-B blank antigen showing Mendelian segregation together with the haplotype A1, Cw2, DR11, DQ7 (a father and one of his children, cells NO. 5958641 and No. 1958125). A more extensive serological analysis was done by using additional polyclonal and monoclonal antibodies (mAb; One-Lambda BL-60 and LM172 plates) as well as the 12th International Workshop class I mAb plate. Both cells showed no conclusive typing reactions with sera towards HLA-B27 and HLA-B37 antigens. Two mAb, PAMELA (27,44,38) and FAY (13,27,37,47), were able to recognize this antigen. The great majority ofmore » polyclonal reagents against B37 showed negative reactions, while weak results were frequently observed with anti-B27 allosera. 8 refs., 1 fig., 1 tab.« less

Performance analysis of cascaded h-bridge multilevel inverter using mixed switching frequency with various dc-link voltages

NASA Astrophysics Data System (ADS)

Citarsa, I. B. F.; Satiawan, I. N. W.; Wiryajati, I. K.; Supriono

2016-01-01

Multilevel inverters have been widely used in many applications since the technology is advantageous to increase the converter capability as well as to improve the output voltage quality. According to the applied switching frequency, multilevel modulations can be subdivided into three classes, i.e: fundamental switching frequency, high switching frequency and mixed switching frequency. This paper investigates the performance of cascaded H-bridge (CHB) multilevel inverter that is modulated using mixed switching frequency (MSF) PWM with various dc-link voltage ratios. The simulation results show the nearly sinusoidal load output voltages are successfully achieved. It is revealed that there is improvement in output voltages quality in terms of THD and low-order harmonics content. The CHB inverter that is modulated using MSF PWM with equal dc-link voltage ratio (½ Vdc: ½ Vdc) produces output voltage with the lowest low-order harmonics (less than 1% of fundamental) while the CHB inverter that is modulated using MSF PWM with un-equal dc-link voltage ratio (2/3 Vdc: 1/3 Vdc) produces a 7-level output voltage with the lowest THD (16.31%) compared to the other PWM methods. Improvement of the output voltage quality here is also in line with improvement of the number of available levels provided in the output voltage. Here only 2 cells H-bridge inverter (contain 8 switches) are needed to produce a 7- level output voltage, while in the conventional CHB inverter at least 3 cells of H-bridge inverter (contain 12 switches) are needed to produce a 7-level output voltage. Hence it is valuable in term of saving number of component.

Role of the Local Anesthetic Receptor in the State-Dependent Inhibition of Voltage-Gated Sodium Channels by the Insecticide Metaflumizone

PubMed Central

von Stein, Richard T.

2012-01-01

Sodium channel inhibitor (SCI) insecticides selectively target voltage-gated sodium (Nav) channels in the slow-inactivated state by binding at or near the local anesthetic receptor within the sodium channel pore. Metaflumizone is a new insecticide for the treatment of fleas on domesticated pets and has recently been reported to block insect sodium channels in the slow-inactivated state, thereby implying that it is also a member of the SCI class. Using the two-electrode voltage-clamp technique, we examined metaflumizone inhibition of rat Nav1.4 sodium channels expressed in Xenopus laevis oocytes. Metaflumizone selectively inhibited Nav1.4 channels at potentials that promoted slow inactivation and shifted the voltage dependence of slow inactivation in the direction of hyperpolarization. Metaflumizone perfusion at a hyperpolarized holding potential also shifted the conductance-voltage curve for activation in the direction of depolarization and antagonized use-dependent lidocaine inhibition of fast-inactivated sodium channels, actions not previously observed with other SCI insecticides. We expressed mutated Nav1.4/F1579A and Nav1.4/Y1586A channels to investigate whether metaflumizone shares the domain IV segment S6 (DIV-S6) binding determinants identified for other SCI insecticides. Consistent with previous investigations of SCI insecticides on rat Nav1.4 channels, the F1579A mutation reduced sensitivity to block by metaflumizone, whereas the Y1586A mutation paradoxically increased the sensitivity to metaflumizone. We conclude that metaflumizone selectively inhibits slow-inactivated Nav1.4 channels and shares DIV-S6 binding determinants with other SCI insecticides and therapeutic drugs. However, our results suggest that metaflumizone interacts with resting and fast-inactivated channels in a manner that is distinct from other compounds in this insecticide class. PMID:22127519

Structures of closed and open states of a voltage-gated sodium channel

PubMed Central

Lenaeus, Michael J.; Gamal El-Din, Tamer M.; Ramanadane, Karthik; Pomès, Régis; Zheng, Ning; Catterall, William A.

2017-01-01

Bacterial voltage-gated sodium channels (BacNavs) serve as models of their vertebrate counterparts. BacNavs contain conserved voltage-sensing and pore-forming domains, but they are homotetramers of four identical subunits, rather than pseudotetramers of four homologous domains. Here, we present structures of two NaVAb mutants that capture tightly closed and open states at a resolution of 2.8–3.2 Å. Introduction of two humanizing mutations in the S6 segment (NaVAb/FY: T206F and V213Y) generates a persistently closed form of the activation gate in which the intracellular ends of the four S6 segments are drawn tightly together to block ion permeation completely. This construct also revealed the complete structure of the four-helix bundle that forms the C-terminal domain. In contrast, truncation of the C-terminal 40 residues in NavAb/1–226 captures the activation gate in an open conformation, revealing the open state of a BacNav with intact voltage sensors. Comparing these structures illustrates the full range of motion of the activation gate, from closed with its orifice fully occluded to open with an orifice of ∼10 Å. Molecular dynamics and free-energy simulations confirm designation of NaVAb/1–226 as an open state that allows permeation of hydrated Na+, and these results also support a hydrophobic gating mechanism for control of ion permeation. These two structures allow completion of a closed–open–inactivated conformational cycle in a single voltage-gated sodium channel and give insight into the structural basis for state-dependent binding of sodium channel-blocking drugs. PMID:28348242

Size dependent tunnel diode effects in gold tipped CdSe nanodumbbells.

PubMed

Saraf, Deepashri; Kumar, Ashok; Kanhere, Dilip; Kshirsagar, Anjali

2017-02-07

We report simulation results for scanning tunneling spectroscopy of gold-tipped CdSe nanodumbbells of lengths ∼27 Å and ∼78 Å. Present results are based on Bardeen, Tersoff, and Hamann formalism that takes inputs from ab initio calculations. For the shorter nanodumbbell, the current-voltage curves reveal negative differential conductance, the characteristic of a tunnel diode. This behaviour is attributed to highly localized metal induced gap states that rapidly decay towards the center of the nanodumbbell leading to suppression in tunneling. In the longer nanodumbbell, these gap states are absent in the central region, as a consequence of which zero tunneling current is observed in that region. The overall current-voltage characteristics for this nanodumbbell are observed to be largely linear near the metal-semiconductor interface and become rectifying at the central region, the nature being similar to its parent nanorod. The cross-sectional heights of these nanodumbbells also show bias-dependence where we begin to observe giant Stark effect features in the semiconducting central region of the longer nanodumbbell.

The fluorescent treponemal antibody-absorption (FTA-ABS) test for syphilis.

PubMed

Hunter, E F

1975-01-01

The FTA test was developed at a time when immunofluorescence procedures were not well-defined. Through technique control and research, a modification of the FTA test, the FTA-ABS, has attained a position as one of the leading treponemal tests to confirm the reagin tests for syphilis. In this review of the FTA-ABS test, attention has been focused on reagent development, with the anticipation that reagent standardization may soon become a reality. The T. pallidum antigen obtained by extracting infected rabbit testicular tissue has evolved from a preparation in which the treponemes remained in the initial extracting fluid to a reagent that can be free of rabbit tissue and globulin. These washed antigen preparations improve visibility of the treponemes on the microscope slide, reduce background fluorescence, and reduce or prevent from occurring nonspecific reactions that are a result of tissue and globulin components. Both washed and nonwashed antigens are available commercially, and, to date, little differentiation has appeared on the product label. The predominant immunoglobulin that reacts with T. pallidum in the indirect fluorescent antibody tests appears to be IgG. This is the major immunoglobulin detected in the FTA-ABS test. IgM, although increased in early syphilis, is also increased in other clinical conditions. Several reports suggest that adult IgM detection in the present FTA-ABS test would be nonspecific. Until specific IgM antibody in adult syphilis can be detected without a risk to test specificity, the conjugate for the FTA-ABS test should continue to be an anti-IgG reagent. Class-specific, anti-IgG reagents are more expensive than other reagents; however, their use may eliminate the problem of nonspecificity resulting from IgM detection. Additionally, micromethods can be used to reduce cost, and this possibility should be investigated. The sorbent that contains an antigen to the Reiter treponeme may or may not specifically absorb the reactivity that occurs in normal sera; certainly, there are questionable aspects about this reagent. Group antibodies not related to Reiter treponemes may be responsible for some nonspecific reactivity; additionally, antiglobulin factors have been reported to participate in the reaction. Antigens free of rabbit serum factors and class-specific, antiimmunoglobulin reagents are available, and may lead to a better understanding of nonspecific reactions. These reagents should allow resolution of the possible multiplicity of reactivity. In this interim period, the sorbent, with its possible nonspecific nature, appears to maintain a biological balance between natural or group and immune antibodies when used to detect IgG antibody.

Computational understanding of Li-ion batteries

NASA Astrophysics Data System (ADS)

Urban, Alexander; Seo, Dong-Hwa; Ceder, Gerbrand

2016-03-01

Over the last two decades, computational methods have made tremendous advances, and today many key properties of lithium-ion batteries can be accurately predicted by first principles calculations. For this reason, computations have become a cornerstone of battery-related research by providing insight into fundamental processes that are not otherwise accessible, such as ionic diffusion mechanisms and electronic structure effects, as well as a quantitative comparison with experimental results. The aim of this review is to provide an overview of state-of-the-art ab initio approaches for the modelling of battery materials. We consider techniques for the computation of equilibrium cell voltages, 0-Kelvin and finite-temperature voltage profiles, ionic mobility and thermal and electrolyte stability. The strengths and weaknesses of different electronic structure methods, such as DFT+U and hybrid functionals, are discussed in the context of voltage and phase diagram predictions, and we review the merits of lattice models for the evaluation of finite-temperature thermodynamics and kinetics. With such a complete set of methods at hand, first principles calculations of ordered, crystalline solids, i.e., of most electrode materials and solid electrolytes, have become reliable and quantitative. However, the description of molecular materials and disordered or amorphous phases remains an important challenge. We highlight recent exciting progress in this area, especially regarding the modelling of organic electrolytes and solid-electrolyte interfaces.

Investigation of sodium insertion–extraction in olivine Na x FePO 4 (0 ≤ x ≤ 1) using first-principles calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saracibar, A.; Carrasco, J.; Saurel, D.

Olivine NaFePO4 has recently attracted the attention of the scientific community as a promising cathode material for Na-ion batteries. In this work we combine density functional theory (DFT) calculations and high resolution synchrotron X-ray diffraction (HRXRD) experiments to study the phase stability of NaxFePO4 along the whole range of sodium compositions (0 ≤ x ≤ 1). DFT calculations reveal the existence of two intermediate structures governing the phase stability at x = 2/3 and x = 5/6. This is in contrast to isostructural LiFePO4, which is a broadly used cathode in Li-ion batteries. Na2/3FePO4 and Na5/6FePO4 ground states both alignmore » vacancies diagonally within the ab plane, coupled to a Fe2+/Fe3+ alignment. HRXRD data for NaxFePO4 (2/3 < x < 1) materials show common superstructure reflections up to x = 5/6 within the studied compositions. The computed intercalation voltage profile shows a voltage difference of 0.16 V between NaFePO4 and Na2/3FePO4 in agreement with the voltage discontinuity observed experimentally during electrochemical insertion.« less

Unconventional irreversible structural changes in a high-voltage Li–Mn-rich oxide for lithium-ion battery cathodes

DOE PAGES

Mohanty, Debasish; Sefat, Athena S.; Payzant, E. Andrew; ...

2015-02-19

Making all-electric vehicles (EVs) commonplace in transportation applications will require affordable high-power and high-energy-density lithium-ion batteries (LIBs). The quest for suitable cathode materials to meet this end has currently plateaued with the discovery of high-voltage (≥4.7 V vs. Li +), high capacity (~250 mAh/g) lithium–manganese-rich (LMR) layered composite oxides. In spite of the promise of LMR oxides in high-energy-density LIBs, an irreversible structural change has been identified in this work that is governed by the formation of a ‘permanent’ spin-glass type magnetically frustrated phase indicating a dominant AB 2O 4 (A = Li, B = Mn) type spinel after amore » short-term lithium deintercalation (charging) and intercalation (discharging) process. Furthermore, reduction of transition metal (Mn) ions from the 4+ state (pristine LMR) to 3+ (cycled LMR), which alters the intercalation redox chemistry and suggests the presence of ‘unfilled’ lithium vacancies and/or oxygen vacancies in the lattice after cycling, has presented a major stumbling block. Finally, these situations result in both loss of capacity and fading of the voltage profile, and these combined effects significantly reduce the high energy density over even short-term cycling.« less

The Ecological Domain of Warfare

DTIC Science & Technology

2004-06-01

of military performance in terms of e.g., unpredictability, nonlinearity and self organized criticality. [4] The issues of complex interactions...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Kockums AB,SE-371 82 Karlskrona,Sweden, , 8. PERFORMING ORGANIZATION REPORT...by the architechture for Open Computational Systems itself [Alberts & Hayes (2003)] Author: Jens-Olof Lindh, Security class: UNCLASSIFIED Status

Modeling of Stability of Electrostatic and Magnetostatic Systems

DTIC Science & Technology

2017-06-01

unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Electromagnetic systems undergo a variety of different instabilities. A broad class of those...15. SUBJECT TERMS electromagnetism , morphological instabilities, computational algorithm, gradient minimization, morphology patterns, motion by mean...Nordmark AB. Magnetic field and current are zero inside ideal conductors. Prog Electromagn Res B. 2011(27):187–212. 4. Stratton JA. Electromagnetic theory

46 CFR 58.03-1 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Northchase Drive, Houston, TX 77060. (1) Rules for Building and Classing Steel Vessels, Part 4 Vessel Systems and Machinery (2003) (”ABS Steel Vessel Rules”), 58.01-5; 58.05-1; 58.10-15; 58.20-5; 58.25-5; and (2... 193M-98a, Standard Specification for Alloy-Steel and Stainless Steel Bolting Materials for High...

46 CFR 58.03-1 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., Houston, TX 77060. (1) Rules for Building and Classing Steel Vessels, Part 4 Vessel Systems and Machinery (2003) (”ABS Steel Vessel Rules”), 58.01-5; 58.05-1; 58.10-15; 58.20-5; 58.25-5; and (2) [Reserved] (d... 193M-98a, Standard Specification for Alloy-Steel and Stainless Steel Bolting Materials for High...

46 CFR 58.03-1 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., Houston, TX 77060. (1) Rules for Building and Classing Steel Vessels, Part 4 Vessel Systems and Machinery (2003) (”ABS Steel Vessel Rules”), 58.01-5; 58.05-1; 58.10-15; 58.20-5; 58.25-5; and (2) [Reserved] (d... 193M-98a, Standard Specification for Alloy-Steel and Stainless Steel Bolting Materials for High...

A universal procedure for evaluation and application of surge-protective devices

NASA Technical Reports Server (NTRS)

1980-01-01

The source, nature, and frequency of occurrence of transients must be identified and a representative standard test wave chosen for proof testing. The performance of candidate suppressor devices then can be evaluated against the withstand goals set for the equipment. The various suppressors divide into two classes of generic behavior. The key to a universal procedure for evaluating both classes lies in representing transients as quasi-current sources of defined current impulse duration. The available surge current is established by the Thevenin equivalent transient voltage and source impedance. A load line drawn on the V-I characteristic graph of the suppressor quickly determines the clamping voltage and peak current. These values then can be compared to the requirement. The deposited energy and average power dissipation for multiple transients also can be calculated. The method is illustrated with a design example for motor vehicle alternator load dump suppression.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdellahi, Aziz; Urban, Alexander; Dacek, Stephen

Cation disorder is a phenomenon that is becoming increasingly important for the design of high-energy lithium transition metal oxide cathodes (LiMO 2) for Li-ion batteries. Disordered Li-excess rocksalts have recently been shown to achieve high reversible capacity, while in operando cation disorder has been observed in a large class of ordered compounds. The voltage slope (dV/dx u )is a critical quantity for the design of cation-disordered rocksalts, as it controls the Li capacity accessible at voltages below the stability limit of the electrolyte (~4.5-4.7 V). In this study, we develop a lattice model based on first principles to understand andmore » quantify the voltage slope of cation-disordered LiMO 2. We show that cation disorder increases the voltage slope of Li transition metal oxides by creating a statistical distribution of transition metal environments around Li sites, as well as by allowing Li occupation of highvoltage tetrahedral sites. We further demonstrate that the voltage slope increase upon disorder is generally smaller for highvoltage transition metals than for low-voltage transition metals due to a more effective screening of Li-M interactions by oxygen electrons. Short-range order in practical disordered compounds is found to further mitigate the voltage slope increase upon disorder. In conclusion, our analysis shows that the additional high-voltage tetrahedral capacity induced by disorder is smaller in Liexcess compounds than in stoichiometric LiMO 2 compounds.« less

Electronic voltage and current transformers testing device.

PubMed

Pan, Feng; Chen, Ruimin; Xiao, Yong; Sun, Weiming

2012-01-01

A method for testing electronic instrument transformers is described, including electronic voltage and current transformers (EVTs, ECTs) with both analog and digital outputs. A testing device prototype is developed. It is based on digital signal processing of the signals that are measured at the secondary outputs of the tested transformer and the reference transformer when the same excitation signal is fed to their primaries. The test that estimates the performance of the prototype has been carried out at the National Centre for High Voltage Measurement and the prototype is approved for testing transformers with precision class up to 0.2 at the industrial frequency (50 Hz or 60 Hz). The device is suitable for on-site testing due to its high accuracy, simple structure and low-cost hardware.

Mixed polyanion glass cathodes: Glass-state conversion reactions

DOE PAGES

Kercher, Andrew K.; Kolopus, James A.; Carroll, Kyler; ...

2015-11-10

Mixed polyanion (MP) glasses can undergo glass-state conversion (GSC) reactions to provide an alternate class of high-capacity cathode materials. GSC reactions have been demonstrated in phosphate/vanadate glasses with Ag, Co, Cu, Fe, and Ni cations. These MP glasses provided high capacity and good high power performance, but suffer from moderate voltages, large voltage hysteresis, and significant capacity fade with cycling. Details of the GSC reaction have been revealed by x-ray absorption spectroscopy, electron microscopy, and energy dispersive x-ray spectroscopy of ex situ cathodes at key states of charge. Using the Open Quantum Materials Database (OQMD), a computational thermodynamic model hasmore » been developed to predict the near-equilibrium voltages of glass-state conversion reactions in MP glasses.« less

International Comparison Test in Asia-Pacific Region for Impulse Voltage Measurements

NASA Astrophysics Data System (ADS)

Wakimoto, Takayuki; Ishii, Masaru; Goshima, Hisashi; Hino, Etsuhiro; Shimizu, Hiroyuki; Li, Yi; Ik-Soo, Kim

The national standard class divider for the lightning impulse voltage measurements in Japan was developed in 1998. After three years, the standard impulse voltage calibrator was manufactured, too. These standard equipment are used as an industrial standard, and the performance had been evaluated annually supported by Ministry of Economy, Trade and Industry (METI). The standard impulse measuring system including the standard divider participated in the worldwide comparison test and its good performance was confirmed in 1999. Another international comparison test was carried out among three countries in the Asia-Pacific region in 2004 again and the standard measuring system participated in the test. In this paper, the details and the results of the international comparison tests in 2004 are described.

Mixed isotype class II antigen expression. A novel class II molecule is expressed on a murine B cell lymphoma

PubMed Central

1989-01-01

The structures of Ia molecules expressed by two BALB/c B cell lymphoma lines, A20-1.11 (A20) and 2PK3, were analyzed in an effort to explain the differences in antigen-presenting capacity displayed by these cells. Alloreactive T cell hybridomas specific for I-Ad and antigen- specific, I-Ad-restricted T cells responded well to A20 as the APC. The same alloreactive T cell hybridomas responded weakly or not at all to 2PK3 and the responses of the antigen-specific, I-Ad-restricted T cells were consistently lower to antigen presented by 2PK3 as compared with A20. T cells restricted to I-Ed responded equally well to either A20 or 2PK3 as APC. Additionally 2PK3, but not A20, stimulated a strong syngeneic mixed lymphocyte response. Structural analyses of the Ia antigens revealed that I-A and I-E molecules were expressed by A20, whereas an I-E and a novel I-A-like molecule were expressed by 2PK3. The novel class II molecule was affinity purified from 2PK3 cells using an mAb specific for Ad beta (MK-D6), and this molecule was subsequently shown by an RIA to react with an E alpha-specific mAb (14-4-4S) as well. Chain-specific polyclonal antisera raised against I-A and I-E alpha and beta chains indicated that the 2PK3 "I-A" alpha chain reacted in immunoblot with E alpha-specific and not A alpha-specific antisera, whereas the beta chain reacted with A beta- and not E beta-specific antisera. Peptide map and partial amino acid sequence analyses indicated that the "I-A" molecule expressed by 2PK3 represented a mixed isotype structure resulting from the pairing of Ed alpha with Ad beta. By immunofluorescence staining analysis, 2PK3 did not react with an mAb specific for Ad alpha. 2PK3 was capable of limited antigen presentation through the mixed isotype molecule to I-Ad-restricted OVA-specific T cell hybridomas, although the responses induced were low compared with presentation through I-A on A20. Previous descriptions of the expression of mixed isotype class II molecules in the mouse have resulted primarily from DNA-mediated gene transfer experiments. The results presented indicate that a mixed isotype class II molecule can be expressed naturally. PMID:2647893

Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.

PubMed

Kostenko, L; Kjer-Nielsen, L; Nicholson, I; Hudson, F; Lucas, A; Foley, B; Chen, K; Lynch, K; Nguyen, J; Wu, A H B; Tait, B D; Holdsworth, R; Mallal, S; Rossjohn, J; Bharadwaj, M; McCluskey, J

2011-07-01

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol. © 2011 John Wiley & Sons A/S.

Understanding the Effect of Cation Disorder on the Voltage Profile of Lithium Transition-Metal Oxides

DOE PAGES

Abdellahi, Aziz; Urban, Alexander; Dacek, Stephen; ...

2016-07-13

Cation disorder is a phenomenon that is becoming increasingly important for the design of high-energy lithium transition metal oxide cathodes (LiMO 2) for Li-ion batteries. Disordered Li-excess rocksalts have recently been shown to achieve high reversible capacity, while in operando cation disorder has been observed in a large class of ordered compounds. The voltage slope (dV/dx u )is a critical quantity for the design of cation-disordered rocksalts, as it controls the Li capacity accessible at voltages below the stability limit of the electrolyte (~4.5-4.7 V). In this study, we develop a lattice model based on first principles to understand andmore » quantify the voltage slope of cation-disordered LiMO 2. We show that cation disorder increases the voltage slope of Li transition metal oxides by creating a statistical distribution of transition metal environments around Li sites, as well as by allowing Li occupation of highvoltage tetrahedral sites. We further demonstrate that the voltage slope increase upon disorder is generally smaller for highvoltage transition metals than for low-voltage transition metals due to a more effective screening of Li-M interactions by oxygen electrons. Short-range order in practical disordered compounds is found to further mitigate the voltage slope increase upon disorder. In conclusion, our analysis shows that the additional high-voltage tetrahedral capacity induced by disorder is smaller in Liexcess compounds than in stoichiometric LiMO 2 compounds.« less

Exploring Partonic Structure of Hadrons Using ab initio Lattice QCD Calculations

DOE PAGES

Ma, Yan-Qing; Qiu, Jian-Wei

2018-01-10

Following our previous proposal, we construct a class of good "lattice cross sections" (LCSs), from which we can study the partonic structure of hadrons from ab initio lattice QCD calculations. These good LCSs, on the one hand, can be calculated directly in lattice QCD, and on the other hand, can be factorized into parton distribution functions (PDFs) with calculable coefficients, in the same way as QCD factorization for factorizable hadronic cross sections. PDFs could be extracted from QCD global analysis of the lattice QCD generated data of LCSs. In conclusion, we also show that the proposed functions for lattice QCDmore » calculation of PDFs in the literature are special cases of these good LCSs.« less

Static and Dynamical Properties of Ferroelectrics and Related Materials in Bulk and Nanostructure Forms

NASA Astrophysics Data System (ADS)

Gui, Zhigang

Ferroelectrics (FE) and multiferroics (MFE) have attracted a lot of attentions due to their rich and novel properties. Studies towards FE and MFE are of both fundamental and technological importance. We use a first-principles-based effective Hamiltonian method, conventional ab-initio packages and linear-scale three-dimension fragment method to investigate several important issues about FE and MFE. Tuning the properties of FE and MFE films are essential for miniaturized device applications, which can be realized through epitaxial strain and growth direction. In this dissertation, we use the effective Hamiltonian method to study (i) BaTiO3 films grown along the (110) pseudocubic direction on various substrates, (ii) BaTiO3 films grown on a single substrate along directions varying from [001] to [110] via [111] pseudocubic direction. Optimized physical responses or curie temperatures are found along some special directions or under epitaxial strain of certain range. FE and MFE nanostructures are shown to possess electrical vortices (known as one type topological defect), which have the potential to be used in new memory devices. However, the dynamic mechanism behind them is barely known. We use the effective Hamiltonian method to reveal that there exists a distinct mode which is shown to be responsible for the formation of the electrical vortices and in the THz region. Spin-canted magnetic structures are commonly seen in MFE, which results in the coexistence of two or more magnetic order parameters in the same structure. Understanding the physics behind such coupled magnetic order parameters is of obvious benefit for the sake of control of the magnetic properties of such systems. We employ both the effective Hamiltonian and ab-initio methods to derive and prove there is a universal law that explicitly correlates various magnetic order parameters with the different types of oxygen octahedra rotations. FE or MFE possessing electrical vortices are experimentally shown to have a much lower critical voltage in current-voltage curves. However, the exact underlying reason is unknown. In this dissertation, we take the advantage of the effective Hamiltonian method and linear-scale three-dimension fragment method to study the electronic properties of electrical vortices. Such combined procedure clearly shows the existence of electrical vortices doesn't decrease the band gap, but increases it instead, which suggests the lower critical voltage in current-voltage curves is likely to result from the defects inside the vortices.

Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers

PubMed Central

Moore, Ellen C.; Cash, Harrison A.; Caruso, Andria M.; Uppaluri, Ravindra; Hodge, James W.; Van Waes, Carter; Allen, Clint T.

2016-01-01

Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which was stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T cell, and not NK cell, -dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell–mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment–associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. This data conflicts with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggests that this treatment combination deserves careful evaluation in the clinical setting. PMID:27076449

Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4.

PubMed

Eriksson, Olof; Korsgren, Olle; Selvaraju, Ram Kumar; Mollaret, Marjorie; de Boysson, Yann; Chimienti, Fabrice; Altai, Mohamed

2018-01-01

The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion. In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was performed in a direct comparison with radio-iodinated Exendin-4. Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with high yield and > 95% purity. [ 125 I]Ab31 binding to insulinoma and pancreas was higher than for [ 125 I]Exendin-4, but could only by partially competed away by 200 nM Ab31 in excess. The in vivo uptake of [ 125 I]Ab31 was higher than [ 125 I]Exendin-4 in most tissues, mainly due to slower clearance from blood. We report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development with respect to ligand miniaturization and radionuclide selection is required for further progress. Transcription analysis indicates ZnT8 as a suitable target for visualization of the human endocrine pancreas.

Antibody Fragments as Potential Biopharmaceuticals for Cancer Therapy: Success and Limitations.

PubMed

Kholodenko, Roman V; Kalinovsky, Daniel V; Doronin, Igor I; Ponomarev, Eugene D; Kholodenko, Irina V

2017-08-17

Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system. Fragments of antibodies retain antigen specificity and part of functional properties of conventional mAbs and at the same time have much better penetration into the tumors and a greatly reduced level of adverse effects. Recent advantages in antibody engineering allowed to produce different types of antibody fragments with improved structure and properties for efficient elimination of tumor cells. These molecules opened up new perspectives for anticancer therapy. Here we will overview the structural features of the various types of antibody fragments and their applications for anticancer therapy as separate molecules and as part of complex conjugates or structures. Mechanisms of antitumor action of antibody fragments as well as their advantages and disadvantages for clinical application will be discussed in this review. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Solar array experiments on the Sphinx satellite

NASA Technical Reports Server (NTRS)

Stevens, N. J.

1973-01-01

The Space Plasma, High Voltage Interaction Experiment (SPHINX) is the name given to an auxiliary payload satellite scheduled to be launched in January 1974. The principal experiments carried on this satellite are specifically designed to obtain the engineering data on the interaction of high voltage systems with the space plasma. The classes of experiments are solar array segments, insulators, insulators with pin holes and conductors. The satellite is also carrying experiments to obtain flight data on three new solar array configurations; the edge illuminated-multijunction cells, the Teflon encased cells and the violet cells.

Voltage THD Improvement for an Outer Rotor Permanent Magnet Synchronous Machine

NASA Astrophysics Data System (ADS)

de la Cruz, Javier; Ramirez, Juan M.; Leyva, Luis

2013-08-01

This article deals with the design of an outer rotor Permanent Magnet Synchronous Machines (PMSM) driven by wind turbines. The Voltage Total Harmonic Distortion (VTHD) is especially addressed, under design parameters' handling, i.e., the geometry of the stator, the polar arc percentage, the air gap, the skew angle in rotor poles, the pole length and the core steel class. Seventy-six cases are simulated and the results provide information useful for designing this kind of machines. The study is conducted on a 5 kW PMSM.

Lightning protection of distribution lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, T.E.; Short, T.A.; Anderson, J.G.

1994-01-01

This paper reports a study of distribution line lightning performance, using computer simulations of lightning overvoltages. The results of previous investigations are extended with a detailed model of induced voltages from nearby strokes, coupled into a realistic power system model. The paper also considers the energy duty of distribution-class surge arresters exposed to direct strokes. The principal result is that widely separated pole-top arresters can effectively protect a distribution line from induced-voltage flashovers. This means that nearby lightning strokes need not be a significant lightning performance problem for most distribution lines.

Serum miR-338-5p, soluble B-cell-activating factor, allo-antibodies, and renal transplantation.

PubMed

Xu, H; Ma, X; He, X; Dong, P; Xue, D; Zhang, Y; Zhang, X

2015-03-01

The objective of the study was to explore the expression features of serum miR-338-5p and soluble B-cell-activating factor (sBAFF) in renal transplant recipients. Follow-up renal transplant recipients (n = 49) were enrolled in this study (male/female: 38/11). Healthy volunteers were controlled; 2 mL of peripheral blood from each subject was collected. Total RNA was extracted from serum by use of the miRNeasy Serum/Plasma Kit (QIAGEN), and miR-338-5p was amplified by means of quantitative real-time reverse transcriptase-polymerase chain reaction. sBAFF was detected by means of enzyme-linked immunoassay. LABScreen Mix (LSM12) (One Lambda) was used to test the level of anti-human leukocyte antigen (HLA) I antibody (Ab), anti-HLA II Ab, and anti-major histocompatibility complex class I chain-related A (MICA) Ab. All data are shown as mean ± SD and were analyzed by use of SPSS software 17.0. Compared with healthy volunteers, serum miR-338-5p in recipients was statistically downregulated (2.79 ± 2.5 versus 0.09 ± 0.12, P < .001); sBAFF in recipients was significantly upregulated (1321 ± 950 pg/mL versus 534 ± 327 pg/mL, P < .01); serum anti-HLAII Ab, anti-MICA Ab, and anti-HLA+MICA Abs all statistically increased in recipients (P < .05). Spearman correlation analysis showed that miR-338-5p was significantly negatively correlated with sBAFF (r = -0.51, P < .001) and anti-HLA II antibody with mean fluorescence intensity value >1000 (r = -0.322, P < .05). Analysis results also suggested that sBAFF was significantly negatively correlated with anti-MICA Ab, with mean fluorescence intensity value >1000 (r = -0.579, P < .05). miR-338-5p is closely correlated with the procedure of renal allograft antibody-mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

Some case studies of skewed (and other ab-normal) data distributions arising in low-level environmental research.

PubMed

Currie, L A

2001-07-01

Three general classes of skewed data distributions have been encountered in research on background radiation, chemical and radiochemical blanks, and low levels of 85Kr and 14C in the atmosphere and the cryosphere. The first class of skewed data can be considered to be theoretically, or fundamentally skewed. It is typified by the exponential distribution of inter-arrival times for nuclear counting events for a Poisson process. As part of a study of the nature of low-level (anti-coincidence) Geiger-Muller counter background radiation, tests were performed on the Poisson distribution of counts, the uniform distribution of arrival times, and the exponential distribution of inter-arrival times. The real laboratory system, of course, failed the (inter-arrival time) test--for very interesting reasons, linked to the physics of the measurement process. The second, computationally skewed, class relates to skewness induced by non-linear transformations. It is illustrated by non-linear concentration estimates from inverse calibration, and bivariate blank corrections for low-level 14C-12C aerosol data that led to highly asymmetric uncertainty intervals for the biomass carbon contribution to urban "soot". The third, environmentally, skewed, data class relates to a universal problem for the detection of excursions above blank or baseline levels: namely, the widespread occurrence of ab-normal distributions of environmental and laboratory blanks. This is illustrated by the search for fundamental factors that lurk behind skewed frequency distributions of sulfur laboratory blanks and 85Kr environmental baselines, and the application of robust statistical procedures for reliable detection decisions in the face of skewed isotopic carbon procedural blanks with few degrees of freedom.

Minority Student Success: The Role of Teachers in Advanced Placement Program® (AP®) Courses. Research Report No. 2002-8. ETS RR-02-17

ERIC Educational Resources Information Center

Burton, Nancy W.; Whitman, Nancy Burgess; Yepes-Baraya, Mario; Cline, Frederick; Kim, R. Myung-in

2002-01-01

This project described the characteristics and teaching behaviors of those successfully teaching AP® Calculus AB and AP English Literature and Composition to underrepresented minority students. Its purpose was to assist educators in improving the participation and performance of underrepresented minority students in AP classes. Study results…

Quantum probability and conceptual combination in conjunctions.

PubMed

Hampton, James A

2013-06-01

I consider the general problem of category conjunctions in the light of Pothos & Busemeyer (P&B)'s quantum probability (QP) account of the conjunction fallacy. I argue that their account as presented cannot capture the "guppy effect" - the case in which a class is a better member of a conjunction A^B than it is of either A or B alone.

78 FR 35984 - Interim Eligible Class of NRC-Licensed Facilities; Docket Nos. (as Shown in Attachment 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... consisting of a fingerprint-based background check against applicable Federal Bureau of Investigation (FBI... completed hard-copy FBI Form FD- 258, ``Fingerprint Card,'' to the NRC as specified in Attachment 3, for all... Section 161A.b. shall be subject to a background check by the Attorney General, based on fingerprints and...

Diffusion Monte Carlo calculations of Xenon and Krypton at High Pressure

NASA Astrophysics Data System (ADS)

Shulenburger, Luke; Mattsson, Thomas R.

2011-06-01

Ab initio calculations based on density functional theory (DFT) have proven a valuable tool in understanding the properties of materials at extreme conditions. However, there are entire classes of materials where the current limitations of DFT cast doubt upon the predictive power of the method. These include so called strongly correlated systems and materials where van der Waals forces are important. Diffusion Monte Carlo (DMC) can treat materials with a different class of approximations that have generally proven to be more accurate. The use of DMC together with DFT may therefore improve the predictive capability of the ab initio calculation of materials at extreme conditions. We present two examples of this approach. In the first we use DMC total energies to address the discrepancy between DFT and diamond anvil cell melt curves of Xe. In the second, DMC is used to address the choice of density functional used in calculations of the Kr hugoniot. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000. Belonoshko et al. PRB 74, 054114 (2006).

Performance of a low cost interdigitated flow design on a 1 kW class all vanadium mixed acid redox flow battery

NASA Astrophysics Data System (ADS)

Reed, David; Thomsen, Edwin; Li, Bin; Wang, Wei; Nie, Zimin; Koeppel, Brian; Sprenkle, Vincent

2016-02-01

Three flow designs were operated in a 3-cell 1 kW class all vanadium mixed acid redox flow battery. The influence of electrode surface area and flow rate on the coulombic, voltage, and energy efficiency and the pressure drop in the flow circuit will be discussed and correlated to the flow design. Material cost associated with each flow design will also be discussed.

Ion properties in a Hall current thruster operating at high voltage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garrigues, L., E-mail: laurent.garrigues@laplace.univ-tlse.fr

2016-04-28

Operation of a 5 kW-class Hall current Thruster for various voltages from 400 V to 800 V and a xenon mass flow rate of 6 mg s{sup −1} have been studied with a quasi-neutral hybrid model. In this model, anomalous electron transport is fitted from ion mean velocity measurements, and energy losses due to electron–wall interactions are used as a tuned parameter to match expected electron temperature strength for same class of thruster. Doubly charged ions production has been taken into account and detailed collisions between heavy species included. As the electron temperature increases, the main channel of Xe{sup 2+} ion production becomes stepwisemore » ionization of Xe{sup +} ions. For an applied voltage of 800 V, the mass utilization efficiency is in the range of 0.8–1.1, and the current fraction of doubly charged ions varies between 0.1 and 0.2. Results show that the region of ion production of each species is located at the same place inside the thruster channel. Because collision processes mean free path is larger than the acceleration region, each type of ions experiences same potential drop, and ion energy distributions of singly and doubly charged are very similar.« less

The staging mechanism of AlCl4 intercalation in a graphite electrode for an aluminium-ion battery.

PubMed

Bhauriyal, Preeti; Mahata, Arup; Pathak, Biswarup

2017-03-15

Identifying a suitable electrode material with desirable electrochemical properties remains a primary challenge for rechargeable Al-ion batteries. Recently an ultrafast rechargeable Al-ion battery was reported with high charge/discharge rate, (relatively) high discharge voltage and high capacity that uses a graphite-based cathode. Using calculations from first-principles, we have investigated the staging mechanism of AlCl 4 intercalation into bulk graphite and evaluated the stability, specific capacity and voltage profile of AlCl 4 intercalated compounds. Ab initio molecular dynamics is performed to investigate the thermal stability of AlCl 4 intercalated graphite structures. Our voltage profiles show that the first AlCl 4 intercalation step could be a more sluggish step than the successive intercalation steps. However, the diffusion of AlCl 4 is very fast in the expanded graphite host layers with a diffusion barrier of ∼0.01 eV, which justifies the ultrafast charging rate of a graphite based Al-ion battery. And such an AlCl 4 intercalated battery provides an average voltage of 2.01-2.3 V with a maximum specific capacity of 69.62 mA h g -1 , which is excellent for anion intercalated batteries. Our density of states and Bader charge analysis shows that the AlCl 4 intercalation into the bulk graphite is a charging process. Hence, we believe that our present study will be helpful in understanding the staging mechanism of AlCl 4 intercalation into graphite-like layered electrodes for Al-ion batteries, thus encouraging further experimental work.

Electronic Voltage and Current Transformers Testing Device

PubMed Central

Pan, Feng; Chen, Ruimin; Xiao, Yong; Sun, Weiming

2012-01-01

A method for testing electronic instrument transformers is described, including electronic voltage and current transformers (EVTs, ECTs) with both analog and digital outputs. A testing device prototype is developed. It is based on digital signal processing of the signals that are measured at the secondary outputs of the tested transformer and the reference transformer when the same excitation signal is fed to their primaries. The test that estimates the performance of the prototype has been carried out at the National Centre for High Voltage Measurement and the prototype is approved for testing transformers with precision class up to 0.2 at the industrial frequency (50 Hz or 60 Hz). The device is suitable for on-site testing due to its high accuracy, simple structure and low-cost hardware. PMID:22368510

Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors

PubMed Central

Giritch, Anatoli; Marillonnet, Sylvestre; Engler, Carola; van Eldik, Gerben; Botterman, Johan; Klimyuk, Victor; Gleba, Yuri

2006-01-01

Plant viral vectors allow expression of heterologous proteins at high yields, but so far, they have been unable to express heterooligomeric proteins efficiently. We describe here a rapid and indefinitely scalable process for high-level expression of functional full-size mAbs of the IgG class in plants. The process relies on synchronous coinfection and coreplication of two viral vectors, each expressing a separate antibody chain. The two vectors are derived from two different plant viruses that were found to be noncompeting. Unlike vectors derived from the same virus, noncompeting vectors effectively coexpress the heavy and light chains in the same cell throughout the plant body, resulting in yields of up to 0.5 g of assembled mAbs per kg of fresh-leaf biomass. This technology allows production of gram quantities of mAbs for research purposes in just several days, and the same protocol can be used on an industrial scale in situations requiring rapid response, such as pandemic or terrorism events. PMID:16973752

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

PubMed

Kreiner, A J; Castell, W; Di Paolo, H; Baldo, M; Bergueiro, J; Burlon, A A; Cartelli, D; Vento, V Thatar; Kesque, J M; Erhardt, J; Ilardo, J C; Valda, A A; Debray, M E; Somacal, H R; Sandin, J C Suarez; Igarzabal, M; Huck, H; Estrada, L; Repetto, M; Obligado, M; Padulo, J; Minsky, D M; Herrera, M; Gonzalez, S J; Capoulat, M E

2011-12-01

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas. Copyright © 2011 Elsevier Ltd. All rights reserved.

Voltage clustering in redox-active ligand complexes: mitigating electronic communication through choice of metal ion

DOE PAGES

Zarkesh, Ryan A.; Ichimura, Andrew S.; Monson, Todd C.; ...

2016-02-01

We used the redox-active bis(imino)acenapthene (BIAN) ligand to synthesize homoleptic aluminum, chromium, and gallium complexes of the general formula (BIAN) 3M. The resulting compounds were characterized using X-ray crystallography, NMR, EPR, magnetic susceptibility and cyclic voltammetry measurements and modeled using both DFT and ab initio wavefunction calculations to compare the orbital contributions of main group elements and transition metals in ligand-based redox events. Ultimately, complexes of this type have the potential to improve the energy density and electrolyte stability of grid-scale energy storage technologies, such as redox flow batteries, through thermodynamically-clustered redox events.

Magnetic field cycling effect on the non-linear current-voltage characteristics and magnetic field induced negative differential resistance in α-Fe1.64Ga0.36O3 oxide

NASA Astrophysics Data System (ADS)

Bhowmik, R. N.; Vijayasri, G.

2015-06-01

We have studied current-voltage (I-V) characteristics of α-Fe1.64Ga0.36O3, a typical canted ferromagnetic semiconductor. The sample showed a transformation of the I-V curves from linear to non-linear character with the increase of bias voltage. The I-V curves showed irreversible features with hysteresis loop and bi-stable electronic states for up and down modes of voltage sweep. We report positive magnetoresistance and magnetic field induced negative differential resistance as the first time observed phenomena in metal doped hematite system. The magnitudes of critical voltage at which I-V curve showed peak and corresponding peak current are affected by magnetic field cycling. The shift of the peak voltage with magnetic field showed a step-wise jump between two discrete voltage levels with least gap (ΔVP) 0.345(± 0.001) V. The magnetic spin dependent electronic charge transport in this new class of magnetic semiconductor opens a wide scope for tuning large electroresistance (˜500-700%), magnetoresistance (70-135 %) and charge-spin dependent conductivity under suitable control of electric and magnetic fields. The electric and magnetic field controlled charge-spin transport is interesting for applications of the magnetic materials in spintronics, e.g., magnetic sensor, memory devices and digital switching.

Effects of a meaningful, a discriminative, and a meaningless stimulus on equivalence class formation.

PubMed

Fields, Lanny; Arntzen, Erik; Nartey, Richard K; Eilifsen, Christoffer

2012-03-01

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A-E stimuli were all abstract shapes, none of 10 participants formed classes. When the A, B, D, and E stimuli were abstract shapes and the C stimuli were meaningful pictures, 8 of 10 participants formed classes. This high yield may reflect the expansion of existing classes that consist of the associates of the meaningful stimuli, rather than the formation of the ABCDE classes, per se. When the A-E stimuli were abstract shapes and the C stimuli became S(D)s prior to class formation, 5 out of 10 participants formed classes. Thus, the discriminative functions served by the meaningful stimuli can account for some of the enhancement of class formation produced by the inclusion of a meaningful stimulus as a class member. A sorting task, which provided a secondary measure of class formation, indicated the formation of all three classes when the emergent relations probes indicated the same outcome. In contrast, the sorting test indicated "partial" class formation when the emergent relations test indicated no class formation. Finally, the effects of nodal distance on the relatedness of stimuli in the equivalence classes were not influenced by the functions served by the C stimuli in the equivalence classes.

Effects of a Meaningful, a Discriminative, and a Meaningless Stimulus on Equivalence Class Formation

PubMed Central

Fields, Lanny; Arntzen, Erik; Nartey, Richard K; Eilifsen, Christoffer

2012-01-01

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A–E stimuli were all abstract shapes, none of 10 participants formed classes. When the A, B, D, and E stimuli were abstract shapes and the C stimuli were meaningful pictures, 8 of 10 participants formed classes. This high yield may reflect the expansion of existing classes that consist of the associates of the meaningful stimuli, rather than the formation of the ABCDE classes, per se. When the A–E stimuli were abstract shapes and the C stimuli became SDs prior to class formation, 5 out of 10 participants formed classes. Thus, the discriminative functions served by the meaningful stimuli can account for some of the enhancement of class formation produced by the inclusion of a meaningful stimulus as a class member. A sorting task, which provided a secondary measure of class formation, indicated the formation of all three classes when the emergent relations probes indicated the same outcome. In contrast, the sorting test indicated “partial” class formation when the emergent relations test indicated no class formation. Finally, the effects of nodal distance on the relatedness of stimuli in the equivalence classes were not influenced by the functions served by the C stimuli in the equivalence classes. PMID:22389524

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing

NASA Astrophysics Data System (ADS)

Spatz, J. M.; Ellman, R.; Cloutier, A. M.; Louis, L.; van Vliet, M.; Dwyer, D.; Stolina, M.; Ke, H. Z.; Bouxsein, M. L.

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25 mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p < 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p < 0.05), and was 2-3 fold higher in SclAbII-treated groups (p < 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing.

PubMed

Spatz, J M; Ellman, R; Cloutier, A M; Louis, L; van Vliet, M; Dwyer, D; Stolina, M; Ke, H Z; Bouxsein, M L

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p< 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p< 0.05), and was 2-3 fold higher in SclAbII-treated groups (p< 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Natural antibodies to glycans.

PubMed

Bovin, N V

2013-07-01

A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in KD terms) were found to be within the range 10(-4)-10(-6) M. Antibodies to Galβ1-3GlcNAc (Le(C)), 4-HSO3Galβ1-4GalNAc (4'-O-SuLN), Fucα1-3GlcNAc, Fucα1-4GlcNAc, GalNAcα1-3Gal (Adi), Galα1-4Galβ1-4Glc (P(k)), Galα1-4Galβ1-4GlcNAc (P1), GlcNAcα-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of "taboo" is observed for a number of glycans: antibodies to Le(X) and Le(Y), and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on quantitation of anti-glycan nAbs are reported.

Integration Testing of a Modular Discharge Supply for NASA's High Voltage Hall Accelerator Thruster

NASA Technical Reports Server (NTRS)

Pinero, Luis R.; Kamhawi, hani; Drummond, Geoff

2010-01-01

NASA s In-Space Propulsion Technology Program is developing a high performance Hall thruster that can fulfill the needs of future Discovery-class missions. The result of this effort is the High Voltage Hall Accelerator thruster that can operate over a power range from 0.3 to 3.5 kW and a specific impulse from 1,000 to 2,800 sec, and process 300 kg of xenon propellant. Simultaneously, a 4.0 kW discharge power supply comprised of two parallel modules was developed. These power modules use an innovative three-phase resonant topology that can efficiently supply full power to the thruster at an output voltage range of 200 to 700 V at an input voltage range of 80 to 160 V. Efficiencies as high as 95.9 percent were measured during an integration test with the NASA103M.XL thruster. The accuracy of the master/slave current sharing circuit and various thruster ignition techniques were evaluated.

Discriminant forest classification method and system

DOEpatents

Chen, Barry Y.; Hanley, William G.; Lemmond, Tracy D.; Hiller, Lawrence J.; Knapp, David A.; Mugge, Marshall J.

2012-11-06

A hybrid machine learning methodology and system for classification that combines classical random forest (RF) methodology with discriminant analysis (DA) techniques to provide enhanced classification capability. A DA technique which uses feature measurements of an object to predict its class membership, such as linear discriminant analysis (LDA) or Andersen-Bahadur linear discriminant technique (AB), is used to split the data at each node in each of its classification trees to train and grow the trees and the forest. When training is finished, a set of n DA-based decision trees of a discriminant forest is produced for use in predicting the classification of new samples of unknown class.

Linear transmitter design for MSAT terminals

NASA Technical Reports Server (NTRS)

Wilkinson, Ross; Macleod, John; Beach, Mark; Bateman, Andrew

1990-01-01

One of the factors that will undoubtedly influence the choice of modulation format for mobile satellites, is the availability of cheap, power-efficient, linear amplifiers for mobile terminal equipment operating in the 1.5-1.7 GHz band. Transmitter linearity is not easily achieved at these frequencies, although high power (20W) class A/AB devices are becoming available. However, these components are expensive and require careful design to achieve a modest degree of linearity. In this paper an alternative approach to radio frequency (RF) power amplifier design for mobile satellite (MSAT) terminals using readily-available, power-efficient, and cheap class C devices in a feedback amplifier architecture is presented.

Immunoglobulin A with protease activity secreted in human milk activates PAR-2 receptors, of intestinal epithelial cells HT-29, and promotes beta-defensin-2 expression.

PubMed

Barrera, G J; Portillo, R; Mijares, A; Rocafull, M A; del Castillo, J R; Thomas, L E

2009-03-24

Secretory antibodies of the immunoglobulin A (sIgA) class constitute the first line of antigen-specific immune protection against pathogens and other antigens at mucosal surfaces. Although initially perceived as potentially deleterious, catalytic antibodies have been proposed to participate in the removal of metabolic wastes and in protection against infection. Here we show that the presence of sIgA endowed with serine protease-like hydrolytic activity in milk strongly correlates with PAR-2 activation in human intestinal epithelial cells. F(ab')(2) fragments of sIgA activated the epithelial cells in culture to produce beta-defensin-2 (hBD2). Intracellular Ca(2+) mobilization was induced by treatment with (1) sIgA-F(ab')(2) fragments; (2) trypsin, a recognized PAR-2 agonist; or (3) a synthetic PAR-2 agonist peptide (SLIGKV). The co-treatment with a synthetic PAR-2 antagonist peptide (FSLLRY) and sIgA-F(ab')(2) fragments eliminates the latter's effect; nevertheless, cells were not refractory to subsequent stimulation with sIgA-F(ab')(2) fragments. Both the induction of hBD-2 expression in epithelial cells and the increase in intracellular [Ca(2+)] stimulated by sIgA-F(ab')(2) fragments were inhibited by treatment with serine protease inhibitors or pertussis toxin (PTX). These findings suggest that catalytic antibodies can activate intestinal epithelial cells through G-protein-coupled PAR-2, and could actively participate in the immune system of breastfed babies inducing the production of peptides related to innate defense, such as defensins.

Fructose 1,6-Bisphosphate Aldolase, a Novel Immunogenic Surface Protein on Listeria Species

PubMed Central

Conceição, Fabricio Rochedo; Hust, Michael; Mendonça, Karla Sequeira; Moreira, Ângela Nunes; França, Rodrigo Correa; da Silva, Wladimir Padilha; Aleixo, José Antonio G.

2016-01-01

Listeria monocytogenes is a ubiquitous food-borne pathogen, and its presence in food or production facilities highlights the importance of surveillance. Increased understanding of the surface exposed antigens on Listeria would provide potential diagnostic and therapeutic targets. In the present work, using mass spectrometry and genetic cloning, we show that fructose-1,6-bisphosphate aldolase (FBA) class II in Listeria species is the antigen target of the previously described mAb-3F8. Western and dot blot assays confirmed that the mAb-3F8 could distinguish all tested Listeria species from close-related bacteria. Localization studies indicated that FBA is present in every fraction of Listeria cells, including supernatant and the cell wall, setting Listeria spp. as one of the few bacteria described to have this protein on their cell surface. Epitope mapping using ORFeome display and a peptide membrane revealed a 14-amino acid peptide as the potential mAb-3F8 epitope. The target epitope in FBA allowed distinguishing Listeria spp. from closely-related bacteria, and was identified as part of the active site in the dimeric enzyme. However, its function in cell surface seems not to be host cell adhesion-related. Western and dot blot assays further demonstrated that mAb-3F8 together with anti-InlA mAb-2D12 could differentiate pathogenic from non-pathogenic Listeria isolated from artificially contaminated cheese. In summary, we report FBA as a novel immunogenic surface target useful for the detection of Listeria genus. PMID:27489951

Fructose 1,6-Bisphosphate Aldolase, a Novel Immunogenic Surface Protein on Listeria Species.

PubMed

Mendonça, Marcelo; Moreira, Gustavo Marçal Schmidt Garcia; Conceição, Fabricio Rochedo; Hust, Michael; Mendonça, Karla Sequeira; Moreira, Ângela Nunes; França, Rodrigo Correa; da Silva, Wladimir Padilha; Bhunia, Arun K; Aleixo, José Antonio G

2016-01-01

Listeria monocytogenes is a ubiquitous food-borne pathogen, and its presence in food or production facilities highlights the importance of surveillance. Increased understanding of the surface exposed antigens on Listeria would provide potential diagnostic and therapeutic targets. In the present work, using mass spectrometry and genetic cloning, we show that fructose-1,6-bisphosphate aldolase (FBA) class II in Listeria species is the antigen target of the previously described mAb-3F8. Western and dot blot assays confirmed that the mAb-3F8 could distinguish all tested Listeria species from close-related bacteria. Localization studies indicated that FBA is present in every fraction of Listeria cells, including supernatant and the cell wall, setting Listeria spp. as one of the few bacteria described to have this protein on their cell surface. Epitope mapping using ORFeome display and a peptide membrane revealed a 14-amino acid peptide as the potential mAb-3F8 epitope. The target epitope in FBA allowed distinguishing Listeria spp. from closely-related bacteria, and was identified as part of the active site in the dimeric enzyme. However, its function in cell surface seems not to be host cell adhesion-related. Western and dot blot assays further demonstrated that mAb-3F8 together with anti-InlA mAb-2D12 could differentiate pathogenic from non-pathogenic Listeria isolated from artificially contaminated cheese. In summary, we report FBA as a novel immunogenic surface target useful for the detection of Listeria genus.

Time-domain electromagnetic tests in the Wadi Bidah District, Kingdom of Saudi Arabia

USGS Publications Warehouse

Flanigan, Vincent J.; Sadek, Hamdy; Smith, Bruce; Tippens, C.L.

1983-01-01

A time-domain electromagnetic (TDEM) method was tested in two areas of mineralization in Precambrian rocks in the Wadi Bidah district, Kingdom of Saudi Arabia. Transient-decay voltages in profile mode were measured across the Sha'ab at Tare and Rabathan prospects by use of three transmitterreceiver loop configurations. At the Sha'ab at Tare prospect all of the loop configurations indicated the mineralized zone. Analysis of the coincident loop data at Sha'ab at Tare reveals that gossanous and altered rock of i0 ohm-m resistivity extends to a depth of 35 m, where there is an unweathered, dry mineralized zone of about 1 ohm-m resistivity. The model further suggests that the rocks at a depth of 55 m and below the water table are even less resistive (0. 1 ohm-m). The TDEM method successfully discriminated conductors within from those below the weathered zone at the Rabathan prospect. Conductors below the weathered zone are identified by a lack of transient response in the early part of the transient decay curve, followed by an increasing response in the middle to late parts of the transient decay curve. Results of these limited tests suggest the potential value of integrating TDEM with other geophysical tools in the Kingdom. Recommendations are made to expand these tests into a more comprehensive program that will evaluate the TDEM potential in various geologic environments that are host to mineral deposits of diverse origin.

A Photostable Silicon Rhodamine Platform for Optical Voltage Sensing

PubMed Central

Huang, Yi-Lin; Walker, Alison S.; Miller, Evan W.

2015-01-01

This paper describes the design and synthesis of a photostable, far-red to near-infrared (NIR) platform for optical voltage sensing. We developed a new, sulfonated silicon rhodamine fluorophore and integrated it with a phenylenevinylene molecular wire to create a Berkeley Red Sensor of Transmembrane potential, or BeRST 1 (“burst”). BeRST 1 is the first member of a class of farred to NIR voltage sensitive dyes that make use of a photoinduced electron transfer (PeT) trigger for optical interrogation of membrane voltage. We show that BeRST 1 displays bright, membrane-localized fluorescence in living cells, high photostability, and excellent voltage sensitivity in neurons. Depolarization of the plasma membrane results in rapid fluorescence increases (24% ΔF/F per 100 mV). BeRST 1 can be used in conjunction with fluorescent stains for organelles, Ca2+ indicators, and voltage-sensitive fluorescent proteins. In addition, the red-shifted spectral profile of BeRST 1, relative to commonly employed optogenetic actuators like ChannelRhodopsin2 (ChR2), which require blue light, enables optical electrophysiology in neurons. The high speed, sensitivity, photostability and long-wavelength fluorescence profiles of BeRST 1 make it a useful platform for the non-invasive, optical dissection of neuronal activity. PMID:26237573

PRED-CLASS: cascading neural networks for generalized protein classification and genome-wide applications.

PubMed

Pasquier, C; Promponas, V J; Hamodrakas, S J

2001-08-15

A cascading system of hierarchical, artificial neural networks (named PRED-CLASS) is presented for the generalized classification of proteins into four distinct classes-transmembrane, fibrous, globular, and mixed-from information solely encoded in their amino acid sequences. The architecture of the individual component networks is kept very simple, reducing the number of free parameters (network synaptic weights) for faster training, improved generalization, and the avoidance of data overfitting. Capturing information from as few as 50 protein sequences spread among the four target classes (6 transmembrane, 10 fibrous, 13 globular, and 17 mixed), PRED-CLASS was able to obtain 371 correct predictions out of a set of 387 proteins (success rate approximately 96%) unambiguously assigned into one of the target classes. The application of PRED-CLASS to several test sets and complete proteomes of several organisms demonstrates that such a method could serve as a valuable tool in the annotation of genomic open reading frames with no functional assignment or as a preliminary step in fold recognition and ab initio structure prediction methods. Detailed results obtained for various data sets and completed genomes, along with a web sever running the PRED-CLASS algorithm, can be accessed over the World Wide Web at http://o2.biol.uoa.gr/PRED-CLASS.

Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

USGS Publications Warehouse

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

Contrasting evolutionary histories of MHC class I and class II loci in grouse—effects of selection and gene conversion

PubMed Central

Minias, P; Bateson, Z W; Whittingham, L A; Johnson, J A; Oyler-McCance, S; Dunn, P O

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens. PMID:26860199

Molecular characterization of kappa class glutathione S-transferase from the disk abalone (Haliotis discus discus) and changes in expression following immune and stress challenges.

PubMed

Sandamalika, W M Gayashani; Priyathilaka, Thanthrige Thiunuwan; Liyanage, D S; Lee, Sukkyoung; Lim, Han-Kyu; Lee, Jehee

2018-06-01

Glutathione S-transferase (GST; EC 2.5.1.18) isoenzymes represent a complex group of proteins that are involved in phase II detoxification in several organisms. In this study, GST kappa (GSTκ) from the disk abalone (Haliotis discus discus; AbGSTκ) was characterized at both the transcriptional and functional levels to determine its potential capacity to perform as a detoxification agent under conditions of different stress. The predicted AbGSTκ protein consists of 227 amino acids, with a predicted molecular weight of 25.6 kDa and a theoretical isoelectric point (pI) of 7.78. In silico analysis reveals that AbGSTκ is a disulfide bond formation protein A (DsbA), consisting of a thioredoxin domain, GSH binding sites (G-sites), and a catalytic residue. In contrast, no hydrophobic ligand binding site (H-site), or signal peptides, were detected. AbGSTκ showed the highest sequence identity with the orthologue from pufferfish (Takifugu obscurus) (60.0%). In a phylogenetic tree, AbGSTκ clustered closely together with other fish GSTκs, and was evolutionarily distanced from other cytosolic GSTs. The predicted three-dimensional structure clearly demonstrates that the dimer adopts a butterfly-like shape. A tissue distribution analysis revealed that GSTκ was highly expressed in the digestive tract, suggesting it has detoxification ability. Depending on the tissue and time, AbGSTκ showed different expression patterns, and levels of expression, following challenge of the abalone with immune stimulants. Enzyme kinetics of the purified recombinant proteins demonstrated its conjugating ability using 1-Chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH) as substrates, and suggested it has a low affinity for both substrates. The optimum temperature and pH for the rAbGSTκ GSH: CDNB conjugating activity were found to be 35 °C and pH 8, respectively indicating that the abalone is well adapted to a wide range of environmental conditions. Cibacron blue (100 μM) was capable of completely inhibiting rAbGSTκ (100%) with an IC 50 (half maximal inhibitory concentration) of 0.05 μM. A disk diffusion assay revealed that rAbGSTκ could significantly protect cells from H 2 O 2 , CdCl 2, and ZnCl 2 . Altogether, this current study suggests that AbGSTκ is involved in detoxification and immunological host defense mechanisms and allows abalones to overcome stresses in order for them to have an increased chance of survival. Copyright © 2018. Published by Elsevier Ltd.

Single-Cell Genome and Group-Specific dsrAB Sequencing Implicate Marine Members of the Class Dehalococcoidia (Phylum Chloroflexi) in Sulfur Cycling

PubMed Central

Cooper, Myriel; Schreiber, Lars; Lloyd, Karen G.; Baker, Brett J.; Petersen, Dorthe G.; Jørgensen, Bo Barker; Stepanauskas, Ramunas; Reinhardt, Richard; Schramm, Andreas; Loy, Alexander; Adrian, Lorenz

2016-01-01

ABSTRACT The marine subsurface sediment biosphere is widely inhabited by bacteria affiliated with the class Dehalococcoidia (DEH), phylum Chloroflexi, and yet little is known regarding their metabolisms. In this report, genomic content from a single DEH cell (DEH-C11) with a 16S rRNA gene that was affiliated with a diverse cluster of 16S rRNA gene sequences prevalent in marine sediments was obtained from sediments of Aarhus Bay, Denmark. The distinctive gene content of this cell suggests metabolic characteristics that differ from those of known DEH and Chloroflexi. The presence of genes encoding dissimilatory sulfite reductase (Dsr) suggests that DEH could respire oxidized sulfur compounds, although Chloroflexi have never been implicated in this mode of sulfur cycling. Using long-range PCR assays targeting DEH dsr loci, dsrAB genes were amplified and sequenced from various marine sediments. Many of the amplified dsrAB sequences were affiliated with the DEH Dsr clade, which we propose equates to a family-level clade. This provides supporting evidence for the potential for sulfite reduction by diverse DEH species. DEH-C11 also harbored genes encoding reductases for arsenate, dimethyl sulfoxide, and halogenated organics. The reductive dehalogenase homolog (RdhA) forms a monophyletic clade along with RdhA sequences from various DEH-derived contigs retrieved from available metagenomes. Multiple facts indicate that this RdhA may not be a terminal reductase. The presence of other genes indicated that nutrients and energy may be derived from the oxidation of substituted homocyclic and heterocyclic aromatic compounds. Together, these results suggest that marine DEH play a previously unrecognized role in sulfur cycling and reveal the potential for expanded catabolic and respiratory functions among subsurface DEH. PMID:27143384

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2014-08-29

amphibious assault vehicles; AN/ALE-50 electronic countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush...54 243 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon Coproduce Patriot...systems) $340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with 176 AESA

27 CFR 5.32 - Mandatory label information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Distilled Spirits § 5.32 Mandatory label information. There shall be stated: (a) On the brand label: (1) Brand name. (2) Class and type, in accordance with § 5.35. (3) Alcoholic content, in accordance with § 5... prescribed in § 5.47, net contents in accordance with § 5.38(b) or § 5.38a(b)(2). (b) On the brand label or...

Reduction of Residual Stress and Distortion in HY100 and HY130 High Strength Steels During Welding

DTIC Science & Technology

1989-06-01

SMAW), Gas Tungsten Arc Welding ( GTAW ), Gas Metal Arc Welding (GMAW), Submerged Arc Welding (SAW), and Stud Welding (SW) the recommended joint...3.2 4.83 Cr Chromium -(3) 1.5 .55 M0 Molybdium -(3) .40 .40 V Vanadium -(3) .08 T i Titanium -(3) .005 Identifier ABS Class B USX TAG328 Lukens

New Cadets and Other College Freshmen: Class of 1987,

DTIC Science & Technology

1984-04-01

72.2 78.1 60.6 Live in a coeducational orm 70.9 ab 93.6 28.7 25.4 55.8 72.3 Be satisfied with college 6 7 .3a 60.9 49.5 60.9 64.2 72.0 Make at least a...general). (9 Ethnic Studies ....... 0 Liye insa coeducational dorm?............... (y) i’s) (Lt N Finance (. Geography .0 Play varsity

Evaluation of a competitive enzyme-linked immunosorbent assay for measurements of soluble HLA-G protein.

PubMed

Rasmussen, M; Dahl, M; Buus, S; Djurisic, S; Ohlsson, J; Hviid, T V F

2014-08-01

The human leukocyte antigen (HLA) class Ib molecule, HLA-G, has gained increased attention because of its assumed important role in immune regulation. The HLA-G protein exists in several soluble isoforms. Most important are the actively secreted HLA-G5 full-length isoform generated by alternative splicing retaining intron 4 with a premature stop codon, and the cleavage of full-length membrane-bound HLA-G1 from the cell surface, so-called soluble HLA-G1 (sHLA-G1). A specific and sensitive immunoassay for measurements of soluble HLA-G is mandatory for conceivable routine testing and research projects. We report a novel method, a competitive immunoassay, for measuring HLA-G5/sHLA-G1 in biological fluids. The sHLA-G immunoassay is based upon a competitive enzyme-linked immunosorbent assay (ELISA) principle. It includes a recombinant sHLA-G1 protein in complex with β2-microglobulin and a peptide as a standard, biotinylated recombinant sHLA-G1 as an indicator, and the MEM-G/9 anti-HLA-G monoclonal antibody (mAb) as the capture antibody. The specificity and sensitivity of the assay were evaluated. Testing with different recombinant HLA class I proteins and different anti-HLA class I mAbs showed that the sHLA-G immunoassay was highly specific. Optimal combinations of competitor sHLA-G1 and capture mAb concentrations were determined. Two versions of the assay were tested. One with a relatively wide dynamic range from 3.1 to 100.0 ng/ml, and another more sensitive version ranging from 1.6 to 12.5 ng/ml. An intra-assay coefficient of variation (CV) of 15.5% at 88 ng/ml and an inter-assay CV of 23.1% at 39 ng/ml were determined. An assay based on the competitive sHLA-G ELISA may be important for measurements of sHLA-G proteins in several conditions: assisted reproduction, organ transplantation, cancer, and certain pregnancy complications, both in research studies and possibly in the future also for clinical routine use. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity.

PubMed

Olivier, Stéphane; Jacoby, Marine; Brillon, Cédric; Bouletreau, Sylvana; Mollet, Thomas; Nerriere, Olivier; Angel, Audrey; Danet, Sévérine; Souttou, Boussad; Guehenneux, Fabienne; Gauthier, Laurent; Berthomé, Mathilde; Vié, Henri; Beltraminelli, Nicola; Mehtali, Majid

2010-01-01

Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of monoclonal antibodies and to potentially reduce the therapeutic cost. We report here that the EB66 cell line derived from duck embryonic stem cells can be efficiently genetically engineered to produce mAbs at yields beyond a 1 g/L, as suspension cells grown in serum-free culture media. EB66 cells display additional attractive grown characteristics such as a very short population doubling time of 12 to 14 hours, a capacity to reach very high cell density (> 30 million cells/mL) and a unique metabolic profile resulting in low ammonium and lactate accumulation and low glutamine consumption, even at high cell densities. Furthermore, mAbs produced on EB66 cells display a naturally reduced fucose content resulting in strongly enhanced ADCC activity. The EB66 cells have therefore the potential to evolve as a novel cellular platform for the production of high potency therapeutic antibodies.

Solid-state mAbs and ADCs subjected to heat-stress stability conditions can be covalently modified with buffer and excipient molecules.

PubMed

Valliere-Douglass, John F; Lewis, Patsy; Salas-Solano, Oscar; Jiang, Shan

2015-02-01

We report that a unique type of chemical modification occurs on lyophilized proteins. Freeze-dried mAbs and antibody-drug conjugates (ADCs) can be covalently modified with buffer and excipient molecules on the side chains of Glu, Asp, Thr, and Ser amino acids when subjected to temperature stress. The reaction occurs primarily via condensation of common buffers and excipients such as histidine, tris, trehalose and sucrose, with Glu and Asp carboxylates in the primary sequence of proteins. The reaction was also found to proceed through condensation of carboxylate containing buffers such as citrate, with Thr and Ser hydroxyls in the primary sequence of proteins. Based on the mass of the covalent adducts observed on mAbs and ADCs, it is apparent that the reaction produces water as a product and is thus favored in a low moisture environments such as a lyophilized protein cake. Herein, we present the evidence for the covalent modification of proteins drawn from case studies of in-depth characterization of heat-stressed mAbs and ADCs in the solid state. We also demonstrate how common charge variant assays such as imaged capillary isoelectric focusing and mass spectrometry can be used to monitor this specific class of protein modification. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The "New Polyethylene Glycol Dilemma": Polyethylene Glycol Impurities and Their Paradox Role in mAb Crystallization.

PubMed

Hildebrandt, Christian; Joos, Lea; Saedler, Rainer; Winter, Gerhard

2015-06-01

Polyethylene glycols (PEG) represent the most successful and frequently applied class of excipients used for protein crystallization. PEG auto-oxidation and formation of impurities such as peroxides and formaldehydes that foster protein drug degradation is known. However, their effect on mAb crystallization has not been studied in detail before. During the present study, a model IgG1 antibody (mAb1) was crystallized in PEG solutions. Aggregate formation was observed during crystallization and storage that was ascribed to PEG degradation products. Reduction of peroxide and formaldehyde levels prior to crystallization by vacuum and freeze-drying was investigated for its effect on protein degradation. Vacuum drying was superior in removal of peroxides but inferior in reducing formaldehyde residues. Consequently, double purification allowed extensive removal of both impurities. Applying of purified PEG led to 50% lower aggregate fractions. Surprisingly, PEG double purification or addition of methionine prior to crystallization prevented crystal formation. With increased PEG concentration or spiking with peroxides and formaldehydes, crystal formation could be recovered again. With these results, we demonstrate that minimum amounts of oxidizing impurities and thus in consequence chemically altered proteins are vital to initiate mAb1 crystallization. The present study calls PEG as good precipitant for therapeutic biopharmaceuticals into question. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Half-metallic properties, single-spin negative differential resistance, and large single-spin Seebeck effects induced by chemical doping in zigzag-edged graphene nanoribbons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xi-Feng; Zhou, Wen-Qian; Hong, Xue-Kun

2015-01-14

Ab initio calculations combining density-functional theory and nonequilibrium Green’s function are performed to investigate the effects of either single B atom or single N atom dopant in zigzag-edged graphene nanoribbons (ZGNRs) with the ferromagnetic state on the spin-dependent transport properties and thermospin performances. A spin-up (spin-down) localized state near the Fermi level can be induced by these dopants, resulting in a half-metallic property with 100% negative (positive) spin polarization at the Fermi level due to the destructive quantum interference effects. In addition, the highly spin-polarized electric current in the low bias-voltage regime and single-spin negative differential resistance in the highmore » bias-voltage regime are also observed in these doped ZGNRs. Moreover, the large spin-up (spin-down) Seebeck coefficient and the very weak spin-down (spin-up) Seebeck effect of the B(N)-doped ZGNRs near the Fermi level are simultaneously achieved, indicating that the spin Seebeck effect is comparable to the corresponding charge Seebeck effect.« less

Current-Driven Hydrogen Desorption from Graphene: Experiment and Theory.

PubMed

Gao, Li; Pal, Partha Pratim; Seideman, Tamar; Guisinger, Nathan P; Guest, Jeffrey R

2016-02-04

Electron-stimulated desorption of hydrogen from the graphene/SiC(0001) surface at room temperature was investigated with ultrahigh vacuum scanning tunneling microscopy and ab initio calculations in order to elucidate the desorption mechanisms and pathways. Two different desorption processes were observed. In the high electron energy regime (4-8 eV), the desorption yield is independent of both voltage and current, which is attributed to the direct electronic excitation of the C-H bond. In the low electron energy regime (2-4 eV), however, the desorption yield exhibits a threshold dependence on voltage, which is explained by the vibrational excitation of the C-H bond via transient ionization induced by inelastic tunneling electrons. The observed current independence of the desorption yield suggests that the vibrational excitation is a single-electron process. We also observed that the curvature of graphene dramatically affects hydrogen desorption. Desorption from concave regions was measured to be much more probable than desorption from convex regions in the low electron energy regime (∼2 eV), as would be expected from the identified desorption mechanism.

Current-Driven Hydrogen Desorption from Graphene: Experiment and Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, L.; Pal, Partha P.; Seideman, Tamar

2016-02-04

Electron-stimulated desorption of hydrogen from the graphene/SiC(0001) surface at room temperature was investigated with ultrahigh vacuum scanning tunneling microscopy and ab initio calculations in order to elucidate the desorption mechanisms and pathways. Two different desorption processes were observed. In the high electron energy regime (4-8 eV), the desorption yield is independent of both voltage and current, which is attributed to the direct electronic excitation of the C-H bond. In the low electron energy regime (2-4 eV), however, the desorption yield exhibits a threshold dependence on voltage, which is explained by the vibrational excitation of the C-H bond via transient ionizationmore » induced by inelastic tunneling electrons. The observed current-independence of the desorption yield suggests that the vibrational excitation is a singleelectron process. We also observed that the curvature of graphene dramatically affects hydrogen desorption. Desorption from concave regions was measured to be much more probable than desorption from convex regions in the low electron energy regime (~ 2 eV), as would be expected from the identified desorption mechanism« less

Detection of one-dimensional migration of single self-interstitial atoms in tungsten using high-voltage electron microscopy

PubMed Central

Amino, T.; Arakawa, K.; Mori, H.

2016-01-01

The dynamic behaviour of atomic-size disarrangements of atoms—point defects (self-interstitial atoms (SIAs) and vacancies)—often governs the macroscopic properties of crystalline materials. However, the dynamics of SIAs have not been fully uncovered because of their rapid migration. Using a combination of high-voltage transmission electron microscopy and exhaustive kinetic Monte Carlo simulations, we determine the dynamics of the rapidly migrating SIAs from the formation process of the nanoscale SIA clusters in tungsten as a typical body-centred cubic (BCC) structure metal under the constant-rate production of both types of point defects with high-energy electron irradiation, which must reflect the dynamics of individual SIAs. We reveal that the migration dimension of SIAs is not three-dimensional (3D) but one-dimensional (1D). This result overturns the long-standing and well-accepted view of SIAs in BCC metals and supports recent results obtained by ab-initio simulations. The SIA dynamics clarified here will be one of the key factors to accurately predict the lifetimes of nuclear fission and fusion materials. PMID:27185352

Charge transport in doped zigzag phosphorene nanoribbons

NASA Astrophysics Data System (ADS)

Nourbakhsh, Zahra; Asgari, Reza

2018-06-01

The effects of lattice distortion and chemical disorder on charge transport properties of two-terminal zigzag phosphorene nanoribbons (zPNRs), which shows resonant tunneling behavior under an electrical applied bias, are studied. Our comprehensive study is based on ab initio quantum transport calculations on the basis of the Landauer theory. We use nitrogen and silicon substitutional dopant atoms, and employ different physical quantities such as the I -V curve, voltage drop behavior, transmission spectrum, transmission pathway, and atomic current to explore the transport mechanism of zPNR devices under a bias voltage. The calculated transmission pathways show the transition from a ballistic transport regime to a diffusive and in some particular cases to localized transport regimes. Current flowing via the chemical bonds and hopping are monitored; however, the conductance originates mainly from the charge traveling through the chemical bonds in the vicinity of the zigzag edges. Our results show that in the doped systems, the device conductance decreases and the negative differential resistance characteristic becomes weak or is eliminated. Besides, the conductance in a pure zPNR system is almost independent of the ribbon width.

Analysis of the error of the developed method of determination the active conductivity reducing the insulation level between one phase of the network and ground, and insulation parameters in a non-symmetric network with isolated neutral with voltage above 1000 V

NASA Astrophysics Data System (ADS)

Utegulov, B. B.

2018-02-01

In the work the study of the developed method was carried out for reliability by analyzing the error in indirect determination of the insulation parameters in an asymmetric network with an isolated neutral voltage above 1000 V. The conducted studies of the random relative mean square errors show that the accuracy of indirect measurements in the developed method can be effectively regulated not only by selecting a capacitive additional conductivity, which are connected between phases of the electrical network and the ground, but also by the selection of measuring instruments according to the accuracy class. When choosing meters with accuracy class of 0.5 with the correct selection of capacitive additional conductivity that are connected between the phases of the electrical network and the ground, the errors in measuring the insulation parameters will not exceed 10%.

A Survey of Architectural Techniques for Near-Threshold Computing

DOE PAGES

Mittal, Sparsh

2015-12-28

Energy efficiency has now become the primary obstacle in scaling the performance of all classes of computing systems. In low-voltage computing and specifically, near-threshold voltage computing (NTC), which involves operating the transistor very close to and yet above its threshold voltage, holds the promise of providing many-fold improvement in energy efficiency. However, use of NTC also presents several challenges such as increased parametric variation, failure rate and performance loss etc. Our paper surveys several re- cent techniques which aim to offset these challenges for fully leveraging the potential of NTC. By classifying these techniques along several dimensions, we also highlightmore » their similarities and differences. Ultimately, we hope that this paper will provide insights into state-of-art NTC techniques to researchers and system-designers and inspire further research in this field.« less

A Survey of Architectural Techniques for Near-Threshold Computing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Sparsh

Energy efficiency has now become the primary obstacle in scaling the performance of all classes of computing systems. In low-voltage computing and specifically, near-threshold voltage computing (NTC), which involves operating the transistor very close to and yet above its threshold voltage, holds the promise of providing many-fold improvement in energy efficiency. However, use of NTC also presents several challenges such as increased parametric variation, failure rate and performance loss etc. Our paper surveys several re- cent techniques which aim to offset these challenges for fully leveraging the potential of NTC. By classifying these techniques along several dimensions, we also highlightmore » their similarities and differences. Ultimately, we hope that this paper will provide insights into state-of-art NTC techniques to researchers and system-designers and inspire further research in this field.« less

Conditioning of high voltage radio frequency cavities by using fuzzy logic in connection with rule based programming

NASA Astrophysics Data System (ADS)

Perreard, S.; Wildner, E.

1994-12-01

Many processes are controlled by experts using some kind of mental model to decide on actions and make conclusions. This model, based on heuristic knowledge, can often be represented by rules and does not have to be particularly accurate. Such is the case for the problem of conditioning high voltage RF cavities; the expert has to decide, by observing some criteria, whether to increase or to decrease the voltage and by how much. A program has been implemented which can be applied to a class of similar problems. The kernel of the program is a small rule base, which is independent of the kind of cavity. To model a specific cavity, we use fuzzy logic which is implemented as a separate routine called by the rule base, to translate from numeric to symbolic information.

The allosteric site regulates the voltage sensitivity of muscarinic receptors.

PubMed

Hoppe, Anika; Marti-Solano, Maria; Drabek, Matthäus; Bünemann, Moritz; Kolb, Peter; Rinne, Andreas

2018-01-01

Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Here, we compared the modulation of M 1 -Rs and M 3 -Rs induced by changes in voltage to their allosteric modulation by chemical compounds. We quantified changes in receptor signaling in single HEK 293 cells with a FRET biosensor for the G q protein cycle. In the presence of ACh, M 1 -R signaling was potentiated by voltage, similarly to positive allosteric modulation by benzyl quinolone carboxylic acid. Conversely, signaling of M 3 -R was attenuated by voltage or the negative allosteric modulator gallamine. Because the orthosteric site is highly conserved among M-Rs, but allosteric sites vary, we constructed "allosteric site" M 3 /M 1 -R chimeras and analyzed their voltage dependencies. Exchanging the entire allosteric sites eliminated the voltage sensitivity of ACh responses for both receptors, but did not affect their modulation by allosteric compounds. Furthermore, a point mutation in M 3 -Rs caused functional uncoupling of the allosteric and orthosteric sites and abolished voltage dependence. Molecular dynamics simulations of the receptor variants indicated a subtype-specific crosstalk between both sites, involving the conserved tyrosine lid structure of the orthosteric site. This molecular crosstalk leads to receptor subtype-specific voltage effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic field cycling effect on the non-linear current-voltage characteristics and magnetic field induced negative differential resistance in α-Fe{sub 1.64}Ga{sub 0.36}O{sub 3} oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhowmik, R. N., E-mail: rnbhowmik.phy@pondiuni.edu.in; Vijayasri, G.

2015-06-15

We have studied current-voltage (I-V) characteristics of α-Fe{sub 1.64}Ga{sub 0.36}O{sub 3}, a typical canted ferromagnetic semiconductor. The sample showed a transformation of the I-V curves from linear to non-linear character with the increase of bias voltage. The I-V curves showed irreversible features with hysteresis loop and bi-stable electronic states for up and down modes of voltage sweep. We report positive magnetoresistance and magnetic field induced negative differential resistance as the first time observed phenomena in metal doped hematite system. The magnitudes of critical voltage at which I-V curve showed peak and corresponding peak current are affected by magnetic field cycling.more » The shift of the peak voltage with magnetic field showed a step-wise jump between two discrete voltage levels with least gap (ΔV{sub P}) 0.345(± 0.001) V. The magnetic spin dependent electronic charge transport in this new class of magnetic semiconductor opens a wide scope for tuning large electroresistance (∼500-700%), magnetoresistance (70-135 %) and charge-spin dependent conductivity under suitable control of electric and magnetic fields. The electric and magnetic field controlled charge-spin transport is interesting for applications of the magnetic materials in spintronics, e.g., magnetic sensor, memory devices and digital switching.« less

TOWARDS A GENERIC PBPK MODEL OF PYRETHROID PESTICIDES: MODELING DELTAMETHRIN AND PERMETHIN IN THE RAT

EPA Science Inventory

Pyrethroids have emerged as a major class of insecticide due to their selective potency in insects and their relatively low potency in mammalian studies. Pyrethroids exert toxicity by binding to voltage-gated sodium channels, thereby eliciting excitatory neurotoxicity. The Food...

TOWARDS A GENERIC PBPK MODEL OF PYRETHROID PESTICIDES: MODELING DELTAMETHRIN AND PERMETHRIN IN THE RAT

EPA Science Inventory

Pyrethroids have emerged as a major class of insecticide due to their selective potency in insects and their relatively low potency in mammalian studies. Pyrethroids exert toxicity by binding to voltage-gated sodium channels, thereby eliciting excitatory neurotoxicity. The Fo...

Single String Integration Test of the High Voltage Hall Accelerator System

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Haag, Thomas W.; Huang, Wensheng; Pinero, Luis; Peterson, Todd; Shastry, Rohit

2013-01-01

HiVHAc Task Objectives:-Develop and demonstrate low-power, long-life Hall thruster technology to enable cost effective EP for Discovery-class missions-Advance the TRL level of potential power processing units and xenon feed systems to integrate with the HiVHAc thruster.

A new adaptive control strategy for a class of nonlinear system using RBF neuro-sliding-mode technique: application to SEIG wind turbine control system

NASA Astrophysics Data System (ADS)

Kenné, Godpromesse; Fotso, Armel Simo; Lamnabhi-Lagarrigue, Françoise

2017-04-01

In this paper, a new hybrid method which combines radial basis function (RBF) neural network with a sliding-mode technique to take advantage of their common features is used to control a class of nonlinear systems. A real-time dynamic nonlinear learning law of the weight vector is synthesized and the closed-loop stability has been demonstrated using Lyapunov theory. The solution presented in this work does not need the knowledge of the perturbation bounds, neither the knowledge of the full state of the nonlinear system. In addition, the bounds of the nonlinear functions are assumed to be unknown and the proposed RBF structure uses reduced number of hidden units. This hybrid control strategy is applied to extract the maximum available energy from a stand-alone self-excited variable low-wind speed energy conversion system and design the dc-voltage and rotor flux controllers as well as the load-side frequency and voltage regulators assuming that the measured outputs are the rotor speed, stator currents, load-side currents and voltages despite large variation of the rotor resistance and uncertainties on the inductances. Finally, simulation results compared with those obtained using the well-known second-order sliding-mode controller are given to show the effectiveness and feasibility of the proposed approach.

Feeder Voltage Regulation with High-Penetration PV Using Advanced Inverters and a Distribution Management System: A Duke Energy Case Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Giraldez, Julieta; Gruchalla, Kenny

2016-11-01

Duke Energy, Alstom Grid, and the National Renewable Energy Laboratory teamed up to better understand the impacts of solar photovoltaics (PV) on distribution system operations. The core goal of the project is to compare the operational - specifically, voltage regulation - impacts of three classes of PV inverter operations: 1.) Active power only (Baseline); 2.) Local inverter control (e.g., PF...not equal...1, Q(V), etc.); and 3.) Integrated volt-VAR control (centralized through the distribution management system). These comparisons were made using multiple approaches, each of which represents an important research-and-development effort on its own: a) Quasi-steady-state time-series modeling for approximately 1 yearmore » of operations using the Alstom eTerra (DOTS) system as a simulation engine, augmented by Python scripting for scenario and time-series control and using external models for an advanced inverter; b) Power-hardware-in-the-loop (PHIL) testing of a 500-kVA-class advanced inverter and traditional voltage regulating equipment. This PHIL testing used cosimulation to link full-scale feeder simulation using DOTS in real time to hardware testing; c) Advanced visualization to provide improved insights into time-series results and other PV operational impacts; and d) Cost-benefit analysis to compare the financial and business-model impacts of each integration approach.« less

Calcium currents and graded synaptic transmission between heart interneurons of the leech.

PubMed

Angstadt, J D; Calabrese, R L

1991-03-01

Synaptic transmission between reciprocally inhibitory heart interneurons (HN cells) of the medicinal leech was examined in the absence of Na-mediated action potentials. Under voltage clamp, depolarizing steps from a holding potential of -60 mV elicited 2 kinetically distinct components of inward current in the presynaptic HN cell: an early transient current that inactivates within 200 msec and a persistent current that only partially decays over several seconds. Both currents begin to activate near -60 mV. Steady-state inactivation occurs over the voltage range between -70 and -45 mV and is completely removed by 1-2-sec hyperpolarizing voltage steps to -80 mV. The inward currents are carried by Ca2+, Ba2+, or Sr2+ ions, but not by Co2+, Mn2+, or Ni2+. These same inward currents underlie the burst-generating plateau potentials previously described in HN cells (Arbas and Calabrese, 1987a,b). With a presynaptic holding potential of -60 mV, the threshold for transmitter release is near -45 mV. Postsynaptic currents in the contralateral HN cell have a reversal potential near -60 mV. The largest postsynaptic currents (300-400 pA) exhibit an initial peak response that is followed by a more slowly decaying component. The persistent component of Ca2+ current in the presynaptic neuron is strongly correlated with the prolonged component of the postsynaptic current, while the transient presynaptic Ca2+ current appears to correspond to the early peak of postsynaptic current. These data are consistent with the hypothesis that voltage-dependent calcium currents contribute to the oscillatory capability of reciprocally inhibitory HN cells by (1) generating the plateau potential that drives the burst of action potentials and (2) underlying the release of inhibitory transmitter onto the contralateral cell.

Spinel compounds as multivalent battery cathodes: A systematic evaluation based on ab initio calculations

DOE PAGES

Liu, Miao; Rong, Ziqin; Malik, Rahul; ...

2014-12-16

In this study, batteries that shuttle multivalent ions such as Mg 2+ and Ca 2+ ions are promising candidates for achieving higher energy density than available with current Li-ion technology. Finding electrode materials that reversibly store and release these multivalent cations is considered a major challenge for enabling such multivalent battery technology. In this paper, we use recent advances in high-throughput first-principles calculations to systematically evaluate the performance of compounds with the spinel structure as multivalent intercalation cathode materials, spanning a matrix of five different intercalating ions and seven transition metal redox active cations. We estimate the insertion voltage, capacity,more » thermodynamic stability of charged and discharged states, as well as the intercalating ion mobility and use these properties to evaluate promising directions. Our calculations indicate that the Mn 2O 4 spinel phase based on Mg and Ca are feasible cathode materials. In general, we find that multivalent cathodes exhibit lower voltages compared to Li cathodes; the voltages of Ca spinels are ~0.2 V higher than those of Mg compounds (versus their corresponding metals), and the voltages of Mg compounds are ~1.4 V higher than Zn compounds; consequently, Ca and Mg spinels exhibit the highest energy densities amongst all the multivalent cation species. The activation barrier for the Al³⁺ ion migration in the Mn₂O₄ spinel is very high (~1400 meV for Al 3+ in the dilute limit); thus, the use of an Al based Mn spinel intercalation cathode is unlikely. Amongst the choice of transition metals, Mn-based spinel structures rank highest when balancing all the considered properties.« less

Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates.

PubMed

Pi, Borui; Yu, Meihong; Chen, Yagang; Yu, Yunsong; Li, Lanjuan

2009-06-01

The aim of this study was to investigate the prevalence and characteristics of ACME (arginine catabolic mobile element)-arcA-positive isolates among meticillin-resistant Staphylococcus haemolyticus (MRSH). ACME-arcA, native arcA and SCCmec elements were detected by PCR. Susceptibilities to 10 antimicrobial agents were compared between ACME-arcA-positive and -negative isolates by chi-square test. PFGE was used to investigate the clonal relatedness of ACME-arcA-positive isolates. The phylogenetic relationships of ACME-arcA and native arcA were analysed using the neighbour-joining methods of mega software. A total of 42 (47.7 %) of 88 isolates distributed in 13 PFGE types were positive for the ACME-arcA gene. There were no significant differences in antimicrobial susceptibility between ACME-arcA-positive and -negative isolates. A novel ccr allotype (ccrAB(SHP)) was identified in ACME-arcA-positive isolates. Among 42 ACME-arcA-positive isolates: 8 isolates harboured SCCmec V, 8 isolates harboured class C1 mec complex and ccrAB(SHP); 22 isolates harbouring class C1 mec complex and 4 isolates harbouring class C2 mec complex were negative for all known ccr allotypes. The ACME-arcA-positive isolates were first found in MRSH with high prevalence and clonal diversity, which suggests a mobility of ACME within MRSH. The results from this study revealed that MRSH is likely to be one of the potential reservoirs of ACME for Staphylococcus aureus.

A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.

PubMed

Dejnirattisai, Wanwisa; Wongwiwat, Wiyada; Supasa, Sunpetchuda; Zhang, Xiaokang; Dai, Xinghong; Rouvinski, Alexander; Jumnainsong, Amonrat; Edwards, Carolyn; Quyen, Nguyen Than Ha; Duangchinda, Thaneeya; Grimes, Jonathan M; Tsai, Wen-Yang; Lai, Chih-Yun; Wang, Wei-Kung; Malasit, Prida; Farrar, Jeremy; Simmons, Cameron P; Zhou, Z Hong; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

2015-02-01

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

A high efficiency PWM CMOS class-D audio power amplifier

NASA Astrophysics Data System (ADS)

Zhangming, Zhu; Lianxi, Liu; Yintang, Yang; Han, Lei

2009-02-01

Based on the difference close-loop feedback technique and the difference pre-amp, a high efficiency PWM CMOS class-D audio power amplifier is proposed. A rail-to-rail PWM comparator with window function has been embedded in the class-D audio power amplifier. Design results based on the CSMC 0.5 μm CMOS process show that the max efficiency is 90%, the PSRR is -75 dB, the power supply voltage range is 2.5-5.5 V, the THD+N in 1 kHz input frequency is less than 0.20%, the quiescent current in no load is 2.8 mA, and the shutdown current is 0.5 μA. The active area of the class-D audio power amplifier is about 1.47 × 1.52 mm2. With the good performance, the class-D audio power amplifier can be applied to several audio power systems.

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2013-07-03

amphibious assault vehicles; AN/ALE-50 electronic countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush...235 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon Coproduce Patriot,” Defense News, February 22-28...systems) $340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with 176 AESA

Stability and electronic properties of Gex(BN)y monolayers

NASA Astrophysics Data System (ADS)

Freitas, A.; Machado, L. D.; Tromer, R. M.; Bezerra, C. G.; Azevedo, S.

2017-10-01

In this work, we employ ab initio simulations to propose a new class of monolayers with stoichiometry Gex(BN)y . These monolayers belong to a family of 2D materials combining B, N and group IV atoms, such as BxCyNz and SixByNz . We calculated the formation energy for ten atomic arrangements, and found that it increases when the number of Bsbnd Ge and Nsbnd Ge bonds increases, and decreases when the number of Bsbnd N and Gesbnd Ge bonds increases. We found that the lowest energy monolayer presented a Ge2 BN stoichiometry, and maximized the number of Bsbnd N and Gesbnd Ge bonds. This structure also presented mixed sp2 and sp3 bonds and out-of-plane buckling. Moreover, it remained stable in our ab initio molecular dynamics simulations carried out at T = 300 K. The calculated electronic properties revealed that Gex(BN)y monolayers might present conductor or semiconductor behavior, with band gaps ranging from 0.0 to 0.74 eV, depending on atomic arrangement. Tunable values of band gap can be useful in applications. In optoelectronics, for instance, this property might be employed to control absorbed light wavelengths. Our calculations add a new class of monolayers to the increasing library of 2D materials.

Immunoglobulin domain interface exchange as a platform technology for the generation of Fc heterodimers and bispecific antibodies.

PubMed

Skegro, Darko; Stutz, Cian; Ollier, Romain; Svensson, Emelie; Wassmann, Paul; Bourquin, Florence; Monney, Thierry; Gn, Sunitha; Blein, Stanislas

2017-06-09

Bispecific antibodies (bsAbs) are of significant importance to the development of novel antibody-based therapies, and heavy chain (Hc) heterodimers represent a major class of bispecific drug candidates. Current technologies for the generation of Hc heterodimers are suboptimal and often suffer from contamination by homodimers posing purification challenges. Here, we introduce a new technology based on biomimicry wherein the protein-protein interfaces of two different immunoglobulin (Ig) constant domain pairs are exchanged in part or fully to design new heterodimeric domains. The method can be applied across Igs to design Fc heterodimers and bsAbs. We investigated interfaces from human IgA CH3, IgD CH3, IgG1 CH3, IgM CH4, T-cell receptor (TCR) α/β, and TCR γ/δ constant domain pairs, and we found that they successfully drive human IgG1 CH3 or IgM CH4 heterodimerization to levels similar to or above those of reference methods. A comprehensive interface exchange between the TCR α/β constant domain pair and the IgG1 CH3 homodimer was evidenced by X-ray crystallography and used to engineer examples of bsAbs for cancer therapy. Parental antibody pairs were rapidly reformatted into scalable bsAbs that were free of homodimer traces by combining interface exchange, asymmetric Protein A binding, and the scFv × Fab format. In summary, we successfully built several new CH3- or CH4-based heterodimers that may prove useful for designing new bsAb-based therapeutics, and we anticipate that our approach could be broadly implemented across the Ig constant domain family. To our knowledge, CH4-based heterodimers have not been previously reported. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

On the Signaling of Electrochemical Aptamer-Based Sensors: Collision- and Folding-Based Mechanisms

PubMed Central

Xiao, Yi; Uzawa, Takanori; White, Ryan J.; DeMartini, Daniel; Plaxco, Kevin W.

2010-01-01

Recent years have seen the emergence of a new class of electrochemical sensors predicated on target binding-induced folding of electrode-bound redox-modified aptamers and directed against targets ranging from small molecules to proteins. Previous studies of the relationship between gain and probe-density for these electrochemical, aptamer-based (E-AB) sensors suggest that signal transduction is linked to binding-induced changes in the efficiency with which the attached redox tag strikes the electrode. This, in turn, suggests that even well folded aptamers may support E-AB signaling if target binding sufficiently alters their flexibility. Here we investigate this using a thrombin-binding aptamer that undergoes binding-induced folding at low ionic strength but can be forced to adopt a folded conformation at higher ionic strength even in the absence of its protein target. We find that, under conditions in which the thrombin aptamer is fully folded prior to target binding, we still obtain a ca. 30% change in E-AB signal upon saturated target levels. In contrast, however, under conditions in which the aptamer is unfolded in the absence of target and thus undergoes binding-induced folding the observed signal change is twice as great. The ability of folded aptamers to support E-AB signaling, however, is not universal: a fully folded anti-IgE aptamer, for example, produces only an extremely small, ca. 2.5% signal change in the presence of target despite the larger steric bulk of this protein. Thus, while it appears that binding-induced changes in the dynamics in fully folded aptamers can support E-AB signaling, this signaling mechanism may not be general, and in order to ensure the design of high-gain sensors binding must be linked to a large-scale conformational change. PMID:20436787

Virtual Screening as a Strategy for the Identification of Xenobiotics Disrupting Corticosteroid Action

PubMed Central

Praxmarer, Lukas; Chantong, Boonrat; Cereghetti, Diego; Winiger, Rahel; Schuster, Daniela; Odermatt, Alex

2012-01-01

Background Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) and mineralocorticoid receptors (MR) are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations. Methods and Principal Findings We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico predicted chemicals in a 11β-HSD2 bioassay. The identified antibiotic lasalocid and the silane-coupling agent AB110873 were found to concentration-dependently inhibit 11β-HSD2. Moreover, the silane AB110873 was shown to activate MR and stimulate mitochondrial ROS generation and the production of the proinflammatory cytokine interleukin-6 (IL-6). Finally, we constructed a MR pharmacophore, which successfully identified the silane AB110873. Conclusions Screening of virtual chemical structure libraries can facilitate the identification of xenobiotics inhibiting 11β-HSD2 and/or activating MR. Lasalocid and AB110873 belong to new classes of 11β-HSD2 inhibitors. The silane AB110873 represents to the best of our knowledge the first industrial chemical shown to activate MR. Furthermore, the MR pharmacophore can now be used for future screening purposes. PMID:23056542

A process-oriented guided inquiry approach to teaching medicinal chemistry.

PubMed

Brown, Stacy D

2010-09-10

To integrate process-oriented guided-inquiry learning (POGIL) team-based activities into a 1-semester medicinal chemistry course for doctor of pharmacy (PharmD) students and determine the outcomes. Students in the fall 2007 section of the Medicinal Chemistry course were taught in a traditional teacher-centered manner, with the majority of class time spent on lectures and a few practice question sets. Students in the fall 2008 and fall 2009 sections of Medicinal Chemistry spent approximately 40% of class time in structured self-selected teams where they worked through guided-inquiry exercises to supplement the lecture material. The mean examination score of students in the guided-inquiry sections (fall 2008 and fall 2009) was almost 3 percentage points higher than that of students in the fall 2007 class (P < 0.05). Furthermore, the grade distribution shifted from a B-C centered distribution (fall 2007 class) to an A-B centered distribution (fall 2008 and fall 2009 classes). The inclusion of the POGIL style team-based learning exercises improved grade outcomes for the students, encouraged active engagement with the material during class time, provided immediate feedback to the instructor regarding student-knowledge deficiencies, and created a classroom environment that was well received by students.

Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias.

PubMed

Barik, Sailen

2017-12-01

A significant number of proteins in all living species contains amino acid repeats (AARs) of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(A)n] and double [(AB)n] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1) One class of amino acid repeats (Class I) uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2) The second class (Class II) disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons); and finally, (3) In all AARs (including Class I, Class II, and the in-betweens), the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

Genetically Encoded Voltage Indicators: Opportunities and Challenges

PubMed Central

Yang, Helen H.

2016-01-01

A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions. PMID:27683896

The neonatal splice variant of Nav1.5 potentiates in vitro invasive behaviour of MDA-MB-231 human breast cancer cells

PubMed Central

Brackenbury, William J.; Chioni, Athina-Myrto; Diss, James K. J.; Djamgoz, Mustafa B. A.

2014-01-01

Upregulation of functional voltage-gated Na+ channels (VGSCs) occurs in metastatic human breast cancer (BCa) in vitro and in vivo. The present study aimed to ascertain the specific involvement of the ‘neonatal’ splice variant of Nav1.5 (nNav1.5), thought to be predominant, in the VGSC-dependent invasive behaviour of MDA-MB-231 cells. Functional activity of nNav1.5 was suppressed by two different methods targeting nNav1.5: (i) small interfering RNA (siRNA), and (ii) a polyclonal antibody (NESO-pAb); effects upon migration and invasion were determined. nNav1.5 mRNA, protein and signalling were measured using real-time PCR, Western blotting, and patch clamp recording, respectively. Treatment with the siRNA rapidly reduced (by ~90 %) the level of nNav1.5 (but not adult Nav1.5) mRNA, but the protein reduction was much smaller (~30 %), even after 13 days. Nevertheless, the siRNA reduced peak VGSC current density by 33 %, and significantly increased the cells’ sensitivity to nanomolar tetrodotoxin (TTX). Importantly, the siRNA suppressed in vitro migration by 43 %, and eliminated the normally inhibitory effect of TTX. Migrated MDA-MB-231 cells expressed more nNav1.5 protein at the plasma membrane than non-migrated cells. Furthermore, NESO-pAb reduced migration by up to 42 %, in a dose-dependent manner. NESO-pAb also reduced Matrigel invasion without affecting proliferation. TTX had no effect on cells already treated with NESO-pAb. It was concluded that nNav1.5 is primarily responsible for the VGSC-dependent enhancement of invasive behaviour in MDA-MB-231 cells. Accordingly, targeting nNav1.5 expression/activity may be useful in clinical management of metastatic BCa. PMID:16838113

Co@Co3 O4 @PPD Core@bishell Nanoparticle-Based Composite as an Efficient Electrocatalyst for Oxygen Reduction Reaction.

PubMed

Wang, Zhijuan; Li, Bing; Ge, Xiaoming; Goh, F W Thomas; Zhang, Xiao; Du, Guojun; Wuu, Delvin; Liu, Zhaolin; Andy Hor, T S; Zhang, Hua; Zong, Yun

2016-05-01

Durable electrocatalysts with high catalytic activity toward oxygen reduction reaction (ORR) are crucial to high-performance primary zinc-air batteries (ZnABs) and direct methanol fuel cells (DMFCs). An efficient composite electrocatalyst, Co@Co3 O4 core@shell nanoparticles (NPs) embedded in pyrolyzed polydopamine (PPD) is reported, i.e., in Co@Co3 O4 @PPD core@bishell structure, obtained via a three-step sequential process involving hydrothermal synthesis, high temperature calcination under nitrogen atmosphere, and gentle heating in air. With Co@Co3 O4 NPs encapsulated by ultrathin highly graphitized N-doped carbon, the catalyst exhibits excellent stability in aqueous alkaline solution over extended period and good tolerance to methanol crossover effect. The integration of N-doped graphitic carbon outer shell and ultrathin nanocrystalline Co3 O4 inner shell enable high ORR activity of the core@bishell NPs, as evidenced by ZnABs using catalyst of Co@Co3 O4 @PPD in air-cathode which delivers a stable voltage profile over 40 h at a discharge current density of as high as 20 mA cm(-2) . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced equivalence class formation by the delay and relational functions of meaningful stimuli.

PubMed

Arntzen, Erik; Nartey, Richard K; Fields, Lanny

2015-05-01

Undergraduates in six groups of 10 attempted to form three 3-node 5-member equivalence classes (A → B → C → D → E) under the simultaneous protocol. In five of six groups, all stimuli were abstract shapes; in the PIC group, C stimuli were pictures with the remainder being abstract shapes. Before class formation, participants in the Identity-S and Identity-D groups were given preliminary training to form identity conditional discriminations with the C stimuli using simultaneous and 6 s delayed matching-to-sample procedures, respectively. In the Arbitrary-S and Arbitrary-D groups, before class formation, arbitrary conditional discriminations were formed between C and X stimuli using simultaneous and 6 s delayed matching-to-sample procedures, respectively. With no preliminary training, classes in the PIC and ABS groups were formed by 80% and 0% of participants, respectively. After preliminary training, class formation (yield) increased with delay, regardless of relational type. For each of the two delays, yield was slightly greater after forming arbitrary- instead of identity-relations. Yield was greatest, however, when a class contained a meaningful stimulus (PIC). During failed class formation, probes produced experimenter-defined relations, participant-defined relations, and unsystematic responding; delay, but not the relation type in preliminary training influenced relational and indeterminate responding. These results suggest how meaningful stimuli enhance equivalence class formation. © Society for the Experimental Analysis of Behavior.

Mammalian cell culture process for monoclonal antibody production: nonlinear modelling and parameter estimation.

PubMed

Selişteanu, Dan; Șendrescu, Dorin; Georgeanu, Vlad; Roman, Monica

2015-01-01

Monoclonal antibodies (mAbs) are at present one of the fastest growing products of pharmaceutical industry, with widespread applications in biochemistry, biology, and medicine. The operation of mAbs production processes is predominantly based on empirical knowledge, the improvements being achieved by using trial-and-error experiments and precedent practices. The nonlinearity of these processes and the absence of suitable instrumentation require an enhanced modelling effort and modern kinetic parameter estimation strategies. The present work is dedicated to nonlinear dynamic modelling and parameter estimation for a mammalian cell culture process used for mAb production. By using a dynamical model of such kind of processes, an optimization-based technique for estimation of kinetic parameters in the model of mammalian cell culture process is developed. The estimation is achieved as a result of minimizing an error function by a particle swarm optimization (PSO) algorithm. The proposed estimation approach is analyzed in this work by using a particular model of mammalian cell culture, as a case study, but is generic for this class of bioprocesses. The presented case study shows that the proposed parameter estimation technique provides a more accurate simulation of the experimentally observed process behaviour than reported in previous studies.

Mammalian Cell Culture Process for Monoclonal Antibody Production: Nonlinear Modelling and Parameter Estimation

PubMed Central

Selişteanu, Dan; Șendrescu, Dorin; Georgeanu, Vlad

2015-01-01

Monoclonal antibodies (mAbs) are at present one of the fastest growing products of pharmaceutical industry, with widespread applications in biochemistry, biology, and medicine. The operation of mAbs production processes is predominantly based on empirical knowledge, the improvements being achieved by using trial-and-error experiments and precedent practices. The nonlinearity of these processes and the absence of suitable instrumentation require an enhanced modelling effort and modern kinetic parameter estimation strategies. The present work is dedicated to nonlinear dynamic modelling and parameter estimation for a mammalian cell culture process used for mAb production. By using a dynamical model of such kind of processes, an optimization-based technique for estimation of kinetic parameters in the model of mammalian cell culture process is developed. The estimation is achieved as a result of minimizing an error function by a particle swarm optimization (PSO) algorithm. The proposed estimation approach is analyzed in this work by using a particular model of mammalian cell culture, as a case study, but is generic for this class of bioprocesses. The presented case study shows that the proposed parameter estimation technique provides a more accurate simulation of the experimentally observed process behaviour than reported in previous studies. PMID:25685797

Training order and structural location of meaningful stimuli: effects on equivalence class formation.

PubMed

Nartey, Richard K; Arntzen, Erik; Fields, Lanny

2015-12-01

In the present study, equivalence class formation was influenced by the temporal point of inclusion of a meaningful stimulus when baseline relations were serially or sequentially trained, and much less so by the location of the meaningful stimulus in the nodal structure of the class. In Experiment 1, participants attempted to form three 3-node, 5-member classes (A→B→C→D→E) under the simultaneous protocol. After serially training the baseline relations AB, BC, CD, and DE, in that order, the emergence of all emergent relations was tested concurrently. In the A-as-PIC condition, A was meaningful stimulus and B to E were meaningless stimulus, and 60 % of the participants formed classes. In addition, classes were formed by 40 %, 70 %, 40 %, and 20 % of the participants in the B-as-PIC, C-as-PIC, D-as-PIC, and E-as-PIC groups, respectively. Thus, the likelihood of class formation could have been influenced by the location of a meaningful stimulus in the class structure and/or by its order of introduction during training. In Experiment 2, we controlled for any effect of order of introduction by the concurrent training of all of the baseline relations. Regardless of the location of the meaningful stimulus, 0-20 % of participants formed classes. Thus, the temporal order of introducing a meaningful stimulus was the primary modulator of the class-enhancing property of meaningful stimuli, and not the location of the meaningful stimulus in the class structure.

Two integrator loop quadrature oscillators: A review.

PubMed

Soliman, Ahmed M

2013-01-01

A review of the two integrator loop oscillator circuits providing two quadrature sinusoidal output voltages is given. All the circuits considered employ the minimum number of capacitors namely two except one circuit which uses three capacitors. The circuits considered are classified to four different classes. The first class includes floating capacitors and floating resistors and the active building blocks realizing these circuits are the Op Amp or the OTRA. The second class employs grounded capacitors and includes floating resistors and the active building blocks realizing these circuits are the DCVC or the unity gain cells or the CFOA. The third class employs grounded capacitors and grounded resistors and the active building blocks realizing these circuits are the CCII. The fourth class employs grounded capacitors and no resistors and the active building blocks realizing these circuits are the TA. Transformation methods showing the generation of different classes from each other is given in details and this is one of the main objectives of this paper.

Monitoring the metering performance of an electronic voltage transformer on-line based on cyber-physics correlation analysis

NASA Astrophysics Data System (ADS)

Zhang, Zhu; Li, Hongbin; Tang, Dengping; Hu, Chen; Jiao, Yang

2017-10-01

Metering performance is the key parameter of an electronic voltage transformer (EVT), and it requires high accuracy. The conventional off-line calibration method using a standard voltage transformer is not suitable for the key equipment in a smart substation, which needs on-line monitoring. In this article, we propose a method for monitoring the metering performance of an EVT on-line based on cyber-physics correlation analysis. By the electrical and physical properties of a substation running in three-phase symmetry, the principal component analysis method is used to separate the metering deviation caused by the primary fluctuation and the EVT anomaly. The characteristic statistics of the measured data during operation are extracted, and the metering performance of the EVT is evaluated by analyzing the change in statistics. The experimental results show that the method successfully monitors the metering deviation of a Class 0.2 EVT accurately. The method demonstrates the accurate evaluation of on-line monitoring of the metering performance on an EVT without a standard voltage transformer.

An Inexpensive Source of High Voltage

NASA Astrophysics Data System (ADS)

Saraiva, Carlos

2012-04-01

As a physics teacher I like recycling old apparatus and using them for demonstrations in my classes.1-4 In physics laboratories in schools, sources of high voltage include induction coils or electronic systems that can be bought from companies that sell lab equipment. But these sources can be very expensive. In this article, I will explain how you can use a car ignition coil as a high voltage source. Such a coil can be obtained from an old car found in a car salvage yard and used to power cathode ray tubes and discharge tubes to observe the spectra. It can also be used as a source of ignition to simulate explosive combustion that occurs in car engines, rockets, etc. You can also buy these coils in shops that sell car accessories and they are cheaper than induction coils. In Fig. 1 you can see a coil that I used.

Metallic VS2 Monolayer Polytypes as Potential Sodium-Ion Battery Anode via ab Initio Random Structure Searching.

PubMed

Putungan, Darwin Barayang; Lin, Shi-Hsin; Kuo, Jer-Lai

2016-07-27

We systematically investigated the potential of single-layer VS2 polytypes as Na-battery anode materials via density functional theory calculations. We found that sodiation tends to inhibit the 1H-to-1T structural phase transition, in contrast to lithiation-induced transition on monolayer MoS2. Thus, VS2 can have better structural stability in the cycles of charging and discharging. Diffussion of Na atom was found to be very fast on both polytypes, with very small diffusion barriers of 0.085 eV (1H) and 0.088 eV (1T). Ab initio random structure searching was performed in order to explore stable configurations of Na on VS2. Our search found that both the V top and the hexagonal center sites are preferred adsorption sites for Na, with the 1H phase showing a relatively stronger binding. Notably, our random structures search revealed that Na clusters can form as a stacked second layer at full Na concentration, which is not reported in earlier works wherein uniform, single-layer Na adsorption phases were assumed. With reasonably high specific energy capacity (232.91 and 116.45 mAh/g for 1H and 1T phases, respectively) and open-circuit voltage (1.30 and 1.42 V for 1H and 1T phases, respectively), VS2 is a promising alternative material for Na-ion battery anodes with great structural sturdiness. Finally, we have shown the capability of the ab initio random structure searching in the assessment of potential materials for energy storage applications.

Performance of laying hens fed diets containing DAS-59122-7 maize grain compared with diets containing nontransgenic maize grain.

PubMed

Jacobs, C M; Utterback, P L; Parsons, C M; Rice, D; Smith, B; Hinds, M; Liebergesell, M; Sauber, T

2008-03-01

An experiment using 216 Hy-Line W-36 pullets was conducted to evaluate transgenic maize grain containing the cry34Ab1 and cry35Ab1 genes from a Bacillus thuringiensis (Bt) strain and the phosphinothricin ace-tyltransferase (pat) gene from Streptomyces viridochromogenes. Expression of the cry34Ab1 and cry35Ab1 genes confers resistance to corn rootworms, and the pat gene confers tolerance to herbicides containing glufosinate-ammonium. Pullets (20 wk of age) were placed in cage lots (3 hens/cage, 2 cages/lot) and were randomly assigned to 1 of 3 corn-soybean meal dietary treatments (12 lots/treatment) formulated with the following maize grains: near-isogenic control (control), conventional maize, and transgenic test corn line 59122 containing event DAS-59122-7. Differences between 59122 and control group means were evaluated with statistical significance at P < 0.05. Body weight and gain, egg production, egg mass, and feed efficiency for hens fed the 59122 corn were not significantly different from the respective values for hens fed diets formulated with control maize grain. Egg component weights, Haugh unit measures, and egg weight class distribution were similar regardless of the corn source. This research indicates that performance of hens fed diets containing 59122 maize grain, as measured by egg production and egg quality, was similar to that of hens fed diets formulated with near-isogenic corn grain.

A Systematic Review and Meta-Analyses of the Association Between Anti-Hypertensive Classes and the Risk of Falls Among Older Adults.

PubMed

Ang, Hui Ting; Lim, Ka Keat; Kwan, Yu Heng; Tan, Pui San; Yap, Kai Zhen; Banu, Zafirah; Tan, Chuen Seng; Fong, Warren; Thumboo, Julian; Ostbye, Truls; Low, Lian Leng

2018-06-23

Falls in individuals aged ≥ 60 years may result in injury, hospitalisation or death. The role of anti-hypertensive medications in falls among older adults is unclear. The objective of this study was to assess the association of six anti-hypertensive medication classes, namely α-blockers (AB), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), β-blockers (BB), calcium channel blockers (CCB) and diuretics, with the risk of falls, injurious falls or recurrent falls in individuals aged ≥ 60 years compared with non-users. We performed systematic searches in PubMed, EMBASE and CINAHL and included cohort, case-control and cross-sectional studies that investigated the associations between the use of anti-hypertensive medication classes and the risk of falls, injurious falls or recurrent falls in older adults (≥ 60 years) reported in English. We assessed study quality using the Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted odds ratios (ORs) were pooled using random effects model. We performed meta-analyses for each anti-hypertensive medication class and each fall outcome. We also performed sensitivity analyses by pooling studies of high quality and subgroup analyses among studies with an average age of ≥ 80 years. Seventy-eight articles (where 74, 34, 27, 18, 13 and 11 of them examined diuretics, BB, CCB, ACEi, AB and ARB, respectively) met our inclusion and exclusion criteria; we pooled estimates from 60 articles. ACEi [OR 0.85, 95% confidence interval (CI) 0.81-0.89], BB (OR 0.84, 95% CI 0.76-0.93) and CCB (OR 0.81, 95% CI 0.74-0.90) use were associated with a lower risk of injurious falls than in non-users. Results in sensitivity and subgroup analyses were largely consistent. The use of ACEi, BB or CCB among older adults may be associated with a lower risk of injurious falls than non-use.

Multiple modes of a-type potassium current regulation.

PubMed

Cai, Shi-Qing; Li, Wenchao; Sesti, Federico

2007-01-01

Voltage-dependent potassium (K+) channels (Kv) regulate cell excitability by controlling the movement of K+ ions across the membrane in response to changes in the cell voltage. The Kv family, which includes A-type channels, constitute the largest group of K+ channel genes within the superfamily of Na+, Ca2+ and K+ voltage-gated channels. The name "A-type" stems from the typical profile of these currents that results form the opposing effects of fast activation and inactivation. In neuronal cells, A-type currents (I(A)), determine the interval between two consecutive action potentials during repetitive firing. In cardiac muscle, A-type currents (I(to)), control the initial repolarization of the myocardium. Structurally, A-type channels are tetramers of alpha-subunits each containing six putative transmembrane domains including a voltage-sensor. A-type channels can be modulated by means of protein-protein interactions with so-called beta-subunits that control inactivation voltage sensitivity and other properties, and by post-transcriptional modifications such as phosphorylation or oxidation. Recently a new mode of A-type regulation has been discovered in the form of a class of hybrid beta-subunits that posses their own enzymatic activity. Here, we review the biophysical and physiological properties of these multiple modes of A-type channel regulation.

Locating the route of entry and binding sites of benzocaine and phenytoin in a bacterial voltage gated sodium channel.

PubMed

Martin, Lewis J; Corry, Ben

2014-07-01

Sodium channel blockers are used to control electrical excitability in cells as a treatment for epileptic seizures and cardiac arrhythmia, and to provide short term control of pain. Development of the next generation of drugs that can selectively target one of the nine types of voltage-gated sodium channel expressed in the body requires a much better understanding of how current channel blockers work. Here we make use of the recently determined crystal structure of the bacterial voltage gated sodium channel NavAb in molecular dynamics simulations to elucidate the position at which the sodium channel blocking drugs benzocaine and phenytoin bind to the protein as well as to understand how these drugs find their way into resting channels. We show that both drugs have two likely binding sites in the pore characterised by nonspecific, hydrophobic interactions: one just above the activation gate, and one at the entrance to the the lateral lipid filled fenestrations. Three independent methods find the same sites and all suggest that binding to the activation gate is slightly more favourable than at the fenestration. Both drugs are found to be able to pass through the fenestrations into the lipid with only small energy barriers, suggesting that this can represent the long posited hydrophobic entrance route for neutral drugs. Our simulations highlight the importance of a number of residues in directing drugs into and through the fenestration, and in forming the drug binding sites.

Locating the Route of Entry and Binding Sites of Benzocaine and Phenytoin in a Bacterial Voltage Gated Sodium Channel

PubMed Central

Martin, Lewis J.; Corry, Ben

2014-01-01

Sodium channel blockers are used to control electrical excitability in cells as a treatment for epileptic seizures and cardiac arrhythmia, and to provide short term control of pain. Development of the next generation of drugs that can selectively target one of the nine types of voltage-gated sodium channel expressed in the body requires a much better understanding of how current channel blockers work. Here we make use of the recently determined crystal structure of the bacterial voltage gated sodium channel NavAb in molecular dynamics simulations to elucidate the position at which the sodium channel blocking drugs benzocaine and phenytoin bind to the protein as well as to understand how these drugs find their way into resting channels. We show that both drugs have two likely binding sites in the pore characterised by nonspecific, hydrophobic interactions: one just above the activation gate, and one at the entrance to the the lateral lipid filled fenestrations. Three independent methods find the same sites and all suggest that binding to the activation gate is slightly more favourable than at the fenestration. Both drugs are found to be able to pass through the fenestrations into the lipid with only small energy barriers, suggesting that this can represent the long posited hydrophobic entrance route for neutral drugs. Our simulations highlight the importance of a number of residues in directing drugs into and through the fenestration, and in forming the drug binding sites. PMID:24992293

Reflections on Over Fifty Years in Research and Development; Some Lessons Learned

DTIC Science & Technology

2012-02-01

his career in chemical research and development at the Monsanto Chemical Company. Dr. Lyons received his AB in chemistry from Harvard College and...developing new uses for its products (applications research). Chemical Applications in the Field My first task at the Monsanto Research Laboratory was...permanent employees, post-doctoral fellows, and guest workers. When I was at Monsanto Company, a special class of “stars” was singled out by management

World Reference Center and Arbovirus Diagnosis.

DTIC Science & Technology

1980-10-01

protect personnel working with CDC class 3 viruses and unknown viruses from possible infection 1. GENERAL STATEMENT This contract proposal is submitted...Carey, A.B., and Downs, W.G. Powassan virus in Ixodes cookei and Mustelidae in New England. J. Wildlife Dis. 15: 585-591, 1979. Main, A.J., Smith...those at CDC (25) showed that the FA test detects antibody earlier and longer than the CF test and is thus a more sensitive diagnostic technique. The

Co3O4 nanoparticles decorated carbon nanofiber mat as binder-free air-cathode for high performance rechargeable zinc-air batteries

NASA Astrophysics Data System (ADS)

Li, Bing; Ge, Xiaoming; Goh, F. W. Thomas; Hor, T. S. Andy; Geng, Dongsheng; Du, Guojun; Liu, Zhaolin; Zhang, Jie; Liu, Xiaogang; Zong, Yun

2015-01-01

An efficient, durable and low cost air-cathode is essential for a high performance metal-air battery for practical applications. Herein, we report a composite bifunctional catalyst, Co3O4 nanoparticles-decorated carbon nanofibers (CNFs), working as an efficient air-cathode in high performance rechargeable Zn-air batteries (ZnABs). The particles-on-fibers nanohybrid materials were derived from electrospun metal-ion containing polymer fibers followed by thermal carbonization and a post annealing process in air at a moderate temperature. Electrochemical studies suggest that the nanohybrid material effectively catalyzes oxygen reduction reaction via an ideal 4-electron transfer process and outperforms Pt/C in catalyzing oxygen evolution reactions. Accordingly, the prototype ZnABs exhibit a low discharge-charge voltage gap (e.g. 0.7 V, discharge-charge at 2 mA cm-2) with higher stability and longer cycle life compared to their counterparts constructed using Pt/C in air-cathode. Importantly, the hybrid nanofiber mat readily serves as an integrated air-cathode without the need of any further modification. Benefitting from its efficient catalytic activities and structural advantages, particularly the 3D architecture of highly conductive CNFs and the high loading density of strongly attached Co3O4 NPs on their surfaces, the resultant ZnABs show significantly improved performance with respect to the rate capability, cycling stability and current density, promising good potential in practical applications.An efficient, durable and low cost air-cathode is essential for a high performance metal-air battery for practical applications. Herein, we report a composite bifunctional catalyst, Co3O4 nanoparticles-decorated carbon nanofibers (CNFs), working as an efficient air-cathode in high performance rechargeable Zn-air batteries (ZnABs). The particles-on-fibers nanohybrid materials were derived from electrospun metal-ion containing polymer fibers followed by thermal carbonization and a post annealing process in air at a moderate temperature. Electrochemical studies suggest that the nanohybrid material effectively catalyzes oxygen reduction reaction via an ideal 4-electron transfer process and outperforms Pt/C in catalyzing oxygen evolution reactions. Accordingly, the prototype ZnABs exhibit a low discharge-charge voltage gap (e.g. 0.7 V, discharge-charge at 2 mA cm-2) with higher stability and longer cycle life compared to their counterparts constructed using Pt/C in air-cathode. Importantly, the hybrid nanofiber mat readily serves as an integrated air-cathode without the need of any further modification. Benefitting from its efficient catalytic activities and structural advantages, particularly the 3D architecture of highly conductive CNFs and the high loading density of strongly attached Co3O4 NPs on their surfaces, the resultant ZnABs show significantly improved performance with respect to the rate capability, cycling stability and current density, promising good potential in practical applications. Electronic supplementary information (ESI) available: TGA curves of as electrospun Co(ii)-PAN fiber and C-CoPAN900 EDX and XPS spectra of the C-CoPAN900 photo of a home-built Zn-air cell and the preparation method of conventional catalyst electrode; polarization curves and corresponding power density plots of the battery using conventional type cathode of C-CoPN900 and commercial Pt/C catalyst; the electrocatalytic properties of hybrid CNFs obtained from varied weight ratios of PAN to cobalt acetate, e.g. 16 : 1 and 8 : 1, and their corresponding TGA curves; a comparison of the Zn-air battery performance of this work with recent literatures. See DOI: 10.1039/c4nr05988c

Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer.

PubMed

Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

2018-05-01

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined. Results: Different proportions of α2δ1 + cells were identified in SCLC cell lines and PDX models. α2δ1 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1 + cells instead of CD133 + cells in PDXs, and an increased proportion of α2δ1 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148-58. ©2018 AACR . ©2018 American Association for Cancer Research.

In vivo RF powering for advanced biological research.

PubMed

Zimmerman, Mark D; Chaimanonart, Nattapon; Young, Darrin J

2006-01-01

An optimized remote powering architecture with a miniature and implantable RF power converter for an untethered small laboratory animal inside a cage is proposed. The proposed implantable device exhibits dimensions less than 6 mmx6 mmx1 mm, and a mass of 100 mg including a medical-grade silicon coating. The external system consists of a Class-E power amplifier driving a tuned 15 cmx25 cm external coil placed underneath the cage. The implant device is located in the animal's abdomen in a plane parallel to the external coil and utilizes inductive coupling to receive power from the external system. A half-wave rectifier rectifies the received AC voltage and passes the resulting DC current to a 2.5 kOmega resistor, which represents the loading of an implantable microsystem. An optimal operating point with respect to operating frequency and number of turns in each coil inductor was determined by analyzing the system efficiency. The determined optimal operating condition is based on a 4-turn external coil and a 20-turn internal coil operating at 4 MHz. With the Class-E amplifier consuming a constant power of 25 W, this operating condition is sufficient to supply a desired 3.2 V with 1.3 mA to the load over a cage size of 10 cmx20 cm with an animal tilting angle of up to 60 degrees, which is the worst case considered for the prototype design. A voltage regulator can be designed to regulate the received DC power to a stable supply for the bio-implant microsystem.

Weighted stacking of seismic AVO data using hybrid AB semblance and local similarity

NASA Astrophysics Data System (ADS)

Deng, Pan; Chen, Yangkang; Zhang, Yu; Zhou, Hua-Wei

2016-04-01

The common-midpoint (CMP) stacking technique plays an important role in enhancing the signal-to-noise ratio (SNR) in seismic data processing and imaging. Weighted stacking is often used to improve the performance of conventional equal-weight stacking in further attenuating random noise and handling the amplitude variations in real seismic data. In this study, we propose to use a hybrid framework of combining AB semblance and a local-similarity-weighted stacking scheme. The objective is to achieve an optimal stacking of the CMP gathers with class II amplitude-variation-with-offset (AVO) polarity-reversal anomaly. The selection of high-quality near-offset reference trace is another innovation of this work because of its better preservation of useful energy. Applications to synthetic and field seismic data demonstrate a great improvement using our method to capture the true locations of weak reflections, distinguish thin-bed tuning artifacts, and effectively attenuate random noise.

VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells.

PubMed

Ren, Xueyan; Xie, Wei; Wang, Youfu; Xu, Menghuai; Liu, Fang; Tang, Mingying; Li, Chenchen; Wang, Min; Zhang, Juan

2016-08-01

MHC class I polypeptide-related sequence A (MICA), which is normally expressed on cancer cells, activates NK cells via NK group 2-member D pathway. However, some cancer cells escape NK-mediated immune surveillance by shedding membrane MICA causing immune suppression. To address this issue, we designed an antibody-MICA fusion targeting tumor-specific antigen (vascular endothelial growth factor receptor 2, VEGFR2) based on our patented antibody (mAb04) against VEGFR2. In vitro results demonstrate that the fusion antibody retains both the antineoplastic and the immunomodulatory activity of mAb04. Further, we revealed that it enhanced NK-mediated immunosurveillance against K562 cells through increasing degranulation and cytokine production of NK cells. The overall data suggest our new fusion protein provides a promising approach for cancer-targeted immunotherapy and has prospects for potential application of chronic myeloid leukemia.

Quantitative structure activity relationships from optimised ab initio bond lengths: steroid binding affinity and antibacterial activity of nitrofuran derivatives

NASA Astrophysics Data System (ADS)

Smith, P. J.; Popelier, P. L. A.

2004-02-01

The present day abundance of cheap computing power enables the use of quantum chemical ab initio data in Quantitative Structure-Activity Relationships (QSARs). Optimised bond lengths are a new such class of descriptors, which we have successfully used previously in representing electronic effects in medicinal and ecological QSARs (enzyme inhibitory activity, hydrolysis rate constants and pKas). Here we use AM1 and HF/3-21G* bond lengths in conjunction with Partial Least Squares (PLS) and a Genetic Algorithm (GA) to predict the Corticosteroid-Binding Globulin (CBG) binding activity of the classic steroid data set, and the antibacterial activity of nitrofuran derivatives. The current procedure, which does not require molecular alignment, produces good r2 and q2 values. Moreover, it highlights regions in the common steroid skeleton deemed relevant to the active regions of the steroids and nitrofuran derivatives.

Quantifying Ab Initio Equation of State Errors for Hydrogen-Helium Mixtures

NASA Astrophysics Data System (ADS)

Clay, Raymond; Morales, Miguel

2017-06-01

In order to produce predictive models of Jovian planets, an accurate equation of state for hydrogen-helium mixtures is needed over pressure and temperature ranges spanning multiple orders of magnitude. While extensive theoretical work has been done in this area, previous controversies regarding the equation of state of pure hydrogen have demonstrated exceptional sensitivity to approximations commonly employed in ab initio calculations. To this end, we present the results of our quantum Monte Carlo based benchmarking studies for several major classes of density functionals. Additionally, we expand upon our published results by considering the impact that ionic finite size effects and density functional errors translate to errors in the equation of state. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Studies on hydride-forming alloys as the active material of a metal hydride electrode for a nickel metal hydride cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, H.S.; Zelter, G.R.; Allison, D.U.

1997-12-01

Multi-component AB{sub 5} hydrides are attractive replacements for the cadmium electrode in nickel-cadmium batteries. The archetype compound of the AB{sub 5} alloy class is LaNi{sub 5}, but in a typical battery electrode mischmetal is substituted for La and Ni is substituted in part by variety of metals. This paper deals with the effect on cycle life upon the partial substitution of various lanthanides for La and Sn, In, Al, Co, and Mn for Ni. The presence of Ce was shown to enhance cycle life as did Sn in some cases. An electrode of La{sub 0.67}Ce{sub 0.33}B{sub 5} alloy gave overmore » 3,500 cycles (to specific capacity of 200 mAh/g), indicating that it is a very attractive alloy for a practical Ni/MH{sub x} cell.« less

New force field for molecular simulation of guanidinium-based ionic liquids.

PubMed

Liu, Xiaomin; Zhang, Suojiang; Zhou, Guohui; Wu, Guangwen; Yuan, Xiaoliang; Yao, Xiaoqian

2006-06-22

An all-atom force field was proposed for a new class of room temperature ionic liquids (RTILs), N,N,N',N'-tetramethylguanidinium (TMG) RTILs. The model is based on the AMBER force field with modifications on several parameters. The refinements include (1) fitting the vibration frequencies for obtaining force coefficients of bonds and angles against the data obtained by ab initio calculations and/or by experiments and (2) fitting the torsion energy profiles of dihedral angles for obtaining torsion parameters against the data obtained by ab initio calculations. To validate the force field, molecular dynamics (MD) simulations at different temperatures were performed for five kinds of RTILs, where TMG acts as a cation and formate, lactate, perchlorate, trifluoroacetate, and trifluoromethylsulfonate act as anions. The predicted densities were in good agreement with the experimental data. Radial distribution functions (RDFs) and spatial distribution functions (SDFs) were investigated to depict the microscopic structures of the RTILs.

Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.

PubMed

Kang, H W; Weissleder, R; Bogdanov, A

2002-01-01

Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.

Integron, Plasmid and Host Strain Characteristics of Escherichia coli from Humans and Food Included in the Norwegian Antimicrobial Resistance Monitoring Programs.

PubMed

Sunde, Marianne; Simonsen, Gunnar Skov; Slettemeås, Jannice Schau; Böckerman, Inger; Norström, Madelaine

2015-01-01

Antimicrobial resistant Escherichia coli (n=331) isolates from humans with bloodstream infections were investigated for the presence of class 1 and class 2 integrons. The integron cassettes arrays were characterized and the findings were compared with data from similar investigations on resistant E. coli from meat and meat products (n=241) produced during the same time period. All isolates were obtained from the Norwegian monitoring programs for antimicrobial resistance in human pathogens and in the veterinary sector. Methods used included PCR, sequencing, conjugation experiments, plasmid replicon typing and subtyping, pulsed-field-gel-electrophoresis and serotyping. Integrons of class 1 and 2 occurred significantly more frequently among human isolates; 45.4% (95% CI: 39.9-50.9) than among isolates from meat; 18% (95% CI: 13.2 -23.3), (p<0.01, Chi-square test). Identical cassette arrays including dfrA1-aadA1, aadA1, dfrA12-orfF-aadA2, oxa-30-aadA1 (class 1 integrons) and dfrA1-sat1-aadA1 (class 2 integrons) were detected from both humans and meat. However, the most prevalent cassette array in human isolates, dfrA17-aadA5, did not occur in isolates from meat, suggesting a possible linkage between this class 1 integron and a subpopulation of E. coli adapted to a human host. The drfA1-aadA1 and aadA1 class 1 integrons were found frequently in both human and meat isolates. These isolates were subjected to further studies to investigate similarities with regard to transferability, plasmid and host strain characteristics. We detected incF plasmids with pMLST profile F24:A-:B1 carrying drfA1-aadA1 integrons in isolates from pork and in a more distantly related E. coli strain from a human with septicaemia. Furthermore, we showed that most of the class 1 integrons with aadA1 were located on incF plasmids with pMLST profile F51:A-:B10 in human isolates. The plasmid was present in unrelated as well as closely related host strains, demonstrating that dissemination of this integron also could be attributed to clonal spread. In conclusion, among the systematically collected isolates from two different sources, some significant differences concerning integron prevalence and integron variants were observed. However, closely related plasmids as vehicles for specific class 1 integrons in isolates from meat and from a human with bloodstream infection were found. The occurrence of similar multi-resistance plasmids in bacteria from a food source and from a human clinical sample highlights the possible role of meat as a source of resistance elements for pathogenic bacteria.

Fuel Cell System Contaminants Material Screening Data | Hydrogen and Fuel

Science.gov Websites

contaminants; solution conductivity; pH; total organic carbon (TOC); cyclic voltammetry (CV); membrane conductivity) and organics (measured as total organic carbon) in leachate solutions. Each plot shows the ) contaminants on voltage loss over time for each materials class. GCMS Summary: Top 4 Organic Compounds by

77 FR 9204 - Large Power Transformers From the Republic of Korea: Preliminary Determination of Sales at Less...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

...; (12) low voltage winding basic insulation level; (13) load loss at maximum MVA rating; (14) no-load loss; (15) cooling class designation; (16) overload requirement; (17) decibel rating; and (18... Transformers from Korea: Investigation No. 731-TA-1189 (Preliminary).'' On September 16, 2011, we selected...

30 CFR 75.818 - Use of insulated cable handling equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... personal protective equipment capable of providing protection against shock hazard must be used to prevent... protective equipment must— (1) Have a voltage rating of at least Class 1 (7,500 volts) that meets or exceeds... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Use of insulated cable handling equipment. 75...

30 CFR 75.818 - Use of insulated cable handling equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... personal protective equipment capable of providing protection against shock hazard must be used to prevent... protective equipment must— (1) Have a voltage rating of at least Class 1 (7,500 volts) that meets or exceeds... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of insulated cable handling equipment. 75...

If it’s pinched it’s a memristor

NASA Astrophysics Data System (ADS)

Chua, Leon

2014-10-01

This paper presents an in-depth review of the memristor from a rigorous circuit-theoretic perspective, independent of the material the device is made of. From an experimental perspective, a memristor is best defined as any two-terminal device that exhibits a pinched hysteresis loop in the voltage-current plane when driven by any periodic voltage or current signal that elicits a periodic response of the same frequency. This definition greatly broadens the scope of memristive devices to encompass even non-semiconductor devices, both organic and inorganic, from many unrelated disciplines, including biology, botany, brain science, etc. For pedagogical reasons, the broad terrain of memristors is partitioned into three classes of increasing generality, dubbed Ideal Memristors, Generic Memristors, and Extended Memristors. Each class is distinguished from the others via unique fingerprints and signatures. This paper clarifies many confusing issues, such as non-volatility, dc V-I curves, high-frequency v-i curves, local activity, as well as nonlinear dynamical and bifurcation phenomena that are the hallmarks of memristive devices. Above all, this paper addresses several fundamental issues and questions that many memristor researchers do not comprehend but are afraid to ask.

Analysis and Optimization of Pulse Dynamics for Magnetic Stimulation

PubMed Central

Goetz, Stefan M.; Truong, Cong Nam; Gerhofer, Manuel G.; Peterchev, Angel V.; Herzog, Hans-Georg; Weyh, Thomas

2013-01-01

Magnetic stimulation is a standard tool in brain research and has found important clinical applications in neurology, psychiatry, and rehabilitation. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received less attention. Typically, the magnetic field waveform is determined by available device circuit topologies rather than by consideration of what is optimal for neural stimulation. This paper analyzes and optimizes the waveform dynamics using a nonlinear model of a mammalian axon. The optimization objective was to minimize the pulse energy loss. The energy loss drives power consumption and heating, which are the dominating limitations of magnetic stimulation. The optimization approach is based on a hybrid global-local method. Different coordinate systems for describing the continuous waveforms in a limited parameter space are defined for numerical stability. The optimization results suggest that there are waveforms with substantially higher efficiency than that of traditional pulse shapes. One class of optimal pulses is analyzed further. Although the coil voltage profile of these waveforms is almost rectangular, the corresponding current shape presents distinctive characteristics, such as a slow low-amplitude first phase which precedes the main pulse and reduces the losses. Representatives of this class of waveforms corresponding to different maximum voltages are linked by a nonlinear transformation. The main phase, however, scales with time only. As with conventional magnetic stimulation pulses, briefer pulses result in lower energy loss but require higher coil voltage than longer pulses. PMID:23469168

Genetically Encoded Voltage Indicators: Opportunities and Challenges.

PubMed

Yang, Helen H; St-Pierre, François

2016-09-28

A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions. Copyright © 2016 the authors 0270-6474/16/369977-13$15.00/0.

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

PubMed Central

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems. PMID:25816008

Transport properties of two-dimensional metal-phthalocyanine junctions: An ab initio study

NASA Astrophysics Data System (ADS)

Liu, Shuang-Long; Wang, Yun-Peng; Li, Xiang-Guo; Cheng, Hai-Ping

We study two dimensional (2D) electronic/spintronic junctions made of metal-organic frameworks via first-principles simulation. The system consists of two Mn-phthalocyanine leads and a Ni-phthalocyanine center. A 2D Mn phthalocyanine sheet is ferromagnetic half metal and a 2D Ni phthalocyanine sheet is nonmagnetic semiconductor. Our results show that this system has a large tunnel magnetic resistance. The transmission coefficient at Fermi energy decays exponentially with the length of the central region which is not surprising. However, the transmission of the junction can be tuned using gate voltage by up to two orders of magnitude. The origin of the change lies in the mode matching between the lead and the center electronic states. Moreover, the threshold gate voltage varies with the length of the center region which provides a way of engineering the transport properties. Finally, we combine non-equilibrium Green's function and Boltzmann transport equation to compute conductance of the junction. This work was supported by the US Department of Energy (DOE), Office of Basic Energy Sciences (BES), under Contract No. DE-FG02-02ER45995. Computations were done using the utilities of NERSC and University of Florida Research Computing.

Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel

PubMed Central

Boiteux, Céline; Vorobyov, Igor; French, Robert J.; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W.

2014-01-01

Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the “hinged lid”-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water–protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

Enhancement of the magnetoelectric coupling in an A-line shape magnetostrictive/piezoelectric structure

NASA Astrophysics Data System (ADS)

Zhang, Juanjuan; Kang, Yan; Yu, Yang; Gao, Yuanwen

2017-01-01

In this study, a new kind of magnetoelectric (ME) structure is designed with Terfenol-D, PZT-5A and nonmagnetic and nonelectric trestle. The configuration of this ME structure presents "A-line" type, PZT-5A and Terfenol-D are respectively bonded with the trestles, which adopt the knuckle joint assembly. Differently from the conventional ME layered structure, in the new structure, the deformation of the PZT-5A of larger size is driven by a Terfenol-D layer of smaller size at an external magnetic field. Since the driven force is applied at the ends of piezoelectric layer through the trestles, the whole piezoelectric layer can be completely stretched or compressed, and the larger voltage should be induced. For the new ME structure with mica trestle, the maximum value of αE is twice higher than that for the conventional laminated ME structure. Furthermore, a wider range of response frequency is also observed in this structure. For the new ME structure with ABS trestle, the experimental results indicate that the maximum ME voltage coefficient is measured as high as 31.85 V/cm Oe at 405 Oe.

Early Hematopoietic Zinc Finger Protein Prevents Tumor Cell Recognition by Natural Killer Cells1

PubMed Central

La Rocca, Rosanna; Fulciniti, Mariateresa; Lakshmikanth, Tadepally; Mesuraca, Maria; Ali, Talib Hassan; Mazzei, Valerio; Amodio, Nicola; Catalano, Lucio; Rotoli, Bruno; Ouerfelli, Ouathek; Grieco, Michele; Gulletta, Elio; Bond, Heather M.; Morrone, Giovanni; Ferrone, Soldano; Carbone, Ennio

2009-01-01

Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells. PMID:19342626

VGKC positive autoimmune encephalopathy mimicking dementia.

PubMed

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O' Toole, Orna

2011-12-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan's syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment.

Transcutaneous RF-Powered Implantable Minipump Driven by a Class-E Transmitter

PubMed Central

Moore, William H.; Holschneider, Daniel P.; Givrad, Tina K.

2007-01-01

We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation. PMID:16916107

Transcutaneous RF-powered implantable minipump driven by a class-E transmitter.

PubMed

Moore, William H; Holschneider, Daniel P; Givrad, Tina K; Maarek, Jean-Michel I

2006-08-01

We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation.

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2012-11-29

vehicles; AN/ALE-50 electronic countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush approved four...Review Process, by Richard F. Grimmett. 256 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon Coproduce Patriot,” Defense News...Sheng C4 systems) $340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with 176

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2012-02-24

howitzers; 54 AAV7A1 amphibious assault vehicles; AN/ALE-50 electronic countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters...Grimmett. 279 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon Coproduce Patriot,” Defense News, February 22-28, 1993...Sheng C4 systems) $340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with

Taiwan: Major U.S. Arms Sales Since 1990

DTIC Science & Technology

2014-03-03

vehicles; AN/ALE-50 electronic countermeasure (ECM) systems for F-16s; and 12 MH-53 mine -sweeping helicopters. President Bush approved four...resolution of disapproval) as stipulated under Section 36(b) of the AECA. 239 Commercial sale. Opall Barbara and David Silverberg, “Taiwanese May Soon...Sheng C4 systems) $340 01/29 (2) Osprey-class mine hunting ships (refurbished and upgraded) $105 2011 09/21 Retrofit of 145 F-16A/B fighters, with

Finite-Amplitude Standing Waves in a Cavity with Boundary Perturbations.

DTIC Science & Technology

1982-04-01

report is authorized. This report was prepared by: A.B. PEN .------ 7 V. -SANDERS Pro of Physics .. Professor of Physics Approved by: / J . Rilliam H...Toi " Department of Physics Dean of Research +ECUNITY CLASS IICATION OP TNI PAGE fUm e. be, _ _ REPOR DOCUMNTTO PAGE 1. NUPORT RuIMIKN ILOV-ACCESION...capacities,and t an operator describing the physical processes for absorption and dispersion. The term on the right can be interpreted as a

Towards A Predictive First Principles Understanding Of Molecular Adsorption On Graphene

DTIC Science & Technology

2016-10-05

used and developed state-of-the-art quantum mechanical methods to make accurate predictions about the interaction strength and adsorption structure...density functional theory, ab initio methods 16.  SECURITY CLASSIFICATION OF: 17.  LIMITATION OF ABSTRACT SAR 18.  NUMBER OF PAGES   11   19a.  NAME OF...important physical properties for a whole class of systems with weak non-covalent interactions, for example those involving the binding between water

B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6

PubMed Central

Jackson, Shaun W.; Jacobs, Holly M.; Arkatkar, Tanvi; Dam, Elizabeth M.; Scharping, Nicole E.; Kolhatkar, Nikita S.; Hou, Baidong; Buckner, Jane H.

2016-01-01

Dysregulated germinal center (GC) responses are implicated in the pathogenesis of human autoimmune diseases, including systemic lupus erythematosus (SLE). Although both type 1 and type 2 interferons (IFNs) are involved in lupus pathogenesis, their respective impacts on the establishment of autoimmune GCs has not been addressed. In this study, using a chimeric model of B cell-driven autoimmunity, we demonstrate that B cell type 1 IFN receptor signals accelerate, but are not required for, lupus development. In contrast, B cells functioning as antigen-presenting cells initiate CD4+ T cell activation and IFN-γ production, and strikingly, B cell–intrinsic deletion of the IFN-γ receptor (IFN-γR) abrogates autoimmune GCs, class-switched autoantibodies (auto-Abs), and systemic autoimmunity. Mechanistically, although IFN-γR signals increase B cell T-bet expression, B cell–intrinsic deletion of T-bet exerts an isolated impact on class-switch recombination to pathogenic auto-Ab subclasses without impacting GC development. Rather, in both mouse and human B cells, IFN-γ synergized with B cell receptor, toll-like receptor, and/or CD40 activation signals to promote cell-intrinsic expression of the GC master transcription factor, B cell lymphoma 6 protein. Our combined findings identify a novel B cell–intrinsic mechanism whereby IFN signals promote lupus pathogenesis, implicating this pathway as a potential therapeutic target in SLE. PMID:27069113

Towards a new class of heavy ion doped magnetic semiconductors for room temperature applications

PubMed Central

Lee, Juwon; Subramaniam, Nagarajan Ganapathi; Agnieszka Kowalik, Iwona; Nisar, Jawad; Lee, Jaechul; Kwon, Younghae; Lee, Jaechoon; Kang, Taewon; Peng, Xiangyang; Arvanitis, Dimitri; Ahuja, Rajeev

2015-01-01

The article presents, using Bi doped ZnO, an example of a heavy ion doped oxide semiconductor, highlighting a novel p-symmetry interaction of the electronic states to stabilize ferromagnetism. The study includes both ab initio theory and experiments, which yield clear evidence for above room temperature ferromagnetism. ZnBixO1−x thin films are grown using the pulsed laser deposition technique. The room temperature ferromagnetism finds its origin in the holes introduced by the Bi doping and the p-p coupling between Bi and the host atoms. A sizeable magnetic moment is measured by means of x-ray magnetic circular dichroism at the O K-edge, probing directly the spin polarization of the O(2p) states. This result is in agreement with the theoretical predictions and inductive magnetometry measurements. Ab initio calculations of the electronic and magnetic structure of ZnBixO1−x at various doping levels allow to trace the origin of the ferromagnetic character of this material. It appears, that the spin-orbit energy of the heavy ion Bi stabilizes the ferromagnetic phase. Thus, ZnBixO1−x doped with a heavy non-ferromagnetic element, such as Bi, is a credible example of a candidate material for a new class of compounds for spintronics applications, based on the spin polarization of the p states. PMID:26592564

[Distal movement of the mandibular dentition in the treatment of patients with Class III skeletal pattern].

PubMed

Mou, Lan; Xu, Gengchi; Han, Yaohui; Ge, Zhenlin

2015-06-01

To evaluate the outcome of patients with skeletal Class III malocclusion treated with extraction of mandibular third molars and distalization of molars using implant anchorage combined with MBT appliance. Fifteen patients (mean age 24.0 ± 5.8) with skeletal Class III malocclusion were selected. The mandibular third molars were extracted and the mandibular molars were moved distally using implant combined with MBT appliance. Cephalometric analysis was carried out before and after treatment. After active treatment, ANB, Wits distance, AB-NP and the distance between upper and lower lip position to SnPg' increased by 1.65° ± 1.04°, (4.39 ± 1.93) mm, 3.20° ± 1.61° and (1.13 ± 0.99) mm, respectively. The differences were statistically significant (P < 0.05). The skeletal Class III patients in the permanent dentition could be treated successfully with extraction of mandibular third molars and distalization of mandibular molars using implant anchorage combined with MBT appliance. The soft-tissue profile was improved.

miR394 and LCR are involved in Arabidopsis salt and drought stress responses in an abscisic acid-dependent manner

PubMed Central

2013-01-01

Background MicroRNAs (miRNAs) are a class of short, endogenous non-coding small RNAs that have ability to base pair with their target mRNAs to induce their degradation in plants. miR394a/b are conserved small RNAs and its target gene LCR (LEAF CURLING RESPONSIVENESS) encodes an F-box protein (SKP1-Cullin/CDC53-F-box) but whether miR394a/b and its target gene LCR are involved in regulation of plant response to abscisic acid (ABA) and abiotic stresses is unknown. Results Mature miR394 and precursor miR394a/b are shown to be slightly induced by ABA. By contrast, LCR expression is depressed by ABA. Analysis of LCR and its promoter (pLCR::GUS) revealed that LCR is expressed at all development stages. MIR394a/b over-expression (35S::MIR394a/b) and lcr (LCR loss of function) mutant plants are hypersensitive to salt stress, but LCR over-expressing (35S::m5LCR) plants display the salt-tolerant phenotype. Both 35S::MIR394a/b and lcr plants are highly tolerant to severe drought stress compared with wild-type, but 35S::m5LCR plants are susceptible to water deficiency. Over-expression of MIR394a/b led to ABA hypersensitivity and ABA-associated phenotypes, whereas 35S::m5LCR plants show ABA resistance phenotypes. Moreover, 35S::MIR394a/b plants accumulated higher levels of ABA-induced hydrogen peroxide and superoxide anion radicals than wild-type and 35S::m5LCR plants. Expressions of ABA- and stress-responsive genes, ABI3, ABI4, ABI5, ABF3, and ABF4 are up-regulated in MIR394a/b over-expressing plants but down-regulated in 35S::m5LCR plants. Over-expression of MIR394a in abi4-1 or abi5-1 background resulted in loss of ABA-sensitivity in 35S::MIR394a plants. Conclusions The silencing of LCR mRNA by miR394 is essential to maintain a certain phenotype favorable for the adaptive response to abiotic stresses. The contrasting phenotypes of salt and drought responses may be mediated by a functional balance between miR394 and LCR. If the balance is perturbed in case of the abiotic stress, an identical phenotype related to the stress response occurs, resulting in either ABA sensitive or insensitive response. Thus, miR394-regulated LCR abundance may allow plants to fine-tune their responses to ABA and abiotic stress. PMID:24330668

miR394 and LCR are involved in Arabidopsis salt and drought stress responses in an abscisic acid-dependent manner.

PubMed

Song, Jian Bo; Gao, Shuai; Sun, Di; Li, Hua; Shu, Xia Xia; Yang, Zhi Min

2013-12-11

MicroRNAs (miRNAs) are a class of short, endogenous non-coding small RNAs that have ability to base pair with their target mRNAs to induce their degradation in plants. miR394a/b are conserved small RNAs and its target gene LCR (LEAF CURLING RESPONSIVENESS) encodes an F-box protein (SKP1-Cullin/CDC53-F-box) but whether miR394a/b and its target gene LCR are involved in regulation of plant response to abscisic acid (ABA) and abiotic stresses is unknown. Mature miR394 and precursor miR394a/b are shown to be slightly induced by ABA. By contrast, LCR expression is depressed by ABA. Analysis of LCR and its promoter (pLCR::GUS) revealed that LCR is expressed at all development stages. MIR394a/b over-expression (35S::MIR394a/b) and lcr (LCR loss of function) mutant plants are hypersensitive to salt stress, but LCR over-expressing (35S::m5LCR) plants display the salt-tolerant phenotype. Both 35S::MIR394a/b and lcr plants are highly tolerant to severe drought stress compared with wild-type, but 35S::m5LCR plants are susceptible to water deficiency. Over-expression of MIR394a/b led to ABA hypersensitivity and ABA-associated phenotypes, whereas 35S::m5LCR plants show ABA resistance phenotypes. Moreover, 35S::MIR394a/b plants accumulated higher levels of ABA-induced hydrogen peroxide and superoxide anion radicals than wild-type and 35S::m5LCR plants. Expressions of ABA- and stress-responsive genes, ABI3, ABI4, ABI5, ABF3, and ABF4 are up-regulated in MIR394a/b over-expressing plants but down-regulated in 35S::m5LCR plants. Over-expression of MIR394a in abi4-1 or abi5-1 background resulted in loss of ABA-sensitivity in 35S::MIR394a plants. The silencing of LCR mRNA by miR394 is essential to maintain a certain phenotype favorable for the adaptive response to abiotic stresses. The contrasting phenotypes of salt and drought responses may be mediated by a functional balance between miR394 and LCR. If the balance is perturbed in case of the abiotic stress, an identical phenotype related to the stress response occurs, resulting in either ABA sensitive or insensitive response. Thus, miR394-regulated LCR abundance may allow plants to fine-tune their responses to ABA and abiotic stress.

A Novel indole compound that inhibits Pseudomonas aeruginosa growth by targeting MreB is a substrate for MexAB-OprM.

PubMed

Robertson, Gregory T; Doyle, Timothy B; Du, Qun; Duncan, Leonard; Mdluli, Khisimuzi E; Lynch, A Simon

2007-10-01

Drug efflux systems contribute to the intrinsic resistance of Pseudomonas aeruginosa to many antibiotics and biocides and hamper research focused on the discovery and development of new antimicrobial agents targeted against this important opportunistic pathogen. Using a P. aeruginosa PAO1 derivative bearing deletions of opmH, encoding an outer membrane channel for efflux substrates, and four efflux pumps belonging to the resistance nodulation/cell division class including mexAB-oprM, we identified a small-molecule indole-class compound (CBR-4830) that is inhibitory to growth of this efflux-compromised strain. Genetic studies established MexAB-OprM as the principal pump for CBR-4830 and revealed MreB, a prokaryotic actin homolog, as the proximal cellular target of CBR-4830. Additional studies establish MreB as an essential protein in P. aeruginosa, and efflux-compromised strains treated with CBR-4830 transition to coccoid shape, consistent with MreB inhibition or depletion. Resistance genetics further suggest that CBR-4830 interacts with the putative ATP-binding pocket in MreB and demonstrate significant cross-resistance with A22, a structurally unrelated compound that has been shown to promote rapid dispersion of MreB filaments in vivo. Interestingly, however, ATP-dependent polymerization of purified recombinant P. aeruginosa MreB is blocked in vitro in a dose-dependent manner by CBR-4830 but not by A22. Neither compound exhibits significant inhibitory activity against mutant forms of MreB protein that bear mutations identified in CBR-4830-resistant strains. Finally, employing the strains and reagents prepared and characterized during the course of these studies, we have begun to investigate the ability of analogues of CBR-4830 to inhibit the growth of both efflux-proficient and efflux-compromised P. aeruginosa through specific inhibition of MreB function.

Rapid Two-Millisecond Interrogation of Electrochemical, Aptamer-Based Sensor Response Using Intermittent Pulse Amperometry.

PubMed

Santos-Cancel, Mirelis; Lazenby, Robert A; White, Ryan J

2018-06-22

In this manuscript, we employ the technique intermittent pulse amperometry (IPA) to interrogate equilibrium and kinetic target binding to the surface of electrochemical, aptamer-based (E-AB) sensors, achieving as fast as 2 ms time resolution. E-AB sensors comprise an electrode surface modified with a flexible nucleic acid aptamer tethered at the 3'-terminus with a redox-active molecule. The introduction of a target changes the conformation and flexibility of the nucleic acid, which alters the charge transfer rate of the appended redox molecule. Typically, changes in charge transfer rate within this class of sensor are monitored via voltammetric methods. Here, we demonstrate that the use of IPA enables the detection of changes in charge transfer rates (i.e., current) at times <100 μs after the application of a potential pulse. Changes in sensor current are quantitatively related to target analyte concentration and can be used to create binding isotherms. Furthermore, the application of IPA enables rapid probing of the electrochemical surface with a time resolution equivalent to as low as twice the applied potential pulse width, not previously demonstrated with traditional voltammetric techniques employed with E-AB sensors (alternating current, square wave, cyclic). To visualize binding, we developed false-color plots analogous to those used in the field of fast-scan cyclic voltammetry. The use of IPA is universal, as demonstrated with two representative small molecule E-AB sensors directed against the aminoglycoside antibiotic tobramycin and adenosine triphosphate (ATP). Intermittent pulse amperometry exhibits an unprecedented sub-microsecond temporal response and is a general method for measuring rapid sensor performance.

Kinetic analysis of a monoclonal therapeutic antibody and its single-chain homolog by surface plasmon resonance.

PubMed

Patel, Rekha; Andrien, Bruce A

2010-01-01

Monoclonal antibodies (mAbs) and antibody fragments have become an emerging class of therapeutics since 1986. Their versatility enables them to be engineered for optimal efficiency and decreased immunogenicity, and the path to market has been set by recent regulatory approvals. One of the initial criteria for success of any protein or antibody therapeutic is to understand its binding characteristics to the target antigen. Surface plasmon resonance (SPR) has been widely used and is an important tool for ligand-antigen binding characterization. In this work, the binding kinetics of a recombinant mAb and its single-chain antibody homolog, single-chain variable fragment (scFv), was analyzed by SPR. These two proteins target the same antigen. The binding kinetics of the mAb (bivalent antibody) and scFv (monovalent scFv) for this antigen was analyzed along with an assessment of the thermodynamics of the binding interactions. Alternative binding configurations were investigated to evaluate potential experimental bias because theoretically experimental binding configuration should have no impact on binding kinetics. Self-association binding kinetics in the proteins' respective formulation solutions and antigen epitope mapping were also evaluated. Functional characterization of monoclonal and single-chain antibodies has become just as important as structural characterization in the biotechnology field.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, David; Thomsen, Edwin; Li, Bin

Three flow designs were operated in a 3-cell 1 kW class all vanadium mixed acid redox flow battery. The influence of electrode surface area and flow rate on the coulombic, voltage, and energy efficiency and the pressure drop in the flow circuit will be discussed and correlated to the flow design. Material cost associated with each flow design will also be discussed.

76 FR 2924 - Proposed Generic Communications; Draft NRC Regulatory Issue Summary 2011-XX; Adequacy of Station...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... positions. No specific action or written response is required. DATES: Comment period expires 30 days after... new requirements or staff positions. No specific action or written response is required. Background... on the operation of Class 1E loads. These degraded voltage conditions will not be detected by the...

The Phelix Pulsed Power Project: Bringing Portable Magnetic Drive to World Class Radiography

DTIC Science & Technology

2011-06-01

vitreous carbon damping resistors are used on the output headers of each module for a total of 25.1 mΩ of resistance. Figure 6. The PHELIX portable...4 MA peak current in the secondary winding for driving a liner. In order to not produce too much reverse voltage on the capacitors, reticulated

Quantum-ring spin interference device tuned by quantum point contacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diago-Cisneros, Leo; Mireles, Francisco

2013-11-21

We introduce a spin-interference device that comprises a quantum ring (QR) with three embedded quantum point contacts (QPCs) and study theoretically its spin transport properties in the presence of Rashba spin-orbit interaction. Two of the QPCs conform the lead-to-ring junctions while a third one is placed symmetrically in the upper arm of the QR. Using an appropriate scattering model for the QPCs and the S-matrix scattering approach, we analyze the role of the QPCs on the Aharonov-Bohm (AB) and Aharonov-Casher (AC) conductance oscillations of the QR-device. Exact formulas are obtained for the spin-resolved conductances of the QR-device as a functionmore » of the confinement of the QPCs and the AB/AC phases. Conditions for the appearance of resonances and anti-resonances in the spin-conductance are derived and discussed. We predict very distinctive variations of the QR-conductance oscillations not seen in previous QR proposals. In particular, we find that the interference pattern in the QR can be manipulated to a large extend by varying electrically the lead-to-ring topological parameters. The latter can be used to modulate the AB and AC phases by applying gate voltage only. We have shown also that the conductance oscillations exhibits a crossover to well-defined resonances as the lateral QPC confinement strength is increased, mapping the eigenenergies of the QR. In addition, unique features of the conductance arise by varying the aperture of the upper-arm QPC and the Rashba spin-orbit coupling. Our results may be of relevance for promising spin-orbitronics devices based on quantum interference mechanisms.« less

Graphene-Based Linear Tandem Micro-Supercapacitors with Metal-Free Current Collectors and High-Voltage Output.

PubMed

Shi, Xiaoyu; Wu, Zhong-Shuai; Qin, Jieqiong; Zheng, Shuanghao; Wang, Sen; Zhou, Feng; Sun, Chenglin; Bao, Xinhe

2017-11-01

Printable supercapacitors are regarded as a promising class of microscale power source, but are facing challenges derived from conventional sandwich-like geometry. Herein, the printable fabrication of new-type planar graphene-based linear tandem micro-supercapacitors (LTMSs) on diverse substrates with symmetric and asymmetric configuration, high-voltage output, tailored capacitance, and outstanding flexibility is demonstrated. The resulting graphene-based LTMSs consisting of 10 micro-supercapacitors (MSs) present efficient high-voltage output of 8.0 V, suggestive of superior uniformity of the entire integrated device. Meanwhile, LTMSs possess remarkable flexibility without obvious capacitance degradation under different bending states. Moreover, areal capacitance of LTMSs can be sufficiently modulated by incorporating polyaniline-based pseudocapacitive nanosheets into graphene electrodes, showing enhanced capacitance of 7.6 mF cm -2 . To further improve the voltage output and energy density, asymmetric LTMSs are fabricated through controlled printing of linear-patterned graphene as negative electrodes and MnO 2 nanosheets as positive electrodes. Notably, the asymmetric LTMSs from three serially connected MSs are easily extended to 5.4 V, triple voltage output of the single cell (1.8 V), suggestive of the versatile applicability of this technique. Therefore, this work offers numerous opportunities of graphene and analogous nanosheets for one-step scalable fabrication of flexible tandem energy storage devices integrating with printed electronics on same substrate. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Topological insulator nanowires and nanowire hetero-junctions

NASA Astrophysics Data System (ADS)

Deng, Haiming; Zhao, Lukas; Wade, Travis; Konczykowski, Marcin; Krusin-Elbaum, Lia

2014-03-01

The existing topological insulator materials (TIs) continue to present a number of challenges to complete understanding of the physics of topological spin-helical Dirac surface conduction channels, owing to a relatively large charge conduction in the bulk. One way to reduce the bulk contribution and to increase surface-to-volume ratio is by nanostructuring. Here we report on the synthesis and characterization of Sb2Te3, Bi2Te3 nanowires and nanotubes and Sb2Te3/Bi2Te3 heterojunctions electrochemically grown in porous anodic aluminum oxide (AAO) membranes with varied (from 50 to 150 nm) pore diameters. Stoichiometric rigid polycrystalline nanowires with controllable cross-sections were obtained using cell voltages in the 30 - 150 mV range. Transport measurements in up to 14 T magnetic fields applied along the nanowires show Aharonov-Bohm (A-B) quantum oscillations with periods corresponding to the nanowire diameters. All nanowires were found to exhibit sharp weak anti-localization (WAL) cusps, a characteristic signature of TIs. In addition to A-B oscillations, new quantization plateaus in magnetoresistance (MR) at low fields (< 0 . 7T) were observed. The analysis of MR as well as I - V characteristics of heterojunctions will be presented. Supported in part by NSF-DMR-1122594, NSF-DMR-1312483-MWN, and DOD-W911NF-13-1-0159.

Voltage tunable plasmon propagation in dual gated bilayer graphene

NASA Astrophysics Data System (ADS)

Farzaneh, Seyed M.; Rakheja, Shaloo

2017-10-01

In this paper, we theoretically investigate plasmon propagation characteristics in AB and AA stacked bilayer graphene (BLG) in the presence of energy asymmetry due to an electrostatic field oriented perpendicularly to the plane of the graphene sheet. We first derive the optical conductivity of BLG using the Kubo formalism incorporating energy asymmetry and finite electron scattering. All results are obtained for room temperature (300 K) operation. By solving Maxwell's equations in a dual gate device setup, we obtain the wavevector of propagating plasmon modes in the transverse electric (TE) and transverse magnetic (TM) directions at terahertz frequencies. The plasmon wavevector allows us to compare the compression factor, propagation length, and the mode confinement of TE and TM plasmon modes in bilayer and monolayer graphene sheets and also to study the impact of material parameters on plasmon characteristics. Our results show that the energy asymmetry can be harnessed to increase the propagation length of TM plasmons in BLG. AA stacked BLG shows a larger increase in the propagation length than AB stacked BLG; conversely, it is very insensitive to the Fermi level variations. Additionally, the dual gate structure allows independent modulation of the energy asymmetry and the Fermi level in BLG, which is advantageous for reconfiguring plasmon characteristics post device fabrication.

CMOS compatible electrode materials selection in oxide-based memory devices

NASA Astrophysics Data System (ADS)

Zhuo, V. Y.-Q.; Li, M.; Guo, Y.; Wang, W.; Yang, Y.; Jiang, Y.; Robertson, J.

2016-07-01

Electrode materials selection guidelines for oxide-based memory devices are constructed from the combined knowledge of observed device operation characteristics, ab-initio calculations, and nano-material characterization. It is demonstrated that changing the top electrode material from Ge to Cr to Ta in the Ta2O5-based memory devices resulted in a reduction of the operation voltages and current. Energy Dispersed X-ray (EDX) Spectrometer analysis clearly shows that the different top electrode materials scavenge oxygen ions from the Ta2O5 memory layer at various degrees, leading to different oxygen vacancy concentrations within the Ta2O5, thus the observed trends in the device performance. Replacing the Pt bottom electrode material with CMOS compatible materials (Ru and Ir) further reduces the power consumption and can be attributed to the modification of the Schottky barrier height and oxygen vacancy concentration at the electrode/oxide interface. Both trends in the device performance and EDX results are corroborated by the ab-initio calculations which reveal that the electrode material tunes the oxygen vacancy concentration via the oxygen chemical potential and defect formation energy. This experimental-theoretical approach strongly suggests that the proper selection of CMOS compatible electrode materials will create the critical oxygen vacancy concentration to attain low power memory performance.

Red shift of the SF6 vibration spectrum induced by the electron absorption: An ab initio study

NASA Astrophysics Data System (ADS)

Tang, Bin; Zhang, Long-Fei; Han, Fang-Yuan; Luo, Zong-Chang; Liang, Qin-Qin; Liu, Chen-Yao; Zhu, Li-Ping; Zhang, Jie-Ming

2018-01-01

As a widely used gas insulator, sulfur hexafluoride (SF6) has a large cross section for electron absorption, which may make the molecule ionized to the -1 charge state in the high-voltage environment. Using ab initio calculations, we show that the absorbed electron is located averagely on the six F atoms, occupying the antibonding level of the s-p σ bonds and increasing the S-F bond length. The ionized SF6- molecule decreases its decomposition energy to only 1.5 eV, much lower than that of the neutral molecule (4.8 eV), which can be understood according to the occupying of the antibonding orbital and thus weakening of the s-p σ bonds. The weakening of the bonds results in an obvious red shift in the vibrational modes of the ionized SF6- molecule by 120-270 cm-1, compared to those of the neutral molecule. The detailed origin of these vibrational modes is analyzed. Since the appearance of the ionized SF6- molecules is before the decomposition reaction of the SF6- molecule into low-fluoride sulfides, this method may improve the sensitivity of the defection of the partial discharge and save more time for the prevention of the insulation failure in advance.

Role of voltage-gated L-type Ca2+ channel isoforms for brain function.

PubMed

Striessnig, J; Koschak, A; Sinnegger-Brauns, M J; Hetzenauer, A; Nguyen, N K; Busquet, P; Pelster, G; Singewald, N

2006-11-01

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1 .2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

A dielectric elastomer actuator coupled with water: snap-through instability and giant deformation

NASA Astrophysics Data System (ADS)

Godaba, Hareesh; Foo, Choon Chiang; Zhang, Zhi Qian; Khoo, Boo Cheong; Zhu, Jian

2015-04-01

A dielectric elastomer actuator is one class of soft actuators which can deform in response to voltage. Dielectric elastomer actuators coupled with liquid have recently been developed as soft pumps, soft lenses, Braille displays, etc. In this paper, we conduct experiments to investigate the performance of a dielectric elastomer actuator which is coupled with water. The membrane is subject to a constant water pressure, which is found to significantly affect the electromechanical behaviour of the membrane. When the pressure is small, the membrane suffers electrical breakdown before snap-through instability, and achieves a small voltage-induced deformation. When the pressure is higher to make the membrane near the verge of the instability, the membrane can achieve a giant voltage-induced deformation, with an area strain of 1165%. When the pressure is large, the membrane suffers pressure-induced snap-through instability and may collapse due to a large amount of liquid enclosed by the membrane. Theoretical analyses are conducted to interpret these experimental observations.

Low-cost wireless voltage & current grid monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hines, Jacqueline

This report describes the development and demonstration of a novel low-cost wireless power distribution line monitoring system. This system measures voltage, current, and relative phase on power lines of up to 35 kV-class. The line units operate without any batteries, and without harvesting energy from the power line. Thus, data on grid condition is provided even in outage conditions, when line current is zero. This enhances worker safety by detecting the presence of voltage and current that may appear from stray sources on nominally isolated lines. Availability of low-cost power line monitoring systems will enable widespread monitoring of the distributionmore » grid. Real-time data on local grid operating conditions will enable grid operators to optimize grid operation, implement grid automation, and understand the impact of solar and other distributed sources on grid stability. The latter will enable utilities to implement eneygy storage and control systems to enable greater penetration of solar into the grid.« less

Electroencephalography (EEG) in the Study of Equivalence Class Formation. An Explorative Study.

PubMed

Arntzen, Erik; Steingrimsdottir, Hanna S

2017-01-01

Teaching arbitrary conditional discriminations and testing for derived relations may be essential for understanding changes in cognitive skills. Such conditional discrimination procedures are often used within stimulus equivalence research. For example, the participant is taught AB and BC relations and tested if emergent relations as BA, CB, AC and CA occur. The purpose of the current explorative experiment was to study stimulus equivalence class formation in older adults with electroencephalography (EEG) recordings as an additional measure. The EEG was used to learn about whether there was an indication of cognitive changes such as those observed in neurocognitive disorders (NCD). The present study included four participants who did conditional discrimination training and testing. The experimental design employed pre-class formation sorting and post-class formation sorting of the stimuli used in the experiment. EEG recordings were conducted before training, after training and after testing. The results showed that two participants formed equivalence classes, one participant failed in one of the three test relations, and one participant failed in two of the three test relations. This fourth participant also failed to sort the stimuli in accordance with the experimenter-defined stimulus equivalence classes during post-class formation sorting. The EEG indicated no cognitive decline in the first three participants but possible mild cognitive impairment (MCI) in the fourth participant. The results suggest that equivalence class formation may provide information about cognitive impairments such as those that are likely to occur in the early stages of NCD. The study recommends replications with broader samples.

Effect of structure variation of the aptamer-DNA duplex probe on the performance of displacement-based electrochemical aptamer sensors.

PubMed

Pang, Jie; Zhang, Ziping; Jin, Haizhu

2016-03-15

Electrochemical aptamer-based (E-AB) sensors employing electrode-immobilized, redox-tagged aptamer probes have emerged as a promising platform for the sensitive and quick detection of target analytes ranging from small molecules to proteins. Signal generation in this class of sensor is linked to change in electron transfer efficiency upon binding-induced change in flexibility/conformation of the aptamer probe. Because of this signaling mechanism, signal gains of these sensors can be improved by employing a displacement-based recognition system, which links target binding with a large-scale flexibility/conformation shift from the aptamer-DNA duplex to the single-stranded DNA or the native aptamer. Despite the relatively large number of displacement-based E-AB sensor samples, little attention has been paid to the structure variation of the aptamer-DNA duplex probe. Here we detail the effects of complementary length and position of the aptamer-DNA duplex probe on the performance of a model displacement-based E-AB sensor for ATP. We find that, greater background suppression and signal gain are observed with longer complementary length of the aptamer-DNA duplex probe. However, sensor equilibration time slows monotonically with increasing complementary length; and with too many target binding sites in aptamer sequence being occupied by the complementary DNA, the aptamer-target binding does not occur and no signal gain observed. We also demonstrate that signal gain of the displacement-based E-AB sensor is strongly dependent on the complementary position of the aptamer-DNA duplex probe, with complementary position located at the electrode-attached or redox-tagged end of the duplex probe, larger background suppression and signal increase than that of the middle position are observed. These results highlight the importance of rational structure design of the aptamer-DNA duplex probe and provide new insights into the optimization of displacement-based E-AB sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Review of the U.S. Department of Energy's "Deep Dive" Effort to Understand Voltage Fade in Li- and Mn-rich Cathodes

DOE PAGES

Croy, Jason R.; Balasubramanian, Mahalingam; Gallagher, Kevin G.; ...

2015-11-01

With roughly two-thirds of daily oil consumption in the United States allotted for transportation, the possibility of efficient and affordable electric vehicles suggests a way to substantially alleviate the Country’s dependence on oil and mitigate the rise of greenhouse gases. Although commercialized Li-ion batteries do not currently meet the stringent demands of a would-be, economically competitive, electrified vehicle fleet, significant efforts are being focused on promising new materials for the next generation of Li-ion batteries. The leading class of materials most suitable for the challenge is the Li- and manganese-rich class of oxides. Denoted as LMR-NMC (Li-manganese-rich, nickel, manganese, cobalt),more » these materials could significantly improve energy densities, cost, and safety, relative to state-of-the-art Ni- and Co-rich Li-ion cells, if successfully developed.1 The success or failure of such a development relies heavily on understanding two defining characteristics of LMR-NMC cathodes. The first is a mechanism whereby the average voltage of cells continuously decreases with each successive charge and discharge cycle. This phenomenon, known as voltage fade, decreases the energy output of cells to unacceptable levels too early in cycling. The second characteristic is a pronounced hysteresis, or voltage difference, between charge and discharge cycles. The hysteresis represents not only an energy inefficiency (i.e., energy in vs energy out) but may also complicate the state of charge/depth of discharge management of larger systems, especially when accompanied by voltage fade. n 2012, the United States Department of Energy’s Office of Vehicle Technologies, well aware of the inherent potential of LMR-NMC materials for improving the energy density of automotive energy storage systems, tasked a team of scientists across the National Laboratory Complex to investigate the phenomenon of voltage fade. Unique studies using synchrotron X-ray absorption (XAS) and high-resolution diffraction (HR-XRD) were coupled with nuclear magnetic resonance spectroscopy (NMR), neutron diffraction, high-resolution transmission electron microscopy (HR-TEM), first-principles calculations, molecular dynamics simulations, and detailed electrochemical analyses. These studies demonstrated for the first time the atomic-scale, structure–property relationships that exist between nanoscale inhomogeneities and defects, and the macroscale, electrochemical performance of these layered oxides. These inhomogeneities and defects have been directly correlated with voltage fade and hysteresis, and a model describing these mechanisms has been proposed. This Account gives a brief summary of the findings of this recently concluded, approximately three-year investigation. Lastly, the interested reader is directed to the extensive body of work cited in the given references for a more comprehensive review of the subject.« less

Investigation of the Effects of Facility Background Pressure on the Performance and Voltage-Current Characteristics of the High Voltage Hall Accelerator

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Huang, Wensheng; Haag, Thomas; Spektor, Rostislav

2014-01-01

The National Aeronautics and Space Administration (NASA) Science Mission Directorate In-Space Propulsion Technology office is sponsoring NASA Glenn Research Center to develop a 4 kW-class Hall thruster propulsion system for implementation in NASA science missions. A study was conducted to assess the impact of varying the facility background pressure on the High Voltage Hall Accelerator (HiVHAc) thruster performance and voltage-current characteristics. This present study evaluated the HiVHAc thruster performance in the lowest attainable background pressure condition at NASA GRC Vacuum Facility 5 to best simulate space-like conditions. Additional tests were performed at selected thruster operating conditions to investigate and elucidate the underlying physics that change during thruster operation at elevated facility background pressure. Tests were performed at background pressure conditions that are three and ten times higher than the lowest realized background pressure. Results indicated that the thruster discharge specific impulse and efficiency increased with elevated facility background pressure. The voltage-current profiles indicated a narrower stable operating region with increased background pressure. Experimental observations of the thruster operation indicated that increasing the facility background pressure shifted the ionization and acceleration zones upstream towards the thrusters anode. Future tests of the HiVHAc thruster are planned at background pressure conditions that are expected to be two to three times lower than what was achieved during this test campaign. These tests will not only assess the impact of reduced facility background pressure on thruster performance, voltage-current characteristics, and plume properties; but will also attempt to quantify the magnitude of the ionization.

Electron transmission through a class of anthracene aldehyde molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petreska, Irina, E-mail: irina.petreska@pmf.ukim.mk; Ohanesjan, Vladimir, E-mail: ohanesjan.vladimir@gmail.com; Pejov, Ljupco, E-mail: ljupcop@pmf.ukim.mk

2016-03-25

Transmission of electrons via metal-molecule-metal junctions, involving rotor-stator anthracene aldehyde molecules is investigated. Two model barriers having input parameters evaluated from accurate ab initio calculations are proposed and the transmission coefficients are obtained by using the quasiclassical approximation. Transmission coefficients further enter in the integral for the net current, utilizing Simmons’ method. Conformational dependence of the tunneling processes is evident and the presence of the side groups enhances the functionality of the future single-molecule based electronic devices.

Antiandrogenic steroidal sulfonyl heterocycles. Utility of electrostatic complementarity in defining bioisosteric sulfonyl heterocycles.

PubMed

Mallamo, J P; Pilling, G M; Wetzel, J R; Kowalczyk, P J; Bell, M R; Kullnig, R K; Batzold, F H; Juniewicz, P E; Winneker, R C; Luss, H R

1992-05-15

Complementarity of electrostatic potential surface maps was utilized in defining bioisosteric steroidal androgen receptor antagonists. Semiempirical and ab initio level calculations performed on a series of methanesulfonyl heterocycles indicated the requirement for a partial negative charge at the heteroatom attached to C-3 of the steroid nucleus to attain androgen receptor affinity. Synthesis and testing of six heterocycle A-ring-fused dihydroethisterone derivatives support this hypothesis, and we have identified two new androgen receptor antagonists of this class.

The non-autonomous YdKN equation and generalized symmetries of Boll equations

NASA Astrophysics Data System (ADS)

Gubbiotti, G.; Scimiterna, C.; Levi, D.

2017-05-01

In this paper, we study the integrability of a class of nonlinear non-autonomous quad graph equations compatible around the cube introduced by Boll in the framework of the generalized Adler, Bobenko, and Suris (ABS) classification. We show that all these equations possess three-point generalized symmetries which are subcases of either the Yamilov discretization of the Krichever-Novikov equation or of its non-autonomous extension. We also prove that all those symmetries are integrable as they pass the algebraic entropy test.

Revised Uniform Summary of Surface Weather Observations (RUSSWO) Misawa AB, Japan

DTIC Science & Technology

1980-07-03

HOURLY OBSERVATIONS) Ii hTATIN k15510 TEAM NONIN CLASS NOV10 (LV S . J , r 1,. Tr ,r:: .. - SPEED A-DEAN =* .,, .. ’ *I * ’__ _i ___ -__ J___...1o 51.: 65.] 72.7 77* .84.1 87.8 90.2 93.7 95.0 97.1 98931 98.61 99.2 99.8 99.9 999j a 0 5116 72.7 77.L±84..§87.d 90,1 93 9590 [9791 8@31 98dIAk61~2

Unsupervised Cryo-EM Data Clustering through Adaptively Constrained K-Means Algorithm

PubMed Central

Xu, Yaofang; Wu, Jiayi; Yin, Chang-Cheng; Mao, Youdong

2016-01-01

In single-particle cryo-electron microscopy (cryo-EM), K-means clustering algorithm is widely used in unsupervised 2D classification of projection images of biological macromolecules. 3D ab initio reconstruction requires accurate unsupervised classification in order to separate molecular projections of distinct orientations. Due to background noise in single-particle images and uncertainty of molecular orientations, traditional K-means clustering algorithm may classify images into wrong classes and produce classes with a large variation in membership. Overcoming these limitations requires further development on clustering algorithms for cryo-EM data analysis. We propose a novel unsupervised data clustering method building upon the traditional K-means algorithm. By introducing an adaptive constraint term in the objective function, our algorithm not only avoids a large variation in class sizes but also produces more accurate data clustering. Applications of this approach to both simulated and experimental cryo-EM data demonstrate that our algorithm is a significantly improved alterative to the traditional K-means algorithm in single-particle cryo-EM analysis. PMID:27959895

Unsupervised Cryo-EM Data Clustering through Adaptively Constrained K-Means Algorithm.

PubMed

Xu, Yaofang; Wu, Jiayi; Yin, Chang-Cheng; Mao, Youdong

2016-01-01

In single-particle cryo-electron microscopy (cryo-EM), K-means clustering algorithm is widely used in unsupervised 2D classification of projection images of biological macromolecules. 3D ab initio reconstruction requires accurate unsupervised classification in order to separate molecular projections of distinct orientations. Due to background noise in single-particle images and uncertainty of molecular orientations, traditional K-means clustering algorithm may classify images into wrong classes and produce classes with a large variation in membership. Overcoming these limitations requires further development on clustering algorithms for cryo-EM data analysis. We propose a novel unsupervised data clustering method building upon the traditional K-means algorithm. By introducing an adaptive constraint term in the objective function, our algorithm not only avoids a large variation in class sizes but also produces more accurate data clustering. Applications of this approach to both simulated and experimental cryo-EM data demonstrate that our algorithm is a significantly improved alterative to the traditional K-means algorithm in single-particle cryo-EM analysis.

Electrostatic Discharge (ESD) Simulator Experiment (Testing of Some Switches/Relays for Application to an ESD Simulation Circuit)

DTIC Science & Technology

1983-10-01

will be: V(t) = 4,100 et/RC = 4,100 e 5/100 3,900 Volts Note that failure of a device during such test will classify the device as being Class 3 of DOD...Volts) 50 mV/small div., 50 nsec 0.1 mV/small div., 50 nsec (Inverted) NU-N E U Figure 12: (Charging Voltage: +1000 Volts) Figure 13: (Charging Voltage...Ij stchari I-,, i-1)401)0 1 It (uIrllis wi th vovy rt’~dIt- e l b (’i a, Ch .11it(! 11 1~ lit u t’ ~ 0 KV vult*.ge, I’Zinge anld at hw nFgrs 3~s. it

Synthesis of novel carbazole derived substances using some organoboron compounds by palladium catalyzed and investigation of its semiconductor device characteristics

NASA Astrophysics Data System (ADS)

Gorgun, Kamuran; Caglar, Yasemin

2018-04-01

Carbazole compounds in particular represent one of the most intensely used and studied class of semiconducting materials. In this study, considering the information given in the literature the Ullman and Suzuki-Miyaura coupling reaction were carried out using carbazole, 1,4-dibromobenzene and pyrene-1-boronic acid. The synthesized carbazole derivatives are characterized by 1H NMR and elemental analysis. The spectroscopic and thermal properties of the synthesized novel carbazole derivative 9-(4-(pyren-4-yl)phenyl)-9H-carbazole (Cz-py) were investigated. And also, the n-Si/p-Cz:py heterojunction diode was fabricated. The electrical properties of this diode were characterized by current-voltage (I-V) and capacitance-voltage (C-V) measurements.

Quantum shot noise in tunnel junctions

NASA Technical Reports Server (NTRS)

Ben-Jacob, E.; Mottola, E.; Schoen, G.

1983-01-01

The current and voltage fluctuations in a normal tunnel junction are calculated from microscopic theory. The power spectrum can deviate from the familiar Johnson-Nyquist form when the self-capacitance of the junction is small, at low temperatures permitting experimental verification. The deviation reflects the discrete nature of the charge transfer across the junction and should be present in a wide class of similar systems.

Low Voltage Low Light Imager and Photodetector

NASA Technical Reports Server (NTRS)

Nikzad, Shouleh (Inventor); Martin, Chris (Inventor); Hoenk, Michael E. (Inventor)

2013-01-01

Highly efficient, low energy, low light level imagers and photodetectors are provided. In particular, a novel class of Della-Doped Electron Bombarded Array (DDEBA) photodetectors that will reduce the size, mass, power, complexity, and cost of conventional imaging systems while improving performance by using a thinned imager that is capable of detecting low-energy electrons, has high gain, and is of low noise.

Integration Tests of the 4 kW-class High Voltage Hall Accelerator Power Processing Unit with the HiVHAc and the SPT-140 Hall Effect Thrusters

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Pinero, Luis; Haag, Thomas; Huang, Wensheng; Ahern, Drew; Liang, Ray; Shilo, Vlad

2016-01-01

NASAs Science Mission Directorate is sponsoring the development of a 4 kW-class Hall propulsion system for implementation in NASA science and exploration missions. The main components of the system include the High Voltage Hall Accelerator (HiVHAc), an engineering model power processing unit (PPU) developed by Colorado Power Electronics, and a xenon flow control module (XFCM) developed by VACCO Industries. NASA Glenn Research Center is performing integrated tests of the Hall thruster propulsion system. This presentation presents results from integrated tests of the PPU and XFCM with the HiVHAc engineering development thruster and a SPT-140 thruster provided by Space System Loral. The results presented in this paper demonstrate thruster discharge initiation, open-loop and closed-loop control of the discharge current with anode flow for both the HiVHAc and the SPT-140 thrusters. Integrated tests with the SPT-140 thruster indicated that the PPU was able to repeatedly initiate the thrusters discharge, achieve steady state operation, and successfully throttle the thruster between 1.5 and 4.5 kW. The measured SPT-140 performance was identical to levels reported by Space Systems Loral.

VGKC positive autoimmune encephalopathy mimicking dementia

PubMed Central

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O’ Toole, Orna

2011-01-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan’s syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment. PMID:22674939

Influence of the spatially inhomogeneous gap distribution on the quasiparticle current in c-axis junctions involving d-wave superconductors with charge density waves.

PubMed

Ekino, T; Gabovich, A M; Suan Li, Mai; Szymczak, H; Voitenko, A I

2016-11-09

The quasiparticle tunnel current J(V) between the superconducting ab-planes along the c-axis and the corresponding conductance [Formula: see text] were calculated for symmetric junctions composed of disordered d-wave layered superconductors partially gapped by charge density waves (CDWs). Here, V is the voltage. Both the checkerboard and unidirectional CDWs were considered. It was shown that the spatial spread of the CDW-pairing strength substantially smears the peculiarities of G(V) appropriate to uniform superconductors. The resulting curves G(V) become very similar to those observed for a number of cuprates in intrinsic junctions, e.g. mesas. In particular, the influence of CDWs may explain the peak-dip-hump structures frequently found for high-T c oxides.

Effects of Sabbagh Universal Spring 2 fixed functional appliance on class II/1 patients at their postpubertal-peak growth period compared with the extraction method : A randomized clinical trial.

PubMed

Hemmatpour, Siamak; Mokhtar, Ali; Rakhshan, Vahid

2017-01-01

The aim of this study was to evaluate the therapeutic effects of the Sabbagh Universal Spring 2 (SUS 2) fixed functional appliance compared to the premolar extraction method in correcting class II/1 malocclusion in patients who had passed their peak of postpubertal growth (stages 4-6 of Cervical Vertebral Maturation Index). In all, 40 class II/1 patients were randomized to receive SUS 2 application (7 males, 13 females, age 15.75 ± 1.02 years) or maxillary premolar extraction (8 males, 12 females, age 15.40 ± 0.99 years). Pre- and posttreatment digital cephalographs were traced at least twice. A paired t test was used to compare the pre- and posttreatment measurements. Treatment changes were compared using an independent samples t test (P ≤ 0.05). The extent of change was significant in the following variables: ANB, nasolabial angle, Mand1-ML, 1L-NB, anterior and posterior facial heights, N-A-Pog, 1U-NF, 6L-MP, Ar-Go, OP-HP, A-B, A-Sn, B-Sm, APDI, NAPog, AB-NPog, POr-DOP, SN-OcP, POr-OcP, Wits, 1 l-APog, 1LMeLm, S-Go:N-Me, N-ANS-Pog, Ap1LAp1u-DOP, ANS-Cond, Pog-Cond, SS-Ls, A-N-Pog, Pog-Pog', MeGoOcP, 1L-Npog, Go-Me, Go-Me:N-S, S-Me, Ls-(Sn-Pog'), Stms-Stmi, N'-Gn', N'NsPog', 6u-PTV, 1u-NA, FMIA, and IMPA. SUS 2 corrected class II/1 malocclusion of patients in the postpubertal growth period by inhibiting the maxilla's forward growth, advancing the mandible, decreasing the nasolabial and interincisal angles, proclining the incisors, increasing the facial height, and clockwise rotation of the occlusal plane. Extraction reduced the interincisal angle and protruded the lower incisors. However, it did not change the soft tissue thickness and did not cause a clockwise rotation in the occlusal plane.

Longitudinal evaluation of the microleakage of dentin bonding agents used to seal resected root apices.

PubMed

Vignaroli, P A; Anderson, R W; Pashley, D H

1995-10-01

A material that bonds to dentin and seals both the root canal and exposed dentinal tubules would be desirable following root resection. The purpose of this study was to measure the sealing ability of four dentin bonding agents on the resected root end. The bonding systems evaluated were Amalgambond (AMB), Scotchbond Multi-Purpose (SMP), Prisma Universal Bond 3 (PUB 3), and All-Bond 2 (AB2). All materials were applied directly to the resected root end without a class I preparation. One-half of the roots in each group were contaminated with human blood before bonding. Microleakage was measured using fluid filtration at various time intervals from 1 to 24 wk. Results indicated that all dentin bonding agents significantly reduced apical microleakage compared with prebonded controls at all time intervals. Blood contamination did not adversely affect the sealing ability of AMB, PUB 3, or SMP. The blood-contaminated AB2 group displayed significantly greater microleakage after 12 and 24 wk than the uncontaminated roots.

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE PAGES

De Boer, Rob J.; Perelson, Alan S.

2017-09-06

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Boer, Rob J.; Perelson, Alan S.

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less

Assessment of types of synthetic cannabinoids in narcotic cases assessed by the Council of Forensic Medicine between 2011-2015, Ankara, Turkey.

PubMed

Göl, Ersin; Çok, İsmet

2017-11-01

Synthetic cannabinoids mimic the effects of cannabis and are the largest and fastest growing class of newly appearing designer drugs. Reports have revealed that various types of synthetic cannabinoids are mixed with herbal substances. The present study investigated the herbal substance cases involving synthetic cannabinoids in Ankara and nearby cities in Turkey. Data were collected from the reports of synthetic cannabinoids that were analyzed between January 01, 2011 and December 31, 2015 in the Ankara Narcotic Department of the Council of Forensic Medicine at the request of the judicial authorities. In all, 4610 narcotic reports were obtained and reviewed. Among these narcotic reports during the period, 370 reports (8%) were related to synthetic cannabinoids. 28 synthetic cannabinoid compounds could be identified in herbals: 5-F-AB-PINACA, 5-F-AKB-48, 5-F-NNEI, 5-F-PB-22, AB-CHMINACA, AB-FUBINACA, AB-PINACA, ADB-CHMINACA, ADB-FUBINACA, AKB-48, AM-2201, EAM-2201, JWH-018, JWH-022, JWH-031, JWH-122, JWH-201, JWH-210, JWH-250, JWH-251, JWH-307, MAM-2201, NM-2201, PB-22, RCS-4, THJ-2201, UR-144, XLR-11. The amount of herbals was 30.72g, 329.22g, 665.89g, 4844.7g, and 5684.3g in 2011, 2012, 2013, 2014, and 2015, respectively. Generally, herbals contained more than one synthetic cannabinoids. ADB-FUBINACA was the most common synthetic cannabinoid among the herbals determined in this study, which was 3132.43g, excepting multi-synthetic cannabinoid herbals. The amount and diversity of synthetic cannabinoid compounds have increased dramatically between 2011 and 2015. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a soft untethered robot using artificial muscle actuators

NASA Astrophysics Data System (ADS)

Cao, Jiawei; Qin, Lei; Lee, Heow Pueh; Zhu, Jian

2017-04-01

Soft robots have attracted much interest recently, due to their potential capability to work effectively in unstructured environment. Soft actuators are key components in soft robots. Dielectric elastomer actuators are one class of soft actuators, which can deform in response to voltage. Dielectric elastomer actuators exhibit interesting attributes including large voltage-induced deformation and high energy density. These attributes make dielectric elastomer actuators capable of functioning as artificial muscles for soft robots. It is significant to develop untethered robots, since connecting the cables to external power sources greatly limits the robots' functionalities, especially autonomous movements. In this paper we develop a soft untethered robot based on dielectric elastomer actuators. This robot mainly consists of a deformable robotic body and two paper-based feet. The robotic body is essentially a dielectric elastomer actuator, which can expand or shrink at voltage on or off. In addition, the two feet can achieve adhesion or detachment based on the mechanism of electroadhesion. In general, the entire robotic system can be controlled by electricity or voltage. By optimizing the mechanical design of the robot (the size and weight of electric circuits), we put all these components (such as batteries, voltage amplifiers, control circuits, etc.) onto the robotic feet, and the robot is capable of realizing autonomous movements. Experiments are conducted to study the robot's locomotion. Finite element method is employed to interpret the deformation of dielectric elastomer actuators, and the simulations are qualitatively consistent with the experimental observations.

Assessment of High-Voltage Photovoltaic Technologies for the Design of a Direct Drive Hall Effect Thruster Solar Array

NASA Technical Reports Server (NTRS)

Mikellides, I. G.; Jongeward, G. A.; Schneider, T.; Carruth, M. R.; Peterson, T.; Kerslake, T. W.; Snyder, D.; Ferguson, D.; Hoskins, A.

2004-01-01

A three-year program to develop a Direct Drive Hall-Effect Thruster system (D2HET) begun in 2001 as part of the NASA Advanced Cross-Enterprise Technology Development initiative. The system, which is expected to reduce significantly the power processing, complexity, weight, and cost over conventional low-voltage systems, will employ solar arrays that operate at voltages higher than (or equal to) 300 V. The lessons learned from the development of the technology also promise to become a stepping-stone for the production of the next generation of power systems employing high voltage solar arrays. This paper summarizes the results from experiments conducted mainly at the NASA Marshal Space Flight Center with two main solar array technologies. The experiments focused on electron collection and arcing studies, when the solar cells operated at high voltages. The tests utilized small coupons representative of each solar array technology. A hollow cathode was used to emulate parts of the induced environment on the solar arrays, mostly the low-energy charge-exchange plasma (1012-1013 m-3 and 0.5-1 eV). Results and conclusions from modeling of electron collection are also summarized. The observations from the total effort are used to propose a preliminary, new solar array design for 2 kW and 30-40 kW class, deep space missions that may employ a single or a cluster of Hall- Effect thrusters.

Nonlinear control of voltage source converters in AC-DC power system.

PubMed

Dash, P K; Nayak, N

2014-07-01

This paper presents the design of a robust nonlinear controller for a parallel AC-DC power system using a Lyapunov function-based sliding mode control (LYPSMC) strategy. The inputs for the proposed control scheme are the DC voltage and reactive power errors at the converter station and the active and reactive power errors at the inverter station of the voltage-source converter-based high voltage direct current transmission (VSC-HVDC) link. The stability and robust tracking of the system parameters are ensured by applying the Lyapunov direct method. Also the gains of the sliding mode control (SMC) are made adaptive using the stability conditions of the Lyapunov function. The proposed control strategy offers invariant stability to a class of systems having modeling uncertainties due to parameter changes and exogenous inputs. Comprehensive computer simulations are carried out to verify the proposed control scheme under several system disturbances like changes in short-circuit ratio, converter parametric changes, and faults on the converter and inverter buses for single generating system connected to the power grid in a single machine infinite-bus AC-DC network and also for a 3-machine two-area power system. Furthermore, a second order super twisting sliding mode control scheme has been presented in this paper that provides a higher degree of nonlinearity than the LYPSMC and damps faster the converter and inverter voltage and power oscillations. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Cryogenic lifetime tests on a commercial epoxy resin high voltage bushing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwenterly, S W; Pleva, Ed; Ha, Tam T

2012-06-12

High-temperature superconducting (HTS) power devices operating in liquid nitrogen frequently require high-voltage bushings to carry the current leads from the superconducting windings to the room temperature grid connections. Oak Ridge National Laboratory is collaborating with Waukesha Electric Systems, SuperPower, and Southern California Edison to develop and demonstrate an HTS utility power transformer. Previous dielectric high voltage tests in support of this program have been carried out in test cryostats with commercial epoxy resin bushings from Electro Composites Inc. (ECI). Though the bushings performed well in these short-term tests, their long-term operation at high voltage in liquid nitrogen needs to bemore » verified for use on the utility grid. Long-term tests are being carried out on a sample 28-kV-class ECI bushing. The bushing has a monolithic cast, cycloaliphatic resin body and is fire- and shatter-resistant. The test cryostat is located in an interlocked cage and is energized at 25 kVac around the clock. Liquid nitrogen (LN) is automatically refilled every 9.5 hours. Partial discharge, capacitance, and leakage resistance tests are periodically performed to check for deviations from factory values. At present, over 2400 hours have been accumulated with no changes in these parameters. The tests are scheduled to run for four to six months.« less

Sustainable and Superior Heat-Resistant Alginate Nonwoven Separator of LiNi0.5Mn1.5O4/Li Batteries Operated at 55 °C.

PubMed

Wen, Huijie; Zhang, Jianjun; Chai, Jingchao; Ma, Jun; Yue, Liping; Dong, Tiantian; Zang, Xiao; Liu, Zhihong; Zhang, Botao; Cui, Guanglei

2017-02-01

High-voltage lithium-ion batteries have become a major research focus. As a major part of lithium batteries, the separator plays a critical role in the development of high-voltage lithium batteries. Herein, we demonstrated a sustainable and superior heat-resistant alginate nonwoven separator for high-voltage (5 V) lithium batteries. It was demonstrated that the resultant alginate nonwoven separator exhibited better mechanical property (37 MPa), superior thermal stability (up to 150 °C), and higher ionic conductivity (1.4 × 10 -3 S/cm) as compared to commercially available polyolefin (PP) separator. More impressively, the 5 V class LiNi 0.5 Mn 1.5 O 4 (LNMO)/Li cell with this alginate nonwoven separator delivered much better cycling stability (maintaining 79.6% of its initial discharge capacity) than that (69.3%) of PP separator after 200 cycles at an elevated temperature of 55 °C. In addition, the LiFePO 4 /Li cell assembled with such alginate nonwoven separator could still charge and discharge normally even at an elevated temperature of 150 °C. The above-mentioned fascinating characteristics of alginate separator provide great probability for its application for high-voltage (5 V) lithium batteries at elevated temperatures.

Cryogenic lifetime tests on a commercial epoxy resin high voltage bushing

NASA Astrophysics Data System (ADS)

Schwenterly, S. W.; Pleva, E. F.; Ha, T. T.

2012-06-01

High-temperature superconducting (HTS) power devices operating in liquid nitrogen frequently require high-voltage bushings to carry the current leads from the superconducting windings to the room temperature grid connections. Oak Ridge National Laboratory (ORNL) is collaborating with Waukesha Electric Systems (WES), SuperPower (SP), and Southern California Edison (SCE) to develop and demonstrate an HTS utility power transformer. Previous dielectric high voltage tests in support of this program have been carried out in test cryostats with commercial epoxy resin bushings from Electro Composites Inc. (ECI). Though the bushings performed well in these short-term tests, their long-term operation at high voltage in liquid nitrogen (LN) needs to be verified for use on the utility grid. Long-term tests are being carried out on a sample 28-kV-rms-class ECI bushing. The bushing has a monolithic cast, cycloaliphatic resin body and is fire- and shatter-resistant. The test cryostat is located in an interlocked cage and is continuously energized at 25 kVac rms. LN is automatically refilled every 9.5 hours. Partial discharge, capacitance, and leakage resistance tests are periodically performed to check for deviations from factory values. At present, over 2400 hours have been accumulated with no changes in these parameters. The tests are scheduled to run for four to six months.

Experimental study on the 300W class planar type solid oxide fuel cell stack: Investigation for appropriate fuel provision control and the transient capability of the cell performance

NASA Astrophysics Data System (ADS)

Komatsu, Y.; Brus, G.; Kimijima, S.; Szmyd, J. S.

2012-11-01

The present paper reports the experimental study on the dynamic behavior of a solid oxide fuel cell (SOFC). The cell stack consists of planar type cells with standard power output 300W. A Major subject of the present study is characterization of the transient response to the electric current change, assuming load-following operation. The present studies particularly focus on fuel provision control to the load change. Optimized fuel provision improves power generation efficiency. However, the capability of SOFC must be restricted by a few operative parameters. Fuel utilization factor, which is defined as the ratio of the consumed fuel to the supplied fuel is adopted for a reference in the control scheme. The fuel flow rate was regulated to keep the fuel utilization at 50%, 60% and 70% during the current ramping. Lower voltage was observed with the higher fuel utilization, but achieved efficiency was higher. The appropriate mass flow control is required not to violate the voltage transient behavior. Appropriate fuel flow manipulation can contribute to moderate the overshoot on the voltage that may appear to the current change. The overshoot on the voltage response resulted from the gradual temperature behavior in the SOFC stack module.

Isolation of dengue virus-specific memory B cells with live virus antigen from human subjects following natural infection reveals the presence of diverse novel functional groups of antibody clones.

PubMed

Smith, Scott A; de Alwis, A Ruklanthi; Kose, Nurgun; Jadi, Ramesh S; de Silva, Aravinda M; Crowe, James E

2014-11-01

Natural dengue virus (DENV) infection in humans induces antibodies (Abs) that neutralize the serotype of infection in a potent and type-specific manner; however, most Abs generated in response to infection are serotype cross-reactive and poorly neutralizing. Such cross-reactive Abs may enhance disease during subsequent infection with a virus of a different DENV serotype. Previous screening assays for DENV-specific human B cells and antibodies, using viral and recombinant antigens, mainly led to the isolation of dominant nonneutralizing B cell clones. To improve upon our ability to recover and study rare but durable and potently neutralizing DENV-specific Abs, we isolated human DENV-specific B cells by using a primary screen of binding to live virus, followed by a secondary screen with a high-throughput, flow cytometry-based neutralization assay to identify DENV-specific B cell lines prior to generation of hybridomas. Using this strategy, we identified several new classes of serotype-specific and serotype-cross-neutralizing anti-DENV monoclonal Abs (MAbs), including ultrapotent inhibitory antibodies with neutralizing activity concentrations of <10 ng/ml. We isolated serotype-specific neutralizing Abs that target diverse regions of the E protein, including epitopes present only on the intact, fully assembled viral particle. We also isolated a number of serotype-cross-neutralizing MAbs, most of which recognized a region in E protein domain I/II containing the fusion loop. These data provide insights into targets of the protective Ab-mediated immune response to natural DENV infection, which will prove valuable in the design and testing of new experimental DENV vaccines. Dengue virus infection is one of the most common mosquito-borne diseases and occurs in most countries of the world. Infection of humans with dengue virus induces a small number of antibodies that inhibit the infecting strain but also induces a large number of antibodies that can bind but do not inhibit dengue virus strains of other serotypes. We used a focused screening strategy to discover a large number of rare potently inhibiting antibodies, and we mapped the regions on the virus that were recognized by such antibodies. Our studies revealed that humans have the potential to generate very potent antibodies directed to diverse regions of the dengue virus surface protein. These studies provide important new information about protection from dengue virus infection that will be useful in the design and testing of new experimental dengue vaccines for humans. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Isolation of Dengue Virus-Specific Memory B Cells with Live Virus Antigen from Human Subjects following Natural Infection Reveals the Presence of Diverse Novel Functional Groups of Antibody Clones

PubMed Central

Smith, Scott A.; de Alwis, A. Ruklanthi; Kose, Nurgun; Jadi, Ramesh S.; de Silva, Aravinda M.

2014-01-01

ABSTRACT Natural dengue virus (DENV) infection in humans induces antibodies (Abs) that neutralize the serotype of infection in a potent and type-specific manner; however, most Abs generated in response to infection are serotype cross-reactive and poorly neutralizing. Such cross-reactive Abs may enhance disease during subsequent infection with a virus of a different DENV serotype. Previous screening assays for DENV-specific human B cells and antibodies, using viral and recombinant antigens, mainly led to the isolation of dominant nonneutralizing B cell clones. To improve upon our ability to recover and study rare but durable and potently neutralizing DENV-specific Abs, we isolated human DENV-specific B cells by using a primary screen of binding to live virus, followed by a secondary screen with a high-throughput, flow cytometry-based neutralization assay to identify DENV-specific B cell lines prior to generation of hybridomas. Using this strategy, we identified several new classes of serotype-specific and serotype-cross-neutralizing anti-DENV monoclonal Abs (MAbs), including ultrapotent inhibitory antibodies with neutralizing activity concentrations of <10 ng/ml. We isolated serotype-specific neutralizing Abs that target diverse regions of the E protein, including epitopes present only on the intact, fully assembled viral particle. We also isolated a number of serotype-cross-neutralizing MAbs, most of which recognized a region in E protein domain I/II containing the fusion loop. These data provide insights into targets of the protective Ab-mediated immune response to natural DENV infection, which will prove valuable in the design and testing of new experimental DENV vaccines. IMPORTANCE Dengue virus infection is one of the most common mosquito-borne diseases and occurs in most countries of the world. Infection of humans with dengue virus induces a small number of antibodies that inhibit the infecting strain but also induces a large number of antibodies that can bind but do not inhibit dengue virus strains of other serotypes. We used a focused screening strategy to discover a large number of rare potently inhibiting antibodies, and we mapped the regions on the virus that were recognized by such antibodies. Our studies revealed that humans have the potential to generate very potent antibodies directed to diverse regions of the dengue virus surface protein. These studies provide important new information about protection from dengue virus infection that will be useful in the design and testing of new experimental dengue vaccines for humans. PMID:25100837

Nanomicrointerface to read molecular potentials into current-voltage based electronics.

PubMed

Rangel, Norma L; Seminario, Jorge M

2008-03-21

Molecular potentials are unreadable and unaddressable by any present technology. It is known that the proper assembly of molecules can implement an entire numerical processing system based on digital or even analogical computation. In turn, the outputs of this molecular processing unit need to be amplified in order to be useful. We have developed a nanomicrointerface to read information encoded in molecular level potentials and to amplify this signal to microelectronic levels. The amplification is performed by making the output molecular potential slightly twist the torsional angle between two rings of a pyridazine, 3,6-bis(phenylethynyl) (aza-OPE) molecule, requiring only fractions of kcal/mol energies. In addition, even if the signal from the molecular potentials is not enough to turn the ring or even if the angles are the same for different combinations of outputs, still the current output yields results that resemble the device as a field effect transistor, providing the possibility to reduce channel lengths to the range of just 1 or 2 nm. The slight change in the torsional angle yields readable changes in the current through the aza-OPE biased by an external applied voltage. Using ab initio methods, we computationally demonstrate the amplification of molecular potential signals into currents that can be read by standard circuits.

Derivatization and diffusive motion of molecular fullerenes: Ab initio and atomistic simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berdiyorov, G., E-mail: gberdiyorov@qf.org.qa; Tabet, N.; Harrabi, K.

2015-07-14

Using first principles density functional theory in combination with the nonequilibrium Green's function formalism, we study the effect of derivatization on the electronic and transport properties of C{sub 60} fullerene. As a typical example, we consider [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM), which forms one of the most efficient organic photovoltaic materials in combination with electron donating polymers. Extra peaks are observed in the density of states (DOS) due to the formation of new electronic states localized at/near the attached molecule. Despite such peculiar behavior in the DOS of an isolated molecule, derivatization does not have a pronounced effect onmore » the electronic transport properties of the fullerene molecular junctions. Both C{sub 60} and PCBM show the same response to finite voltage biasing with new features in the transmission spectrum due to voltage induced delocalization of some electronic states. We also study the diffusive motion of molecular fullerenes in ethanol solvent and inside poly(3-hexylthiophene) lamella using reactive molecular dynamics simulations. We found that the mobility of the fullerene reduces considerably due to derivatization; the diffusion coefficient of C{sub 60} is an order of magnitude larger than the one for PCBM.« less

Development of a 66kV Class Rectifier Type Fault Current Limiter System

NASA Astrophysics Data System (ADS)

Ohkuma, Takeshi; Sato, Yoshibumi; Takahashi, Yoshihisa; Tokuda, Noriaki; Murai, Masaki; Nagasaki, Norihisa; Yuguchi, Kyousuke

A fault current limiter (FCL) is extensively expected to suppress fault current, particularly required for trunk power systems heavily connected high-voltage transmission lines, such as 500 kV class power system which constitutes the nucleus of the electric power system. By installing such FCL in the power system, the system interconnection is possible without the need to raise the capacity of the circuit breakers, and it is expected that FCLs may be used in more efficient power system design. For these reasons, FCLs based on various principles of operation have been developed in the world. In this paper, we have proposed a new type of FCL system, consisting of solid-state diodes, DC coil and bypass AC coil, and described the specification of distribution power system and 66 kV class FCL model. Also we have proposed a 66 kV class prototype single-phase model and the current limiting performance of this model was evaluated using a short circuit generator.

Electroencephalography (EEG) in the Study of Equivalence Class Formation. An Explorative Study

PubMed Central

Arntzen, Erik; Steingrimsdottir, Hanna S.

2017-01-01

Teaching arbitrary conditional discriminations and testing for derived relations may be essential for understanding changes in cognitive skills. Such conditional discrimination procedures are often used within stimulus equivalence research. For example, the participant is taught AB and BC relations and tested if emergent relations as BA, CB, AC and CA occur. The purpose of the current explorative experiment was to study stimulus equivalence class formation in older adults with electroencephalography (EEG) recordings as an additional measure. The EEG was used to learn about whether there was an indication of cognitive changes such as those observed in neurocognitive disorders (NCD). The present study included four participants who did conditional discrimination training and testing. The experimental design employed pre-class formation sorting and post-class formation sorting of the stimuli used in the experiment. EEG recordings were conducted before training, after training and after testing. The results showed that two participants formed equivalence classes, one participant failed in one of the three test relations, and one participant failed in two of the three test relations. This fourth participant also failed to sort the stimuli in accordance with the experimenter-defined stimulus equivalence classes during post-class formation sorting. The EEG indicated no cognitive decline in the first three participants but possible mild cognitive impairment (MCI) in the fourth participant. The results suggest that equivalence class formation may provide information about cognitive impairments such as those that are likely to occur in the early stages of NCD. The study recommends replications with broader samples. PMID:28377704

Investigation of the Effects of Facility Background Pressure on the Performance and Voltage-Current Characteristics of the High Voltage Hall Accelerator

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Huang, Wensheng; Haag, Thomas; Spektor, Rostislav

2014-01-01

The National Aeronautics and Space Administration (NASA) Science Mission Directorate In-Space Propulsion Technology office is sponsoring NASA Glenn Research Center to develop a 4 kW-class Hall thruster propulsion system for implementation in NASA science missions. A study was conducted to assess the impact of varying the facility background pressure on the High Voltage Hall Accelerator (HiVHAc) thruster performance and voltage-current characteristics. This present study evaluated the HiVHAc thruster performance in the lowest attainable background pressure condition at NASA GRC Vacuum Facility 5 to best simulate space-like conditions. Additional tests were performed at selected thruster operating conditions to investigate and elucidate the underlying physics that change during thruster operation at elevated facility background pressure. Tests were performed at background pressure conditions that are three and ten times higher than the lowest realized background pressure. Results indicated that the thruster discharge specific impulse and efficiency increased with elevated facility background pressure. The voltage-current profiles indicated a narrower stable operating region with increased background pressure. Experimental observations of the thruster operation indicated that increasing the facility background pressure shifted the ionization and acceleration zones upstream towards the thruster's anode. Future tests of the HiVHAc thruster are planned at background pressure conditions that are expected to be two to three times lower than what was achieved during this test campaign. These tests will not only assess the impact of reduced facility background pressure on thruster performance, voltage-current characteristics, and plume properties; but will also attempt to quantify the magnitude of the ionization and acceleration zones upstream shifting as a function of increased background pressure.

Extracting electron transfer coupling elements from constrained density functional theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu Qin; Van Voorhis, Troy

2006-10-28

Constrained density functional theory (DFT) is a useful tool for studying electron transfer (ET) reactions. It can straightforwardly construct the charge-localized diabatic states and give a direct measure of the inner-sphere reorganization energy. In this work, a method is presented for calculating the electronic coupling matrix element (H{sub ab}) based on constrained DFT. This method completely avoids the use of ground-state DFT energies because they are known to irrationally predict fractional electron transfer in many cases. Instead it makes use of the constrained DFT energies and the Kohn-Sham wave functions for the diabatic states in a careful way. Test calculationsmore » on the Zn{sub 2}{sup +} and the benzene-Cl atom systems show that the new prescription yields reasonable agreement with the standard generalized Mulliken-Hush method. We then proceed to produce the diabatic and adiabatic potential energy curves along the reaction pathway for intervalence ET in the tetrathiafulvalene-diquinone (Q-TTF-Q) anion. While the unconstrained DFT curve has no reaction barrier and gives H{sub ab}{approx_equal}17 kcal/mol, which qualitatively disagrees with experimental results, the H{sub ab} calculated from constrained DFT is about 3 kcal/mol and the generated ground state has a barrier height of 1.70 kcal/mol, successfully predicting (Q-TTF-Q){sup -} to be a class II mixed-valence compound.« less

Benefits of an exercise wellness program after spinal cord injury.

PubMed

Crane, Deborah A; Hoffman, Jeanne M; Reyes, Maria R

2017-03-01

To describe the initial benefits of a structured group exercise program on exercise frequency and intensity, perceived health, pain, mood, and television watching habits. Pre-test/post-test. Eighty-nine persons with SCI participated voluntarily in a no-cost, twice weekly physical therapy group exercise class over 3 months. Forty-five persons completed pre- and post-participation interviews on exercise frequency and intensity, perceived health, pain, mood, sleep, and television watching habits. Mean participant age of the respondents was 43.82 years. 49% had AIS C or D injuries, 24% had AIS A,B paraplegia, 9% had AIS A,B C1-C4 and 18% had AIS A,B C5-C8. 75.6% of participants were male and 84.4% had a traumatic etiology as the cause of their SCI. There was a significant improvement in days of strenuous and moderate exercise as well as health state. There was an average decrease in pain scores, depression scores, number of hours spent watching television, and days/week of mild exercise. Participation in structured, small group exercise as a component of a wellness program after SCI shows promise for improving regular exercise participation and health state, but benefits may also occur across other areas of health and function including mood, pain, and hours spent watching television. Further follow-up is needed to determine whether improvements can be maintained after program completion and across all neurological levels.

Large Scale Generation and Characterization of Anti-Human CD34 Monoclonal Antibody in Ascetic Fluid of Balb/c Mice

PubMed Central

Aghebati Maleki, Leili; Majidi, Jafar; Baradaran, Behzad; Abdolalizadeh, Jalal; Kazemi, Tohid; Aghebati Maleki, Ali; Sineh sepehr, Koushan

2013-01-01

Purpose: Monoclonal antibodies or specific antibodies are now an essential tool of biomedical research and are of great commercial and medical value. The purpose of this study was to produce large scale of monoclonal antibody against CD34 in order to diagnostic application in leukemia and purification of human hematopoietic stem/progenitor cells. Methods: For large scale production of monoclonal antibody, hybridoma cells that produce monoclonal antibody against human CD34 were injected into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. 5 ml ascitic fluid was harvested from each mouse in two times. Evaluation of mAb titration was assessed by ELISA method. The ascitic fluid was examined for class and subclasses by ELISA mouse mAb isotyping Kit. mAb was purified from ascitic fluid by affinity chromatography on Protein A-Sepharose. Purity of monoclonal antibody was monitored by SDS -PAGE and the purified monoclonal antibody was conjugated with FITC. Results: Monoclonal antibodies with high specificity and sensitivity against human CD34 by hybridoma technology were prepared. The subclass of antibody was IgG1 and its light chain was kappa. Conclusion: The conjugated monoclonal antibody could be a useful tool for isolation, purification and characterization of human hematopoietic stem cells. PMID:24312838

A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

PubMed Central

Aghebati Maleki, Leili; Baradaran, Behzad; Abdolalizadeh, Jalal; Ezzatifar, Fatemeh; Majidi, Jafar

2013-01-01

Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG). Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases. PMID:24312857

A Proposed Approach for Joint Modeling of the Longitudinal and Time-To-Event Data in Heterogeneous Populations: An Application to HIV/AIDS's Disease.

PubMed

Roustaei, Narges; Ayatollahi, Seyyed Mohammad Taghi; Zare, Najaf

2018-01-01

In recent years, the joint models have been widely used for modeling the longitudinal and time-to-event data simultaneously. In this study, we proposed an approach (PA) to study the longitudinal and survival outcomes simultaneously in heterogeneous populations. PA relaxes the assumption of conditional independence (CI). We also compared PA with joint latent class model (JLCM) and separate approach (SA) for various sample sizes (150, 300, and 600) and different association parameters (0, 0.2, and 0.5). The average bias of parameters estimation (AB-PE), average SE of parameters estimation (ASE-PE), and coverage probability of the 95% confidence interval (CP) among the three approaches were compared. In most cases, when the sample sizes increased, AB-PE and ASE-PE decreased for the three approaches, and CP got closer to the nominal level of 0.95. When there was a considerable association, PA in comparison with SA and JLCM performed better in the sense that PA had the smallest AB-PE and ASE-PE for the longitudinal submodel among the three approaches for the small and moderate sample sizes. Moreover, JLCM was desirable for the none-association and the large sample size. Finally, the evaluated approaches were applied on a real HIV/AIDS dataset for validation, and the results were compared.

Universal scaling of potential energy functions describing intermolecular interactions. II. The halide-water and alkali metal-water interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werhahn, Jasper C.; Akase, Dai; Xantheas, Sotiris S.

2014-08-14

The scaled versions of the newly introduced [S. S. Xantheas and J. C. Werhahn, J. Chem. Phys.141, 064117 (2014)] generalized forms of some popular potential energy functions (PEFs) describing intermolecular interactions – Mie, Lennard-Jones, Morse, and Buckingham exponential-6 – have been used to fit the ab initio relaxed approach paths and fixed approach paths for the halide-water, X -(H 2O), X = F, Cl, Br, I, and alkali metal-water, M +(H 2O), M = Li, Na, K, Rb, Cs, interactions. The generalized forms of those PEFs have an additional parameter with respect to the original forms and produce fits tomore » the ab initio data that are between one and two orders of magnitude better in the χ 2 than the original PEFs. They were found to describe both the long-range, minimum and repulsive wall of the respective potential energy surfaces quite accurately. Overall the 4-parameter extended Morse (eM) and generalized Buckingham exponential-6 (gBe-6) potentials were found to best fit the ab initio data for these two classes of ion-water interactions. Finally, the fitted values of the parameter of the (eM) and (gBe-6) PEFs that control the repulsive wall of the potential correlate remarkably well with the ionic radii of the halide and alkali metal ions.« less

Mutations at Several Loci Cause Increased Expression of Ribonucleotide Reductase in Escherichia coli

PubMed Central

Feeney, Morgan Anne; Ke, Na

2012-01-01

Production of deoxyribonucleotides for DNA synthesis is an essential and tightly regulated process. The class Ia ribonucleotide reductase (RNR), the product of the nrdAB genes, is required for aerobic growth of Escherichia coli. In catalyzing the reduction of ribonucleotides, two of the cysteines of RNR become oxidized, forming a disulfide bond. To regenerate active RNR, the cell uses thioredoxins and glutaredoxins to reduce the disulfide bond. Strains that lack thioredoxins 1 and 2 and glutaredoxin 1 do not grow because RNR remains in its oxidized, inactive form. However, suppressor mutations that lead to RNR overproduction allow glutaredoxin 3 to reduce sufficient RNR for growth of these mutant strains. We previously described suppressor mutations in the dnaA and dnaN genes that had such effects. Here we report the isolation of new mutations that lead to increased levels of RNR. These include mutations that were not known to influence production of RNR previously, such as a mutation in the hda gene and insertions in the nrdAB promoter region of insertion elements IS1 and IS5. Bioinformatic analysis raises the possibility that IS element insertion in this region represents an adaptive mechanism in nrdAB regulation in E. coli and closely related species. We also characterize mutations altering different amino acids in DnaA and DnaN from those isolated before. PMID:22247510

Biophysical characterization and structure of the Fab fragment from the NIST reference antibody, RM 8671.

PubMed

Karageorgos, Ioannis; Gallagher, Elyssia S; Galvin, Connor; Gallagher, D Travis; Hudgens, Jeffrey W

2017-11-01

Monoclonal antibody pharmaceuticals are the fastest-growing class of therapeutics, with a wide range of clinical applications. To assure their safety, these protein drugs must demonstrate highly consistent purity and stability. Key to these objectives is higher order structure measurements validated by calibration to reference materials. We describe preparation, characterization, and crystal structure of the Fab fragment prepared from the NIST Reference Antibody RM 8671 (NISTmAb). NISTmAb is a humanized IgG1κ antibody, produced in murine cell culture and purified by standard biopharmaceutical production methods, developed at the National Institute of Standards and Technology (NIST) to serve as a reference material. The Fab fragment was derived from NISTmAb through papain cleavage followed by protein A based purification. The purified Fab fragment was characterized by SDS-PAGE, capillary gel electrophoresis, multi-angle light scattering, size exclusion chromatography, mass spectrometry, and x-ray crystallography. The crystal structure at 0.2 nm resolution includes four independent Fab molecules with complete light chains and heavy chains through Cys 223, enabling assessment of conformational variability and providing a well-characterized reference structure for research and engineering applications. This nonproprietary, publically available reference material of known higher-order structure can support metrology in biopharmaceutical applications, and it is a suitable platform for validation of molecular modeling studies. Published by Elsevier Ltd.

Possible stretched exponential parametrization for humidity absorption in polymers.

PubMed

Hacinliyan, A; Skarlatos, Y; Sahin, G; Atak, K; Aybar, O O

2009-04-01

Polymer thin films have irregular transient current characteristics under constant voltage. In hydrophilic and hydrophobic polymers, the irregularity is also known to depend on the humidity absorbed by the polymer sample. Different stretched exponential models are studied and it is shown that the absorption of humidity as a function of time can be adequately modelled by a class of these stretched exponential absorption models.

Kumaraswamy autoregressive moving average models for double bounded environmental data

NASA Astrophysics Data System (ADS)

Bayer, Fábio Mariano; Bayer, Débora Missio; Pumi, Guilherme

2017-12-01

In this paper we introduce the Kumaraswamy autoregressive moving average models (KARMA), which is a dynamic class of models for time series taking values in the double bounded interval (a,b) following the Kumaraswamy distribution. The Kumaraswamy family of distribution is widely applied in many areas, especially hydrology and related fields. Classical examples are time series representing rates and proportions observed over time. In the proposed KARMA model, the median is modeled by a dynamic structure containing autoregressive and moving average terms, time-varying regressors, unknown parameters and a link function. We introduce the new class of models and discuss conditional maximum likelihood estimation, hypothesis testing inference, diagnostic analysis and forecasting. In particular, we provide closed-form expressions for the conditional score vector and conditional Fisher information matrix. An application to environmental real data is presented and discussed.

Best uniform approximation to a class of rational functions

NASA Astrophysics Data System (ADS)

Zheng, Zhitong; Yong, Jun-Hai

2007-10-01

We explicitly determine the best uniform polynomial approximation to a class of rational functions of the form 1/(x-c)2+K(a,b,c,n)/(x-c) on [a,b] represented by their Chebyshev expansion, where a, b, and c are real numbers, n-1 denotes the degree of the best approximating polynomial, and K is a constant determined by a, b, c, and n. Our result is based on the explicit determination of a phase angle [eta] in the representation of the approximation error by a trigonometric function. Moreover, we formulate an ansatz which offers a heuristic strategies to determine the best approximating polynomial to a function represented by its Chebyshev expansion. Combined with the phase angle method, this ansatz can be used to find the best uniform approximation to some more functions.

The role of the Serratia marcescens SdeAB multidrug efflux pump and TolC homologue in fluoroquinolone resistance studied via gene-knockout mutagenesis.

PubMed

Begic, Sanela; Worobec, Elizabeth A

2008-02-01

Serratia marcescens is a prominent opportunistic nosocomial pathogen resistant to several classes of antibiotics. The major mechanism for fluoroquinolone resistance in various Gram-negative pathogens is active efflux. Our group previously identified SdeAB, a resistance-nodulation-cell division (RND) efflux pump complex, and a TolC-like outer-membrane protein (HasF), which together mediate energy-dependent fluoroquinolone efflux. In addition, a regulatory protein-encoding gene in the upstream region of sdeAB was identified (sdeR) and found to be 40 % homologous to MarA, an Escherichia coli transcriptional regulator. To provide conclusive evidence as to the role of these components in S. marcescens, sdeB, hasF and sdeR deletion mutants were constructed. Suicide vectors were created and introduced via triparental mating into S. marcescens UOC-67 (wild-type) and, for sdeB and hasF, T-861 (clinical isolate). We have analysed these genetically altered strains using minimal inhibitory concentration (MIC) assays for a wide range of compounds (fluoroquinolones, SDS, novobiocin, ethidium bromide and chloramphenicol). Intracellular accumulation of a variety of fluoroquinolones was measured fluorospectroscopically. The sdeB, hasF and sdeR knockout strains were consistently more susceptible to antibiotics than the parent strains, with the sdeB/hasF double knockout strain showing the highest susceptibility. A marked increase in fluoroquinolone (ciprofloxacin) accumulation was observed for strains deficient in either the sdeB or hasF genes when compared to the parental strains, with the highest ciprofloxacin accumulation observed for the sdeB/hasF double knockout. Antibiotic accumulation assays for the sdeB knockout mutant strains performed in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a proton-motive-force inhibitor, demonstrated that SdeAB-mediated efflux is proton-motive-force dependent. Due to the comparable susceptibility of the sdeB and the hasF individual knockouts, we conclude that S. marcescens HasF is the sole outer-membrane component of the SdeAB pump. In addition, MIC data for sdeR-deficient and overexpressing strains confirm that SdeR is an activator of sdeAB and acts to enhance the overall multidrug resistance of S. marcescens.

Correlation of Beta Angle with Antero-Posterior Dysplasia Indicators and FMA: An Institution Based Cephalometric Study.

PubMed

Singh, Gurinder; Verma, Sanjeev; Singh, Devinder Preet; Yadav, Sumit Kumar; Yadav, Achla Bharti

2016-11-01

Beta angle utilizes three skeletal landmarks - point A, point B, and point C (the apparent axis of the condyle). It is formed between A-B line and point A perpendicular to C-B line. Further this angle indicates the severity and the type of skeletal dysplasia in the sagittal dimension and it changes with the growth pattern of the patient. Hence, it is important to study the dependence of beta angle on the growth pattern. The present study was designed to evaluate the correlation of Beta angle with point A-Nasion-point B (ANB) angle, points A and B to palatal plane (App-Bpp), Wit's appraisal and Maxillary-Mandibular plane angle Bisector (MMB) and Frankfort-Mandibular plane Angle (FMA) in Skeletal Class I, Class II and Class III malocclusion groups. Pre-treatment lateral head cephalo-grams of 120 subjects in age group of 15-25 years were obtained. Three skeletal Class I, Class II and Class III malocclusion groups (40 each) were assorted on the basis of ANB, MMB, App-Bpp, Wit's appraisal and FMA. Analysis of variance (ANOVA) and mean differences were calculated to compare the study groups. Bivariate correlations among different parameters of these groups were obtained. Normal values of beta angle in skeletal Class I group, skeletal Class II group and skeletal Class III group was 31.33±3.25, 25.28±4.28 and 40.93±4.55 respectively. Overall beta angle showed a strong correlation with all parameters of anterio-posterior dysplasia indicators except FMA. Beta angle shows weak correlation with FMA and is not affected by growth pattern/jaw rotation. The normal values are in same range irrespective of the differences in craniofacial morphology.

Correlation of Beta Angle with Antero-Posterior Dysplasia Indicators and FMA: An Institution Based Cephalometric Study

PubMed Central

Singh, Gurinder; Verma, Sanjeev; Singh, Devinder Preet; Yadav, Achla Bharti

2016-01-01

Introduction Beta angle utilizes three skeletal landmarks – point A, point B, and point C (the apparent axis of the condyle). It is formed between A-B line and point A perpendicular to C-B line. Further this angle indicates the severity and the type of skeletal dysplasia in the sagittal dimension and it changes with the growth pattern of the patient. Hence, it is important to study the dependence of beta angle on the growth pattern. Aim The present study was designed to evaluate the correlation of Beta angle with point A–Nasion–point B (ANB) angle, points A and B to palatal plane (App-Bpp), Wit’s appraisal and Maxillary-Mandibular plane angle Bisector (MMB) and Frankfort-Mandibular plane Angle (FMA) in Skeletal Class I, Class II and Class III malocclusion groups. Materials and Methods Pre-treatment lateral head cephalo-grams of 120 subjects in age group of 15-25 years were obtained. Three skeletal Class I, Class II and Class III malocclusion groups (40 each) were assorted on the basis of ANB, MMB, App-Bpp, Wit’s appraisal and FMA. Analysis of variance (ANOVA) and mean differences were calculated to compare the study groups. Bivariate correlations among different parameters of these groups were obtained. Results Normal values of beta angle in skeletal Class I group, skeletal Class II group and skeletal Class III group was 31.33±3.25, 25.28±4.28 and 40.93±4.55 respectively. Overall beta angle showed a strong correlation with all parameters of anterio-posterior dysplasia indicators except FMA. Conclusion Beta angle shows weak correlation with FMA and is not affected by growth pattern/jaw rotation. The normal values are in same range irrespective of the differences in craniofacial morphology. PMID:28050509

Efficient 30-W, 140-MHz rf amplifier for CW CO2 waveguide laser excitation

NASA Technical Reports Server (NTRS)

Hochuli, U. E.; Haldemann, P. R.

1988-01-01

Details of a 30-W, 140-MHz rf amplifier for CW CO2 waveguide laser excitation are presented. The amplifier delivers 30 W into a 50-Ohm load while requiring only 40 W of dc power from a 28-V supply and 100 mW of rf drive power for an overall efficiency of 75 percent. A coupling-starting network design theory is given that provides the initiation over voltage for the discharge plasma from an rf power source of limited output voltage capability. The network then matches the drive circuit to the new input impedance of the operating discharge without any adjustments. This design theory applies to the whole class of networks whose losses can be approximated by a loss conductance in parallel with the gas discharge.

Performance Test Results of the NASA-457M v2 Hall Thruster

NASA Technical Reports Server (NTRS)

Soulas, George C.; Haag, Thomas W.; Herman, Daniel A.; Huang, Wensheng; Kamhawi, Hani; Shastry, Rohit

2012-01-01

Performance testing of a second generation, 50 kW-class Hall thruster labeled NASA-457M v2 was conducted at the NASA Glenn Research Center. This NASA-designed thruster is an excellent candidate for a solar electric propulsion system that supports human exploration missions. Thruster discharge power was varied from 5 to 50 kW over discharge voltage and current ranges of 200 to 500 V and 15 to 100 A, respectively. Anode efficiencies varied from 0.56 to 0.71. The peak efficiency was similar to that of other state-of-the-art high power Hall thrusters, but outperformed these thrusters at lower discharge voltages. The 0.05 to 0.18 higher anode efficiencies of this thruster compared to its predecessor were primarily due to which of two stable discharge modes the thruster was operated. One stable mode was at low magnetic field strengths, which produced high anode efficiencies, and the other at high magnetic fields where its predecessor was operated. Cathode keeper voltages were always within 2.1 to 6.2 V and cathode voltages were within 13 V of tank ground during high anode efficiency operation. However, during operation at high magnetic fields, cathode-to-ground voltage magnitudes increased dramatically, exceeding 30 V, due to the high axial magnetic field strengths in the immediate vicinity of the centrally-mounted cathode. The peak thrust was 2.3 N and this occurred at a total thruster input power of 50.0 kW at a 500 V discharge voltage. The thruster demonstrated a thrust-to-power range of 76.4 mN/kW at low power to 46.1 mN/kW at full power, and a specific impulse range of 1420 to 2740 s. For a discharge voltage of 300 V, where specific impulses would be about 2000 s, thrust efficiencies varied from 0.57 to 0.63.

A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

PubMed

Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

2018-04-21

Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018 Elsevier B.V. All rights reserved.

Superconcentrated electrolytes for a high-voltage lithium-ion battery

PubMed Central

Wang, Jianhui; Yamada, Yuki; Sodeyama, Keitaro; Chiang, Ching Hua; Tateyama, Yoshitaka; Yamada, Atsuo

2016-01-01

Finding a viable electrolyte for next-generation 5 V-class lithium-ion batteries is of primary importance. A long-standing obstacle has been metal-ion dissolution at high voltages. The LiPF6 salt in conventional electrolytes is chemically unstable, which accelerates transition metal dissolution of the electrode material, yet beneficially suppresses oxidative dissolution of the aluminium current collector; replacing LiPF6 with more stable lithium salts may diminish transition metal dissolution but unfortunately encounters severe aluminium oxidation. Here we report an electrolyte design that can solve this dilemma. By mixing a stable lithium salt LiN(SO2F)2 with dimethyl carbonate solvent at extremely high concentrations, we obtain an unusual liquid showing a three-dimensional network of anions and solvent molecules that coordinate strongly to Li+ ions. This simple formulation of superconcentrated LiN(SO2F)2/dimethyl carbonate electrolyte inhibits the dissolution of both aluminium and transition metal at around 5 V, and realizes a high-voltage LiNi0.5Mn1.5O4/graphite battery that exhibits excellent cycling durability, high rate capability and enhanced safety. PMID:27354162

Gate-tunable memristive phenomena mediated by grain boundaries in single-layer MoS2

NASA Astrophysics Data System (ADS)

Sangwan, Vinod K.; Jariwala, Deep; Kim, In Soo; Chen, Kan-Sheng; Marks, Tobin J.; Lauhon, Lincoln J.; Hersam, Mark C.

2015-05-01

Continued progress in high-speed computing depends on breakthroughs in both materials synthesis and device architectures. The performance of logic and memory can be enhanced significantly by introducing a memristor, a two-terminal device with internal resistance that depends on the history of the external bias voltage. State-of-the-art memristors, based on metal-insulator-metal (MIM) structures with insulating oxides, such as TiO2, are limited by a lack of control over the filament formation and external control of the switching voltage. Here, we report a class of memristors based on grain boundaries (GBs) in single-layer MoS2 devices. Specifically, the resistance of GBs emerging from contacts can be easily and repeatedly modulated, with switching ratios up to ˜103 and a dynamic negative differential resistance (NDR). Furthermore, the atomically thin nature of MoS2 enables tuning of the set voltage by a third gate terminal in a field-effect geometry, which provides new functionality that is not observed in other known memristive devices.

Engineering Group-IV Monochalcogenides by Doping and Alloying

NASA Astrophysics Data System (ADS)

Sirikumara, Hansika; Fitzpatrick, Trevor; Jayasekera, Thushari

Group-IV monochalcogenides, MX (M=Sn,Ge and X=S,Se) have shown to be promising materials for thermoelectric and photovoltaic applications. These properties can be further engineered by substitutional doping and alloying. Using the results from ab initio Density Functional Theory calculations, we identified a series of new class of monochalcogenide alloys in the form Ge(1-x)SnxS, Ge(1-x)SnxSe, GeSxSe(1- x), SnSxSe(1-x). Stability of their two-dimensional counterparts will also be discussed in this presentation.