Artifactual responses when recording auditory steady-state responses.

PubMed

Small, Susan A; Stapells, David R

2004-12-01

The goal of this study was to investigate, in hearing-impaired participants who could not hear the stimuli, the possibility of artifactual auditory steady-state responses (ASSRs) when stimuli are presented at high intensities. ASSRs to single (60 dB HL) and multiple (20 to 50 dB HL; 500 to 4000 Hz) bone-conduction stimuli as well as single 114 to 120 dB HL air-conduction stimuli, were obtained using the Rotman MASTER system, using analog-to-digital (A/D) conversion rates of 500, 1000, and 1250 Hz. Responses (p < 0.05) were considered artifactual when their numbers exceeded that expected by chance. In some conditions, we also obtained ASSRs to "alternated" stimuli (stimuli inverted and ASSRs to the two polarities averaged). A total of 17 subjects were tested. Bone conduction results: 500 Hz A/D rate: Large-amplitude (43 to 1558 nV) artifactual ASSRs were seen at 40 and 50 dB HL for the 500 Hz carrier frequency. Smaller responses (28 to 53 nV) were also recorded at 20 dB HL for the 500 Hz carrier frequency. Artifactual ASSRs (17 to 62 nV) were seen at 40 dB HL and above for the 1000 Hz carrier frequency and at 50 dB HL for the 2000 Hz carrier frequency. Alternating the stimulus polarity decreased the amplitude and occurrence of these artifactual responses but did not eliminate responses for the 500 Hz carrier frequency at 40 dB HL and above. No artifactual responses were recorded for 4000 Hz stimuli for any condition. 1000 Hz A/D rate: Artifactual ASSRs (15 to 523 nV) were seen at 50 dB HL and above for the 500 Hz carrier frequency and 40 dB HL and above for the 1000 Hz carrier frequency. Artifactual responses were also obtained at 50 dB HL for a 2000 Hz carrier frequency but not at lower levels. Artifactual responses were not seen for the 4000 Hz carrier frequency. Alternating the stimulus polarity removed the responses for the 1000 and 2000 Hz carrier frequencies but did not change the results for the 500 Hz carrier frequency. 1250 Hz A/D rate: Artifactual ASSRs (16 to 220 nV) were seen at 50 dB HL and above for the 500 Hz carrier frequency and 60 dB HL and above for the 1000 Hz carrier frequency. Alternating the stimulus polarity removed the responses for the 1000 Hz carrier frequency but did not change the results for the 500 Hz carrier frequency. There were no artifactual responses at 2000 and 4000 Hz. Air conduction results: 500 Hz A/D rate: Artifactual ASSRs (49 to 153 nV) were seen for 114 to 120 dB HL stimuli for 500 and 1000 Hz carrier frequencies. Alternating the stimulus polarity removed these responses. There were no artifactual responses at 2000 and 4000 Hz. 1000 and 1250 Hz A/D rates: Artifactual ASSRs (19 to 55 nV) were seen for a 120 dB HL stimulus for a 1000 Hz carrier. Alternating the stimulus polarity removed these responses. High-intensity air- or bone-conduction stimuli can produce spurious ASSRs, especially for 500 and 1000 Hz carrier frequencies. High-amplitude stimulus artifact can result in energy that is aliased to exactly the modulation frequency. Choice of signal conditioning (electroencephalogram filter slope and low-pass cutoff) and processing (A/D rate) can avoid spurious responses due to aliasing. However, artifactual responses due to other causes may still occur for bone-conduction stimuli 50 dB HL and higher (and possibly for high-level air conduction). Because the phases of these spurious responses do not invert with inversion of stimulus, the possibility of nonauditory physiologic responses cannot be ruled out. The clinical implications of these results are that artifactual responses may occur for any patient for bone-conduction stimuli at levels greater than 40 dB HL and for high-intensity air-conduction stimuli used to assess patients with profound hearing loss.

Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

PubMed

Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

2016-09-01

Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.

CONCENTRATION AND DECONTAMINATION OF SOLUTIONS CONTAINING PLUTONIUM VALUES BY BISMUTH PHOSPHATE CARRIER PRECIPITATION METHODS

DOEpatents

Seaborg, G.T.; Thompson, S.G.

1960-08-23

A process is given for isolating plutonium present in the tetravalent state in an aqueous solution together with fission products. First, the plutonium and fission products are coprecipitated on a bismuth phosphate carrier. The precipitate obtained is dissolved, and the plutonium in the solution is oxidized to the hexavalent state (with ceric nitrate, potassium dichromate, Pb/ sub 3/O/sub 4/, sodium bismuthate and/or potassium dichromate). Thereafter a carrier for fission products is added (bismuth phosphate, lanthanum fluoride, ceric phosphate, bismuth oxalate, thorium iodate, or thorium oxalate), and the fission-product precipitation can be repeated with one other of these carriers. After removal of the fission-product-containing precipitate or precipitates. the plutonium in the supernatant is reduced to the tetravalent state (with sulfur dioxide, hydrogen peroxide. or sodium nitrate), and a carrier for tetravalent plutonium is added (lanthanum fluoride, lanthanum hydroxide, lanthanum phosphate, ceric phosphate, thorium iodate, thorium oxalate, bismuth oxalate, or niobium pentoxide). The plutonium-containing precipitate is then dissolved in a relatively small volume of liquid so as to obtain a concentrated solution. Prior to dissolution, the bismuth phosphate precipitates first formed can be metathesized with a mixture of sodium hydroxide and potassium carbonate and plutonium-containing lanthanum fluorides with alkali-metal hydroxide. In the solutions formed from a plutonium-containing lanthanum fluoride carrier the plutonium can be selectively precipitated with a peroxide after the pH was adjusted preferably to a value of between 1 and 2. Various combinations of second, third, and fourth carriers are discussed.

Diagnostic value of cerebrospinal fluid tau, neurofilament, and progranulin in definite frontotemporal lobar degeneration.

PubMed

Goossens, Joery; Bjerke, Maria; Van Mossevelde, Sara; Van den Bossche, Tobi; Goeman, Johan; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan

2018-03-20

We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. CSF levels of routine AD biomarkers (phosphorylated tau (p-tau 181 ), total tau (t-tau), and amyloid-beta (Aβ) 1-42 ) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20). FTLD subgroups were defined by genetic carrier status and/or postmortem neuropathological confirmation (FTLD-TDP: n = 34, including FTLD-C9orf72: n = 19 and FTLD-GRN: n = 9; FTLD-tau: n = 10). GRN mutation carriers had significantly lower progranulin levels compared to other FTLD patients, AD, and controls. Both t-tau and p-tau 181 were normal in FTLD patients, even in FTLD-tau. Aβ 1-42 levels were very variable in FTLD. Neurofilament light chain (Nf-L) was significantly higher in FTLD compared with AD and controls. The reference logistic regression model based on the established AD biomarkers could be improved by the inclusion of CSF Nf-L, which was also important for the differentiation between FTLD and controls. Within the FTLD cohort, no significant differences were found between FTLD-TDP and FTLD-tau, but GRN mutation carriers had higher t-tau and Nf-L levels than C9orf72 mutation carriers and FTLD-tau patients. There is an added value for Nf-L in the differential diagnosis of FTLD. Progranulin levels in CSF depend on mutation status, and GRN mutation carriers seem to be affected by more severe neurodegeneration.

Aircraft Carrier Turbulence Study for Predicting Air Flow Dynamics with Increasing Wind-Over-Deck Velocities

DTIC Science & Technology

1968-03-28

AD-A020 223 AIRCRAFT CARRIER TURBULENCE STUDY FOR PREDICTING AIR FLOW DYNAMICS WITH INCREASING WIND-OVER-DECK VELOCITIES S. Frost Naval Air...Copy NAVAL AIR ENGINEERING CENTERElPILAOUPHBA, PENNSYLVANIA 19112 Q Had-NG7~ CODE IDEN NO. *OOM 28 MARCH 4fe AIRCRAFT CARRIER TUJRBULENCE STUDY FOR...carrier dynamics. Ike- comirendations for future experimental and theoretical studies are give,. DD 1473 EDITIOIN 0F I NOV SS IS O@SOLETE S - ’i02

PROCESS FOR SEPARATING PLUTONIUM BY REPEATED PRECIPITATION WITH AMPHOTERIC HYDROXIDE CARRIERS

DOEpatents

Faris, B.F.

1960-04-01

A multiple carrier precipitation method is described for separating and recovering plutonium from an aqueous solution. The hydroxide of an amphoteric metal is precipitated in an aqueous plutonium-containing solution. This precipitate, which carries plutonium, is then separated from the supernatant liquid and dissolved in an aqueous hydroxide solution, forming a second plutonium- containing solution. lons of an amphoteric metal which forms an insoluble hydroxide under the conditions existing in this second solution are added to the second solution. The precipitate which forms and which carries plutonium is separated from the supernatant liquid. Amphoteric metals which may be employed are aluminum, bibmuth, copper, cobalt, iron, lanthanum, nickel, and zirconium.

CONCENTRATION OF Pu USING OXALATE TYPE CARRIER

DOEpatents

Ritter, D.M.; Black, R.P.S.

1960-04-19

A method is given for dissolving and reprecipitating an oxalate carrier precipitate in a carrier precipitation process for separating and recovering plutonium from an aqueous solution. Uranous oxalate, together with plutonium being carried thereby, is dissolved in an aqueous alkaline solution. Suitable alkaline reagents are the carbonates and oxulates of the alkali metals and ammonium. An oxidizing agent selected from hydroxylamine and hydrogen peroxide is then added to the alkaline solution, thereby oxidizing uranium to the hexavalent state. The resulting solution is then acidified and a source of uranous ions provided in the acidified solution, thereby forming a second plutoniumcarrying uranous oxalate precipitate.

No-carrier-added (/sup 18/F)-N-methylspiroperidol

DOEpatents

Shiue, C.Y.; Fowler, J.S.; Wolf, A.P.

1985-10-04

The present invention is directed to the synthesis of a radioligand, labeled with a positron emitting radionuclide which is suitable for dynamic studies in humans using positron emission transaxial tomography. No-carrier-added (NCA) (/sup 18/F)-N-methylspiroperiodl is prepared from four different sustrates: p-nitrobenzonitrile, cyclopropyl p-nitrophenyl ketone, p-cyclopropanoyl-N,N,N-trimethylanilinium iodide and p-cyclopropanoyl-N,N,N-trimethylanilinium perchlorate. The process for the production of NCA (/sup 18/F)-N-methylspiroperidol is a nucleophilic aromatic substitution reaction. Furthermore, the compound of this invention is shown to be effective as a new drug of choice for in vivo examination of dopamine binding sites in a human brain. In particular, this drug is primarily useful in the noninvasive technique of positron emission transaxial tomography (PETT).

Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population.

PubMed

Rimajova, Mira; Lenzo, Nat P; Wu, Jing-Shan; Bates, Kristyn A; Campbell, Andrew; Dhaliwal, Satvinder S; McCarthy, Michael; Rodrigues, Mark; Paton, Athena; Rowe, Christopher; Foster, Jonathan K; Martins, Ralph N

2008-03-01

Apolipoprotein E-epsilon4 (APOEepsilon4) has been associated with increased risk of developing Alzheimer's disease (AD) and regional cerebral glucose hypometabolism, as measured by fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). We report here preliminary data from studies that aim to determine whether cerebral glucose hypometabolism is observed in APOEepsilon4 positive, cognitively intact individuals between the ages of 50 and 80, and whether there is an additional impact of subjective memory complainer (SMC) status on glucose metabolism determined by NeuroStat analysis. FDG-PET was conducted in 30 community dwelling, APOE-epsilon4 carriers without clinical evidence of dementia and objective cognitive impairment as assessed using a neuropsychological battery. Neurological soft-signs (NSS) were also assessed. Glucose hypometabolism was demonstrated in the anterior and posterior cingulate cortex and in the temporal association cortices in APOEepsilon4 carriers compared to the normative NeuroStat database. This pattern was particularly evident in APOEepsilon4 heterozygous individuals. SMC showed hypometabolism in the aforementioned brain regions, whereas non-SMC showed no significant pattern of glucose hypometabolism. FDG-PET with NeuroStat analysis showed that APOEepsilon4 carriers have mild glucose hypometabolism in areas associated with AD. SMC may be associated with AD-related differences in regional cerebral glucose metabolism. These findings are currently being investigated in a larger group of APOEepsilon4 carriers.

Folic-Acid-Targeted Self-Assembling Supramolecular Carrier for Gene Delivery.

PubMed

Liao, Rongqiang; Yi, Shouhui; Liu, Manshuo; Jin, Wenling; Yang, Bo

2015-07-27

A targeting gene carrier for cancer-specific delivery was successfully developed through a "multilayer bricks-mortar" strategy. The gene carrier was composed of adamantane-functionalized folic acid (FA-AD), an adamantane-functionalized poly(ethylene glycol) derivative (PEG-AD), and β-cyclodextrin-grafted low-molecular-weight branched polyethylenimine (PEI-CD). Carriers produced by two different self-assembly schemes, involving either precomplexation of the PEI-CD with the FA-AD and PEG-AD before pDNA condensation (Method A) or pDNA condensation with the PEI-CD prior to addition of the FA-AD and PEG-AD to engage host-guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI-25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host-guest interactions, could be an effective, targeted, and low-toxicity carrier for delivering nucleic acid to target cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleophilic fluorination of aromatic compounds

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R

2014-03-18

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

Separation of no-carrier-added rhenium from bulk tantalum by the sodium malonate-PEG aqueous biphasic system.

PubMed

Dutta, Binita; Lahiri, Susanta; Tomar, B S

2014-02-01

The aqueous biphasic system (ABS) involving sodium malonate-polyethylene glycol (PEG) phases has been applied for the first time for separation of no-carrier-added (183)Re (T1/2=70 d) from α-particle irradiated bulk tantalum target. The various ABS conditions were applied for investigating the separation by varying pH, temperature, PEG-molecular weight, concentration of salt. The extraction pattern was hardly affected by change in pH and the molecular weight of PEG. One step separation of nca (183)Re from Ta was achieved at the optimal conditions of (i) 50% (w/w) PEG-4000-2 M sodium malonate, 40 °C and (ii) 50% (w/w) PEG-4000-3 M sodium malonate, room temperature (27 °C). © 2013 Published by Elsevier Ltd.

Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease A Cross-sectional Imaging Study

PubMed Central

Dean, Douglas C.; Jerskey, Beth A.; Chen, Kewei; Protas, Hillary; Thiyyagura, Pradeep; Roontiva, Auttawat; O’Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Siniard, Ashley L.; Turk, Mari N.; Hua, Xue; Madsen, Sarah K.; Thompson, Paul M.; Fleisher, Adam S.; Huentelman, Matthew J.; Deoni, Sean C. L.; Reiman, Eric M.

2014-01-01

IMPORTANCE Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. OBJECTIVE To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. DESIGN, SETTING, AND PARTICIPANTS Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. MAIN OUTCOMES AND MEASURES Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. RESULTS Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. CONCLUSIONS AND RELEVANCE While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies. PMID:24276092

Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study.

PubMed

Dean, Douglas C; Jerskey, Beth A; Chen, Kewei; Protas, Hillary; Thiyyagura, Pradeep; Roontiva, Auttawat; O'Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Siniard, Ashley L; Turk, Mari N; Hua, Xue; Madsen, Sarah K; Thompson, Paul M; Fleisher, Adam S; Huentelman, Matthew J; Deoni, Sean C L; Reiman, Eric M

2014-01-01

Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies.

77 FR 18304 - Agency Information Collection; Activity Under OMB Review; Report of Financial and Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... Operating Statistics for Large Certificated Air Carriers AGENCY: Research & Innovative Technology... DEPARTMENT OF TRANSPORTATION Research & Innovative Technology Administration [Docket ID Number... Operating Statistics for Large Certificated Air Carriers. Form No.: BTS Form 41. Type Of Review...

Studies on 66,67Ga- and 199Tl-poly(N-vinylpyrrolidone) complexes.

PubMed

Lahiri, Susanta; Sarkar, Soumi

2007-03-01

Gallium and thallium radionuclides have both diagnostic and therapeutic applications in the field of nuclear medicine. Poly(N-vinylpyrrolidone) (PVP) is routinely used as a drug base because of its excellent biocompatibility. In this paper, complex formation abilities between no-carrier-added (66,)(67)Ga/(199)Tl radionuclides and PVP have been studied. It has been found that aqueous 5% PVP solution can almost quantitatively back extract (66,)(67)Ga/(199)Tl radionuclides from an organic phase, which proves the complexing ability of PVP with (66,)(67)Ga/(199)Tl. Tl(3+) is more efficient to form Tl-PVP complexes than Tl(+). However, Tl(3+)-PVP complexes are less stable than Ga(3+)-PVP complexes.

The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease.

PubMed

Vural, P; Değirmencioğlu, S; Parildar-Karpuzoğlu, H; Doğru-Abbasoğlu, S; Hanagasi, H A; Karadağ, B; Gürvit, H; Emre, M; Uysal, M

2009-12-01

Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with conflicting results. To investigate the TNFalpha-308, IL-6 -174 and IL-10 -1082 gene polymorphisms as susceptibility factors for AD. We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls. Heterozygotes (AG) or combined genotype (AG+AA) for IL-10 -1082 were associated with approximately two-fold increase in the risk of AD. Carriers of A alleles of both TNFalpha-308 and IL-10 -1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNFalpha-308 A and IL-6 -174 C alleles raised three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL-6 -174 polymorphism alone. Our results suggest that TNFalpha and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNFalpha-308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.

Drug delivery strategies for Alzheimer's disease treatment.

PubMed

Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

2011-05-01

Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers.

PubMed

Goverde, A; Spaander, M C W; Nieboer, D; van den Ouweland, A M W; Dinjens, W N M; Dubbink, H J; Tops, C J; Ten Broeke, S W; Bruno, M J; Hofstra, R M W; Steyerberg, E W; Wagner, A

2018-07-01

Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5. The area under the operator receiving characteristic curve (AUC) was compared between MMRpredict and PREMM5 for LS patients in general and for different LS genes specifically. Of 734 index patients, 83 (11%) were diagnosed with LS; 23 MLH1, 17 MSH2, 31 MSH6 and 12 PMS2 mutation carriers. Both prediction models performed well for MLH1 and MSH2 (AUC 0.80 and 0.83 for PREMM5 and 0.79 for MMRpredict) and fair for MSH6 mutation carriers (0.69 for PREMM5 and 0.66 for MMRpredict). MMRpredict performed fair for PMS2 mutation carriers (AUC 0.72), while PREMM5 failed to discriminate PMS2 mutation carriers from non-mutation carriers (AUC 0.51). The only statistically significant difference between PMS2 mutation carriers and non-mutation carriers was proximal location of colorectal cancer (77 vs. 28%, p < 0.001). Adding location of colorectal cancer to PREMM5 considerably improved the models performance for PMS2 mutation carriers (AUC 0.77) and overall (AUC 0.81 vs. 0.72). We validated these results in an external cohort of 376 colorectal cancer patients, including 158 LS patients. MMRpredict and PREMM5 cannot adequately identify PMS2 mutation carriers. Adding location of colorectal cancer to PREMM5 may improve the performance of this model, which should be validated in larger cohorts.

Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease.

PubMed

Quiroz, Yakeel T; Sperling, Reisa A; Norton, Daniel J; Baena, Ana; Arboleda-Velasquez, Joseph F; Cosio, Danielle; Schultz, Aaron; Lapoint, Molly; Guzman-Velez, Edmarie; Miller, John B; Kim, Leo A; Chen, Kewei; Tariot, Pierre N; Lopera, Francisco; Reiman, Eric M; Johnson, Keith A

2018-05-01

It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation. In this cross-sectional imaging study, we leveraged data from a homogeneous autosomal dominant AD kindred, which allowed us to examine measurable tau deposition as a function of individuals' proximity to the expected onset of dementia. Cross-sectional measures of carbon 11-labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F 18 (previously known as AV 1451, T807) PET imaging were assessed in 24 PSEN1 E280A kindred members (age range, 28-55 years), including 12 carriers, 9 of whom were cognitively unimpaired and 3 of whom had mild cognitive impairment, and 12 cognitively unimpaired noncarriers. We compared carbon 11-labeled Pittsburgh Compound B PET cerebral with cerebellar distribution volume ratios as well as flortaucipir F 18 PET cerebral with cerebellar standardized uptake value ratios in mutation carriers and noncarriers. Spearman correlations characterized the associations between age and mean cortical Pittsburgh Compound B distribution volume ratio levels or regional flortaucipir standardized uptake value ratio levels in both groups. Of the 24 individuals, the mean (SD) age was 38.0 (7.4) years, or approximately 6 years younger than the expected onset of clinical symptoms in carriers. Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s, and 7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2). Elevated levels of tau deposition were seen within medial temporal lobe regions in amyloid-positive mutation carriers 6 years before clinical onset of AD in this kindred. Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment. β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment. In carriers, higher levels of tau deposition were associated with worse performance on the Mini-Mental State Examination (entorhinal cortex: r = -0.60; P = .04; inferior temporal lobe: r = -0.54; P = .06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = -0.86; P < .001; inferior temporal lobe: r = -0.70; P = .01). The present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired. The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.

Assessment of Alzheimer's disease risk with functional magnetic resonance imaging: an arterial spin labeling study.

PubMed

Bangen, Katherine J; Restom, Khaled; Liu, Thomas T; Wierenga, Christina E; Jak, Amy J; Salmon, David P; Bondi, Mark W

2012-01-01

Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.

Increased fMRI signal with age in familial Alzheimer’s disease mutation carriers

PubMed Central

Braskie, Meredith N.; Medina, Luis D.; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel Angel; Cummings, Jeffrey L.; Bookheimer, Susan Y.; Ringman, John M.

2010-01-01

Although many Alzheimer’s disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of non-demented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 non-demented autosomal dominant AD mutation carriers with fMRI activity in 8 of their non-carrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects’ distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from non-carriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes. PMID:21129823

Oxidative stress and APO E polymorphisms in Alzheimer's disease and in mild cognitive impairment.

PubMed

Chico, L; Simoncini, C; Lo Gerfo, A; Rocchi, A; Petrozzi, L; Carlesi, C; Volpi, L; Tognoni, G; Siciliano, G; Bonuccelli, U

2013-08-01

A number of evidences indicates oxidative stress as a relevant pathogenic factor in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Considering its recognized major genetic risk factors in AD, apolipoprotein (APO E) has been investigated in several experimental settings regarding its role in the process of reactive oxygen species (ROS) generation. The aim of this work has been to evaluate possible relationships between APO E genotype and plasma levels of selected oxidative stress markers in both AD and MCI patients. APO E genotypes were determined using restriction enzyme analysis. Plasma levels of oxidative markers, advanced oxidation protein products, iron-reducing ability of plasma and, in MCI, activity of superoxide dismutases were evaluated using spectrophotometric analysis. We found, compared to controls, increased levels of oxidized proteins and decreased values of plasma-reducing capacity in both AD patients (p < 0.0001) and MCI patients (p < 0.001); the difference between AD and MCI patients was significant only for plasma-reducing capacity (p < 0.0001), the former showing the lowest values. Superoxide dismutase activity was reduced, although not at statistical level, in MCI compared with that in controls. E4 allele was statistically associated (p < 0.05) with AD patients. When comparing different APO E genotype subgroups, no difference was present, as far as advanced oxidation protein products and iron-reducing ability of plasma levels were concerned, between E4 and non-E4 carriers, in both AD and MCI; on the contrary, E4 carriers MCI patients showed significantly decreased (p < 0.05) superoxide dismutase activity with respect to non-E4 carriers. This study, in confirming the occurrence of oxidative stress in AD and MCI patients, shows how it can be related, at least for superoxide dismutase activity in MCI, to APO E4 allele risk factor.

A Game-Theoretic Measure of Presence for Assessing Aircraft Carrier Options.

DTIC Science & Technology

1982-10-01

AD-A121 599 A GAME -THEORETIC MEASURE 0F PRESENCE FOR ASSESSIN NO ANALYSES ALEXANDRIA VA PROGRAM ANALYR PRE P S IE O ESE UNCLASSIFED JH GPOTTE ET...1. REPORT MNUM 1 L GOVT ACCESRIM IM. REINT5 CPAALOG NUOGG 14. TITLE Cid ubMsj S. TYPE OF REPORT & PERIOD COVERED A Game -Theoretic Measure of...NOTES C Is. KEY wOrS (0mM. 0a No" f .a..eaup meM RSEI’ p eek ... l6t Game theory, Zero-sum games , Col Blotto games , aircraft carriers, alternative

PROCESS USING POTASSIUM LANTHANUM SULFATE FOR FORMING A CARRIER PRECIPITATE FOR PLUTONIUM VALUES

DOEpatents

Angerman, A.A.

1958-10-21

A process is presented for recovering plutonium values in an oxidation state not greater than +4 from fluoride-soluble fission products. The process consists of adding to an aqueous acidic solution of such plutonium values a crystalline potassium lanthanum sulfate precipitate which carries the plutonium values from the solution.

A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

PubMed

Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

2016-02-01

We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Target development for diversified irradiations at a medical cyclotron.

PubMed

Spellerberg, S; Scholten, B; Spahn, I; Bolten, W; Holzgreve, M; Coenen, H H; Qaim, S M

2015-10-01

The irradiation facility at an old medical cyclotron (Ep=17 MeV; Ed=10 MeV) was upgraded by extending the beam line and incorporation of solid state targetry. Tests performed to check the quality of the available beam are outlined. Results on nuclear data measurements and improvement of radiochemical separations are described. Using solid targets, with the proton beam falling at a slanting angle of 20°, a few radionuclides, e.g. (75)Se, (120)I, (124)I, etc. were produced with medium currents (up to 20 µA) in no-carrier-added form in quantities sufficient for local use. The extended irradiation facility has considerably enhanced the utility of the medical cyclotron. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased Carbohydrate Intake is Associated with Poorer Performance in Verbal Memory and Attention in an APOE Genotype-Dependent Manner.

PubMed

Gardener, Samantha L; Rainey-Smith, Stephanie R; Sohrabi, Hamid R; Weinborn, Michael; Verdile, Giuseppe; Fernando, W M A D Binosha; Lim, Yen Ying; Harrington, Karra; Burnham, Samantha; Taddei, Kevin; Masters, Colin L; Macaulay, Stuart L; Rowe, Christopher C; Ames, David; Maruff, Paul; Martins, Ralph N

2017-01-01

Evidence suggests that a diet low in carbohydrates can impact on cognitive performance among those with Alzheimer's disease (AD). However, there is a lack of data assessing this relationship among cognitively normal (CN) older adults at increased future risk of developing AD due to carriage of the apolipoprotein E (APOE) ɛ4 allele. We assessed the cross-sectional association between carbohydrate intake, cognitive performance, and cerebral amyloid-β (Aβ) load in CN older adults, genotyped for APOEɛ4 allele carrier status. Greater carbohydrate intake was associated with poorer performance in verbal memory in APOEɛ4 allele non-carriers, and poorer performance in attention in APOEɛ4 allele carriers. There were no associations between carbohydrate intake and cerebral Aβ load. These results provide support to the idea that decreasing carbohydrate intake may offer neurocognitive benefits, with specific cognitive domains affected in an APOE genotype-dependent manner. These findings warrant further investigation utilizing a longitudinal study design.

Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.

PubMed

Way, Jenilee Dawn; Wuest, Frank

2014-02-01

4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.

A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

PubMed

Mojahedian, Mohammad M; Daneshamouz, Saeid; Samani, Soliman Mohammadi; Zargaran, Arman

2013-09-01

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron microscopy. This method for preparing lipid nanoparticles by warm o/w microemulsion quenching was found to be more cost efficient and proportionally increasable in comparison with other preparation methods such as high pressure homogenization. These lipid nanoparticles, due to the combination of hard lipids with soft and/or liquid lipids, become good candidates for a wide range of medicaments as carriers for pharmaceutical and medicinal purposes. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

A preliminary electron microscopic investigation into the interaction between Aβ1-42 peptide and a novel nanoliposome- coupled retro-inverso peptide inhibitor, developed as a potential treatment for Alzheimer's disease

NASA Astrophysics Data System (ADS)

Sherer, M.; Fullwood, N. J.; Taylor, M.; Allsop, D.

2015-10-01

Alzheimer's disease (AD) is a progressive neurodegenerative condition that results in severe cognitive and functional decline in sufferers and for which there are currently no effective treatments to halt or reverse disease progression. AD is the most common form of dementia and age is the major risk factor for this disease. With worldwide population structures changing as increasing number of individuals survive into old age, there is urgent need for novel disease modifying treatments for this condition, which has profound effects upon sufferers in addition to those around them. Some of us have previously developed a peptide inhibitor of Aβ1-42 aggregation (RI-OR2-TAT) that has been shown to reduce Aβ1-42 pathology in vivo in mouse models of AD. ∼1690 copies of RI-OR2-TAT have been covalently attached to nanoliposome carrier particles forming Peptide Inhibitor NanoParticles (PINPs), and this study investigated the effect of PINPs upon Aβ1-42 aggregation at the molecular level. Our results show that PINPs are able to reduce Aβ1-42 aggregation and do so by binding early (oligomers) and late (fibrillar) stage aggregates. These results highlight the ability of PINPs to disrupt the formation of multiple Aβ1-42 aggregates capable of causing neurotoxicity and thus provide a strong case for PINPs to be carried forward into early stage clinical trials as a novel therapeutic option for the treatment of AD.

Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.

PubMed

Yassine, Hussein N; Braskie, Meredith N; Mack, Wendy J; Castor, Katherine J; Fonteh, Alfred N; Schneider, Lon S; Harrington, Michael G; Chui, Helena C

2017-03-01

The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA, APOE genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature. Although randomized clinical trials of ω-3 in symptomatic AD have had negative findings, several observational and clinical trials of ω-3 in the predementia stage of AD suggest that ω-3 supplementation may slow early memory decline in APOE4 carriers. Several mechanisms by which the APOE4 allele could alter the delivery of DHA to the brain may be amenable to DHA supplementation in predementia stages of AD. Evidence of accelerated DHA catabolism (eg, activation of phospholipases and oxidation pathways) could explain the lack of efficacy of ω-3 supplementation in AD dementia. The association of cognitive benefit with DHA supplementation in predementia but not AD dementia suggests that early ω-3 supplementation may reduce the risk for or delay the onset of AD symptoms in APOE4 carriers. Recent advances in brain imaging may help to identify the optimal timing for future DHA clinical trials. High-dose DHA supplementation in APOE4 carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in APOE4 carriers is warranted.

ASSOCIATION BETWEEN GAB2 HAPLOTYPE AND HIGHER GLUCOSE METABOLISM IN ALZHEIMER'S DISEASE-AFFECTED BRAIN REGIONS IN COGNITIVELY NORMAL APOEε4 CARRIERS

PubMed Central

Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B.S.; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

2010-01-01

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative presymptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk. PMID:20888920

The Relationship Between Apolipoprotein ε4 Carrier Status and Sleep Characteristics in Cognitively Normal Older Adults.

PubMed

Kahya, Melike; Vidoni, Eric; Burns, Jeffrey M; Thompson, Ashley N; Meyer, Kayla; Siengsukon, Catherine F

2017-09-01

The apolipoprotein (APOE) ε4 allele, a well-described genetic risk factor for late-onset Alzheimer disease (AD), is associated with sleep disturbances even in cognitively normal older adults, although it is not clear whether this association is independent of sleep apnea. We sought to extend previous studies by examining whether cognitively normal older adults without self-reported sleep apnea who carry the APOE ε4 allele have altered sleep characteristics compared to noncarriers. Data from N = 36 (APOE ε4 carriers [n = 9], noncarriers [n = 27]) cognitively normal older adults (Clinical Dementia Rating [CDR] scale = 0) without self-reported sleep apnea were used for these analyses. Participants wore an actigraph for 7 days to determine sleep characteristics. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to assess sleep quality and daytime sleepiness, respectively. The APOE ε4 carriers had a higher number of awakenings compared to the noncarriers ( P = .02). There was no significant difference in the PSQI global score and the ESS; however, the PSQI subcomponent of daily disturbances was significantly higher in APOE ε4 carriers ( P = .03), indicating increased daytime dysfunction is related to disrupted sleep. This study provides evidence that individuals who are cognitively normal and genetically at risk of AD may have disrupted sleep. These findings are consistent with prior studies and suggest that sleep disruption may be present in the presymptomatic stages of AD.

Severity-Related Increase and Cognitive Correlates of Serum VEGF Levels in Alzheimer's Disease ApoE4 Carriers.

PubMed

Alvarez, X Anton; Alvarez, Irene; Aleixandre, Manuel; Linares, Carlos; Muresanu, Dafin; Winter, Stefan; Moessler, Herbert

2018-01-01

Vascular endothelial growth factor (VEGF) is an angioneurin involved in the regulation of vascular and neural functions relevant for the pathophysiology of Alzheimer's disease (AD), but the influence of AD severity and ApoE4 status on circulating VEGF and its relationship with cognition has not been investigated. We assessed serum VEGF levels and cognitive performance in AD, amnestic mild cognitive impairment (MCI), and control subjects. VEGF levels were higher in AD patients than in MCI cases and controls (p < 0.05) and showed a progressive increase with clinical severity in the whole study population (p < 0.01). Among AD patients, severity-related VEGF elevations were significant in ApoE4 carriers (p < 0.05), but not in non-carriers. Increased VEGF levels were associated with disease severity and showed mild correlations with cognitive impairment that were only consistent for the ADAS-cog+ items remembering test instructions (memory) and maze task (executive functions) in the group of AD patients (p < 0.05). On the other hand, higher VEGF values were related to better memory and language performance in ApoE4 carriers with moderately-severe AD. According to these results showing severity- and ApoE4-related differences in serum VEGF and its cognitive correlates, it is suggested that increases in VEGF levels might represent an endogenous response driven by pathological factors and could entail cognitive benefits in AD patients, particularly in ApoE4 carriers. Our findings support the notion that VEGF constitutes a relevant molecular target to be further explored in AD pathology and therapy.

An improved performance of copper phthalocyanine OFETs with channel and source/drain contact modifications

NASA Astrophysics Data System (ADS)

Huanqin, Dang; Xiaoming, Wu; Xiaowei, Sun; Runqiu, Zou; Ruochuan, Zhang; Shougen, Yin

2015-10-01

We report an effective method to improve the performance of p-type copper phthalocyanine (CuPc) based organic field-effect transistors (OFETs) by employing a thin para-quaterphenyl (p-4p) film and simultaneously applying V2O5 to the source/drain regions. The p-4p layer was inserted between the insulating layer and the active layer, and V2O5 layer was added between CuPc and Al in the source-drain (S/D) area. As a result, the field-effect saturation mobility and on/off current ratio of the optimized device were improved to 5 × 10-2 cm2/(V·s) and 104, respectively. We believe that because p-4p could induce CuPc to form a highly oriented and continuous film, this resulted in the better injection and transport of the carriers. Moreover, by introducing the V2O5 electrode's modified layers, the height of the carrier injection barrier could be effectively tuned and the contact resistance could be reduced. Project supported by the National Natural Science Foundation of China (No. 60676051), the National High Technology Research and Development Program of China (No. 2013A A014201), the Scientific Developing Foundation of Tianjin Education Commission (No. 2011ZD02), the Key Science and Technology Support Program of Tianjin (No. 14ZCZDGX00006), and the Foundation of Key Discipline of Material Physics and Chemistry of Tianjin.

[The quantitative recovery of microbes during testing of disinfectants for instruments].

PubMed

Höller, C; Gundermann, K O

1990-02-01

The efficacy of a disinfectant can only be determined exactly, when quantitative as well as qualitative tests are being performed. Aim of this study was to ascertain whether the earlier published method of a germ carrier test could be applied also to the testing of disinfectants for instruments. Rubber tubes of 1 cm length were used as germ carriers, Staph. aureus, Pseud. aerug., Proteus mir., E. coli and Cand. alb. as test organisms. The culture media were CASO-agar and -broth, latter containing 20% defibrinated sheep blood in some experiments. Two disinfectants on aldehyde-basis and one disinfectant on phenol-basis and on biguanide-basis, respectively, were used for the disinfectant tests. The rubber tubes were contaminated with bacterial suspension, dried upright on sterile filters and then put into 10 ml CASO-broth. After high speed vortexing of the germ carriers the bacterial count was determined. Following factors that were believed to probably having an influence on the recovery rate of bacteria were investigated: 1. the amount of fluid staying on the rubber tubes; 2. the drying time; 3. the vortexing time; 4. repeated vortexing; 5. variations of the initial concentration of bacteria on the rubber tubes; 6. addition of inactivating substances. ad 1. The mean amount of fluid staying on the tubes was 0.0056 g. ad 2. Drying times longer than 30 to 60 min resulted partly in considerably lower bacterial counts. ad. 3. and 4. Neither extension of vortexing time nor repeated vortexing of the same germ carrier could raise the recovery rate of bacteria. ad 5. Higher initial concentration of bacteria on the rubber tubes could not be achieved. The recovery rate of bacteria was reliable even when the initial bacterial concentration was low. ad 6. Addition of inactivating substances to the CASO-broth had no influence on the recovery rate of bacteria. The test method was checked by testing four disinfectants for instruments and proved itself a good and reliable quantitative method.

[Enterotoxin genes occurance among S. aureus strains isolated from inpatients and carriers].

PubMed

Lawrynowicz-Paciorek, Maja; Kochman, Maria; Piekarska, Katarzyna; Wyrebiak, Agata; Potracka, Ewa; Leniak-Chmiel, Urszula; Magdziak, Agnieszka

2006-01-01

We examined 44 inpatients and 66 carriers Staphylococcus aureus strains, isolated in years 2002-2005, for the presence of 18 enterotoxin genes (se/sel) (by PCR), the ability for A-D enterotoxin production (by SET-RPLA) and antibiotic resistance distribution (by disc diffusion method). se/sel genes were detected in 90,9% of all strains, sea (70,5%) and selk and selq (52,3%) - among inpatients strains and egc (65,2%) - among carriers strains were the most frequently se/sel genes found. Positive results of SET-RPLA were consistent with PCR results. There was no correlation observed between antibiotic resistance and se/sel genes distribution among tested S. aureus strains.

Two cofactors and cytoplasmic chaperonin are required for the folding of alpha- and beta-tubulin.

PubMed Central

Gao, Y; Vainberg, I E; Chow, R L; Cowan, N J

1993-01-01

Though the chaperonins that mediate folding in prokaryotes, mitochondria, and chloroplasts have been relatively well characterized, the folding of proteins in the eukaryotic cytosol is much less well understood. We recently identified a cytoplasmic chaperonin as an 800-kDa multisubunit toroid which forms a binary complex with unfolded actin; the correctly folded polypeptide is released upon incubation with Mg-ATP (Y. Gao, J. O. Thomas, R. L. Chow, G.-H. Lee, and N. J. Cowan, Cell 69:1043-1050, 1992). Here we show that the same chaperonin also forms a binary complex with unfolded alpha- or beta-tubulin; however, there is no detectable release of the correctly folded product, irrespective of the concentration of added Mg-ATP and Mg-GTP or the presence of added carrier tubulin heterodimers with which newly folded alpha- or beta-tubulin polypeptides might exchange. Rather, two additional protein cofactors are required for the generation of properly folded alpha- or beta-tubulin, which is then competent for exchange into preexisting alpha/beta-tubulin heterodimers. We show that actin and tubulins compete efficiently with one another for association with cytoplasmic chaperonin complexes. These data imply that actin and alpha- and beta-tubulin interact with the same site(s) on chaperonin complexes. Images PMID:8096061

Apolipoprotein E ε4 influences on episodic recall and brain structures in aging pilots

PubMed Central

Adamson, Maheen M.; Landy, Kelly M.; Duong, Susan; Fox-Bosetti, Sabrina; Ashford, J. Wesson; Murphy, Greer M.; Weiner, Michael; Taylor, Joy L.

2008-01-01

The apolipoprotein (APOE) ε4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain–cognitive–genetic relationships in actively flying general aviation pilots, half of whom are APOE ε4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE ε4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE ε4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE ε4 -related influences on memory in aging workers. PMID:18760504

Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots.

PubMed

Adamson, Maheen M; Landy, Kelly M; Duong, Susan; Fox-Bosetti, Sabrina; Ashford, J Wesson; Murphy, Greer M; Weiner, Michael; Taylor, Joy L

2010-06-01

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers. Published by Elsevier Inc.

Determination of cadmium in grains by isotope dilution ICP-MS and coprecipitation using sample constituents as carrier precipitants.

PubMed

Inagaki, Kazumi; Narukawa, Tomohiro; Yarita, Takashi; Takatsu, Akiko; Okamoto, Kensaku; Chiba, Koichi

2007-10-01

A coprecipitation method using sample constituents as carrier precipitants was developed that can remove molybdenum, which interferes with the determination of cadmium in grain samples via isotope dilution inductively coupled plasma mass spectrometry (ID-ICPMS). Samples were digested with HNO3, HF, and HClO4, and then purified 6 M sodium hydroxide solution was added to generate colloidal hydrolysis compounds, mainly magnesium hydroxide. Cadmium can be effectively separated from molybdenum because the cadmium forms hydroxides and adsorbs onto and/or is occluded in the colloid, while the molybdenum does not form hydroxides or adsorb onto the hydrolysis colloid. The colloid was separated by centrifugation and then dissolved with 0.2 M HNO3 solution to recover the cadmium. The recovery of Cd achieved using the coprecipitation was >97%, and the removal efficiency of Mo was approximately 99.9%. An extremely low procedural blank (below the detection limit of ICPMS) was achieved by purifying the 6 M sodium hydroxide solution via Mg coprecipitation using Mg(NO3)2 solution. The proposed method was applied to two certified reference materials (NIST SRM 1567a wheat flour and SRM 1568a rice flour) and CCQM-P64 soybean powder. Good analytical results with small uncertainties were obtained for all samples. This method is simple and reliable for the determination of Cd in grain samples by ID-ICPMS.

APOE-ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies.

PubMed

Saeed, Usman; Mirza, Saira S; MacIntosh, Bradley J; Herrmann, Nathan; Keith, Julia; Ramirez, Joel; Nestor, Sean M; Yu, Qinggang; Knight, Jo; Swardfager, Walter; Potkin, Steven G; Rogaeva, Ekaterina; George-Hyslop, Peter St; Black, Sandra E; Masellis, Mario

2018-05-18

Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. We studied 298 patients (AD = 250, DLB = 48; 38 autopsy confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis. Across the AD/DLB spectrum: (1) hippocampal volumes were smaller with increasing APOE-ε4 dosage (no genotype × diagnosis interaction observed), (2) learning performance as assessed by total recall scores was associated with hippocampal volumes only among APOE-ε4 carriers, and (3) APOE-ε4 carriers performed worse on long-delay free word recall. These findings provide evidence that APOE-ε4 is linked to hippocampal atrophy and learning/memory phenotypes across the AD/DLB spectrum, which could be useful as biomarkers of disease progression in therapeutic trials of mixed disease. Copyright © 2018. Published by Elsevier Inc.

Phenotypic Similarities Between Late-Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single-Family Case-Control Study.

PubMed

Day, Gregory S; Musiek, Erik S; Roe, Catherine M; Norton, Joanne; Goate, Alison M; Cruchaga, Carlos; Cairns, Nigel J; Morris, John C

2016-09-01

The amyloid hypothesis posits that disrupted β-amyloid homeostasis initiates the pathological process resulting in Alzheimer disease (AD). Autosomal dominant AD (ADAD) has an early symptomatic onset and is caused by single-gene mutations that result in overproduction of β-amyloid 42. To the extent that sporadic late-onset AD (LOAD) also results from dysregulated β-amyloid 42, the clinical phenotypes of ADAD and LOAD should be similar when controlling for the effects of age. To use a family with late-onset ADAD caused by a presenilin 1 (PSEN1) gene mutation to mitigate the potential confound of age when comparing ADAD and LOAD. This case-control study was conducted at the Knight Alzheimer Disease Research Center at Washington University, St Louis, Missouri, and other National Institutes of Aging-funded AD centers in the United States. Ten PSEN1 A79V mutation carriers from multiple generations of a family with late-onset ADAD and 12 noncarrier family members were followed up at the Knight Alzheimer Disease Research Center (1985-2015) and 1115 individuals with neuropathologically confirmed LOAD were included from the National Alzheimer Coordinating Center database (September 2005-December 2014). Data analysis was completed in January 2016, including Knight Alzheimer Disease Research Center patient data collected up until the end of 2015. Planned comparison of clinical characteristics between cohorts, including age at symptom onset, associated symptoms and signs, rates of progression, and disease duration. Of the PSEN1 A79V carriers in the family with late-onset ADAD, 4 were female (57%); among those with LOAD, 529 were female (47%). Seven mutation carriers (70%) developed AD dementia, while 3 were yet asymptomatic in their seventh and eighth decades of life. No differences were observed between mutation carriers and individuals with LOAD concerning age at symptom onset (mutation carriers: mean, 75 years [range, 63-77 years] vs those with LOAD: mean, 74 years [range, 60-101 years]; P = .29), presenting symptoms (memory loss in 7 of 7 mutation carriers [100%] vs 958 of 1063 individuals with LOAD [90.1%]; P ≥ .99) and duration (mutation carriers: mean, 9.9 years [range, 2.3-12.8 years] vs those with LOAD: 9 years [range, 1-27 years]; P = .73), and rate of progression of dementia (median annualized change in Clinical Dementia Rating-Sum of Boxes score, mutation carriers: 1.2 [range, 0.1-3.3] vs those with LOAD: 1.9 [range, -3.5 to 11.9]; P = .73). Early emergence of comorbid hallucinations and delusions were observed in 57% of individuals with ADAD (4 of 7) vs 19% of individuals with LOAD (137 of 706) (P = .03). Three of 12 noncarriers (25%) from the PSEN1 A79V family are potential phenocopies as they also developed AD dementia (median age at onset, 76.0 years). In this family, the amyloidogenic PSEN1 A79V mutation recapitulates the clinical attributes of LOAD. Previously reported clinical phenotypic differences between individuals with ADAD and LOAD may reflect age- or mutation-dependent effects.

PROCESS OF TREATING OR FORMING AN INSOLUBLE PLUTONIUM PRECIPITATE IN THE PRESENCE OF AN ORGANIC ACTIVE AGENT

DOEpatents

Balthis, J.H.

1961-07-18

Carrier precipitation processes for the separation of plutonium from fission products are described. In a process in which an insoluble precipitate is formed in a solution containing plutonium and fission products under conditions whereby plutonium is carried by the precipitate, and the precipitate is then separated from the remaining solution, an organic surface active agent is added to the mixture of precipitate and solution prior to separation of the precipitate from the supernatant solution, thereby improving the degree of separation of the precipitate from the solution.

49 CFR Appendix I to Subpart A of... - Revenue Need and Allocation to Traffic at Issue

Code of Federal Regulations, 2014 CFR

2014-10-01

... composite carrier basis comprised of all traffic and cost study carriers. Data in part II, line 14 columns... Issue Traffic Based on Ton and Ton-Mile Method (See Note A) Line No. Item Source for columns 3 and 4..., by using Statement No. 6-68, Highway Form B, Schedule A, Line III. Assign the dollars in columns (6...

49 CFR Appendix I to Subpart A of... - Revenue Need and Allocation to Traffic at Issue

Code of Federal Regulations, 2013 CFR

2013-10-01

... composite carrier basis comprised of all traffic and cost study carriers. Data in part II, line 14 columns... Issue Traffic Based on Ton and Ton-Mile Method (See Note A) Line No. Item Source for columns 3 and 4..., by using Statement No. 6-68, Highway Form B, Schedule A, Line III. Assign the dollars in columns (6...

49 CFR Appendix I to Subpart A of... - Revenue Need and Allocation to Traffic at Issue

Code of Federal Regulations, 2010 CFR

2010-10-01

... composite carrier basis comprised of all traffic and cost study carriers. Data in part II, line 14 columns... Issue Traffic Based on Ton and Ton-Mile Method (See Note A) Line No. Item Source for columns 3 and 4..., by using Statement No. 6-68, Highway Form B, Schedule A, Line III. Assign the dollars in columns (6...

49 CFR Appendix I to Subpart A of... - Revenue Need and Allocation to Traffic at Issue

Code of Federal Regulations, 2011 CFR

2011-10-01

... composite carrier basis comprised of all traffic and cost study carriers. Data in part II, line 14 columns... Issue Traffic Based on Ton and Ton-Mile Method (See Note A) Line No. Item Source for columns 3 and 4..., by using Statement No. 6-68, Highway Form B, Schedule A, Line III. Assign the dollars in columns (6...

49 CFR Appendix I to Subpart A of... - Revenue Need and Allocation to Traffic at Issue

Code of Federal Regulations, 2012 CFR

2012-10-01

... composite carrier basis comprised of all traffic and cost study carriers. Data in part II, line 14 columns... Issue Traffic Based on Ton and Ton-Mile Method (See Note A) Line No. Item Source for columns 3 and 4..., by using Statement No. 6-68, Highway Form B, Schedule A, Line III. Assign the dollars in columns (6...

DISSOLUTION OF PLUTONIUM CONTAINING CARRIER PRECIPITATE BY CARBONATE METATHESIS AND SEPARATION OF SULFIDE IMPURITIES THEREFROM BY SULFIDE PRECIPITATION

DOEpatents

Duffield, R.B.

1959-07-14

A process is described for recovering plutonium from foreign products wherein a carrier precipitate of lanthanum fluoride containing plutonium is obtained and includes the steps of dissolving the carrier precipitate in an alkali metal carbonate solution, adding a soluble sulfide, separating the sulfide precipitate, adding an alkali metal hydroxide, separating the resulting precipitate, washing, and dissolving in a strong acid.

Memory Performance and fMRI Signal in Presymptomatic Familial Alzheimer’s Disease

PubMed Central

Braskie, Meredith N.; Medina, Luis D.; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel Angel; Thompson, Paul M.; Cummings, Jeffrey L.; Bookheimer, Susan Y.; Ringman, John M.

2013-01-01

Rare autosomal dominant mutations result in familial Alzheimer’s disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. PMID:22806961

Assessment of the Genetic Architecture of Alzheimer's Disease Risk in Rate of Memory Decline.

PubMed

Del-Aguila, Jorge L; Fernández, Maria Victoria; Schindler, Suzanne; Ibanez, Laura; Deming, Yuetiva; Ma, Shengmei; Saef, Ben; Black, Kathleen; Budde, John; Norton, Joanne; Chasse, Rachel; Harari, Oscar; Goate, Alison; Xiong, Chengjie; Morris, John C; Cruchaga, Carlos

2018-01-01

Many genetic studies for Alzheimer's disease (AD) have been focused on the identification of common genetic variants associated with AD risk and not on other aspects of the disease, such as age at onset or rate of dementia progression. There are multiple approaches to untangling the genetic architecture of these phenotypes. We hypothesized that the genetic architecture of rate of progression is different than the risk for developing AD dementia. To test this hypothesis, we used longitudinal clinical data from ADNI and the Knight-ADRC at Washington University, and we calculated PRS (polygenic risk score) based on the IGAP study to compare the genetic architecture of AD risk and dementia progression. Dementia progression was measured by the change of Clinical Dementia Rating Sum of Boxes (CDR)-SB per year. Out of the 21 loci for AD risk, no association with the rate of dementia progression was found. The PRS rate was significantly associated with the rate of dementia progression (β= 0.146, p = 0.03). In the case of rare variants, TREM2 (β= 0.309, p = 0.02) was also associated with the rate of dementia progression. TREM2 variant carriers showed a 23% faster rate of dementia compared with non-variant carriers. In conclusion, our results indicate that the recently identified common and rare variants for AD susceptibility have a limited impact on the rate of dementia progression in AD patients.

Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population.

PubMed

Bono, G F; Simão-Silva, D P; Batistela, M S; Josviak, N D; Dias, P F R; Nascimento, G A; Souza, R L R; Piovezan, M R; Souza, R K M; Furtado-Alle, L

2015-02-01

Alzheimer's disease (AD) is a neurodegenerative disorder in which there is a decline of cholinergic function. The symptomatic AD treatment involves the use of ChEIs (cholinesterase inhibitors) as rivastigimine, a dual inhibitor. The human butyrylcholinesterase (BChE) is an enzyme that has specific roles in cholinergic neurotransmission and it has been associated with AD. In the serum, BChE is found in four main molecular forms: G1 (monomer); G1-ALB (monomer linked to albumin); G2 (dimer); and G4 (tetramer). The interaction between the products of BCHE gene and CHE2 locus results in CHE2 C5+ and CHE2 C5- phenotypes. CHE2 C5+ phenotype and BChE-K are factors that influence on BChE activity. This work aimed to verify the proportions of BChE molecular forms, total and relative activity in 139 AD patients and 139 elderly controls, taking into account K variant, CHE2 locus, rivastigmine treatment and clinical dementia rating (CDR) of AD patients. Phenotypic frequencies of CHE2 C5+ and frequency of the carriers of the K allele were similar between groups. Total BChE activity in plasma was significantly lower in AD patients than in elderly controls. Furthermore, we found that reduction on plasma BChE activity is associated directly with AD progression in AD patients and that rivastigmine treatment has a stronger effect on BChE activity within the CDR2 group. The reduction in BChE activity did not occur proportionally in all molecular forms. Multiple regression analysis results confirmed that AD acts as the main factor in plasma BChE activity reduction and that severe stages are related with an even greater reduction. These findings suggest that the reduction of total plasma BChE and relative BChE molecular forms activity in AD patients is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic secondary marker for AD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Energy, cost and design aspects of coarse- and fine-bubble aeration systems in the MBBR IFAS process.

PubMed

Sander, S; Behnisch, J; Wagner, M

2017-02-01

With the MBBR IFAS (moving bed biofilm reactor integrated fixed-film activated sludge) process, the biomass required for biological wastewater treatment is either suspended or fixed on free-moving plastic carriers in the reactor. Coarse- or fine-bubble aeration systems are used in the MBBR IFAS process. In this study, the oxygen transfer efficiency (OTE) of a coarse-bubble aeration system was improved significantly by the addition of the investigated carriers, even in-process (∼1% per vol-% of added carrier material). In a fine-bubble aeration system, the carriers had little or no effect on OTE. The effect of carriers on OTE strongly depends on the properties of the aeration system, the volumetric filling rate of the carriers, the properties of the carrier media, and the reactor geometry. This study shows that the effect of carriers on OTE is less pronounced in-process compared to clean water conditions. When designing new carriers in order to improve their effect on OTE further, suppliers should take this into account. Although the energy efficiency and cost effectiveness of coarse-bubble aeration systems can be improved significantly by the addition of carriers, fine-bubble aeration systems remain the more efficient and cost-effective alternative for aeration when applying the investigated MBBR IFAS process.

Radiosynthesis of [13N]dantrolene, a positron emission tomography probe for breast cancer resistant protein, using no-carrier-added [13N]ammonia.

PubMed

Kumata, Katsushi; Ogawa, Masanao; Takei, Makoto; Fujinaga, Masayuki; Yoshida, Yuichiro; Nengaki, Nobuki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Zhang, Ming-Rong

2012-01-01

Dantrolene (1) is a substrate for breast cancer resistant protein, which is widely distributed in the blood-brain-barrier, intestine, gall bladder, and liver. PET study with 1 labeled with a positron emitter can be used to visualize BCRP and to elucidate the effect of BCRP on the pharmacokinetics of drugs. The objective of this study was to label 1 using nitrogen-13 ((13)N, a positron emitter; half-life: 9.9min). Using no-carrier-added [(13)N]NH(3) as the labeling agent, we synthesized [(13)N]dantrolene ([(13)N]1) for the first time. The reaction of carbomyl chloride 2b with [(13)N]NH(3) gave an unsymmetrical urea [(13)N]3, followed by cyclization of [(13)N]3 to afford [(13)N]1. Due to its instability, 2b was prepared in situ by treating amine 5 with triphosgene in a ratio of 4 to 1 and used for subsequent [(13)N]ammonolysis without purification. Copyright © 2011 Elsevier Ltd. All rights reserved.

SEPARATION OF PLUTONYL IONS

DOEpatents

Connick, R.E.; McVey, Wm.H.

1958-07-15

A process is described for separating plutonyl ions from the acetate ions with which they are associated in certaln carrier precipitation methods of concentrating plutonium. The method consists in adding alkaline earth metal ions and subsequently alkalizing the solution, causing formation of an alkaltne earth plutonate precipitate. Barium hydroxide is used in a preferred embodiment since it provides alkaline earth metal ion and alkalizes the solution in one step forming insoluble barium platonate.

Overview of Federal Motor Carrier Safety Administration safety training research for new entrant motor carriers.

DOT National Transportation Integrated Search

2015-07-01

New entrant motor carriers generally are very small and have poorer safety performance than more established carriers. This may be because very small carriers do not have the resources for a safety department or a safety official on staff. To help ad...

Apolipoprotein E genotypes associated with Alzheimer disease and concomitant stroke.

PubMed

Fekih-Mrissa, Najiba; Klai, Sarra; Mrad, Meriem; Mansour, Malek; Zaouali, Jamel; Gritli, Nasreddine; Mrissa, Ridha

2014-04-01

The ɛ4 allele of the apolipoprotein E (APOE) gene is a well-characterized genetic risk factor for Alzheimer disease (AD). The association between stroke and a higher risk for AD has also been reported. Our study sought to determine the relationship between the APOE gene and AD and the comorbid risk of stroke. The subjects of this study consisted of 48 patients with AD and 48 members of a control group. All subjects were genotyped for APOE. The results clearly show a significant increased risk of AD in carriers of the APOE ε3/ε4 genotype (P = .003, odds ratio [OR] = 4.1) or ε4 allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also increased for carriers of the APOE ε3/ε4 genotype (P = .02, OR = 9.0) and for carriers of the APOE ε4 allele (P = .004, OR = 5.5). The present study is the first to establish a relationship between APOE ε4 and concomitant AD and stroke in the Tunisian population. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A FDG-PET Study of Metabolic Networks in Apolipoprotein E ε4 Allele Carriers

PubMed Central

Yao, Zhijun; Hu, Bin; Zheng, Jiaxiang; Zheng, Weihao; Chen, Xuejiao; Gao, Xiang; Xie, Yuanwei; Fang, Lei

2015-01-01

Recently, some studies have applied the graph theory in brain network analysis in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). However, relatively little research has specifically explored the properties of the metabolic network in apolipoprotein E (APOE) ε4 allele carriers. In our study, all the subjects, including ADs, MCIs and NCs (normal controls) were divided into 165 APOE ε4 carriers and 165 APOE ε4 noncarriers. To establish the metabolic network for all brain regions except the cerebellum, cerebral glucose metabolism data obtained from FDG-PET (18F-fluorodeoxyglu-cose positron emission tomography) were segmented into 90 areas with automated anatomical labeling (AAL) template. Then, the properties of the networks were computed to explore the between-group differences. Our results suggested that both APOE ε4 carriers and noncarriers showed the small-world properties. Besides, compared with APOE ε4 noncarriers, the carriers showed a lower clustering coefficient. In addition, significant changes in 6 hub brain regions were found in between-group nodal centrality. Namely, compared with APOE ε4 noncarriers, significant decreases of the nodal centrality were found in left insula, right insula, right anterior cingulate, right paracingulate gyri, left cuneus, as well as significant increases in left paracentral lobule and left heschl gyrus in APOE ε4 carriers. Increased local short distance interregional correlations and disrupted long distance interregional correlations were found, which may support the point that the APOE ε4 carriers were more similar with AD or MCI in FDG uptake. In summary, the organization of metabolic network in APOE ε4 carriers indicated a less optimal pattern and APOE ε4 might be a risk factor for AD. PMID:26161964

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

PubMed

Kobayashi, Eiji; Nakano, Masako; Kubota, Kenta; Himuro, Nobuaki; Mizoguchi, Shougo; Chikenji, Takako; Otani, Miho; Mizue, Yuka; Nagaishi, Kanna; Fujimiya, Mineko

2018-01-26

Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Implications of adipose-derived stromal cells in a 3D culture system for osteogenic differentiation: an in vitro and in vivo investigation.

PubMed

Shen, Francis H; Werner, Brian C; Liang, Haixiang; Shang, Hulan; Yang, Ning; Li, Xudong; Shimer, Adam L; Balian, Gary; Katz, Adam J

2013-01-01

Healthy mammalian cells in normal tissues are organized in complex three-dimensional (3D) networks that display nutrient and signaling gradients. Conventional techniques that grow cells in a 2D monolayer fail to reproduce the environment that is observed in vivo. In recent years, 3D culture systems have been used to mimic tumor microenvironments in cancer research and to emulate embryogenesis in stem cell cultures. However, there have been no studies exploring the ability for adipose-derived stromal (ADS) cells in a 3D culture system to undergo osteogenic differentiation. To characterize and investigate the in vitro and in vivo potential for human ADS cells in a novel 3D culture system to undergo osteogenic differentiation. Basic science and laboratory study. Human ADS cells were isolated and prepared as either a 2D monolayer or 3D multicellular aggregates (MAs). Multicellular aggregates were formed using the hanging droplet technique. Cells were treated in osteogenic medium in vitro, and cellular differentiation was investigated using gene expression, histology, and microCT at 1-, 2-, and 4-week time points. In vivo investigation involved creating a muscle pouch by developing the avascular muscular interval in the vastus lateralis of male athymic rats. Specimens were then pretreated with osteogenic medium and surgically implanted as (1) carrier (Matrigel) alone (control), (2) carrier with human ADS cells in monolayer, or (3) human ADS cells as MAs. In vivo evidence of osteogenic differentiation was evaluated with micro computed tomography and histologic sectioning at a 2-week time point. Human ADS cells cultured by the hanging droplet technique successfully formed MAs at the air-fluid interface. Adipose-derived stromal cells cultured in monolayer or as 3D MAs retain their ability to self-replicate and undergo multilineage differentiation as confirmed by increased runx2/Cbfa2, ALP, and OCN and increased matrix mineralization on histologic sectioning. Multicellular aggregate cells expressed increased differentiation potential and extracellular matrix production over the same human ADS cells cultured in monolayer. Furthermore, MAs reseeded onto monolayer retained their stem cell capabilities. When implanted in vivo, significantly greater bone volume and extracellular matrix were present in the implanted specimens of MAs confirmed on both microCT and histological sectioning. This is the first study to investigate the capability of human ADS cells in a 3D culture system to undergo osteogenic differentiation. The results confirm that MAs maintain their stem cell characteristics. Compared with analogous cells in monolayer culture, the human ADS cells as MAs exhibit elevated levels of osteogenic differentiation and increased matrix mineralization. Furthermore, the creation of uniform spheroids allows for improved handling and manipulation during transplantation. These findings strongly support the concept that 3D culture systems remain not only a viable option for stem cell culture but also possibly a more attractive alternative to traditional culture techniques to improve the osteogenic potential of human adipose stem cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic Risk for Age-Related Cognitive Impairment Does Not Predict Cognitive Performance in Middle Age.

PubMed

Korthauer, Laura E; Awe, Elizabeth; Frahmand, Marijam; Driscoll, Ira

2018-05-26

Alzheimer's disease (AD) is characterized by memory loss and executive dysfunction, which correspond to structural changes to the medial temporal lobes (MTL) and prefrontal cortex (PFC), respectively. Given the overlap in cognitive deficits between healthy aging and the earliest stages of AD, early detection of AD remains a challenge. The goal of the present study was to study MTL- and PFC-dependent cognitive functioning in middle-aged individuals at genetic risk for AD or cognitive impairment who do not currently manifest any clinical symptoms. Participants (N = 150; aged 40-60 years) underwent genotyping of 47 single nucleotide polymorphisms (SNPs) in six genes previously associated with memory or executive functioning: APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT. They completed two MTL-dependent tasks, the virtual Morris Water Task (vMWT) and transverse patterning discriminations task (TPDT), and the PFC-dependent reversal learning task. Although age was associated with poorer performance on the vMWT and TPDT within this middle-aged sample, there were no genotype-associated differences in cognitive performance. Although the vMWT and TPDT may be sensitive to age-related changes in cognition, carriers of APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT risk alleles do not exhibit alteration in MTL- and PFC-dependent functioning in middle age compared to non-carriers.

Healthy versus Entorhinal Cortical Atrophy Identification in Asymptomatic APOE4 Carriers at Risk for Alzheimer’s Disease

PubMed Central

Konishi, Kyoko; Joober, Ridha; Poirier, Judes; MacDonald, Kathleen; Chakravarty, Mallar; Patel, Raihaan; Breitner, John; Bohbot, Véronique D.

2018-01-01

Early detection of Alzheimer’s disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ4 allele carriers. APOE ɛ4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ4 allele carriers who use spatial strategies. In contrast, APOE ɛ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy. PMID:29278888

Healthy versus Entorhinal Cortical Atrophy Identification in Asymptomatic APOE4 Carriers at Risk for Alzheimer's Disease.

PubMed

Konishi, Kyoko; Joober, Ridha; Poirier, Judes; MacDonald, Kathleen; Chakravarty, Mallar; Patel, Raihaan; Breitner, John; Bohbot, Véronique D

2018-01-01

Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ4 allele carriers. APOE ɛ4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ4 allele carriers who use spatial strategies. In contrast, APOE ɛ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy.

Irreversibility and carriers control in two-dimensional electron gas at LaTiO3/SrTiO3 interface

NASA Astrophysics Data System (ADS)

Bergeal, N.; Biscaras, J.; Hurand, S.; Feuillet-Palma, C.; Lesueur, J.; Rastogi, A.; Budhani, R. C.; Reyren, N.; Lesne, E.; Leboeuf, D.; Proust, C.

2013-03-01

It has been shown recently that a two-dimensional electron gas 2DEG could form at the interface of two insulators such as LaAlO3 and SrTiO3, or LaTiO3 (a Mott insulator) and SrTiO3. We present low temperature transport measurements on LaTiO3/SrTiO3 and LaAlO3/SrTiO3 hetero-structures, whose properties can be modulated by field effect using a metallic gate on the back of the substrate. Here we show that when the carrier density is electrostatically increased beyond a critical value, the added electrons escape into the SrTiO3 leading to an irreversible doping regime where all the electronic properties of the 2DEG saturate (carrier density, resistivity, superconducting transition...). The dynamic of leakage was studied using time resolved measurement. Based on a complete self-consistent description of the confinement well, a thermal model for the carriers escape has been developed, which quantitatively accounts for the data.

APOE4 carriers and non-carriers with the clinical diagnosis of Alzheimer’s dementia and minimal amyloid plaques

PubMed Central

Monsell, Sarah E.; Kukull, Walter A.; Roher, Alex E.; Maarouf, Chera L.; Serrano, Geidy; Beach, Thomas G.; Caselli, Richard J.; Montine, Thomas J.; Reiman, Eric M.

2016-01-01

Importance Amyloid-β (Aβ) plaques are a cardinal neuropathological feature of Alzheimer’s disease (AD), yet over a third of apolipoprotein E ε4 (APOE4) non-carriers with the clinical diagnosis of mild-to-moderate Alzheimer’s dementia may not meet positron emission tomography (PET) criteria for significant cerebral amyloidosis. Objective This study sought to clarify the percentage of APOE4 carriers and non-carriers with the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia near the end of life and minimal Aβ plaques at autopsy—and the extent to which these cases are associated with appreciable neurofibrillary degeneration or a primary neuropathologic diagnosis other than AD. Design Participants in this study were obtained from the National Alzheimer’s Coordinating Center’s Uniform Data Set (UDS). Setting The UDS comprises longitudinal clinical assessments performed at the Alzheimer's Disease Centers funded by the National Institute on Aging. Neuropathology data is available for the subset of expired participants. Participants Exactly 100 APOE4 non-carriers and 100 carriers had the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia at their last visit, known APOE4 genotype, died within the ensuing 24 months, and underwent neuropathologic evaluation. Main Outcomes and Measures Standardized histopathologic assessments of Alzheimer’s disease neuropathologic changes were the primary measures of interest in this study, specifically CERAD neuritic plaque density score, diffuse plaque density score, and Braak stage for neurofibrillary degeneration. Results 37% of APOE4 non-carriers and 13% of carriers with the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia had nonexistent or sparse neuritic plaques. 44% of the carriers and non-carriers with minimal neuritic plaques had Braak stage III–VI ratings and 38% met neuropathological criteria for other dementia-related diseases. Conclusions and relevance More than a third of APOE4 non-carriers with the primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia had minimal Alzheimer’s disease plaque accumulation in cerebral cortex and, thus may show limited or no benefit from an otherwise effective anti-Aβ treatment. Almost half of participants with a primary clinical diagnosis of mild-to-moderate Alzheimer’s dementia and minimal plaque accumulation had an extensive topographical distribution of neurofibrillary degeneration. Additional studies are needed to better understand and treat patients with this unexpectedly common clinico-neuropathological condition. PMID:26302353

Symmetry operators of Killing spinors and superalgebras in AdS5

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2016-04-01

We construct the first-order symmetry operators of Killing spinor equation in terms of odd Killing-Yano forms. By modifying the Schouten-Nijenhuis bracket of Killing-Yano forms, we show that the symmetry operators of Killing spinors close into an algebra in AdS5 spacetime. Since the symmetry operator algebra of Killing spinors corresponds to a Jacobi identity in extended Killing superalgebras, we investigate the possible extensions of Killing superalgebras to include higher-degree Killing-Yano forms. We found that there is a superalgebra extension but no Lie superalgebra extension of the Killing superalgebra constructed out of Killing spinors and odd Killing-Yano forms in AdS5 background.

Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF)

PubMed Central

Kailainathan, Sumangali; Piers, Thomas M.; Yi, Jee Hyun; Choi, Seongmin; Fahey, Mark S.; Borger, Eva; Gunn-Moore, Frank J.; O’Neill, Laurie; Lever, Michael; Whitcomb, Daniel J.; Cho, Kwangwook; Allen, Shelley J.

2016-01-01

This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ∼30% Caucasians) have reduced hippocampal volume and impaired hippocampal-dependent memory function, yet the same polymorphic population shows enhanced cognitive recovery after traumatic brain injury, delayed cognitive dysfunction during aging, and lower risk of late-onset Alzheimer’s disease (AD) compared to those with the more common Val66 polymorphism. To examine the differences between the protein polymorphisms in structure, kinetics of binding to proBDNF receptors and in vitro function, we generated purified cleavage-resistant human variants. Intriguingly, we found no statistical differences in those characteristics. As anticipated, exogenous application of proBDNF Val66 to rat hippocampal slices dysregulated synaptic plasticity, inhibiting long-term potentiation (LTP) and facilitating long-term depression (LTD). We subsequently observed that this occurred via the glycogen synthase kinase 3β (GSK3β) activation pathway. However, surprisingly, we found that Met66 had no such effects on either LTP or LTD. These novel findings suggest that, unlike Val66, the Met66 variant does not facilitate synapse weakening signaling, perhaps accounting for its protective effects with aging. PMID:26687096

20 CFR 703.111 - Submission of new forms of policies for approval; other endorsements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Submission of new forms of policies for... INSURANCE REGULATIONS Authorization of Insurance Carriers § 703.111 Submission of new forms of policies for approval; other endorsements. No new forms of policies or modification of existing forms of policies shall...

Enhancing oxidative stability in heated oils using core/shell structures of collagen and α-tocopherol complex.

PubMed

Gim, Seo Yeong; Hong, Seungmi; Kim, Jisu; Kwon, YongJun; Kim, Mi-Ja; Kim, GeunHyung; Lee, JaeHwan

2017-11-15

In this study, collagen mesh structure was prepared by carrying α-tocopherol in the form of core/shell complex. Antioxidant properties of α-tocopherol loaded carriers were tested in moisture added bulk oils at 140°C. From one gram of collagen core/shell complex, 138mg α-tocopherol was released in medium chain triacylglycerol (MCT). α-Tocopherol was substantially protected against heat treatment when α-tocopherol was complexed in collagen core/shell. Oxidative stability in bulk oil was significantly enhanced by added collagen mesh structure or collagen core/shell complex with α-tocopherol compared to that in control bulk oils (p<0.05), although no significant difference was observed between oils containing collagen mesh structure and collagen core/shell with α-tocopherol (p>0.05). Results of DPPH loss in methanol demonstrated that collagen core/shell with α-tocopherol had significantly (p<0.05) higher antioxidant properties than collagen mesh structure up to a certain period. Therefore, collagen core/shell complex is a promising way to enhance the stability of α-tocopherol and oxidative stability in oil-rich foods prepared at high temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stability of astaxanthin-loaded nanostructured lipid carriers in beverage systems.

PubMed

Tamjidi, Fardin; Shahedi, Mohammad; Varshosaz, Jaleh; Nasirpour, Ali

2018-01-01

Nanostructured lipid carriers (NLCs) offer many potential benefits for incorporating lipophilic molecules into clear to opaque food systems. This study examined the stability of astaxanthin-loaded NLCs (Ax-NLCs) in model (solutions with 0 or 12% sucrose; pH 3, 7), semi-actual (whey) and actual (non-alcoholic beer) beverages during 30-60 days storage at 6 or 20 °C. Ax-NLCs (Z-average size: 94 nm), containing α-tocopherol and EDTA as antioxidants, were stabilised with Tween 80 and lecithin, and mixed with the aforementioned beverages at the volume ratio of 3:97. The presence of sucrose, improved the physical stability of Ax-NLCs in acidic model beverage. No astaxanthin loss and particle size growth were observed for Ax-NLCs-added whey. Carbonation and/or thermal pasteurisation of NLCs-added beer led to a major increase in its particles size and astaxanthin loss. Stability of Ax-NLCs in non-pasteurised CO 2 -free beer improved at low storage temperature. The organoleptic quality of NLCs-added beers was still acceptable. These results indicate that NLCs containing hydrophobic nutraceuticals have potential to be used for functional beverages/foods development. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

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Investigation of C9orf72 in 4 Neurodegenerative Disorders

PubMed Central

Xi, Zhengrui; Zinman, Lorne; Grinberg, Yakov; Moreno, Danielle; Sato, Christine; Bilbao, Juan M.; Ghani, Mahdi; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Morón, Francisco J.; Lang, Anthony E.; Marras, Connie; Bruni, Amalia; Colao, Rosanna; Maletta, Raffaele G.; Puccio, Gianfranco; Rainero, Innocenzo; Pinessi, Lorenzo; Galimberti, Daniela; Morrison, Karen E.; Moorby, Catriona; Stockton, Joanne D.; Masellis, Mario; Black, Sandra E.; Hazrati, Lili-Naz; Liang, Yan; van Haersma de With, Jan; Fornazzari, Luis; Villagra, Roque; Rojas-Garcia, Ricardo; Clarimón, Jordi; Mayeux, Richard; Robertson, Janice; St George-Hyslop, Peter; Rogaeva, Ekaterina

2014-01-01

Objective To estimate the allele frequency of C9orf72 (G4C2) repeats in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer disease (AD), and Parkinson disease (PD). Design The number of repeats was estimated by a 2-step genotyping strategy. For expansion carriers, we sequenced the repeat flanking regions and obtained APOE genotypes and MAPT H1/H2 haplotypes. Setting Hospitals specializing in neurodegenerative disorders. Subjects We analyzed 520 patients with FTLD, 389 patients with ALS, 424 patients with AD, 289 patients with PD, 602 controls, 18 families, and 29 patients with PD with the LRRK2 G2019S mutation. Main Outcome Measure The expansion frequency. Results Based on a prior cutoff (>30 repeats), the expansion was detected in 9.3% of patients with ALS, 5.2% of patients with FTLD, and 0.7% of patients with PD but not in controls or patients with AD. It was significantly associated with family history of ALS or FTLD and age at onset of FTLD. Phenotype variation (ALS vs FTLD) was not associated with MAPT, APOE, or variability in the repeat flanking regions. Two patients with PD were carriers of 39 and 32 repeats with questionable pathological significance, since the 39-repeat allele does not segregate with PD. No expansion or intermediate alleles (20–29 repeats) were found among the G2019S carriers and AD cases with TAR DNA-binding protein 43–positive inclusions. Surprisingly, the frequency of the 10-repeat allele was marginally increased in all 4 neurodegenerative diseases compared with controls, indicating the presence of an unknown risk variation in the C9orf72 locus. Conclusions The C9orf72 expansion is a common cause of ALS and FTLD, but not of AD or PD. Our study raises concern about a reliable cutoff for the pathological repeat number, which is important in the utility of genetic screening. PMID:22964832

Factors Affecting the Dissolution of Indomethacin Solid Dispersions.

PubMed

Zhang, Wei; Zhang, Chen-Ning; He, Yue; Duan, Ban-Yan; Yang, Guang-Yi; Ma, Wei-Dong; Zhang, Yong-Hong

2017-11-01

The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.

Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study.

PubMed

Fleisher, Adam S; Chen, Kewei; Quiroz, Yakeel T; Jakimovich, Laura J; Gutierrez Gomez, Madelyn; Langois, Carolyn M; Langbaum, Jessica B S; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J; Tariot, Pierre N; Lopera, Francisco; Reiman, Eric M

2015-03-01

Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and noncarriers from the world's largest known autosomal dominant Alzheimer disease (AD) kindred. To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindred's estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma Aβ1-42 or Aβ1-40. This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD.

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2010-04-26

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2013-10-02

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Method for producing high carrier concentration p-Type transparent conducting oxides

DOEpatents

Li, Xiaonan; Yan, Yanfa; Coutts, Timothy J.; Gessert, Timothy A.; Dehart, Clay M.

2009-04-14

A method for producing transparent p-type conducting oxide films without co-doping plasma enhancement or high temperature comprising: a) introducing a dialkyl metal at ambient temperature and a saturated pressure in a carrier gas into a low pressure deposition chamber, and b) introducing NO alone or with an oxidizer into the chamber under an environment sufficient to produce a metal-rich condition to enable NO decomposition and atomic nitrogen incorporation into the formed transparent metal conducting oxide.

SURFACE FLUID REGISTRATION OF CONFORMAL REPRESENTATION: APPLICATION TO DETECT DISEASE BURDEN AND GENETIC INFLUENCE ON HIPPOCAMPUS

PubMed Central

Shi, Jie; Thompson, Paul M.; Gutman, Boris; Wang, Yalin

2013-01-01

In this paper, we develop a new automated surface registration system based on surface conformal parameterization by holomorphic 1-forms, inverse consistentsurface fluid registration, and multivariate tensor-based morphometry (mTBM). First, we conformally map a surface onto a planar rectangle space with holomorphic 1-forms. Second, we compute surface conformal representation by combining its local conformal factor and mean curvature and linearly scale the dynamic range of the conformal representation to form the feature image of the surface. Third, we align the feature image with a chosen template image via the fluid image registration algorithm, which has been extended into the curvilinear coordinates to adjust for the distortion introduced by surface parameterization. The inverse consistent image registration algorithm is also incorporated in the system to jointly estimate the forward and inverse transformations between the study and template images. This alignment induces a corresponding deformation on the surface. We tested the system on Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset to study AD symptoms on hippocampus. In our system, by modeling a hippocampus as a 3D parametric surface, we nonlinearly registered each surface with a selected template surface. Then we used mTBM to analyze the morphometrydifference between diagnostic groups. Experimental results show that the new system has better performance than two publically available subcortical surface registration tools: FIRST and SPHARM. We also analyzed the genetic influence of the Apolipoprotein E ε4 allele (ApoE4),which is considered as the most prevalent risk factor for AD.Our work successfully detected statistically significant difference between ApoE4 carriers and non-carriers in both patients of mild cognitive impairment (MCI) and healthy control subjects. The results show evidence that the ApoE genotype may be associated with accelerated brain atrophy so that our workprovides a new MRI analysis tool that may help presymptomatic AD research. PMID:23587689

No association of dynamin binding protein (DNMBP) gene SNPs and Alzheimer's disease.

PubMed

Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

2008-10-01

A recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10q found significant association of six correlated SNPs with late-onset Alzheimer's disease (AD) among Japanese. We examined the SNP with the highest statistical significance (rs3740058) in a large Caucasian American case-control cohort and the remaining five SNPs in a smaller subset of cases and controls. We observed no association of statistical significance in either the total sample or the APOE*4 non-carriers for any of the SNPs.

Event-related potential markers of brain changes in preclinical familial Alzheimer disease

PubMed Central

Ally, B.A.; Celone, K.; McKeever, J.; Ruiz-Rizzo, A.L.; Lopera, F.; Stern, C.E.; Budson, A.E.

2011-01-01

Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45. Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded. Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200–300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions: Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. PMID:21775732

Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional-executive network function in Alzheimer's disease.

PubMed

Wolk, David A; Dickerson, Bradford C

2010-06-01

The epsilon4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer's disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the epsilon4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of epsilon4 carriers (n = 67) vs. noncarriers (n = 24) with mild AD from the Alzheimer's Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.

Frequency and Clinicopathological Characteristics of Presenilin 1 Gly206Ala Mutation in Puerto Rican Hispanics with Dementia

PubMed Central

Arnold, Steven E.; Vega, Irving E.; Karlawish, Jason H.; WoIk, David A.; Nunez, Jessica; Negron, Mirna; Xie, Sharon X.; Wang, Li-San; Dubroff, Jacob G.; McCarty-Wood, Elisabeth; Trojanowski, John Q.; Van Deerlin, Vivianna

2012-01-01

The frequency and clinical and pathological characteristics associated with the Gly206Ala presenilin 1 (PSEN1) mutation in Puerto Rican and non-Puerto Rican Hispanics were evaluated at the University of Pennsylvania’s Alzheimer’s Disease Center. DNAs from all cohort subjects were genotyped for the Gly206Ala PSEN1 mutation. Carriers and non-carriers with neurodegenerative disease dementias were compared for demographic, clinical, psychometric, and biomarker variables. Nineteen (12.6%) of 151 unrelated subjects with dementia were discovered to carry the PSEN1 Gly 206Ala mutation. Microsatellite marker genotyping determined a common ancestral haplotype for all carriers. Carriers were all of Puerto Rican heritage with significantly younger age of onset, but otherwise were clinically and neuropsychologically comparable to those of non-carriers with AD. Three subjects had extensive topographic and biochemical biomarker assessments that were also typical of non-carriers with AD. Neuropathological examination in one subject revealed severe, widespread plaque and tangle pathology without other meaningful disease lesions. The PSEN1 Gly206Ala mutation is notably frequent in unrelated Puerto Rican immigrants with dementia in Philadelphia. Considered together with the increased prevalence and mortality of AD reported in Puerto Rico, these high rates may reflect hereditary risk concentrated in the island which warrants further study. PMID:23114514

Drug delivery systems: optimising the structure of peptide carriers for synthetic antimicrobial drugs.

PubMed

Payne, J W

1986-01-01

This paper discusses the concept of smugglins, i.e., molecules that are formed by attaching to, or incorporating into, normal cell nutrients varied moieties as a means of transporting otherwise impermeant substances into cells. Examples of antimicrobial smugglins that use this principle in Nature are described. The rationally designed antibiotic smugglins investigated to date are critically reviewed. Criteria for the design of optimal peptide carriers for antimicrobial smugglins are considered. A computer-linked, continuous-flow system for rapid measurement of the kinetic parameters for substrate transport via peptide permeases is described which, together with current molecular, genetic and biochemical techniques, now provides the means to obtain the information on which rational design should be based; examples are given for Escherichia coli and Candida albicans. After an uncertain commercial start, it now seems likely that increasing understanding of the uptake processes and other relevant features will make drug targeting using peptide carriers an achievable goal. Certainly their widespread occurrence in Nature should provide added incentive for the design of synthetic smugglins.

Carrier Estimation Using Classic Spectral Estimation Techniques for the Proposed Demand Assignment Multiple Access Service

NASA Technical Reports Server (NTRS)

Scaife, Bradley James

1999-01-01

In any satellite communication, the Doppler shift associated with the satellite's position and velocity must be calculated in order to determine the carrier frequency. If the satellite state vector is unknown then some estimate must be formed of the Doppler-shifted carrier frequency. One elementary technique is to examine the signal spectrum and base the estimate on the dominant spectral component. If, however, the carrier is spread (as in most satellite communications) this technique may fail unless the chip rate-to-data rate ratio (processing gain) associated with the carrier is small. In this case, there may be enough spectral energy to allow peak detection against a noise background. In this thesis, we present a method to estimate the frequency (without knowledge of the Doppler shift) of a spread-spectrum carrier assuming a small processing gain and binary-phase shift keying (BPSK) modulation. Our method relies on an averaged discrete Fourier transform along with peak detection on spectral match filtered data. We provide theory and simulation results indicating the accuracy of this method. In addition, we will describe an all-digital hardware design based around a Motorola DSP56303 and high-speed A/D which implements this technique in real-time. The hardware design is to be used in NMSU's implementation of NASA's demand assignment, multiple access (DAMA) service.

Characterisation of spray dried soy sauce powders made by adding crystalline carbohydrates to drying carrier.

PubMed

Wang, Wei; Zhou, Weibiao

2015-02-01

This study aimed to reduce stickiness and caking of spray dried soy sauce powders by introducing a new crystalline structure into powder particles. To perform this task, soy sauce powders were formulated by using mixtures of cellulose and maltodextrin or mixtures of waxy starch and maltodextrin as drying carriers, with a fixed carrier addition rate of 30% (w/v) in the feed solution. The microstructure, crystallinity, solubility as well as stickiness and caking strength of all the different powders were analysed and compared. Incorporating crystalline carbohydrates in the drying carrier could significantly reduce the stickiness and caking strength of the powders when the ratio of crystalline carbohydrates to maltodextrin was above 1:5 and 1:2, respectively. X-ray Diffraction (XRD) results showed that adding cellulose or waxy starch could induce the crystallinity of powders. Differential Scanning Calorimetry (DSC) results demonstrated that the native starch added to the soy sauce powders did not fully gelatinize during spray drying. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

PubMed Central

DiBattista, Amanda Marie; Stevens, Benson W.; Rebeck, G. William; Green, Adam E.

2014-01-01

Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry (VBM) in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. Apolipoprotein E-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root. PMID:25339884

Different quantitative EEG alterations induced by TBI among patients with different APOE genotypes.

PubMed

Jiang, Li; Yin, Xiaohong; Yin, Cheng; Zhou, Shuai; Dan, Wei; Sun, Xiaochuan

2011-11-14

Although several studies have revealed the EEG alterations in AD and TBI patients, the influence of APOE (apolipoprotein E) genotype in EEG at the early stage of TBI has not been reported yet. We have previously studied EEG alterations caused by TBI among different APOE genotype carriers. In this study, we firstly investigated the relationship between APOE polymorphisms and quantitative EEG (QEEG) changes after TBI. A total of 118 consecutive TBI patients with a Glasgow Coma Scale (GCS) of 9 or higher were recruited, and 40 normal adults were also included as a control group. APOE genotype was determined by PCR-RFLP for each subject, and QEEG recordings were performed in rest, relaxed, awake and with eyes closed in normal subjects and TBI patients during 1-3 days after TBI. In the normal control group, both APOEɛ4 carriers and non-carriers had normal EEG, and no significant difference of QEEG data was found between APOEɛ4 carriers and non-carriers. But in the TBI group, APOEɛ4 carriers had more focal or global irregular slow wave activities than APOEɛ4 non-carriers. APOE gene did not influence brain electrical activity under normal conditions, but TBI can induce different alterations among different APOE gene carriers, and APOEɛ4 allele enhances the EEG abnormalities at the early stage of TBI. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Alzheimer’s Prevention Initiative composite cognitive test score: Sample size estimates for the evaluation of preclinical Alzheimer’s disease treatments in presenilin 1 E280A mutation carriers

PubMed Central

Ayutyanont, Napatkamon; Langbaum, Jessica B.; Hendrix, Suzanne B.; Chen, Kewei; Fleisher, Adam S.; Friesenhahn, Michel; Ward, Michael; Aguirre, Camilo; Acosta-Baena, Natalia; Madrigal, Lucìa; Muñoz, Claudia; Tirado, Victoria; Moreno, Sonia; Tariot, Pierre N.; Lopera, Francisco; Reiman, Eric M.

2014-01-01

Objective There is a need to identify a cognitive composite that is sensitive to tracking preclinical AD decline to be used as a primary endpoint in treatment trials. Method We capitalized on longitudinal data, collected from 1995 to 2010, from cognitively unimpaired presenilin 1 (PSEN1) E280A mutation carriers from the world’s largest known early-onset autosomal dominant AD (ADAD) kindred to identify a composite cognitive test with the greatest statistical power to track preclinical AD decline and estimate the number of carriers age 30 and older needed to detect a treatment effect in the Alzheimer’s Prevention Initiative’s (API) preclinical AD treatment trial. The mean-to-standard-deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of one to seven cognitive tests/sub-tests drawn from the neuropsychological test battery in cognitively unimpaired mutation carriers during a two and five year follow-up period, using data from non-carriers during the same time period to correct for aging and practice effects. Combinations that performed well were then evaluated for robustness across follow-up years, occurrence of selected items within top performing combinations and representation of relevant cognitive domains. Results This optimal test combination included CERAD Word List Recall, CERAD Boston Naming Test (high frequency items), MMSE Orientation to Time, CERAD Constructional Praxis and Ravens Progressive Matrices (Set A) with an MSDR of 1.62. This composite is more sensitive than using either the CERAD Word List Recall (MSDR=0.38) or the entire CERAD-Col battery (MSDR=0.76). A sample size of 75 cognitively normal PSEN1-E280A mutation carriers age 30 and older per treatment arm allows for a detectable treatment effect of 29% in a 60-month trial (80% power, p=0.05). Conclusions We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared to the most sensitive single test item to track preclinical AD decline in ADAD mutation carriers and evaluate preclinical AD treatments. This API composite cognitive test score will be used as the primary endpoint in the first API trial in cognitively unimpaired ADAD carriers within 15 years of their estimated age at clinical onset. We have independently confirmed our findings in a separate cohort of cognitively healthy older adults who progressed to the clinical stages of late-onset AD, described in a separate report, and continue to refine the composite in independent cohorts and compared with other analytical approaches. PMID:24816373

Monooxorhenium(V) complexes with 222-N2S2 MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation

PubMed Central

Demoin, Dustin Wayne; Dame, Ashley N.; Minard, William D.; Gallazzi, Fabio; Seickman, Gary L.; Rold, Tammy L.; Bernskoetter, Nicole; Fassbender, Michael E.; Hoffman, Timothy J.; Deakyne, Carol A.; Jurisson, Silvia S.

2016-01-01

Introduction Targeted radiotherapy using the bifunctional chelate approach with 186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications. Methods A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222- MAMA(N-6-Ahx-BBN(7-14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc and 186Re (carrier added and no carrier added), and evaluated in initial biological distribution studies. Results An IC50 value of 2.0 ± 0.7 nM for natReO-222-MAMA(N-6-Ahx-BBN(7-14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed little gastric uptake and blockable pancreatic uptake in normal mice. Conclusions The 186ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed stability in biological media, which indicates that the 222-N2S2 chelator is appropriate for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting. PMID:27694058

BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

PubMed Central

Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

2013-01-01

Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological test scores, or proportion of apolipoprotein E (APOE) ε4 carriers. Compared to the non-carriers, carriers had higher CSF Aβ1-42 levels (p=0·008), plasma Aβ1-42 levels (p=0·01), and plasma Aβ1-42/Aβ1-40 ratios (p=0·001), consistent with Aβ1-42 overproduction. They also had greater hippocampal/parahippocampal activations (as low as p=0·008, after correction for multiple comparisons), less precuneus/posterior cingulate deactivations (as low as p=0·001, after correction), less gray matter in several regions (p-values <0·005, uncorrected, and corrected p=0·008 in the parietal search region), similar to findings in the later preclinical and clinical stages of autosomal dominant and late-onset AD. Interpretation Young adults at genetic risk for autosomal dominant AD have functional and structural MRI abnormalities, along with CSF and plasma biomarker findings consistent with Aβ1-42 over-production. While the extent to which the underlying brain changes are progressive or developmental remain to be determined, this study demonstrates the earliest known biomarker changes in cognitively normal people at genetic risk for autosomal dominant AD. Funding Banner Alzheimer’s Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Boston University Department of Psychology, Colciencias (1115-408-20512, 1115-545-31651), National Institute on Aging (R01 AG031581, P30 AG19610, UO1 AG024904, RO1 AG025526, RF1AG041705), National Institute of Neurological Disorders and Stroke (F31-NS078786) and state of Arizona. PMID:23137948

78 FR 43272 - Agency Information Collection; Activity Under OMB Review; Report of Passengers Denied Confirmed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... Confirmed Space--BTS Form 251 AGENCY: Research & Innovative Technology Administration (RITA), Bureau of...: Report of Passengers Denied Confirmed Space. Form No.: BTS Form 251. Type of Review: Reinstatement of an.... Because the rate of denied boarding is released quarterly, travelers and travel agents can select carriers...

Release modeling and comparison of nanoarchaeosomal, nanoliposomal and pegylated nanoliposomal carriers for paclitaxel.

PubMed

Movahedi, Fatemeh; Ebrahimi Shahmabadi, Hasan; Alavi, Seyed Ebrahim; Koohi Moftakhari Esfahani, Maedeh

2014-09-01

Breast cancer is the most prevalent cancer among women. Recently, delivering by nanocarriers has resulted in a remarkable evolution in treatment of numerous cancers. Lipid nanocarriers are important ones while liposomes and archaeosomes are common lipid nanocarriers. In this work, paclitaxel was used and characterized in nanoliposomal and nanoarchaeosomal form to improve efficiency. To increase stability, efficiency and solubility, polyethylene glycol 2000 (PEG 2000) was added to some samples. MTT assay confirmed effectiveness of nanocarriers on MCF-7 cell line and size measuring validated nano-scale of particles. Nanoarchaeosomal carriers demonstrated highest encapsulation efficiency and lowest release rate. On the other hand, pegylated nanoliposomal carrier showed higher loading efficiency and less release compared with nanoliposomal carrier which verifies effect of PEG on improvement of stability and efficiency. Additionally, release pattern was modeled using artificial neural network (ANN) and genetic algorithm (GA). Using ANN modeling for release prediction, resulted in R values of 0.976, 0.989 and 0.999 for nanoliposomal, pegylated nanoliposomal and nanoarchaeosomal paclitaxel and GA modeling led to values of 0.954, 0.951 and 0.976, respectively. ANN modeling was more successful in predicting release compared with the GA strategy.

PLUTONIUM PURIFICATION PROCESS EMPLOYING THORIUM PYROPHOSPHATE CARRIER

DOEpatents

King, E.L.

1959-04-28

The separation and purification of plutonium from the radioactive elements of lower atomic weight is described. The process of this invention comprises forming a 0.5 to 2 M aqueous acidffc solution containing plutonium fons in the tetravalent state and elements with which it is normally contaminated in neutron irradiated uranium, treating the solution with a double thorium compound and a soluble pyrophosphate compound (Na/sub 4/P/sub 2/O/sub 7/) whereby a carrier precipitate of thorium A method is presented of reducing neptunium and - trite is advantageous since it destroys any hydrazine f so that they can be removed from solutions in which they are contained is described. In the carrier precipitation process for the separation of plutonium from uranium and fission products including zirconium and columbium, the precipitated blsmuth phosphate carries some zirconium, columbium, and uranium impurities. According to the invention such impurities can be complexed and removed by dissolving the contaminated carrier precipitate in 10M nitric acid, followed by addition of fluosilicic acid to about 1M, diluting the solution to about 1M in nitric acid, and then adding phosphoric acid to re-precipitate bismuth phosphate carrying plutonium.

Post Hoc Analyses of ApoE Genotype-Defined Subgroups in Clinical Trials.

PubMed

Kennedy, Richard E; Cutter, Gary R; Wang, Guoqiao; Schneider, Lon S

2016-01-01

Many post hoc analyses of clinical trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are in small Phase 2 trials. Subject heterogeneity may lead to statistically significant post hoc results that cannot be replicated in larger follow-up studies. We investigated the extent of this problem using simulation studies mimicking current trial methods with post hoc analyses based on ApoE4 carrier status. We used a meta-database of 24 studies, including 3,574 subjects with mild AD and 1,171 subjects with MCI/prodromal AD, to simulate clinical trial scenarios. Post hoc analyses examined if rates of progression on the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) differed between ApoE4 carriers and non-carriers. Across studies, ApoE4 carriers were younger and had lower baseline scores, greater rates of progression, and greater variability on the ADAS-cog. Up to 18% of post hoc analyses for 18-month trials in AD showed greater rates of progression for ApoE4 non-carriers that were statistically significant but unlikely to be confirmed in follow-up studies. The frequency of erroneous conclusions dropped below 3% with trials of 100 subjects per arm. In MCI, rates of statistically significant differences with greater progression in ApoE4 non-carriers remained below 3% unless sample sizes were below 25 subjects per arm. Statistically significant differences for ApoE4 in post hoc analyses often reflect heterogeneity among small samples rather than true differential effect among ApoE4 subtypes. Such analyses must be viewed cautiously. ApoE genotype should be incorporated into the design stage to minimize erroneous conclusions.

APOE ε4-TOMM40 ‘523 haplotypes and the risk of Alzheimer’s disease in older Caucasian and African Americans

PubMed Central

Yu, Lei; Wilson, Robert S.; Burns, Daniel K.; Roses, Allen D.; Yang, Jingyun; Gaiteri, Chris; De Jager, Philip L.; Barnes, Lisa L.; Bennett, David A.

2017-01-01

Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and ‘523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer’s disease (AD) is unclear. We compared the APOE ε4-TOMM40 ‘523 haplotypes between older Caucasian and African Americans, and examined their relationship with AD dementia. Data came from three community based cohort studies of diverse participants. APOE genotypes were determined by polymorphisms of rs429358 and rs7412. TOMM40 ‘523 genotypes were defined by the poly-T repeat length of rs10524523 (short [‘523-S]: poly-T ≤ 19, long [‘523-L]: 20 ≤ poly-T ≤ 29, and very long [‘523-VL]: poly-T ≥ 30). Cox proportional hazards models examined the effect of haplotype variation on the risk of incident AD dementia. A total of 1,848 Caucasian and 540 African American individuals were included in the study. In Caucasians, nearly none (0.8%) of the non-ε4 carriers and almost all (94.2%) of the ε4 carriers had ‘523-L. The classification was highly concordant. Each ε4 allele doubled the risk for AD dementia and the dose effect was evident. Almost identical effect size and effect pattern were observed for TOMM40 ‘523-L. In African Americans, nearly none (1.1%) of the non-ε4 carriers had ‘523-L, but only 47.8% of the ε4 carriers had ‘523-L. The concordance was weaker compared with Caucasians. The effect patterns on incident AD dementia differed distinctively between ε4 and ‘523-L carriers. Further, both genotypic and allelic data support that among African Americans the ε4-‘523-L haplotype had stronger effect on risk of AD dementia than other ε4-‘523 haplotypes. PMID:28672022

Big Missiles and Big Decks: The Viability of Aircraft Carriers in an A2/AD World

DTIC Science & Technology

2016-06-01

RESEARCH DESIGN This thesis centers on a historical case study of two periods in which the United States and its carrier fleet faced some degree...19 3. Lessons Learned ...........................................................................21 C. APPLICABILITY OF CASE STUDIES ...employed the strategic concepts behind A2/AD since the Persian War of 480 BC. In his analysis of several historic case studies , Tangredi notes that a

Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network

PubMed Central

Morris, John C.; Aisen, Paul S.; Bateman, Randall J.; Benzinger, Tammie L.S.; Cairns, Nigel J.; Fagan, Anne M.; Ghetti, Bernardino; Goate, Alison M.; Holtzman, David M.; Klunk, William E.; McDade, Eric; Marcus, Daniel S.; Martins, Ralph N.; Masters, Colin L.; Mayeux, Richard; Oliver, Angela; Quaid, Kimberly; Ringman, John M.; Rossor, Martin N.; Salloway, Stephen; Schofield, Peter R.; Selsor, Natalie J.; Sperling, Reisa A.; Weiner, Michael W.; Xiong, Chengjie; Moulder, Krista L.; Buckles, Virginia D.

2012-01-01

The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort. PMID:23139856

Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network.

PubMed

Morris, John C; Aisen, Paul S; Bateman, Randall J; Benzinger, Tammie L S; Cairns, Nigel J; Fagan, Anne M; Ghetti, Bernardino; Goate, Alison M; Holtzman, David M; Klunk, William E; McDade, Eric; Marcus, Daniel S; Martins, Ralph N; Masters, Colin L; Mayeux, Richard; Oliver, Angela; Quaid, Kimberly; Ringman, John M; Rossor, Martin N; Salloway, Stephen; Schofield, Peter R; Selsor, Natalie J; Sperling, Reisa A; Weiner, Michael W; Xiong, Chengjie; Moulder, Krista L; Buckles, Virginia D

2012-10-01

The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort.

8 CFR 299.4 - Reproduction of Public Use Forms by public and private entities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... read, or displays added or missing data elements, will be rejected by the Service. Any problems... official form. The wording and punctuation of all data elements and identifying information must match exactly. No data elements may be added or deleted. The sequence and format for each item on the form must...

Chemical Looping Autothermal Reforming at a 120 kW Pilot Rig

NASA Astrophysics Data System (ADS)

Bofhàr-Nordenkampf, Johannes; Pröll, Tobias; Kolbitsch, Philipp; Hofbauer, Hermann

Chemical looping with selective oxygen transport allows two step combustion or autothermal reforming without mixing of fuel and air. The reactor system consists of two reactors, an air reactor and a fuel reactor with a suitable oxygen carrier that transports the necessary oxygen for operation. In the present study, a highly active nickel based oxygen carrier is tested in a novel dual circulating fluidized bed (DCFB) system at a scale of 120 kW fuel power. The mean particle size of the oxygen carrier is 120 μm and the pilot rig is fueled with natural gas. For the investigated oxygen carrier high CH4 conversion is achieved. Air/fuel ratio is varied at three different fuel reactor temperatures. For chemical looping reforming one can observe synthesis gas composition close to thermodynamic equilibrium. In spite of the fact that no additional steam has been added to the fuel besides the one present through steam fluidization of the loop seals, coke formation does not occur at global stoichiometric air/fuel ratios above 0.46.

Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4.

PubMed

Argyri, Letta; Dafnis, Ioannis; Theodossiou, Theodossis A; Gantz, Donald; Stratikos, Efstratios; Chroni, Angeliki

2014-05-02

The apolipoprotein (apo) E4 isoform has consistently emerged as a susceptibility factor for late-onset Alzheimer disease (AD), although the exact mechanism is not clear. A rare apoE4 mutant, apoE4[L28P] Pittsburgh, burdens carriers with an added risk for late-onset AD and may be a useful tool for gaining insights into the role of apoE4 in disease pathogenesis. Toward this end, we evaluated the effect of the L28P mutation on the structural and functional properties of apoE4. ApoE4[L28P] was found to have significantly perturbed thermodynamic properties, to have reduced helical content, and to expose a larger portion of the hydrophobic surface to the solvent. Furthermore, this mutant is thermodynamically destabilized and more prone to proteolysis. When interacting with lipids, apoE4[L28P] formed populations of lipoprotein particles with structural defects. The structural perturbations brought about by the mutation were accompanied by aberrant functions associated with the pathogenesis of AD. Specifically, apoE4[L28P] promoted the cellular uptake of extracellular amyloid β peptide 42 (Aβ42) by human neuroblastoma SK-N-SH cells as well as by primary mouse neuronal cells and led to increased formation of intracellular reactive oxygen species that persisted for at least 24 h. Furthermore, lipoprotein particles containing apoE4[L28P] induced intracellular reactive oxygen species formation and reduced SK-N-SH cell viability. Overall, our findings suggest that the L28P mutation leads to significant structural and conformational perturbations in apoE4 and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. We propose that these structural and functional changes underlie the observed added risk for AD development in carriers of apoE4[L28P].

Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study

PubMed Central

Fleisher, Adam S.; Chen, Kewei; Quiroz, Yakeel T.; Jakimovich, Laura J.; Gomez, Madelyn Gutierrez; Langois, Carolyn M.; Langbaum, Jessica B. S.; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M.; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J.; Tariot, Pierre N.; Lopera, Francisco; Reiman, Eric M.

2015-01-01

IMPORTANCE Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and noncarriers from the world’s largest known autosomal dominant Alzheimer disease (AD) kindred. OBJECTIVE To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). MAIN OUTCOMES AND MEASURES We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. RESULTS Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindred’s estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma Aβ1-42 or Aβ1-40. CONCLUSIONS AND RELEVANCE This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD. PMID:25580592

75 FR 41921 - Agency Information Collection; Activity Under OMB Review; Report of Passengers Denied Confirmed...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... Confirmed Space AGENCY: Research & Innovative Technology Administration (RITA), Bureau of Transportation... Title: Report of passengers Denied Confirmed Space. Form No.: Form 251. Type Of Review: Re-instatement..., travelers and travel agents can select carriers with lower incidences of bumping passengers. This...

77 FR 33808 - Agency Information Collection; Activity Under OMB Review: Report of Passengers Denied Confirmed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

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Joint SOGC-CCMG Opinion for Reproductive Genetic Carrier Screening: An Update for All Canadian Providers of Maternity and Reproductive Healthcare in the Era of Direct-to-Consumer Testing.

PubMed

Wilson, R Douglas; De Bie, Isabelle; Armour, Christine M; Brown, Richard N; Campagnolo, Carla; Carroll, June C; Okun, Nan; Nelson, Tanya; Zwingerman, Rhonda; Audibert, Francois; Brock, Jo-Ann; Brown, Richard N; Campagnolo, Carla; Carroll, June C; De Bie, Isabelle; Johnson, Jo-Ann; Okun, Nan; Pastruck, Melanie; Vallée-Pouliot, Karine; Wilson, R Douglas; Zwingerman, Rhonda; Armour, Christine; Chitayat, David; De Bie, Isabelle; Fernandez, Sara; Kim, Raymond; Lavoie, Josee; Leonard, Norma; Nelson, Tanya; Taylor, Sherry; Van Allen, Margot; Van Karnebeek, Clara

2016-08-01

This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document. All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. Fertile, sexually active females and their fertile, sexually active male partners who are either planning a pregnancy or are pregnant (preferably in the first trimester of pregnancy, but any gestational age is acceptable). Women and their partners will be able to obtain appropriate genetic carrier screening information and possible diagnosis of AR, AD, or XL disorders (preferably pre-conception), thereby allowing an informed choice regarding genetic carrier screening and reproductive options (e.g., prenatal diagnosis, preimplantation genetic diagnosis, egg or sperm donation, or adoption). Informed reproductive decisions related to genetic carrier screening and reproductive outcomes based on family history, ethnic background, past obstetrical history, known carrier status, or genetic diagnosis. SOGC REPRODUCTIVE CARRIER SCREENING SUMMARY STATEMENT (2016): Pre-conception or prenatal education and counselling for reproductive carrier screening requires a discussion about testing within the three perinatal genetic carrier screening/diagnosis time periods, which include pre-conception, prenatal, and neonatal for conditions currently being screened for and diagnosed. This new information should be added to the standard reproductive carrier screening protocols that are already being utilized by the most responsible maternity provider through the informed consent process with the patient. (III-A; GRADE low/moderate) SOGC OVERVIEW OF RECOMMENDATIONS QUALITY AND GRADE: There was a strong observational/expert opinion (quality and grade) for the genetic carrier literature with randomized controlled trial evidence being available only for the invasive testing. Both the Canadian Task Force on Preventive Health Care quality and classification and the GRADE evidence quality and grade are provided. MEDLINE; PubMed; government neonatal screening websites; key words/common reproductive genetic carrier screened diseases/previous SOGC Guidelines/medical academic societies (Society of Maternal-Fetal Medicine [SMFM]; American College of Medical Genetics and Genomics; American College of Obstetricians and Gynecologists [ACOG]; CCMG; Royal College Obstetrics and Gynaecology [RCOG] [UK]; American Society of Human Genetics [ASHG]; International Society of Prenatal Diagnosis [ISPD])/provincial neonatal screening policies and programs; search terms (carrier screening, prenatal screening, neonatal genetic/metabolic screening, cystic fibrosis (CF), thalassemia, hemoglobinopathy, hemophilia, Fragile X syndrome (FXS), spinal muscular atrophy, Ashkenazi Jewish carrier screening, genetic carrier screening protocols, AR, AD, XL). 10 years (June 2005-September 2015); initial search dates June 30, 2015 and September 15, 2015; completed final search January 4, 2016. Validation of articles was completed by primary authors RD Wilson and I De Bie. Benefits are to provide an evidenced based reproductive genetic carrier screening update consensus based on international opinions and publications for the use of Canadian women, who are planning a pregnancy or who are pregnant and have been identified to be at risk (personal or male partner family or reproductive history) for the transmission of a clinically significant genetic condition to their offspring with associated morbidity and/or mortality. Harm may arise from having counselling and informed testing of the carrier status of the mother, their partner, or their fetus, as well as from declining to have this counselling and informed testing or from not having the opportunity for counselling and informed testing. Costs will ensue both from the provision of opportunities for counselling and testing, as well as when no such opportunities are offered or are declined and the birth of a child with a significant inherited condition and resulting morbidity/mortality occurs; these comprise not only the health care costs to the system but also the social/financial/psychological/emotional costs to the family. These recommendations are based on expert opinion and have not been subjected to a health economics assessment and local or provincial implementation will be required. This guideline is an update of four previous joint SOGC-CCMG Genetic Screening Guidelines dated 2002, 2006, 2008, and 2008 developed by the SOGC Genetic Committee in collaboration with the CCMG Prenatal Diagnosis Committee (now Clinical Practice Committee). 2016 CARRIER SCREENING RECOMMENDATIONS. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

Research on energy efficiency design index for sea-going LNG carriers

NASA Astrophysics Data System (ADS)

Lin, Yan; Yu, Yanyun; Guan, Guan

2014-12-01

This paper describes the characteristics of liquefied natural gas (LNG) carriers briefly. The LNG carrier includes power plant selection, vapor treatment, liquid cargo tank type, etc. Two parameters—fuel substitution rate and recovery of boil of gas (BOG) volume to energy efficiency design index (EEDI) formula are added, and EEDI formula of LNG carriers is established based on ship EEDI formula. Then, based on steam turbine propulsion device of LNG carriers, mathematical models of LNG carriers' reference line value are established in this paper. By verification, the EEDI formula of LNG carriers described in this paper can provide a reference for LNG carrier EEDI calculation and green shipbuilding.

Impact of APOE4-CSF Aβ interaction on hippocampal volume loss over 1 year in MCI

PubMed Central

Chiang, G.C.; Insel, P.S.; Tosun, D.; Schuff, N.; Truran-Sacrey, D.; Raptentsetsang, S.T.; Thompson, P.M.; Reiman, E.M.; Jack, C.R.; Fox, N.C.; Jagust, W.J.; Harvey, D.J.; Beckett, L.A.; Gamst, A.; Aisen, P.S.; Petersen, R.C.; Weiner, M.W.

2011-01-01

Background The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein E4 (APOE4), a genetic risk factor for Alzheimer’s disease (AD), is also associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE4 together on longitudinal volume loss. Methods We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal (NC), 144 with mild cognitive impairment (MCI), and 76 with AD. Results An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE4 was associated with hippocampal volume loss only in the NC and MCI groups. APOE4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process. PMID:21889115

MANPRINT Handbook for RFP Development

DTIC Science & Technology

1990-06-01

Fighting Vehicle e. Mortar Weapon System Vehicle f. General Purpose Carrier g. Long Range AntiTnk Vehicle h. Self -Propelled Howitzer i. Target...components and per-form u.-e-o’) set! tests; opete the system and subsystems; execure diagnostic self -tests and inew:readcuts; determine if thie systemr...34ie be evelute. M.4.2.2.6 HeaZ -- d A-ssessme:.’ Th e e;asi of ’::s do~ain s*-wZ cO=S:,;, (r) Resposiveness to the =ad Cb) Iden’ezon of risks en-d im

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

PubMed Central

Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura

2015-01-01

Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people. PMID:26173052

Exploring the protective effects of calcium-containing carrier against drying-induced cellular injuries of probiotics using single droplet drying technique.

PubMed

Zheng, Xufeng; Fu, Nan; Huang, Song; Jeantet, Romain; Chen, Xiao Dong

2016-12-01

Protective carriers that encapsulate probiotics in spray drying could improve the survival ratio of dried cells through different mechanisms. Unveiling the protective mechanism of each carrier will contribute to a rational design of high performance carrier formulation. This study utilized single droplet drying (SDD) technique to investigate the effects of calcium cation in varied carrier formulation. Inactivation histories of Lactobacillus rhamnosus GG (LGG) in different carriers were compared, and cellular injury history of probiotics during droplet drying was studied for the first time. Adding 1mM CaCl 2 to lactose carrier protected cell viability, mitigated cellular injuries, and enhanced regrowth capability as drying progressed, demonstrating the positive effect of Ca 2+ with possible mechanism of stabilizing sub-cellular structures. At later drying stages, cell survival in Lac/Ca carrier was increased by 0.5-1.5 log on selective media compared to lactose carrier. Supplementing calcium-binding agents lowered the protective effect, shortening the initiation of rapid cell inactivation down to 120s of drying. Adding CaCl 2 to trehalose carrier barely improved cell survival, indicating that the protective effect could be influenced by carrier formulation. Pure trehalose carrier exerted excellent protection on LGG, supporting cells to regrow in liquid rich medium even after 180s of drying. The protection of trehalose may stem from stabilization of sub-cellular structures, which possibly overlap the effect of Ca 2+ . The findings suggested that high performance carrier formulation might be developed by combining carrier materials with different protective mechanisms, for maximizing the survival of active dry probiotics in industrial spray drying operation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunohistochemical response in rats of beta-tricalcium phosphate (TCP) with or without BMP-2 in the production of collagen matrix critical defects.

PubMed

Luvizuto, Eloá Rodrigues; de Oliveira, Júlio César Silva; Gomes-Ferreira, Pedro Henrique Silva; Pereira, Cassiano Costa Silva; Faverani, Leonardo Perez; Antoniali, Cristina; Okamoto, Roberta

2017-04-01

This study aimed to assess the biological response of BMP-2 (bone morphogenetic protein-2) in supplementation with β-tricalcium phosphate (TCP) as a carrier in the bone healing of surgical defects in rats' calvaria. A critical-size defect (5mm in diameter) was filled with β-TCP alone or added with that plus 5mg of BMP-2 at 5, 15, and 30 postoperative days. Histomorphometric and immunohistochemical (osteocalcin, collagen type I, and metalloproteinase-9) analysis was performed to assess the features of bone healing. Histological behavior and collagen type I labeling showed increased formation of the collagen matrix, leading to a higher percentage of newly formed bone and biomaterial for tissue and more total mineralization of pure TCP when compared to the other groups. The supplementation with BMP-2 promoted faster TCP remodeling; however, there was no statistically significant difference for the bone formed in both groups (P>0.05). Collagen-matrix formation and new bone formation reached maximum levels when the defects were filled with pure TCP, even exceeding the levels from BMP-2 supplementation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Does an Alzheimer's disease susceptibility gene influence the cognitive effects of cancer therapy?

PubMed

Caselli, Richard J

2014-10-01

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). APOE e4 carriers suffer greater morbidity from head trauma, stroke, and carbon monoxide poisoning, yet possible interactions between APOE genotype and cancer therapy on cognition are unclear. Neuropathological and biomarker studies of young asymptomatic APOE e4 carriers that show elevated neocortical amyloid and medial temporal neurofibrillary tangles and longitudinal neuropsychological studies that show accelerated memory decline beginning around age 55-60 years define preclinical AD and have set the stage for assessing the potential adverse cognitive effects of cancer therapy in APOE e4 carriers. © 2013 Wiley Periodicals, Inc.

Experimental results and model calculations of excitation functions relevant to the production of specific radioisotopes for metabolic radiotherapy and for pet

NASA Astrophysics Data System (ADS)

Menapace, E.; Birattari, C.; Bonardi, M. L.; Groppi, F.

2004-10-01

First results are given from the comparison of experimental values and model calculations on accelerator-produced high specific activity radionuclides in no-carrier-added (NCA) form. The relevant radioisotopes are: 64Cu, produced by natZn(d, αxn) and natZn(d,2p) reactions, for simultaneous positron/negatron metabolic radiotherapy and PET imaging; 66Ga high-energy positron emitter (4.2 MeV), produced by natZn(d, xn) reactions, for metabolic radiotherapy and for PET; 186gRe, produced by 186W(p,n) and 186W(d,2n) reactions, for negatron (1.1 MeV) metabolic radiotherapy; 211At/ 211Po, produced by 209Bi( α,2n) reaction (with spike of gamma emitter 210At produced by 209Bi( α,3n) reaction) and 225Ac/ 213Bi/ 213Po, produced by 226Ra(p,2n) reaction, both for high-LET radiotherapy.

A simple and rapid technique for radiochemical separation of iodine radionuclides from irradiated tellurium using an activated charcoal column.

PubMed

Chattopadhyay, Sankha; Saha Das, Sujata

2009-10-01

A simple and inexpensive method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO(2)) target was developed. The beta(-) emitting (131)I radionuclide, produced by the decay of (131)Te through the (nat)Te(n, gamma)(131)Te nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by column (activated charcoal) chromatography. Quantitative post-irradiation recovery of the TeO(2) target material (98-99%), in a form suitable for reuse in future irradiations, was achieved. The overall radiochemical yield for the complete separation of (131)I was 75-85% (n=8). The separated nca (131)I was of high, approximately 99%, radionuclidic and radiochemical purities and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.

Modeling the Anomalous Microwave Emission with Spinning Nanoparticles: No PAHs Required

NASA Astrophysics Data System (ADS)

Hensley, Brandon S.; Draine, B. T.

2017-02-01

In light of recent observational results indicating an apparent lack of correlation between the anomalous microwave emission (AME) and mid-infrared emission from polycyclic aromatic hydrocarbons, we assess whether rotational emission from spinning silicate and/or iron nanoparticles could account for the observed AME without violating observational constraints on interstellar abundances, ultraviolet extinction, and infrared emission. By modifying the SpDust code to compute the rotational emission from these grains, we find that nanosilicate grains could account for the entirety of the observed AME, whereas iron grains could be responsible for only a fraction, even for extreme assumptions on the amount of interstellar iron concentrated in ultrasmall iron nanoparticles. Given the added complexity of contributions from multiple grain populations to the total spinning dust emission, as well as existing uncertainties due to the poorly constrained grain size, charge, and dipole moment distributions, we discuss generic, carrier-independent predictions of spinning dust theory and observational tests that could help identify the AME carrier(s).

Photocatalytic conversion of CO2 into value-added and renewable fuels

NASA Astrophysics Data System (ADS)

Yuan, Lan; Xu, Yi-Jun

2015-07-01

The increasing energy crisis and the worsening global climate caused by the excessive utilization of fossil fuel have boosted tremendous research activities about CO2 capture, storage and utilization. Artificial photosynthesis that uses solar light energy to convert CO2 to form value-added and renewable fuels such as methane or methanol has been consistently drawing increasing attention. It is like killing two birds with one stone since it can not only reduce the greenhouse effects caused by CO2 emission but also produce value added chemicals for alternative energy supplying. This review provides a brief introduction about the basic principles of artificial photosynthesis of CO2 and the progress made in exploring more efficient photocatalysts from the viewpoint of light harvesting and photogenerated charge carriers boosting. Moreover, the undergoing mechanisms of CO2 photoreduction are discussed with selected examples, in terms of adsorption of reactants, CO2 activation as well as the possible reaction pathways. Finally, perspectives on future research directions and open issues in CO2 photoreduction are outlined.

Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.

PubMed

Ringman, John M; Elashoff, David; Geschwind, Daniel H; Welsh, Brian T; Gylys, Karen H; Lee, Cathy; Cummings, Jeffrey L; Cole, Greg M

2012-06-01

To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. A tertiary referral dementia research center. Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models. Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life.

Linking brain imaging and genomics in the study of Alzheimer's disease and aging.

PubMed

Reiman, Eric M

2007-02-01

My colleagues and I have been using positron emission tomography (PET) and magnetic resonance imaging (MRI) to detect and track the brain changes associated with Alzheimer's disease (AD) and normal brain aging in cognitively normal persons with two copies, one copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common AD susceptibility gene. In this review article, I consider how brain imaging techniques could be used to evaluate putative AD prevention therapies in cognitively normal APOE epsilon4 carriers and putative age-modifying therapies in cognitively normal APOE epsilon4 noncarriers, how they could help investigate the individual and aggregate effects of putative AD risk modifiers, and how they could help guide the investigation of a molecular mechanism associated with AD vulnerability and normal neurological aging. I suggest how high-resolution genome-wide genetic and transcriptomic studies could further help in the scientific understanding of AD, aging, and other common and genetically complex phenotypes, such as variation in normal human memory performance, and in the discovery and evaluation of promising treatments for these phenotypes. Finally, I illustrate the push-pull relationship between brain imaging, genomics research, and other neuroscientific research in the study of AD and aging.

78 FR 19726 - Agency Information Collection Activities: Visa Waiver Program Carrier Agreement (CBP Form I-775)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... Activities: Visa Waiver Program Carrier Agreement (CBP Form I-775) AGENCY: U.S. Customs and Border Protection... information collection requirement concerning the Visa Waiver Program Carrier Agreement (CBP Form I-775). This... concerning the following information collection: Title: Visa Waiver Program Carrier Agreement. OMB Number...

46 CFR 221.5 - Citizenship declarations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING MARITIME CARRIERS AND RELATED ACTIVITIES REGULATED TRANSACTIONS INVOLVING DOCUMENTED VESSELS AND OTHER MARITIME INTERESTS Introduction... Government for filing or recording, the Person filing shall submit therewith Maritime Administration Form No...

Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.

PubMed

Lemaire, C; Libert, L; Franci, X; Genon, J-L; Kuci, S; Giacomelli, F; Luxen, A

2015-06-15

An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment. Copyright © 2015 John Wiley & Sons, Ltd.

Characterizing Apolipoprotein E ε4 Carriers and Noncarriers With the Clinical Diagnosis of Mild to Moderate Alzheimer Dementia and Minimal β-Amyloid Peptide Plaques.

PubMed

Monsell, Sarah E; Kukull, Walter A; Roher, Alex E; Maarouf, Chera L; Serrano, Geidy; Beach, Thomas G; Caselli, Richard J; Montine, Thomas J; Reiman, Eric M

2015-10-01

β-Amyloid peptide (Aβ) plaques are a cardinal neuropathologic feature of Alzheimer disease (AD), yet more than one-third of apolipoprotein E ε4 (APOE4) noncarriers with the clinical diagnosis of mild to moderate Alzheimer dementia may not meet positron emission tomographic criteria for significant cerebral amyloidosis. To clarify the percentage of APOE4 carriers and noncarriers with the primary clinical diagnosis of mild to moderate Alzheimer dementia near the end of life and minimal Aβ plaques noted at autopsy and the extent to which these cases are associated with appreciable neurofibrillary degeneration or a primary neuropathologic diagnosis other than AD. Data on participants included in this study were obtained from the National Alzheimer Coordinating Center's Uniform Data Set, which comprises longitudinal clinical assessments performed at the AD centers funded by the National Institute on Aging. Neuropathology data are available for the subset of participants who died. A total of 100 APOE4 noncarriers and 100 APOE4 carriers had the primary clinical diagnosis of mild to moderate Alzheimer dementia at their last visit, known APOE4 genotype, died within the ensuing 24 months, and underwent neuropathologic evaluation on autopsy. The study was conducted from September 1, 2005, to September 1, 2012; analysis was performed from October 9, 2012, to March 20, 2015. Standardized histopathologic assessments of AD neuropathologic changes were the primary measures of interest in this study, specifically Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque density score, diffuse plaque density score, and Braak stage for neurofibrillary degeneration. The distributions of scores for these measures were the primary outcomes. Of the 37 APOE4 noncarriers with minimal neuritic plaques, 16 individuals (43.2%) had Braak stages III to VI ratings, and 15 of the others (75.0%) met neuropathologic criteria for other dementia-related diseases. Of the 13 APOE4 carriers with minimal neuritic plaques, 6 individuals (46.2%) had Braak stages III to VI ratings and met neuropathologic criteria for other dementia-related diseases. Similarly, of the 7 APOE4 carriers with minimal neuritic plaques and Braak stages 0 to II, 4 participants (57.1%) were thought to have pathologic changes and alterations resulting from non-AD neuropathologic features. In this study, more than one-third of APOE4 noncarriers with the primary clinical diagnosis of mild to moderate Alzheimer dementia had minimal Aβ plaque accumulation in the cerebral cortex and, thus, may show limited or no benefit from otherwise effective anti-Aβ treatment. Almost half of the participants with a primary clinical diagnosis of mild to moderate Alzheimer dementia and minimal Aβ plaque accumulation had an extensive topographic distribution of neurofibrillary degeneration. Additional studies are needed to better understand and provide treatment for patients with this unexpectedly common cliniconeuropathologic condition.

Primary photoexcitations and the origin of the photocurrent in rubrene single crystals.

PubMed

Najafov, Hikmat; Biaggio, Ivan; Podzorov, Vitaly; Calhoun, Matthew F; Gershenson, Michael E

2006-02-10

By simultaneously measuring the excitation spectra of transient luminescence and transient photoconductivity after picosecond pulsed excitation in rubrene single crystals, we show that free excitons are photoexcited starting at photon energies above 2.0 eV. We observe a competition between photoexcitation of free excitons and photoexcitation into vibronic states that subsequently decays into free carriers, while molecular excitons are instead formed predominantly through the free exciton. At photon energies below 2.25 eV, free charge carriers are created only through a long-lived intermediate state with a lifetime of up to 0.1 ms and no free carriers appear during the exciton lifetime.

Two Virasoro symmetries in stringy warped AdS 3

DOE PAGES

Compere, Geoffrey; Guica, Monica; Rodriguez, Maria J.

2014-12-02

We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS 3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS 3. Consequently, for each consistent choice of boundary conditions in AdS 3, we can define a consistent phase space in warped AdS 3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS 3; two different types of Virasoro × Kač-Moody symmetriesmore » are also consistent alternatives. Next, we study the phase space of these theories when propagating modes are included. We show that, as long as one can define a conserved symplectic form without introducing instabilities, the Virasoro × Virasoro asymptotic symmetries can be extended to the entire (linearised) phase space. In conclusion, this implies that, at least at semi-classical level, consistent theories of gravity in warped AdS 3 are described by a two-dimensional conformal field theory, as long as stability is not an issue.« less

Two Virasoro symmetries in stringy warped AdS 3

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

Compere, Geoffrey; Guica, Monica; Rodriguez, Maria J.

We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS 3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS 3. Consequently, for each consistent choice of boundary conditions in AdS 3, we can define a consistent phase space in warped AdS 3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS 3; two different types of Virasoro × Kač-Moody symmetriesmore » are also consistent alternatives. Next, we study the phase space of these theories when propagating modes are included. We show that, as long as one can define a conserved symplectic form without introducing instabilities, the Virasoro × Virasoro asymptotic symmetries can be extended to the entire (linearised) phase space. In conclusion, this implies that, at least at semi-classical level, consistent theories of gravity in warped AdS 3 are described by a two-dimensional conformal field theory, as long as stability is not an issue.« less

Plasma Signaling Proteins in Persons at Genetic Risk for Alzheimer Disease

PubMed Central

Ringman, John M.; Elashoff, David; Geschwind, Daniel H.; Welsh, Brian T.; Gylys, Karen H.; Lee, Cathy; Cummings, Jeffrey L.; Cole, Greg M.

2013-01-01

Objective To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Design Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. Setting A tertiary referral dementia research center. Participants Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Main Outcome Measures Protein levels were compared between FAD mutation carriers (MCs) and non-carriers (NCs) and among APOE genotype groups, using multiple linear regression models. Results Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. Conclusions We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life. PMID:22689192

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.

PubMed

Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-06-30

Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

PubMed Central

Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-01-01

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life.

PubMed

Hüls, Anke; Klümper, Claudia; MacIntyre, Elaina A; Brauer, Michael; Melén, Erik; Bauer, Mario; Berdel, Dietrich; Bergström, Anna; Brunekreef, Bert; Chan-Yeung, Moira; Fuertes, Elaine; Gehring, Ulrike; Gref, Anna; Heinrich, Joachim; Standl, Marie; Lehmann, Irina; Kerkhof, Marjan; Koppelman, Gerard H; Kozyrskyj, Anita L; Pershagen, Göran; Carlsten, Christopher; Krämer, Ursula; Schikowski, Tamara

2018-04-06

Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO 2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. GRS was associated with childhood AD and modified the association between NO 2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

GENETIC INFLUENCE OF APOE4 GENOTYPE ON HIPPOCAMPAL MORPHOMETRY - AN N=725 SURFACE-BASED ADNI STUDY

PubMed Central

Shi, Jie; Leporé, Natasha; Gutman, Boris A.; Thompson, Paul M.; Baxter, Leslie C.; Caselli, Richard L.; Wang, Yalin

2014-01-01

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer’s disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 non-carriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database – the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling’s T2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. PMID:24453132

Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction

PubMed Central

Márquez-Miranda, Valeria; Araya-Durán, Ingrid; Camarada, María Belén; Comer, Jeffrey; Valencia-Gallegos, Jesús A.; González-Nilo, Fernando Danilo

2016-01-01

An ideal nucleic-acid transfection system should combine the physical and chemical characteristics of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of lipids and preserve the high affinity for DNA possessed by cationic dendrimers. These lipid/dendrimer hybrids consist of a low-generation, hydrophilic dendron (G2, G1, or G0) bonded to a hydrophobic tail. The G2-18C AD was reported to be an efficient siRNA vector with significant gene silencing. However, shorter tail ADs (G2-15C and G2-13C) and lower generation (G0 and G1) dendrimers failed as transfection carriers. To date, the self-assembly phenomenon of this class of amphiphilic dendrimers has not been molecularly explored using molecular simulation methods. To gain insight into these systems, the present study used coarse-grained molecular dynamics simulations to describe how ADs are able to self-assemble into an aggregate, and, specifically, how tail length and generation play a key role in this event. Finally, explanations are given for the better efficiency of G2/18-C as gene carrier in terms of binding of siRNA. This knowledge could be relevant for the design of novel, safer ADs with well-optimized affinity for siRNA. PMID:27377641

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

PubMed

Fekih-Mrissa, Najiba; Mansour, Malek; Sayeh, Aicha; Bedoui, Ines; Mrad, Meriem; Riahi, Anis; Mrissa, Ridha; Nsiri, Brahim

2017-09-01

The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P < 10 -3 ; OR = 8.78; 4G/5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10 -3 ). The 4G allele was also more frequently found in patients compared with controls; P < 10 -3 ; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.

The backup is active in Alzheimer's disease: a hypothesis from problem theory.

PubMed

Burnand, Gordon

2015-03-01

Problem theory distinguishes between six general problems of everyday life, which people work through in turn during childhood, learning to switch between them. One of them requires the protection of a cut-out and an override. People who develop Alzheimer's disease (AD), and apolipoprotein allele epsilon 4 carriers, are preoccupied with this problem, or readily switch back to it. It is the freedom problem, of raising hope or confidence of freedom or power to control. Here people try to raise hope of success with any task on which attention happens to rest. This indiscriminateness means that there is no basis for giving up on a task, or for avoiding dangerous environments. Thus the cut-out is needed when someone becomes stuck on a mental task and the override is needed so as to help in avoiding danger. Activity relevant to the freedom problem is confined to the left hemisphere and the right hemisphere operates the cut-out and override. In providing these two forms of protection the right hemisphere can be said to act as a backup. Accordingly EEG, metabolism, and atrophy findings indicate that both cut-out and override are active in mild clinical impairment, especially among patients who later develop AD. The pattern of atrophy of AD matches what would be expected from disuse caused by an overactive cut-out followed by an overactive override. A parallel loss of testosterone might contribute to the weakening of resistance to infections leading to autoimmune effects. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Differences in mortality among bobwhite fed methylmercury chloride dissolved in various carriers

USGS Publications Warehouse

Spann, J.W.; Heinz, G.H.; Camardese, M.B.; Hill, E.F.; Moore, John F.; Murray, H.C.

1986-01-01

Twelve-day-old bobwhite chicks were fed a diet containing 0, 5.4 or 20 ppm methylmercury chloride. The methylmercury chloride was added to the diet either in a dry, pulverized form or dissolved in acetone, propylene glycol or corn oil. Mortality was measured for 6 weeks, and samples of liver were saved for mercury analysis. Mortality was significantly lower in birds fed 20 ppm methylmercury chloride when acetone was the solvent. The reduced mortality could not be explained by effects of acetone on dietary level of mercury or on uptake of mercury into the body.

Zinc interstitial threshold in Al-doped ZnO film: Effect on microstructure and optoelectronic properties

NASA Astrophysics Data System (ADS)

Singh, Chetan C.; Panda, Emila

2018-04-01

In order to know the threshold quantity of the zinc interstitials that contributes to an increase in carrier concentration in the Al-doped ZnO (AZO) films and their effect on the overall microstructure and optoelectronic properties of these films, in this work, Zn-rich-AZO and ZnO thin films are fabricated by adding excess zinc (from a zinc metallic target) during their deposition in RF magnetron sputtering and are then investigated using a wide range of experimental techniques. All these films are found to grow in a ZnO hexagonal wurtzite crystal structure with strong (002) orientation of the crystallites, with no indication of Al2O3, metallic Zn, and Al. The excessively introduced zinc in these AZO and/or ZnO films is found to increase the shallow donor level defects (i.e., zinc interstitials and oxygen-related electronic defect states), which is found to significantly increase the carrier concentration in these films. Additionally, aluminum is seen to enhance the creation of these electronic defect states in these films, thereby contributing more to the overall carrier concentration of these films. However, carrier mobility is found to decrease when the carrier concentration values are higher than 4 × 1020 cm-3, because of the electron-electron scattering. Whereas the optical band gap of the ZnO films is found to increase with increasing carrier concentration because of the Burstein-Moss shift, these decrease for the AZO films due to the band gap narrowing effect caused by excess carrier concentration.

Association between an Alzheimer's Disease-Related Index and APOE ε4 Gene Dose.

PubMed

Schraml, Frank; Chen, Kewei; Ayutyanont, Napatkamon; Auttawut, Roontiva; Langbaum, Jessica B S; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Reeder, Stephanie Q; Alexander, Gene E; Caselli, Richard J; Fleisher, Adam S; Reiman, Eric M

2013-01-01

We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person's fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers. An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers. These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001). The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status.

PubMed

Piccio, Laura; Deming, Yuetiva; Del-Águila, Jorge L; Ghezzi, Laura; Holtzman, David M; Fagan, Anne M; Fenoglio, Chiara; Galimberti, Daniela; Borroni, Barbara; Cruchaga, Carlos

2016-06-01

Low frequency coding variants in TREM2 are associated with increased Alzheimer disease (AD) risk, while loss of functions mutations in the gene lead to an autosomal recessive early-onset dementia, named Nasu-Hakola disease (NHD). TREM2 can be detected as a soluble protein in cerebrospinal fluid (CSF) and plasma, and its CSF levels are elevated in inflammatory CNS diseases. We measured soluble TREM2 (sTREM2) in the CSF of a large AD case-control dataset (n = 180) and 40 TREM2 risk variant carriers to determine whether CSF sTREM2 levels are associated with AD status or mutation status. We also performed genetic studies to identify genetic variants associated with CSF sTREM2 levels. CSF, but not plasma, sTREM2 was highly correlated with CSF total tau and phosphorylated-tau levels (r = 0.35, P < 1×10(-4); r = 0.40, P < 1×10(-4), respectively), but not with CSF Aβ42. AD cases presented higher CSF sTREM2 levels than controls (P = 0.01). Carriers of NHD-associated TREM2 variants presented significantly lower CSF sTREM2 levels, supporting the hypothesis that these mutations lead to reduced protein production/function (R136Q, D87N, Q33X or T66M; P = 1×10(-3)). In contrast, CSF sTREM2 levels were significantly higher in R47H carriers compared to non-carriers (P = 6×10(-3)), suggesting that this variant does not impact protein expression and increases AD risk through a different pathogenic mechanism than NHD variants. In GWAS analyses for CSF sTREM2 levels the most significant signal was located on the MS4A gene locus (P = 5.45 × 10(-07)) corresponding to one of the SNPs reported to be associated with AD risk in this locus. Furthermore, SNPs involved in pathways related to virus cellular entry and vesicular trafficking were overrepresented, suggesting that CSF sTREM2 levels could be an informative phenotype for AD.

Development of a floating drug delivery system with superior buoyancy in gastric fluid using hot-melt extrusion coupled with pressurized CO₂.

PubMed

Almutairy, B K; Alshetaili, A S; Ashour, E A; Patil, H; Tiwari, R V; Alshehri, S M; Repka, M A

2016-03-01

The present study aimed to develop a continuous single-step manufacturing platform to prepare a porous, low-density, and floating multi-particulate system (mini-tablet, 4 mm size). This process involves injecting inert, non-toxic pressurized CO₂gas (P-CO₂) in zone 4 of a 16-mm hot-melt extruder (HME) to continuously generate pores throughout the carrier matrix. Unlike conventional methods for preparing floating drug delivery systems, additional chemical excipients and additives are not needed in this approach to create minute openings on the surface of the matrices. The buoyancy efficiency of the prepared floating system (injection of P-CO₂) in terms of lag time (0 s) significantly improved (P < 0.05), compared to the formulation prepared by adding the excipient sodium bicarbonate (lag time 120 s). The main advantages of this novel manufacturing technique include: (i) no additional chemical excipients need to be incorporated in the formulation, (ii) few manufacturing steps are required, (iii) high buoyancy efficiency is attained, and (iv) the extrudate is free of toxic solvent residues. Floating mini-tablets containing acetaminophen (APAP) as a model drug within the matrix-forming carrier (Eudragit® RL PO) have been successfully processed via this combined technique (P-CO₂/HME). Desired controlled release profile of APAP from the polymer Eudragit® RL PO is attained in the optimized formulation, which remains buoyant on the surface of gastric fluids prior to gastric emptying time (average each 4 h).

A study on using fireclay as a biomass carrier in an activated sludge system.

PubMed

Tilaki, Ramazan Ali Dianati

2011-01-01

By adding a biomass carrier to an activated sludge system, the biomass concentration will increase, and subsequently the organic removal efficiency will be enhanced. In this study, the possibility of using excess sludge from ceramic and tile manufacturing plants as a biomass carrier was investigated. The aim of this study was to determine the effect of using fireclay as a biomass carrier on biomass concentration, organic removal and nitrification efficiency in an activated sludge system. Experiments were conducted by using a bench scale activated sludge system operating in batch and continuous modes. Artificial simulated wastewater was made by using recirculated water in a ceramic manufacturing plant. In the continuous mode, hydraulic detention time in the aeration reactor was 8 and 22 h. In the batch mode, aeration time was 8 and 16 h. Fireclay doses were 500, 1,400 and 2,250 mg l(-1), and were added to the reactors in each experiment separately. The reactor with added fireclay was called a Hybrid Biological Reactor (HBR). A reactor without added fireclay was used as a control. Efficiency parameters such as COD, MLVSS and nitrate were measured in the control and HBR reactors according to standard methods. The average concentration of biomass in the HBR reactor was greater than in the control reactor. The total biomass concentration in the HBR reactor (2.25 g l(-1) fireclay) in the continuous mode was 3,000 mg l(-1) and in the batch mode was 2,400 mg l(-1). The attached biomass concentration in the HBR reactor (2.25 g l(-1) fireclay) in the continuous mode was 1,500 mg l(-1) and in the batch mode was 980 mg l(-1). Efficiency for COD removal in the HBR and control reactor was 95 and 55%, respectively. In the HBR reactor, nitrification was enhanced, and the concentration of nitrate was increased by 80%. By increasing the fireclay dose, total and attached biomass was increased. By adding fireclay as a biomass carrier, the efficiency of an activated sludge system to treat wastewater from ceramic manufacturing plants was increased.

New COL6A6 variant detected by whole-exome sequencing is linked to break points in intron 4 and 3′-UTR, deleting exon 5 of RHO, and causing adRP

PubMed Central

de Sousa Dias, Miguel; Hernan, Imma; Delás, Barbara; Pascual, Beatriz; Borràs, Emma; Gamundi, Maria José; Mañé, Begoña; Fernández-San José, Patricia; Ayuso, Carmen

2015-01-01

Purpose This study aimed to test a newly devised cost-effective multiplex PCR assay for the molecular diagnosis of autosomal dominant retinitis pigmentosa (adRP), as well as the use of whole-exome sequencing (WES) to detect disease-causing mutations in adRP. Methods Genomic DNA was extracted from peripheral blood lymphocytes of index patients with adRP and their affected and unaffected family members. We used a newly devised multiplex PCR assay capable of amplifying the genetic loci of RHO, PRPH2, RP1, PRPF3, PRPF8, PRPF31, IMPDH1, NRL, CRX, KLHL7, and NR2E3 to molecularly diagnose 18 index patients with adRP. We also performed WES in affected and unaffected members of four families with adRP in whom a disease-causing mutation was previously not found. Results We identified five previously reported mutations (p.Arg677X in the RP1 gene, p.Asp133Val and p.Arg195Leu in the PRPH2 gene, and p.Pro171Leu and p.Pro215Leu in the RHO gene) and one novel mutation (p.Val345Gly in the RHO gene) representing 33% detection of causative mutations in our adRP cohort. Comparative WES analysis showed a new variant (p.Gly103Arg in the COL6A6 gene) that segregated with the disease in one family with adRP. As this variant was linked with the RHO locus, we sequenced the complete RHO gene, which revealed a deletion in intron 4 that encompassed all of exon 5 and 28 bp of the 3′-untranslated region (UTR). Conclusions The novel multiplex PCR assay with next-generation sequencing (NGS) proved effective for detecting most of the adRP-causing mutations. A WES approach led to identification of a deletion in RHO through detection of a new linked variant in COL6A6. No pathogenic variants were identified in the remaining three families. Moreover, NGS and WES were inefficient for detecting the complete deletion of exon 5 in the RHO gene in one family with adRP. Carriers of this deletion showed variable clinical status, and two of these carriers had not previously been diagnosed with RP. PMID:26321861

Availability of yttrium-90 from strontium-90: a nuclear medicine perspective.

PubMed

Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A

2012-12-01

Yttrium-90 (T(½) 64.1 hours, E(βmax)=2.28 MeV) is a pure β⁻ particle emitting radionuclide with well-established applications in targeted therapy. There are several advantages of ⁹⁰Y as a therapeutic radionuclide. It has a suitable physical half-life (∼64 hours) and decays to a stable daughter product ⁹⁰Zr by emission of high-energy β⁻ particles. Yttrium has a relatively simple chemistry and its suitability for forming complexes with a variety of chelating agents is well established. The ⁹⁰Sr/⁹⁰Y generator is an ideal source for the long-term continuous availability of no-carrier-added ⁹⁰Y suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The parent radionuclide ⁹⁰Sr, which is a long-lived fission product, is available in large quantities from spent fuel. Several useful technologies have been developed for the preparation of ⁹⁰Sr/⁹⁰Y generators. There are several well-established radiopharmaceuticals based on monoclonal antibodies, peptides, and particulates labeled with ⁹⁰Y, that are in regular use for the treatment of some forms of primary cancers and arthritis. At present, there are no generators for the elution of ⁹⁰Y that can be set up in a hospital radiopharmacy. The radionuclide is procured from manufacturers and the radiopharmaceuticals are formulated on site. This article reviews the development of ⁹⁰Sr/⁹⁰Y generator and the development of ⁹⁰Y radiopharmaceuticals.

Insula and Inferior Frontal Gyrus' Activities Protect Memory Performance Against Alzheimer's Disease Pathology in Old Age.

PubMed

Lin, Feng; Ren, Ping; Lo, Raymond Y; Chapman, Benjamin P; Jacobs, Alanna; Baran, Timothy M; Porsteinsson, Anton P; Foxe, John J

2017-01-01

Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid- β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEɛ4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEɛ4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics.

Ketoprofen-loaded polymer carriers in bigel formulation: an approach to enhancing drug photostability in topical application forms

PubMed Central

Andonova, Velichka; Peneva, Petya; Georgiev, George S; Toncheva, Vencislava T; Apostolova, Elisaveta; Peychev, Zhivko; Dimitrova, Stela; Katsarova, Mariana; Petrova, Nadia; Kassarova, Margarita

2017-01-01

The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release. PMID:28894363

Ketoprofen-loaded polymer carriers in bigel formulation: an approach to enhancing drug photostability in topical application forms.

PubMed

Andonova, Velichka; Peneva, Petya; Georgiev, George S; Toncheva, Vencislava T; Apostolova, Elisaveta; Peychev, Zhivko; Dimitrova, Stela; Katsarova, Mariana; Petrova, Nadia; Kassarova, Margarita

2017-01-01

The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release.

Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics

PubMed Central

Cacabelos, Ramón; Martínez, Rocío; Fernández-Novoa, Lucía; Carril, Juan C.; Lombardi, Valter; Carrera, Iván; Corzo, Lola; Tellado, Iván; Leszek, Jerzy; McKay, Adam; Takeda, Masatoshi

2012-01-01

Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of the APOE gene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. The APOE and CYP2D6 genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs, CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6 may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics. PMID:22482072

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

PubMed

Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan

2015-01-01

Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.

Microencapsulation of Natural Anthocyanin from Purple Rosella Calyces by Freeze Drying

NASA Astrophysics Data System (ADS)

Nafiunisa, A.; Aryanti, N.; Wardhani, D. H.; Kumoro, A. C.

2017-11-01

Anthocyanin extract in powder form will improve its use since the powder is easier to store and more applicable. Microencapsulation method is introduced as an efficient way for protecting pigment such as anthocyanin. This research was aimed to characterise anthocyanin encapsulated products prepared from purple Roselle calyces by freeze drying. The liquid anthocyanin extracts from ultrasound-assisted extraction were freeze-dried with and without the addition of 10% w/w maltodextrins as a carrier and coating agents. The quality attributes of the powders were characterised by their colour intensity, water content, and solubility. Analysis of encapsulated material was performed for the powder added by maltodextrin. The stability of the microencapsulated pigment in solution form was determined for 11 days. Total anthocyanin content was observed through pH differential method. The results of the colour intensity analysis confirm that the product with maltodextrin addition has more intense colour with L* value of 29.69 a* value of 54.29 and b* value of 8.39. The result with the addition of maltodextrin has less moisture content and more soluble in water. It is verified that better results were obtained for powder with maltodextrin addition. Anthocyanin in the powder form with maltodextrin addition exhibits higher stability even after 11 days. In conclusion, the microencapsulation of anthocyanin with maltodextrin as a carrier and coating agent presented a potential method to produce anthocyanin powder from purple Roselle.

Notched-noise precursors improve detection of low-frequency amplitude modulationa)

PubMed Central

Almishaal, Ali; Bidelman, Gavin M.; Jennings, Skyler G.

2017-01-01

Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as a function of carrier level (Experiment I) and modulation frequency (Experiment II) for conditions with or without a notched-noise precursor. A longer carrier (500 ms) was also included in Experiment I. When the carrier was preceded by silence (no precursor condition) AM detection thresholds worsened for moderate-level carriers compared to lower- or higher-level carriers, resulting in a “mid-level hump.” AM detection thresholds with a precursor were better than those without a precursor, primarily for moderate-to-high level carriers, thus eliminating the mid-level hump in AM detection. When the carrier was 500 ms, AM thresholds improved by a constant (across all levels) relative to AM thresholds with a precursor, consistent with the longer carrier providing more “looks” to detect the AM signal. Experiment II revealed that improved AM detection with compared to without a precursor is limited to low-modulation frequencies (<60 Hz). These results are consistent with (1) a reduction in cochlear gain over the course of the precursor perhaps via the medial olivocochlear reflex or (2) a form of perceptual enhancement which may be mediated by adaptation of inhibition. PMID:28147582

Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers.

PubMed

Li, Wenjun; Antuono, Piero G; Xie, Chunming; Chen, Gang; Jones, Jennifer L; Ward, B Douglas; Singh, Suraj P; Franczak, Malgorzata B; Goveas, Joseph S; Li, Shi-Jiang

2014-08-01

The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD. Copyright © 2014. Published by Elsevier Ltd.

Impairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers.

PubMed

Petok, Jessica R; Myers, Catherine E; Pa, Judy; Hobel, Zachary; Wharton, David M; Medina, Luis D; Casado, Maria; Coppola, Giovanni; Gluck, Mark A; Ringman, John M

2018-05-01

Fast, inexpensive, and noninvasive identification of Alzheimer's disease (AD) before clinical symptoms emerge would augment our ability to intervene early in the disease. Individuals with fully penetrant genetic mutations causing autosomal dominant Alzheimer's disease (ADAD) are essentially certain to develop the disease, providing a unique opportunity to examine biomarkers during the preclinical stage. Using a generalization task that has previously shown to be sensitive to medial temporal lobe pathology, we compared preclinical individuals carrying ADAD mutations to noncarrying kin to determine whether generalization (the ability to transfer previous learning to novel but familiar recombinations) is vulnerable early, before overt cognitive decline. As predicted, results revealed that preclinical ADAD mutation carriers made significantly more errors during generalization than noncarrying kin, despite no differences between groups during learning or retention. This impairment correlated with the left hippocampal volume, particularly in mutation carriers. Such identification of generalization deficits in early ADAD may provide an easily implementable and potentially linguistically and culturally neutral way to identify and track cognition in ADAD. Copyright © 2018 Elsevier Inc. All rights reserved.

Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease

PubMed Central

2012-01-01

Objectives Accumulating evidence suggested that dysregulation of cholesterol homeostasis might be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), hepatic lipase (HL, coding genes named LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common polymorphisms (ABCA1R219K, CETPTaqIB and LIPC-250 G/A) with susceptibility to AD and plasma lipid levels. Methods Case–control study of 208 Han Chinese (104 AD patients and 104 non-demented controls) from Changsha area in Hunan Province was performed using the PCR-RFLP analysis. Cognitive decline was assessed using Mini Mental State Examination (MMSE) as a standardized method. Additionally, fasting lipid profile and the cognitive testing scores including Wechsler Memory Scale (WMS) and Wisconsin Card Sorting Test (WCST) were recorded. Results and conclusions We found significant differences among the genotype distributions of these three genes in AD patients when compared with controls. But after adjusting other factors, multivariate logistic regression analysis showed only ABCA1R219K (B = −0.903, P = 0.005, OR = 0.405, 95%CI:0.217-0.758) and LIPC-250 G/A variants(B = −0.905, P = 0.018, OR = 0.405, 95%CI:0.191-0.858) were associated with decreased AD risk. There were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) and apolipoproteinA-I in the carriers of KK genotype and K allele (P < 0.05), and B2B2 genotype of CETP Taq1B showed significant association with higher HDL-C levels than other genotypes (F = 5.598, P = 0.004), while -250 G/A polymorphisms had no significant effect on HDL-C. In total population, subjects carrying ABCA1219K allele or LIPC-250A allele obtained higher MMSE or WMS scores than non-carriers, however, no significant association was observed in AD group or controls. Therefore, this preliminary study showed that the gene variants of ABCA1R219K and LIPC-250 G/A might influence AD susceptibility in South Chinese Han population, but the polymorphism of CETPTaq1B didn't show any association in despite of being a significant determinant of HDL-C. PMID:23181436

Carrier-phase-based two-way satellite time and frequency transfer.

PubMed

Fujieda, Miho; Gotoh, Tadahiro; Nakagawa, Fumimaru; Tabuchi, Ryo; Aida, Masanori; Amagai, Jun

2012-12-01

We performed measurements of carrier-phase-based two-way satellite time and frequency transfer (TWST-FT) with an A/D sampler and conventional TWSTFT system. We found that an instability resulting from a local signal at the satellite transponder was negligible. The short-term stability of 4 × 10(-13) at 1 s was achieved in a short-baseline measurement. The results showed good agreement with the GPS carrier phase.

75 FR 61980 - Airworthiness Directives; Eurocopter France Model SA-365N, SA-365N1, AS-365N2, AS-365N3, SA-366G1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

... gearbox (MGB) planet gear carrier for a crack and replacing any MGB that has a cracked planet gear carrier... planet gear carrier and additional analysis that indicates that the initial inspection interval must be shortened. The actions specified by this AD are intended to detect a crack in the web of the planet gear...

Effect of hardwood process variables on fiberbonding

Treesearch

Otto Suchsland; George E. Woodson; Charles W. Mcmillin

1983-01-01

Severely cooked Masonite gun pulp was used in the laboratory to manufacture these four hardboard types: S1S-wet formed, S2S-wet formed, S1S-dry formed (water added after forming), S2S-dry formed. No resins or other additives were used.

33 CFR 402.7 - Service Incentive Program.

Code of Federal Regulations, 2014 CFR

2014-07-01

... number of calls scheduled for the Navigation Season. Additional calls to the system may be added during the season. (f) The carrier will advise the Manager of port rotation, outlining core ports of calls... carrier must meet 75% schedule adherence with a minimum of four (4) Great Lakes calls during the...

Characterization of glycol chitosan grafted with low molecular weight polyethylenimine as a gene carrier for human adipose-derived mesenchymal stem cells.

PubMed

Bae, Yoonhee; Lee, Young Hwa; Lee, Sunray; Han, Jin; Ko, Kyung Soo; Choi, Joon Sig

2016-11-20

Mesenchymal stem cells (MSCs) have a great capacity for self-renewal while still maintaining their multipotency, and can differentiate into a variety of cell types. The delivery of genes to a site of injury is a current and interesting field of gene therapy. In the present study, we describe a nonviral gene delivery carrier, glycol chitosan-methyl acrylate-polyethylenimine (GMP) polymer targeted towards human adipose-derived mesenchymal stem cells (AD-MSCs). Transfection efficiency, using luciferase (Luc) and a pDNA encoding enhanced green fluorescent protein (EGFP), along with cytotoxicity assays, were performed in human AD-MSCs. The results show that the transfection efficiency of the GMP polymer was similar to that of PEI25kD, and the cytotoxicity was lower. Moreover, human AD-MSCs were treated with the GMP polymer/pDNA polyplex and its cellular uptake and distribution were analyzed by flow cytometry and confocal microscopy. Furthermore, we performed endosomal escape analysis using LysoTracker Red, and found that the conjugated GMP polymer could escape from the endosome to the cytosol. Human AD-MSCs treated with the GMP polymer maintained their potential for osteogenic differentiation and phenotypic expression of human AD-MSCs based on flow cytometry analysis. The present study demonstrates that the GMP polymer can be used as a potential targeted-delivery carrier for effective gene delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hole polaron-polaron interaction in transition metal oxides and its limit to p-type doping

NASA Astrophysics Data System (ADS)

Chen, Shiyou; Wang, Lin-Wang

2014-03-01

Traditionally the origin of the poor p-type conductivity in some transition metal oxides (TMOs) was attributed to the limited hole concentration: the charge-compensating donor defects, such as oxygen vacancies and cation interstitials, can form spontaneously as the Fermi energy shifts down to near the valence band maximum. Besides the thermodynamic limit to the hole concentration, the limit to the hole mobility can be another possible reason, e.g., the hole carrier can form self-trapped polarons with very low carrier mobility. Although isolated hole polarons had been found in some TMOs, the polaron-polaron interaction is not well-studied. Here we show that in TMOs such as TiO2 and V2O5, the hole polarons prefer to bind with each other to form bipolarons, which are more stable than free hole carriers or separated polarons. This pushes the hole states upward into the conduction band and traps the holes. The rise of the Fermi energy suppresses the spontaneous formation of the charge-compensating donor defects, so the conventional mechanism becomes ineffective. Since it can happen in the impurity-free TMO lattices, independent of any extrinsic dopant, it acts as an intrinsic and general limit to the p-type conductivity in these TMOs. This material is based upon work performed by the JCAP, a US DOE Energy Innovation Hub, the NSFC (No. 61106087 and 91233121) and special funds for major state basic research (No. 2012CB921401).

Comparison of Various Kangaroo Mother Care Carriers on Maternal Comfort: A Pilot Study.

PubMed

Amaliya, Sholihatul; Rustina, Yeni; Agustini, Nur

Kangaroo mother care (KMC) is an evidence-based approach that has been scientifically proven to have a positive effect on mothers and infants. One of the barriers to performing KMC at home is the absence of a special KMC carrier. The most widely used KMC carriers in Indonesia are kangaroo pouch, thari, wrap and traditional wraps in the form of a long strip of fabric. This study's aim was to compare the level of maternal comfort when performing KMC with three different KMC carriers. The study used crossover design involving 20 mothers with low birth weight (LBW) infants as responders, selected through a consecutive sampling method. Data were collected using a maternal comfort questionnaire, maternal anxiety questionnaire, and KMC observation sheet. The results of repeated analysis of variance (ANOVA) showed that there was no significant difference in maternal comfort when performing KMC with any of three KMC carriers (maternal comfort p = .366, α = .05). Therefore, KMC can be implemented using any of the types of carriers including kangaroo pouch, thari wrap, and traditional wrap.

Charge-conversional poly(amino acid)s derivatives as a drug delivery carrier in response to the tumor environment.

PubMed

Yoon, Se Rim; Yang, Hee-Man; Park, Chan Woo; Lim, Sujin; Chung, Bong Hyun; Kim, Jong-Duk

2012-08-01

A charge-converting and pH-dependent nanocarrier was achieved by conjugating 2,3-dimethylmaleic anhydride (DMMA) to the amino group of an octadecyl grafted poly (2-hydroxyethyl aspartamide) (PHEA-g-C(18)-NH(2)) backbone, thereby forming a spherical micelle. PHEA, a poly(amino acid)s derivative, was derived from poly(succinimide), which is biocompatible and biodegradable. DMMA, a detachable component at the tumor site, was added, preventing aggregation with negative blood serum and enhancing the nanocarrier's cellular uptake. The polymeric micelle was comprehensively characterized and doxorubicin was encapsulated successively. The cellular uptake and anticancer therapeutic effect were evaluated by flow cytometry, confocal laser scanning microscopy, and a MTT assay. The properties of the nanocarrier can further be exploited to develop an early detection module for cancer. The present work is also expected to advance the study of designing smart carriers for drug and gene delivery. Copyright © 2012 Wiley Periodicals, Inc.

75 FR 5099 - Agency Information Collection Activities: Visa Waiver Program Carrier Agreement (Form I-775)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

... Activities: Visa Waiver Program Carrier Agreement (Form I-775) AGENCY: U.S. Customs and Border Protection... and Budget (OMB) for review and approval in accordance with the Paperwork Reduction Act: Visa Waiver... other technological techniques or other forms of information. Title: Visa Waiver Program Carrier...

APOE ε4 status in healthy older African Americans is associated with deficits in pattern separation and hippocampal hyperactivation.

PubMed

Sinha, Neha; Berg, Chelsie N; Tustison, Nicholas J; Shaw, Ashlee; Hill, Diane; Yassa, Michael A; Gluck, Mark A

2018-05-26

African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation-mnemonic discrimination performance and its corresponding neural computations in the hippocampus. Previous work using the mnemonic discrimination paradigm has localized increased activation in the DG/CA3 hippocampal subregions as being correlated with discrimination deficits. In a case-control high-resolution functional magnetic resonance imaging study of 30 healthy African Americans, aged 60 years and older, we observed APOE ε4-related impairments in mnemonic discrimination, coincident with dysfunctional hyperactivation in the DG/CA3, and CA1 regions, despite no evidence of structural differences in the hippocampus between carriers and noncarriers. Our results add to the growing body of evidence that deficits in pattern separation may be an early marker for AD-related neuronal dysfunction. Copyright © 2018 Elsevier Inc. All rights reserved.

Anyon black holes

NASA Astrophysics Data System (ADS)

Aghaei Abchouyeh, Maryam; Mirza, Behrouz; Karimi Takrami, Moein; Younesizadeh, Younes

2018-05-01

We propose a correspondence between an Anyon Van der Waals fluid and a (2 + 1) dimensional AdS black hole. Anyons are particles with intermediate statistics that interpolates between a Fermi-Dirac statistics and a Bose-Einstein one. A parameter α (0 < α < 1) characterizes this intermediate statistics of Anyons. The equation of state for the Anyon Van der Waals fluid shows that it has a quasi Fermi-Dirac statistics for α >αc, but a quasi Bose-Einstein statistics for α <αc. By defining a general form of the metric for the (2 + 1) dimensional AdS black hole and considering the temperature of the black hole to be equal with that of the Anyon Van der Waals fluid, we construct the exact form of the metric for a (2 + 1) dimensional AdS black hole. The thermodynamic properties of this black hole is consistent with those of the Anyon Van der Waals fluid. For α <αc, the solution exhibits a quasi Bose-Einstein statistics. For α >αc and a range of values of the cosmological constant, there is, however, no event horizon so there is no black hole solution. Thus, for these values of cosmological constants, the AdS Anyon Van der Waals black holes have only quasi Bose-Einstein statistics.

METHOD OF RECOVERING PLUTONIUM VALUES FROM AQUEOUS SOLUTIONS BY CARRIER PRECIPITATION

DOEpatents

James, R.A.; Thompson, S.G.

1959-11-01

A process is presented for pretreating aqueous nitric acid- plutonium solutions containing a small quantity of hydrazine that has formed as a decomposition product during the dissolution of neutron-bombarded uranium in nitric acid and that impairs the precipitation of plutonium on bismuth phosphate. The solution is digested with alkali metal dichromate or potassium permanganate at between 75 and 100 deg C; sulfuric acid at approximately 75 deg C and sodium nitrate, oxaiic acid plus manganous nitrate, or hydroxylamine are added to the solution to secure the plutonium in the tetravalent state and make it suitable for precipitation on BiPO/sub 4/.

Production of ammonia from plasma-catalytic decomposition of urea: Effects of carrier gas composition.

PubMed

Fan, Xing; Li, Jian; Qiu, Danqi; Zhu, Tianle

2018-04-01

Effects of carrier gas composition (N 2 /air) on NH 3 production, energy efficiency regarding NH 3 production and byproducts formation from plasma-catalytic decomposition of urea were systematically investigated using an Al 2 O 3 -packed dielectric barrier discharge (DBD) reactor at room temperature. Results show that the presence of O 2 in the carrier gas accelerates the conversion of urea but leads to less generation of NH 3 . The final yield of NH 3 in the gas phase decreased from 70.5%, 78.7%, 66.6% and 67.2% to 54.1%, 51.7%, 49.6% and 53.4% for applied voltages of 17, 19, 21 and 23kV, respectively when air was used as the carrier gas instead of N 2 . From the viewpoint of energy savings, however, air carrier gas is better than N 2 due to reduced energy consumption and increased energy efficiency for decomposition of a fixed amount of urea. Carrier gas composition has little influence on the major decomposition pathways of urea under the synergetic effects of plasma and Al 2 O 3 catalyst to give NH 3 and CO 2 as the main products. Compared to a small amount of N 2 O formed with N 2 as the carrier gas, however, more byproducts including N 2 O and NO 2 in the gas phase and NH 4 NO 3 in solid deposits were produced with air as the carrier gas, probably due to the unproductive consumption of NH 3 , the possible intermediate HNCO and even urea by the abundant active oxygen species and nitrogen oxides generated in air-DBD plasma. Copyright © 2017. Published by Elsevier B.V.

A retrospective analysis of the Alzheimer's disease vaccine progress - The critical need for new development strategies.

PubMed

Marciani, Dante J

2016-06-01

The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. It has been problematic to use conjugated peptides with Th1/Th2 adjuvants to induce immune responses against conformational epitopes formed by Aβ oligomers, which is critical to induce protective antibodies. Hence, vaccination should mimic natural immunity by using whole or if possible conjugated antigens, but biasing the response to Th2 with anti-inflammatory adjuvants. Also, selection of the carrier and cross-linking agents is important to prevent suppression of the immune response against the antigen. That certain compounds having phosphorylcholine or fucose induce a sole Th2 immunity would allow antigens with T-cell epitopes without inflammatory autoimmune reactions to be used. Another immunization method is DNA vaccines combined with antigenic ones, which favors the clonal selection and expansion of high affinity antibodies needed for immune protection, but this also requires Th2 immunity. Since AD transgenic mouse models have limited value for immunogen selection as shown by the clinical studies, screening may require the use of validated antibodies and biophysical methods to identify the antigens that would be most likely recognized by the human immune system and thus capable to stimulate a protective antibody response. To induce an anti-Alzheimer's disease protective immunity and prevent possible damage triggered by antigens having B-cell epitopes-only, whole antigens might be used; while inducing Th2 immunity with sole anti-inflammatory fucose-based adjuvants. This approach would avert a damaging systemic inflammatory immunity and the suppression of immunoresponse against the antigen because of carrier and cross-linkers; immune requirements that extend to DNA vaccines. © 2016 International Society for Neurochemistry.

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

PubMed

Han, Hyun Jeong; Kim, Byeong C; Lee, Jun-Young; Ryu, Seung-Ho; Na, Hae Ri; Yoon, Soo Jin; Park, Hyun Young; Shin, Joon Hyun; Cho, Soo-Jin; Yi, Hyon-Ah; Choi, Mun Seong; Heo, Jae-Hyeok; Park, Kyung Won; Kim, Kwang K; Choi, Seong Hye

2012-01-01

The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers. Copyright © 2012 S. Karger AG, Basel.

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

PubMed

Burns, Christine M; Chen, Kewei; Kaszniak, Alfred W; Lee, Wendy; Alexander, Gene E; Bandy, Daniel; Fleisher, Adam S; Caselli, Richard J; Reiman, Eric M

2013-04-23

To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD). This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET rCMRgl measurements. As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOEε4 noncarriers and carriers. Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOEε4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.

No-carrier-added (18F)-N-methylspiroperidol

DOEpatents

Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

1993-01-01

There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

No-carrier-added (18F)-N-methylspiroperidol

DOEpatents

Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

1993-07-06

There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.

PubMed

Lee, Seonjoo; Viqar, Fawad; Zimmerman, Molly E; Narkhede, Atul; Tosto, Giuseppe; Benzinger, Tammie L S; Marcus, Daniel S; Fagan, Anne M; Goate, Alison; Fox, Nick C; Cairns, Nigel J; Holtzman, David M; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N; Saykin, Andrew J; Masters, Colin L; Ringman, John M; Ryan, Natalie S; Förster, Stefan; Laske, Christoph; Schofield, Peter R; Sperling, Reisa A; Salloway, Stephen; Correia, Stephen; Jack, Clifford; Weiner, Michael; Bateman, Randall J; Morris, John C; Mayeux, Richard; Brickman, Adam M

2016-06-01

White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939. © 2016 American Neurological Association.

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.

PubMed

Ma, Qiu-Lan; Teng, Edmond; Zuo, Xiaohong; Jones, Mychica; Teter, Bruce; Zhao, Evan Y; Zhu, Cansheng; Bilousova, Tina; Gylys, Karen H; Apostolova, Liana G; LaDu, Mary Jo; Hossain, Mir Ahamed; Frautschy, Sally A; Cole, Gregory M

2018-06-01

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7-8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4 +/+ /FAD +/- ) relative to E4FAD- (non-carrier; APOE4 +/+ /FAD -/- ) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD. Copyright © 2018. Published by Elsevier Inc.

21 CFR 160.110 - Frozen eggs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... or in a water carrier, but the amount added does not exceed 0.5 percent of the weight of the frozen eggs. If a water carrier is used, it shall contain not less than 50 percent by weight of such... paragraph (b) of this section is used, the label shall bear the statement “Monosodium phosphate (or...

21 CFR 160.110 - Frozen eggs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... or in a water carrier, but the amount added does not exceed 0.5 percent of the weight of the frozen eggs. If a water carrier is used, it shall contain not less than 50 percent by weight of such... paragraph (b) of this section is used, the label shall bear the statement “Monosodium phosphate (or...

21 CFR 160.110 - Frozen eggs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... or in a water carrier, but the amount added does not exceed 0.5 percent of the weight of the frozen eggs. If a water carrier is used, it shall contain not less than 50 percent by weight of such... paragraph (b) of this section is used, the label shall bear the statement “Monosodium phosphate (or...

49 CFR 393.9 - Lamps operable, prohibition of obstructions of lamps and reflectors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER... Electrical Wiring § 393.9 Lamps operable, prohibition of obstructions of lamps and reflectors. (a) All lamps... any part of the load, or its covering by dirt, or other added vehicle or work equipment, or otherwise...

Contribution of a KCNH2 variant in genotyped long QT syndrome: Romano-Ward syndrome under double mutations and acquired long QT syndrome under heterozygote.

PubMed

Fujii, Yusuke; Matsumoto, Yuichi; Hayashi, Kenshi; Ding, Wei-Guang; Tomita, Yukinori; Fukumoto, Daisuke; Wada, Yuko; Ichikawa, Mari; Sonoda, Keiko; Ozawa, Junichi; Makiyama, Takeru; Ohno, Seiko; Yamagishi, Masakazu; Matsuura, Hiroshi; Horie, Minoru; Itoh, Hideki

2017-07-01

Long QT syndrome (LQTS) presents two clinical phenotypes, congenital and acquired forms. This study aims to evaluate the genetic contribution of a KCNH2 variant for the two LQTS phenotypes. From 1996 to 2014, genetic screening for LQTS probands was performed for five major genes: KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 and 389 probands were found to be mutation carriers. We analyzed the clinical phenotypes of p.His492Tyr carriers in KCNH2. Heterozygous p.His492Tyr variant was identified in 10 LQTS families. Six probands (mean age, 26±23 years) carried another mutation, and two of six had syncope associated with emotional stress or telephone ringing. The remaining four probands were significantly older at diagnosis (mean age, 42±33 years) and carried no other compound mutations. All the four probands had fatal arrhythmic events in the presence of additional precipitating factors such as culprit drugs in 2, hypokalemia in 1, and bradycardia in 1. The QTc interval of carriers with p.His492Tyr alone was 445±10ms and significantly shorter than that in double mutation carriers (481±40ms, p=0.041). KCNH2 p.His492Tyr variant presented Romano-Ward syndrome in the presence of another mutation and heterozygous carriers had mild phenotypes while even heterozygous carriers should be cared for not to encounter secondary factors because incidental factors could manifest "latent" form of p.His492Tyr heterozygous carriers. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Angiotensin Converting Enzyme Inhibitors and the Reduced Risk of Alzheimer’s Disease in the Absence of Apolipoprotein E4 Allele

PubMed Central

Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M.; Zhu, Haihao; Li, Huajie; Wallack, Max; Phillips, Leslie; Qiao, Liyan; Budson, Andrew E.; Stern, Robert; Kowall, Neil

2014-01-01

Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer’s disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer’s Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype. PMID:23948883

Methane biofiltration using autoclaved aerated concrete as the carrier material.

PubMed

Ganendra, Giovanni; Mercado-Garcia, Daniel; Hernandez-Sanabria, Emma; Boeckx, Pascal; Ho, Adrian; Boon, Nico

2015-09-01

The methane removal capacity of mixed methane-oxidizing bacteria (MOB) culture in a biofilter setup using autoclaved aerated concrete (AAC) as a highly porous carrier material was tested. Batch experiment was performed to optimize MOB immobilization on AAC specimens where optimum methane removal was obtained when calcium chloride was not added during bacterial inoculation step and 10-mm-thick AAC specimens were used. The immobilized MOB could remove methane at low concentration (~1000 ppmv) in a biofilter setup for 127 days at average removal efficiency (RE) of 28.7 %. Unlike a plug flow reactor, increasing the total volume of the filter by adding a biofilter in series did not result in higher total RE. MOB also exhibited a higher abundance at the bottom of the filter, in proximity with the methane gas inlet where a high methane concentration was found. Overall, an efficient methane biofilter performance could be obtained using AAC as the carrier material.

Osteopontin--a fibrosis-related marker--in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy.

PubMed

Niebroj-Dobosz, Irena; Madej-Pilarczyk, Agnieszka; Marchel, Michał; Sokołowska, Beata; Hausmanowa-Petrusewicz, Irena

2011-12-01

As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies--X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.

Absorption process for producing oxygen and nitrogen and solution therefor

DOEpatents

Roman, Ian C.

1984-01-01

Process for the separation and purification of oxygen and nitrogen is disclosed which utilizes solutions of oxygen carriers to selectively absorb oxygen from a gaseous stream, leaving nitrogen as a byproduct. In the process, an oxygen carrier capable of reversibly binding molecular oxygen is dissolved in a solvent solution, which absorbs oxygen from an oxygen-containing gaseous feed stream such as atmospheric air and desorbs oxygen to a gaseous product stream. The feed stream is maintained at a sufficiently high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, while the product stream is maintained at a sufficiently low oxygen pressure to keep the carrier in its deoxygenated form during desorption. In an alternate mode of operation, the carrier solution is maintained at a sufficiently low temperature and high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, and at a sufficiently high temperature to keep the carrier in its deoxygenated form during desorption. Under such conditions, exceptionally high oxygen concentrations on the order of 95% to 99% are obtained, as well as a long carrier lifetime in excess of 3 months, making the process commercially feasible.

Absorption process for producing oxygen and nitrogen and solution therefor

DOEpatents

Roman, Ian C. [Wilmington, DE; Baker, Richard W. [Palo Alto, CA

1990-09-25

Process for the separation and purification of oxygen and nitrogen is disclosed which utilizes solutions of oxygen carriers to selectively absorb oxygen from a gaseous stream, leaving nitrogen as a byproduct. In the process, an oxygen carrier capable of reversibly binding molecular oxygen is dissolved in a solvent solution, which absorbs oxygen from an oxygen-containing gaseous feed stream such as atmospheric air and desorbs oxygen to a gaseous product stream. The feed stream is maintained at a sufficiently high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, while the product stream is maintained at a sufficiently low oxygen pressure to keep the carrier in its deoxygenated form during desorption. In an alternate mode of operation, the carrier solution is maintained at a sufficiently low temperature and high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, and at a sufficiently high temperature to keep the carrier in its deoxygenated form during desorption. Under such conditions, exceptionally high oxygen concentrations on the order of 95% to 99% are obtained, as well as a long carrier lifetime in excess of 3 months, making the process commercially feasible.

Absorption process for producing oxygen and nitrogen and solution therefor

DOEpatents

Roman, I.C.; Baker, R.W.

1990-09-25

Process for the separation and purification of oxygen and nitrogen is disclosed which utilizes solutions of oxygen carriers to selectively absorb oxygen from a gaseous stream, leaving nitrogen as a byproduct. In the process, an oxygen carrier capable of reversibly binding molecular oxygen is dissolved in a solvent solution, which absorbs oxygen from an oxygen-containing gaseous feed stream such as atmospheric air and desorbs oxygen to a gaseous product stream. The feed stream is maintained at a sufficiently high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, while the product stream is maintained at a sufficiently low oxygen pressure to keep the carrier in its deoxygenated form during desorption. In an alternate mode of operation, the carrier solution is maintained at a sufficiently low temperature and high oxygen pressure to keep the oxygen carrier in its oxygenated form during absorption, and at a sufficiently high temperature to keep the carrier in its deoxygenated form during desorption. Under such conditions, exceptionally high oxygen concentrations on the order of 95% to 99% are obtained, as well as a long carrier lifetime in excess of 3 months, making the process commercially feasible. 1 figure

In vitro skin permeation and anti-atopic efficacy of lipid nanocarriers containing water soluble extracts of Houttuynia cordata.

PubMed

Kwon, Taek Kwan; Kim, Jin-Chul

2014-10-01

The aims of this work are to enhance the in vitro skin permeation of Houttuynia cordata (water-soluble extract of H. cordata; HCWSE) and to boost the efficacy of HCWSE against atopic dermatitis (AD) - like skin lesion in hairless mice using lipid nano-carriers (liposome and cubosome). HCWSE was obtained by a hot water extraction. Monoolein cubosomal suspension containing HCWSE and egg phosphatidylcholine liposomal suspension containing the same was prepared by a sonication and a film hydration method, respectively. The lipid nano-carriers, especially cubosome, enhanced the in vitro skin permeation of HCWSE. The inhibitory effects of HCWSE-containing lipid carrier suspensions on the development of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesion in hairless mice were investigated by observing appearance of skin surface, serum immunoglobulin E (IgE) level and cytokine expression. HCWSE-containing preparations suppressed IgE production and interleukin 4 expression, whereas they promoted interferon gamma expression. The order of lymphocyte (B-cell, Th1 cell and Th2 cell) modulating effect was HCWSE-containing cubosomal suspension > HCWSE-containing liposomal suspension > HCWSE solution in phosphate buffered saline, indicating that the cubosomal suspension, among the preparations, was the most efficacious in inhibiting the development of DNCB-induced AD-like skin lesion. It is believed that the cubosomal suspension containing HCWSE would be an efficacious preparation for the treatment of AD.

47 CFR 1.1404 - Complaint.

Code of Federal Regulations, 2010 CFR

2010-10-01

... telecommunications carriers for non-recurring costs. (2) Data and information should be based upon historical or... upon historical or original cost methodology, insofar as possible. Data should be derived from ARMIS...) through (n) and adding new paragraphs (g)(12) and (h) through (j). The added text contains information...

40 CFR 80.74 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., oxygenate blender, carrier, distributor, reseller, retailer, or wholesale-purchaser who sells, offers for... reformulated gasoline or RBOB recovered from transmix and the type and amount of any blendstock added, if... (iii) The volume, type, and purity of the oxygenate which was added, and documents which show the...

USSR Report, Chemistry, No. 108

DTIC Science & Technology

1983-10-21

Savel’yeva, et al.; KHIMICHESKAYA PROMYSHLENNOST’, No 7, Jul 83).., 23 Extracting Fluorine in Producing Extraction Phosphoric Acid From New Forms...the carrier under the influence of the high temperatures and chemical poisoning (primarily by fluorine compounds). Chemical poisoning decreases...source raw materials used in industry is an important re- serve in increasing food stocks. Suffice it to say that in our republic paxnt and varnish

Design concepts for hot carrier-based detectors and energy converters in the near ultraviolet and infrared

NASA Astrophysics Data System (ADS)

Gong, Tao; Krayer, Lisa; Munday, Jeremy N.

2016-10-01

Semiconductor materials are well suited for power conversion when the incident photon energy is slightly larger than the bandgap energy of the semiconductor. However, for photons with energy significantly greater than the bandgap energy, power conversion efficiencies are low. Further, for photons with energy below the bandgap energy, the absence of absorption results in no power generation. Here, we describe photon detection and power conversion of both high- and low-energy photons using hot carrier effects. For the absorption of high-energy photons, excited electrons and holes have excess kinetic energy that is typically lost through thermalization processes between the carriers and the lattice. However, collection of hot carriers before thermalization allows for reduced power loss. Devices utilizing plasmonic nanostructures or simple three-layer stacks (transparent conductor-insulator-metal) can be used to generate and collect these hot carriers. Alternatively, hot carrier collection from sub-bandgap photons can be possible by forming a Schottky junction with an absorbing metal so that hot carriers generated in the metal can be injected across the semiconductor-metal interface. Such structures enable near-IR detection based on sub-bandgap photon absorption. Further, utilization and optimization of localized surface plasmon resonances can increase optical absorption and hot carrier generation (through plasmon decay). Combining these concepts, hot carrier generation and collection can be exploited over a large range of incident wavelengths spanning the UV, visible, and IR.

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

PubMed

Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

2018-06-01

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

Computer Modeling of Electrostatic Aggregation of Granular Materials in Planetary and Astrophysical Settings

NASA Technical Reports Server (NTRS)

Marshall, J.; Sauke, T.

1999-01-01

Electrostatic forces strongly influence the behavior of granular materials in both dispersed (cloud) systems and semi-packed systems. These forces can cause aggregation or dispersion of particles and are important in a variety of astrophysical and planetary settings. There are also many industrial and commercial settings where granular matter and electrostatics become partners for both good and bad. This partnership is important for human exploration on Mars where dust adheres to suits, machines, and habitats. Long-range Coulombic (electrostatic) forces, as opposed to contact-induced dipoles and van der Waals attractions, are generally regarded as resulting from net charge. We have proposed that in addition to net charge interactions, randomly distributed charge carriers on grains will result in a dipole moment regardless of any net charge. If grains are unconfined, or fluidized, they will rotate so that the dipole always induces attraction between grains. Aggregates are readily formed, and Coulombic polarity resulting from the dipole produces end-to-end stacking of grains to form filamentary aggregates. This has been demonstrated in USML experiments on Space Shuttle where microgravity facilitated the unmasking of static forces. It has also been demonstrated in a computer model using grains with charge carriers of both sign. Model results very closely resembled micro-g results with actual sand grains. Further computer modeling of the aggregation process has been conducted to improve our understanding of the aggregation process, and to provide a predictive tool for microgravity experiments slated for Space Station. These experiments will attempt to prove the dipole concept as outlined above. We have considerably enhanced the original computer model: refinements to the algorithm have improved the fidelity of grain behavior during grain contact, special attention has been paid to simulation time steps to enable establishment of a meaningful, quantitative time axis, and calibration of rounding accuracies have been conducted to test cumulative numerical influences in the model. The model has been run for larger grain populations, variable initial cloud densities, and we have introduced random net charging to individual grains, as well as a net charge to the cloud as a whole. The model uses 3 positive and 3 negative charges randomly distributed on each grain, with up to 160 grains contained within various size "boxes" that define the initial number densities in the clouds. Each charge represents localized charged region on a grain, but does not necessarily imply single quantized charge carriers. The Coulomb equations are then allowed to interact for each monopole: dipoles and any higher order charge coupling is a natural product of these "free" interactions over which the modeler exerts no influence. The charges are placed on surfaces of grains at random locations. A series of runs was conducted for neutral grains that had a perfect balance of negative and positive char carriers. Runs were also conducted with grains having additional fractional charges ranging between 0 and 1. By adding fractional charges of one sign, the model created grain populations in which all grains had excess charges the same sign, giving the cloud an overall net charge. This simulates clouds subjected to ionizing radiation (e. protoplanetary debris disk around a protosun), or any other process of charge biasing in a grain population (e.g., volcanic plumes). In another run series, random fractional charges of either sign were added to the grains so th some grains had a slight net positive charge while others had a slight net negative charge. This simulates triboelectrically-charged grain populations in which acquisition of an electron by one surface is at the expense creating a hole elsewhere. This dual sign charging was applied in two ways: in one case the cloud remained neutral by ensuring that all grain excess charges added to zero; in the other case, the cloud was permitted slight net char by not imposing a charge-balance condition. Additional information is contained in the original.

Added-purpose versus rote exercise in female nursing home residents.

PubMed

Yoder, R M; Nelson, D L; Smith, D A

1989-09-01

Seven recent experimental and quasi-experimental studies have compared the exercise of subjects instructed to pursue some added goal (often termed purposeful activity) with the exercise of subjects instructed to exercise without the suggestion of an added goal (often termed nonpurposeful activity). This article suggests a new terminology for this type of independent variable and describes an experiment within this developing tradition. An occupational form designed, through materials and instructions, to elicit a rotary arm exercise with the added purpose of stirring cookie dough was compared with an occupational form designed to elicit the rotary arm exercise with no added purpose. The subjects were 30 elderly female nursing home residents randomly assigned to the occupational forms. Results indicated that the added-purpose, occupationally embedded exercise condition elicited significantly more exercise repetitions than did the rote exercise condition (one-tailed p = .012). Exercise duration and exercise stoppages were also recorded. This study provides additional support for the traditional occupational therapy idea of embedding exercise within occupation. Suggestions are made for future research involving the experimental analysis of therapeutic occupation.

Predictors of Cognitive and Functional Decline in Patients With Alzheimer Disease Dementia From Brazil.

PubMed

Oliveira, Fabricio F; Chen, Elizabeth S; Smith, Marilia C; Bertolucci, Paulo H F

2016-01-01

Little is known on how risk factors for Alzheimer disease (AD) dementia affect disease progression, much less for populations with low mean schooling, whereas the transcription of APOE may be regulated by nongenetic factors. In this 44-month cohort study, 214 consecutive outpatients with late-onset AD were assessed for rates of cognitive and functional decline by way of Clinical Dementia Rating and Mini-Mental State Examination (MMSE) scores, keeping blinded assessment of APOE haplotypes. Subjects were evaluated for sex, schooling, age of dementia onset, and cerebrovascular risk factors (including Framingham risk scores). Of the 214 patients, there were 146 (68.2%) women and 113 (52.8%) APOE4+ carriers. The mean age of AD onset was 73.4±6.5 years-old, negatively correlated with time to Clinical Dementia Rating >1.0 (β=-0.132; ρ<0.001), MMSE=20 (β=-0.105; ρ<0.001), and MMSE=15 (β=-0.124; ρ=0.003), more significantly for women and APOE4+ carriers. Mean schooling was 4.18±3.7 years, correlated with time to MMSE=20 and MMSE=15 for women and APOE4+ carriers. Body mass index was correlated with time to MMSE=20 only for men (ρ=0.006). The 10-year coronary heart disease risk was correlated with time to MMSE=20 only for APOE4+ carriers (ρ=0.015). These outcomes suggest interactions among genomic effects of cognitive reserve, cerebral perfusion, and hormonal changes over mechanisms of neurodegeneration.

78 FR 73916 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

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Evaluation of accessory cell heterogeneity. I. Differential accessory cell requirement for T helper cell activation and for T-B cooperation.

PubMed

Ramila, G; Studer, S; Kennedy, M; Sklenar, I; Erb, P

1985-01-01

Several Ia+ tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen-specific T cells and for T-B cooperation. The macrophages and all the Ia+ tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)-restricted fashion and reconstituted the antibody responses of AC-depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier-specific T helper (Th) cells which help B cells for specific antihapten antibody responses by linked recognition. For T-B cooperation accessory cells were also required, but in contrast to Th cell activation any type of Ia+ AC (e.g. macrophage or tumor line) was effective. Strong MHC-restriction between the lymphocytes and the AC was seen if antigen-pulsed AC were added into the AC-depleted T-B cooperation cultures. If the AC and antigen were concomitantly added to the AC-depleted T-B cultures, MHC-restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC-depleted T-B cultures provided antigen-specific Th cells and the hapten-carrier conjugate were present. If, however, tumor line-activated T cells were added instead of macrophage-induced Th cells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Th cells depending on the differentiation stage of the Th cells.

Preliminary evaluation of a load-bearing BMP-2 carrier for segmental defect regeneration.

PubMed

Chu, Tien-Min G; Sargent, Peter; Warden, Stuart J; Turner, Charles H; Stewart, Rena L

2006-01-01

Large segmental defects in bones can result from tumor removal, massive trauma, congenital malformation, or non-union fractures. Such defects often are difficult to manage and require multiple-phase surgery to achieve adequate union and function. In this study, we propose a novel design of bone morphogenetic protein 2 (BMP-2) carrier for tissue engineering of segmental defect regeneration. The tube-shaped BMP-2 carrier was fabrication from a poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) composite via casting technique developed in our laboratory. An in vitro evaluation showed that the compressive strength of the carrier decreased about 48% in 12 weeks while maintained a pH in the 6.8-7.4 range. In vivo study was conducted by implanting carriers loaded with 10 microg of BMP-2 in 5 mm rat femur gap model for 15 weeks. X-ray evidence of bridging was first found in the BMP group at 3 weeks. Bridging in all animals (N = 4) in the BMP group was found at 9 weeks. No x-ray evidence of bridging was found in the No BMP group (N = 3). pQCT analysis indicated that the bone mineral density of the callus in the BMP group has reached the level of native femur at 15 weeks after implantation, while the callus in the No BMP group has a bone mineral density at a lower level of 84% to the native femur. Histology analysis shows that a normal fatty bone marrow was restored and mineralized callus formed and bridged the segmental defect.

Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children.

PubMed

Hussein, Yousri M; Shalaby, Sally M; Nassar, Amani; Alzahrani, Saad S; Alharbi, Ayman S; Nouh, Maha

2014-07-25

To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, <0.001 respectively), whereas no such association was observed in non-AD group (p=0.52, 0.99 respectively). A significant association between STAT6 polymorphisms and both types of dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD. Copyright © 2014 Elsevier B.V. All rights reserved.

An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications.

PubMed

Chakravarty, Rubel; Das, Tapas; Dash, Ashutosh; Venkatesh, Meera

2010-10-01

A novel two-step separation process for the production of no-carrier-added (NCA) (177)Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. A two-cycle electrolysis procedure was adopted for separation of (177)Lu from (177)Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of (177)Lu. The first electrolysis was performed for 50 min in the (177)Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of (177)Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of (177)Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe(1)-Tyr(3)-octreotate(DOTA-TATE) with (177)Lu. This process could provide NCA (177)Lu with >99.99% radionuclidic purity and an overall separation yield of ∼99% was achieved within 3-4 h. The Hg content in the product was determined to be <1 ppm. Radiolabeling yield of >98% was obtained with DOTA-TATE under the optimized reaction conditions. An efficient strategy for the separation of NCA (177)Lu, suitable for biomedical applications, has been developed. Copyright © 2010 Elsevier Inc. All rights reserved.

Biomarker Exposure-Response Analysis in Mild-To-Moderate Alzheimer's Disease Trials of Bapineuzumab.

PubMed

Russu, Alberto; Samtani, Mahesh N; Xu, Steven; Adedokun, Omoniyi J; Lu, Ming; Ito, Kaori; Corrigan, Brian; Raje, Sangeeta; Liu, Enchi; Brashear, H Robert; Styren, Scot; Hu, Chuanpu

2016-05-03

Bapineuzumab, an anti-amyloid monoclonal antibody, was evaluated as a candidate for immunotherapy in mild-to-moderate Alzheimer's disease (AD) patients. To assess the treatment effect of bapineuzumab therapy on disease-relevant biomarkers in patients with mild-to-moderate AD, using exposure-response modeling. Biomarker data from two Phase III studies were combined to model the impact of bapineuzumab exposure on week-71 change from baseline in brain amyloid burden by 11C-labeled Pittsburgh compound B (PiB) PET imaging (global cortical average of the Standardized Uptake Value ratio values), cerebrospinal fluid (CSF) phosphorylated (p)-tau concentrations, and brain volumetrics (brain boundary shift integral) by magnetic resonance imaging. Bapineuzumab or placebo was administered as a 1-hour intravenous infusion every 13 weeks for 78 weeks. Pharmacokinetic/pharmacodynamic modeling helped determine the most appropriate exposure-response model and estimate the impact of disease-relevant covariates (baseline biomarker value, APOE*E4 allele copy number, and baseline disease status as measured by Mini-Mental State Examination score) on the three biomarkers. Linear exposure-response relationships with negative and significant slope terms were observed for PiB PET and CSF p-tau concentration. Baseline biomarker value and APOE*E4 carrier status were significant covariates for both biomarkers. No exposure-response relationship on brain boundary shift integral was detected. Bapineuzumab treatment induced exposure-dependent reductions in brain amyloid burden. Effects on CSF p-tau concentrations were significant only in APOE*E4 carriers. No apparent influence of bapineuzumab exposure on brain volume could be demonstrated.

Carrier free immobilization and characterization of trypsin.

PubMed

Menfaatli, Esra; Zihnioglu, Figen

2015-04-01

Pancreatic trypsin was immobilized by cross-linked enzyme aggregates (CLEA) which is a carrier free immobilization method. Ammonium sulfate was chosen for enzyme precipitation which was followed by cross linking of formed aggregates via glutaraldehyde. Concentrations of precipitant and cross linker were respectively optimized as 60% ammonium sulfate and 1% glutaraldehyde. Optimum pH and temperature for CLEA was increased compared to free enzyme. Furthermore, pH, thermal and storage stability were improved. Presence of additives had no effects on enzyme activity. Prepared cross-linked trypsin aggregates are convenient for in situ protein fragmentation and can be used for protein identification.

75 FR 16428 - Polyethylene Retail Carrier Bags from the Socialist Republic of Vietnam: Final Affirmative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... Calvert or Jun Jack Zhao, AD/CVD Operations, Office 6, Import Administration, International Trade... Operations, Office 6, ``Verification of the Questionnaire Responses Submitted by Chin Sheng Company, Ltd... concerning banking in Vietnam. See Memorandum to Barbara E. Tillman, Director, AD/ CVD Operations, Office 6...

Direct observation of the carrier transport process in InGaN quantum wells with a pn-junction

NASA Astrophysics Data System (ADS)

Wu, Haiyan; Ma, Ziguang; Jiang, Yang; Wang, Lu; Yang, Haojun; Li, Yangfeng; Zuo, Peng; Jia, Haiqiang; Wang, Wenxin; Zhou, Junming; Liu, Wuming; Chen, Hong

2016-11-01

A new mechanism of light-to-electricity conversion that uses InGaN/GaN QWs with a p-n junction is reported. According to the well established light-to-electricity conversion theory, quantum wells (QWs) cannot be used in solar cells and photodetectors because the photogenerated carriers in QWs usually relax to ground energy levels, owing to quantum confinement, and cannot form a photocurrent. We observe directly that more than 95% of the photoexcited carriers escape from InGaN/GaN QWs to generate a photocurrent, indicating that the thermionic emission and tunneling processes proposed previously cannot explain carriers escaping from QWs. We show that photoexcited carriers can escape directly from the QWs when the device is under working conditions. Our finding challenges the current theory and demonstrates a new prospect for developing highly efficient solar cells and photodetectors. Project supported by the National Natural Science Foundation of China (Grant Nos. 11574362, 61210014, and 11374340) and the Innovative Clean-energy Research and Application Program of Beijing Municipal Science and Technology Commission, China (Grant No. Z151100003515001).

APOE Genotype and Nonrespiratory Sleep Parameters in Cognitively Intact Older Adults.

PubMed

Spira, Adam P; An, Yang; Peng, Yu; Wu, Mark N; Simonsick, Eleanor M; Ferrucci, Luigi; Resnick, Susan M

2017-08-01

The apolipoprotein E (APOE) Ɛ4 allele increases Alzheimer's disease (AD) risk and has been linked to a greater risk of sleep-disordered breathing. We investigated the association of APOE genotype with nonrespiratory sleep parameters. We studied 1264 cognitively normal participants in the Baltimore Longitudinal Study of Aging (mean = 57.5 ± 16.1 years, range 19.9-92.0, 48.2% women, 19.8% African American) with APOE genotyping and self-reported sleep duration (≥9, 7 or 8, ≤6 hours), difficulty falling/staying asleep, and napping. We compared Ɛ4 carriers with all noncarriers and compared persons at reduced (Ɛ2/Ɛ2 or Ɛ2/Ɛ3) or elevated AD risk (≥1 Ɛ4 allele) with those neutral for AD risk (Ɛ3/Ɛ3). In fully adjusted models, those with ≥1 Ɛ4 allele had a greater odds of being in a shorter sleep duration category compared to all noncarriers (odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.06, 1.88) and Ɛ3/Ɛ3 carriers (OR = 1.43, 95% CI 1.06, 1.92). Compared to Ɛ3/Ɛ3 carriers, Ɛ2/Ɛ2 or Ɛ2/Ɛ3 carriers had a lower odds of reporting napping (OR = 0.64, 95% CI 0.43, 0.96). Among participants aged ≥50 years, sleep duration findings remained and Ɛ4 carriers had a greater odds of trouble falling/staying asleep than noncarriers (OR = 1.49, 95% CI 1.02, 2.17). We found some evidence for stronger associations of Ɛ4 with sleep duration among African Americans. Self-reported sleep duration, napping, and trouble falling/staying asleep differ by APOE genotype. Studies are needed to examine whether APOE promotes AD by degrading sleep and to clarify the role of race in these associations. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Hybrid electronic/optical synchronized chaos communication system.

PubMed

Toomey, J P; Kane, D M; Davidović, A; Huntington, E H

2009-04-27

A hybrid electronic/optical system for synchronizing a chaotic receiver to a chaotic transmitter has been demonstrated. The chaotic signal is generated electronically and injected, in addition to a constant bias current, to a semiconductor laser to produce an optical carrier for transmission. The optical chaotic carrier is photodetected to regenerate an electronic signal for synchronization in a matched electronic receiver The system has been successfully used for the transmission and recovery of a chaos masked message that is added to the chaotic optical carrier. Past demonstrations of synchronized chaos based, secure communication systems have used either an electronic chaotic carrier or an optical chaotic carrier (such as the chaotic output of various nonlinear laser systems). This is the first electronic/optical hybrid system to be demonstrated. We call this generation of a chaotic optical carrier by electronic injection.

77 FR 44307 - Notice of Passenger Facility Charge (PFC) Approvals and Disapprovals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

... Required to Collect PFC's: Air taxi/ commercial operators filing FAA Form 1800-31. Determination: Approved... Air Carriers Not Required to Collect PFC's: Nonscheduled/ on-demand air carriers filing FAA Form 1800... Carriers Not Required to Collect PFC's: None. Brief Description of Projects Approved for Collection and Use...

Controlled multistep synthesis in a three-phase droplet reactor

PubMed Central

Nightingale, Adrian M.; Phillips, Thomas W.; Bannock, James H.; de Mello, John C.

2014-01-01

Channel-fouling is a pervasive problem in continuous flow chemistry, causing poor product control and reactor failure. Droplet chemistry, in which the reaction mixture flows as discrete droplets inside an immiscible carrier liquid, prevents fouling by isolating the reaction from the channel walls. Unfortunately, the difficulty of controllably adding new reagents to an existing droplet stream has largely restricted droplet chemistry to simple reactions in which all reagents are supplied at the time of droplet formation. Here we describe an effective method for repeatedly adding controlled quantities of reagents to droplets. The reagents are injected into a multiphase fluid stream, comprising the carrier liquid, droplets of the reaction mixture and an inert gas that maintains a uniform droplet spacing and suppresses new droplet formation. The method, which is suited to many multistep reactions, is applied to a five-stage quantum dot synthesis wherein particle growth is sustained by repeatedly adding fresh feedstock. PMID:24797034

Successful Object Encoding Induces Increased Directed Connectivity in Presymptomatic Early-Onset Alzheimer’s Disease

PubMed Central

Ochoa, John Fredy; Alonso, Joan Francesc; Duque, Jon Edinson; Tobón, Carlos Andrés; Mañanas, Miguel Angel; Lopera, Francisco; Hernández, Alher Mauricio

2016-01-01

Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD. PMID:27792014

Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.

PubMed

Gupta, V B; Laws, S M; Villemagne, V L; Ames, D; Bush, A I; Ellis, K A; Lui, J K; Masters, C; Rowe, C C; Szoeke, C; Taddei, K; Martins, R N

2011-03-22

There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aβ load, as assessed by PET using Pittsburgh compound B (PiB). Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aβ load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging. © 2011 by AAN Enterprises, Inc.

Flow measurement around a model ship with propeller and rudder

NASA Astrophysics Data System (ADS)

van, S. H.; Kim, W. J.; Yoon, H. S.; Lee, Y. Y.; Park, I. R.

2006-04-01

For the design of hull forms with better resistance and propulsive performance, it is essential to understand flow characteristics, such as wave and wake development, around a ship. Experimental data detailing the local flow characteristics are invaluable for the validation of the physical and numerical modeling of computational fluid dynamics (CFD) codes, which are recently gaining attention as efficient tools for hull form evaluation. This paper describes velocity and wave profiles measured in the towing tank for the KRISO 138,000 m3 LNG carrier model with propeller and rudder. The effects of propeller and rudder on the wake and wave profiles in the stern region are clearly identified. The results contained in this paper can provide an opportunity to explore integrated flow phenomena around a model ship in the self-propelled condition, and can be added to the International Towing Tank Conference benchmark data for CFD validation as the previous KCS and KVLCC cases.

Stoichiometric control of lead chalcogenide nanocrystal solids to enhance their electronic and optoelectronic device performance.

PubMed

Oh, Soong Ju; Berry, Nathaniel E; Choi, Ji-Hyuk; Gaulding, E Ashley; Paik, Taejong; Hong, Sung-Hoon; Murray, Christopher B; Kagan, Cherie R

2013-03-26

We investigate the effects of stoichiometric imbalance on the electronic properties of lead chalcogenide nanocrystal films by introducing excess lead (Pb) or selenium (Se) through thermal evaporation. Hall-effect and capacitance-voltage measurements show that the carrier type, concentration, and Fermi level in nanocrystal solids may be precisely controlled through their stoichiometry. By manipulating only the stoichiometry of the nanocrystal solids, we engineer the characteristics of electronic and optoelectronic devices. Lead chalcogenide nanocrystal field-effect transistors (FETs) are fabricated at room temperature to form ambipolar, unipolar n-type, and unipolar p-type semiconducting channels as-prepared and with excess Pb and Se, respectively. Introducing excess Pb forms nanocrystal FETs with electron mobilities of 10 cm(2)/(V s), which is an order of magnitude higher than previously reported in lead chalcogenide nanocrystal devices. Adding excess Se to semiconductor nanocrystal solids in PbSe Schottky solar cells enhances the power conversion efficiency.

Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease.

PubMed

Sundar, Purnima Desai; Feingold, Eleanor; Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

2007-06-01

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder caused by a complex interaction of genetic and environmental factors. Increasing evidence highlights a potential role for cholesterol in the pathophysiology of AD. The ABCA1 gene, located in close vicinity to the 9q linkage peaks identified by genome-wide AD linkage studies, plays an important role in cellular cholesterol efflux, and is likely a good candidate gene. However, results from published genetic association studies between ABCA1 and AD are ambiguous. In the present study, we examined the role of two ABCA1 polymorphisms, R219K (rs2230806) and G-17C (rs2740483) in modifying the risk of late-onset AD (LOAD) in a large American white cohort of 992 AD cases and 699 controls. We observed significant gender x R219K interaction (p=0.00008). Female carriers of the 219K allele showed a 1.75-fold increased risk of developing AD compared to non-219K carrier females (95% CI 1.34-2.29; p=0.00004). The overall two-site haplotype distribution was also significant between female AD cases and controls (p=0.017). The risk associated with the R219K polymorphism was independent of the recently reported significant association in the ubiquilin (UBQLN1) gene in this region on chromosome 9q. Our data suggest a gender-specific and APOE and UBQLN1 independent association between the ABCA1/R219K polymorphism and LOAD.

8 CFR 299.4 - Reproduction of Public Use Forms by public and private entities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... font style as the body of the form. (2) The final form must match the design, format, and dimensions of... official form. The wording and punctuation of all data elements and identifying information must match exactly. No data elements may be added or deleted. The sequence and format for each item on the form must...

8 CFR 299.4 - Reproduction of Public Use Forms by public and private entities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... font style as the body of the form. (2) The final form must match the design, format, and dimensions of... official form. The wording and punctuation of all data elements and identifying information must match exactly. No data elements may be added or deleted. The sequence and format for each item on the form must...

8 CFR 299.4 - Reproduction of Public Use Forms by public and private entities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... font style as the body of the form. (2) The final form must match the design, format, and dimensions of... official form. The wording and punctuation of all data elements and identifying information must match exactly. No data elements may be added or deleted. The sequence and format for each item on the form must...

8 CFR 299.4 - Reproduction of Public Use Forms by public and private entities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... font style as the body of the form. (2) The final form must match the design, format, and dimensions of... official form. The wording and punctuation of all data elements and identifying information must match exactly. No data elements may be added or deleted. The sequence and format for each item on the form must...

75 FR 69443 - Notice of Public Information Collection(s) Being Reviewed by the Federal Communications...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... interconnection revenue does not require massive changes to the ILECs' accounting systems and is a far less...: Part 32, Uniform System of Accounts for Telecommunications Companies. Form No.: N/A. Type of Review...--other. These accounting changes are mandatory only for Class A Incumbent Local Exchange Carriers (ILECs...

Formulation of dark chocolate as a carrier to deliver eicosapentaenoic and docosahexaenoic acids: Effects on product quality.

PubMed

Toker, Omer Said; Konar, Nevzat; Palabiyik, Ibrahim; Rasouli Pirouzian, Haniyeh; Oba, Sirin; Polat, Derya Genc; Poyrazoglu, Ender Sinan; Sagdic, Osman

2018-07-15

In this study, dark chocolate enriched with EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) was developed using various forms and origins. Quality characteristics such as physical, thermo-gravimetric, rheological, textural and sensory properties of chocolates were investigated. The highest EPA/DHA stability was determined in samples prepared by free-flowing powder and microencapsulated forms of omega-3 fatty acids (FA). The L ∗ and C ∗ values varied from 32.16-33.37 and 7.45-8.09, respectively for the all samples. Hardness values ranged between 6422 and 8367 N and the use of EPA/DHA in the triglyceride form caused softer chocolate whereas control sample was the hardest sample. Melting and rheological properties were not significantly affected by the studied EPA/DHA sources (P < 0.05). Microencapsulated EPA/DHA added chocolate was the most preferred source whereas sample with algae oil showed the lowest acceptability. According to the results, dark chocolate can be used for delivering omega-3 FA by considering their origin and physical form. Copyright © 2018 Elsevier Ltd. All rights reserved.

A hybrid voice/data modulation for the VHF aeronautical channels

NASA Technical Reports Server (NTRS)

Akos, Dennis M.

1993-01-01

A method of improving the spectral efficiency of the existing Very High Frequency (VHF) Amplitude Modulation (AM) voice communication channels is proposed. The technique is to phase modulate the existing voice amplitude modulated carrier with digital data. This allows the transmission of digital information over an existing AM voice channel with no change to the existing AM signal format. There is no modification to the existing AM receiver to demodulate the voice signal and an additional receiver module can be added for processing of the digital data. The existing VHF AM transmitter requires only a slight modification for the addition of the digital data signal. The past work in the area is summarized and presented together with an improved system design and the proposed implementation.

Nonallelic heterogeneity in autosomal dominant retinitis pigmentosa with incomplete penetrance

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

Kim, S.K.; Berson, E.L.; Dryja, T.P.

1994-08-01

Retinitis pigmentosa is a group of retinal diseases in which photoreceptor cells throughout the retina degenerate. Although there is considerable genetic heterogeneity (autosomal dominant, autosomal recessive, and X-linked forms exist), there is a possibility that some clinically defined subtypes of the disease may be the result of mutations at the same locus. One possible clinically defined subtype is that of autosomal dominant retinitis pigmentosa (ADRP) with incomplete penetrance. Whereas in most families with ADRP, carriers can be clearly identified because of visual loss, ophthalmological findings, or abnormal electroretinograms (ERGs), in occasional families some obligate carriers are asymptomatic and have normalmore » or nearly normal ERGs even late in life. A recent paper reported the mapping of the diseases locus in one pedigree (designated adRP7) with ADRP with incomplete penetrance to chromosome 7p. To test the idea that ADRP with incomplete penetrance may be genetically homogeneous, we have evaluated whether a different family with incomplete penetrance also has a disease gene linked to the same region. 4 refs., 1 fig., 1 tab.« less

Tailored donor-acceptor polymers with an A-D1-A-D2 structure: controlling intermolecular interactions to enable enhanced polymer photovoltaic devices.

PubMed

Qin, Tianshi; Zajaczkowski, Wojciech; Pisula, Wojciech; Baumgarten, Martin; Chen, Ming; Gao, Mei; Wilson, Gerry; Easton, Christopher D; Müllen, Klaus; Watkins, Scott E

2014-04-23

Extensive efforts have been made to develop novel conjugated polymers that give improved performance in organic photovoltaic devices. The use of polymers based on alternating electron-donating and electron-accepting units not only allows the frontier molecular orbitals to be tuned to maximize the open-circuit voltage of the devices but also controls the optical band gap to increase the number of photons absorbed and thus modifies the other critical device parameter-the short circuit current. In fact, varying the nonchromophoric components of a polymer is often secondary to the efforts to adjust the intermolecular aggregates and improve the charge-carrier mobility. Here, we introduce an approach to polymer synthesis that facilitates simultaneous control over both the structural and electronic properties of the polymers. Through the use of a tailored multicomponent acceptor-donor-acceptor (A-D-A) intermediate, polymers with the unique structure A-D1-A-D2 can be prepared. This approach enables variations in the donor fragment substituents such that control over both the polymer regiochemistry and solubility is possible. This control results in improved intermolecular π-stacking interactions and therefore enhanced charge-carrier mobility. Solar cells using the A-D1-A-D2 structural polymer show short-circuit current densities that are twice that of the simple, random analogue while still maintaining an identical open-circuit voltage. The key finding of this work is that polymers with an A-D1-A-D2 structure offer significant performance benefits over both regioregular and random A-D polymers. The chemical synthesis approach that enables the preparation of A-D1-A-D2 polymers therefore represents a promising new route to materials for high-efficiency organic photovoltaic devices.

CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

PubMed

Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

2016-03-01

The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

Nanostructured lipid carriers for the topical delivery of tretinoin.

PubMed

Ghate, Vivek M; Lewis, Shaila A; Prabhu, Prabhakara; Dubey, Akhilesh; Patel, Nilkumar

2016-11-01

Cosmetic skin care products currently in the market demonstrate an increasing trend toward antiaging products. Selection of the right formulation approach is the key to successful consumer acceptance. Nanostructured lipid carriers (NLCs) for dermal application can render added benefits to the formulation. Tretinoin a derivative of vitamin A, is a retinoid with anti-aging and anti-acne potential. The present study was aimed at formulating NLCs of tretinoin for reducing the skin irritation potential, increasing the drug loading capacity and prolonging the duration of action. The NLCs were optimized using the response surface methodology based on the particle size. Preliminary study, suggested the use of stearic acid, oleic acid, Tween 80 and Span 60 as solid lipid, liquid lipid and surfactants respectively formed a stable dispersion. NLCs of tretinoin were prepared by hot melt microemulsion and hot melt probe sonication methods. The properties of the optimized NLCs such as morphology, size, Zeta potential, stability and in vitro drug release were investigated. Tretinoin loaded NLCs in carbopol gel showed a sustained release pattern with isopropyl alcohol as the receptor fluid compared to the marketed gel using Franz diffusion cells. Eight prepared gel formulations tested were found to follow the Higuchi model of drug release. Stability studies indicated that the formulations stored at refrigeration and room temperature showed no noticeable differences in the drug content and release profiles in vitro, after a period of 4 weeks. In vivo skin irritation test on male Wister rats indicated no irritation or erythema after application of the NLCs loaded gel repeated for a period of 7 days compared to the application of marketed tretinoin gel which showed irritation and slight erythema within 3 days. The results showed that the irritation potential of tretinoin was reduced, the drug loading was increased and the drug release was prolonged by the incorporation into the NLCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Assembling of stimuli-responsive tumor targeting polypyrrole nanotubes drug carrier system for controlled release.

PubMed

Chen, Jian; Li, Xiufang; Li, Jiawen; Li, Jianbing; Huang, Ling; Ren, Tao; Yang, Xiao; Zhong, Shian

2018-08-01

A stimuli-responsive polypyrrole (PPy) nanotubes drug carrier system has been designed to deliver anticancer drugs to tumor cells in a targeted and controlled manner. The PPy nanotubes drug carrier was fabricated by a template method. The nanotubes surface was functionalized with cleavable acylhydrazone and disulfide bonds by attaching thiolated β-cyclodextrin (β-CD). The solubilizing poly(ethylene glycol) polymer (PEG), attached with an adamantane (Ad) entity at one end and a folate (FA) entity at the other end, was introduced onto the nanotubes surface via β-cyclodextrin-adamantane interaction. The synthesized FA-PEG-Ad-β-CD-PPy showed excellent biocompatibility and low cytotoxicity for two cell lines. Doxorubicin (Dox) loaded FA-PEG-Ad-β-CD-PPy nanotubes showed a triggered in vitro drug release behavior in the presence of acidic media and reducing agents. The folate-mediated endocytosis and intracellular release of Dox-loaded nanoparticles were confirmed by fluorescence microscopy and cell viability evaluations. In the in vitro study, Dox loaded within the nanoparticles showed enhanced selectivity for cancerous cells and reduced cytotoxicity for normal cells compared to free Dox. The PPy based targeted drug vehicle shows excellent promise for drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Cementoblast Delivery for Periodontal Tissue Engineering

PubMed Central

Zhao, Ming; Jin, Qiming; Berry, Janice E.; Nociti, Francisco H.; Giannobile, William V.; Somerman, Martha J.

2008-01-01

Background Predictable periodontal regeneration following periodontal disease is a major goal of therapy. The objective of this proof of concept investigation was to evaluate the ability of cementoblasts and dental follicle cells to promote periodontal regeneration in a rodent periodontal fenestration model. Methods The buccal aspect of the distal root of the first mandibular molar was denuded of its periodontal ligament (PDL), cementum, and superficial dentin through a bony window created bilaterally in 12 athymic rats. Treated defects were divided into three groups: 1) carrier alone (PLGA polymer sponges), 2) carrier + follicle cells, and 3) carrier + cementoblasts. Cultured murine primary follicle cells and immortalized cementoblasts were delivered to the defects via biodegradable PLGA polymer sponges, and mandibulae were retrieved 3 weeks and 6 weeks post-surgery for histological evaluation. In situ hybridization, for gene expression of bone sialoprotein (BSP) and osteocalcin (OCN), and histomorphometric analysis were further done on 3-week specimens. Results Three weeks after surgery, histology of defects treated with carrier alone indicated PLGA particles, fibrous tissue, and newly formed bone scattered within the defect area. Defects treated with carrier + follicle cells had a similar appearance, but with less formation of bone. In contrast, in defects treated with carrier + cementoblasts, mineralized tissues were noted at the healing site with extension toward the root surface, PDL region, and laterally beyond the buccal plate envelope of bone. No PDL-bone fibrous attachment was observed in any of the groups at this point. In situ hybridization showed that the mineralized tissue formed by cementoblasts gave strong signals for both BSP and OCN genes, confirming its nature as cementum or bone. The changes noted at 3 weeks were also observed at 6 weeks. Cementoblast-treated and carrier alone-treated defects exhibited complete bone bridging and PDL formation, whereas follicle cell-treated defects showed minimal evidence of osteogenesis. No new cementum was formed along the root surface in the above two groups. Cementoblast-treated defects were filled with trabeculated mineralized tissue similar to, but more mature, than that seen at 3 weeks. Furthermore, the PDL region was maintained with well-organized collagen fibers connecting the adjacent bone to a thin layer of cementum-like tissue observed on the root surface. Neoplastic changes were observed at the superficial portions of the implants in two of the 6-week cementoblast-treated specimens, possibly due in part to the SV40-transformed nature of the implanted cell line. Conclusions This pilot study demonstrates that cementoblasts have a marked ability to induce mineralization in periodontal wounds when delivered via polymer sponges, while implanted dental follicle cells seem to inhibit periodontal healing. These results confirm the selective behaviors of different cell types in vivo and support the role of cementoblasts as a tool to better understand periodontal regeneration and cementogenesis. PMID:15025227

Subjective memory complaints in preclinical autosomal dominant Alzheimer disease.

PubMed

Norton, Daniel J; Amariglio, Rebecca; Protas, Hillary; Chen, Kewei; Aguirre-Acevedo, Daniel C; Pulsifer, Brendan; Castrillon, Gabriel; Tirado, Victoria; Munoz, Claudia; Tariot, Pierre; Langbaum, Jessica B; Reiman, Eric M; Lopera, Francisco; Sperling, Reisa A; Quiroz, Yakeel T

2017-10-03

To cross-sectionally study subjective memory complaints (SMC) in autosomal dominant Alzheimer disease (ADAD). We examined self-reported and study partner-based SMC in 52 young, cognitively unimpaired individuals from a Colombian kindred with early-onset ADAD. Twenty-six carried the PSEN-1 E280A mutation, averaging 7 years of age younger than the kindred's expected clinical onset. Twenty-six were age-matched noncarriers. Participants also underwent structural MRI and cognitive testing. Self-reported SMC were greater in carriers than noncarriers ( p = 0.02). Study partner-based SMC did not differ between groups ( p = 0.21), but in carriers increased with age ( r = 0.66, p < 0.001) and decreased with hippocampal volume ( r = -0.35, p = 0.08). Cognitively unimpaired PSEN-1 carriers have elevated SMC. Self-reported SMC may be a relatively early indicator of preclinical AD, while partner- reported SMC increases later in preclinical AD, closer to clinical onset. © 2017 American Academy of Neurology.

Flexible method for conjugation of phenolic lignin model compounds to carrier proteins

DOE PAGES

Gao, Ruili; Lu, Fachuang; Zhu, Yimin; ...

2016-10-03

Linking lignin model compounds to carrier proteins is required either to raise antibodies to them or to structurally screen antibodies raised against lignins or models. This paper describes a flexible method to link phenolic compounds of interest to cationic bovine serum albumin (cBSA) without interfering with their important structural features. With the guaiacylglycerol- β-guaiacyl ether dimer, for example, the linking was accomplished in 89% yield with the number of dimers per carrier protein being as high as 50; NMR experiments on a 15N- and 13C-labeled conjugation product indicated that 13 dimers were added to the native lysine residues and themore » remainder (~37) to the amine moieties on the ethylenediamine linkers added to BSA; ~32% of the available primary amine groups on cBSA were therefore conjugated to the hapten. As a result, this loading is suitable for attempting to raise new antibodies to plant lignins and for screening.« less

Circular carrier squeezing interferometry: Suppressing phase shift error in simultaneous phase-shifting point-diffraction interferometer

NASA Astrophysics Data System (ADS)

Zheng, Donghui; Chen, Lei; Li, Jinpeng; Sun, Qinyuan; Zhu, Wenhua; Anderson, James; Zhao, Jian; Schülzgen, Axel

2018-03-01

Circular carrier squeezing interferometry (CCSI) is proposed and applied to suppress phase shift error in simultaneous phase-shifting point-diffraction interferometer (SPSPDI). By introducing a defocus, four phase-shifting point-diffraction interferograms with circular carrier are acquired, and then converted into linear carrier interferograms by a coordinate transform. Rearranging the transformed interferograms into a spatial-temporal fringe (STF), so the error lobe will be separated from the phase lobe in the Fourier spectrum of the STF, and filtering the phase lobe to calculate the extended phase, when combined with the corresponding inverse coordinate transform, exactly retrieves the initial phase. Both simulations and experiments validate the ability of CCSI to suppress the ripple error generated by the phase shift error. Compared with carrier squeezing interferometry (CSI), CCSI is effective on some occasions in which a linear carrier is difficult to introduce, and with the added benefit of eliminating retrace error.

Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

NASA Astrophysics Data System (ADS)

Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

2014-03-01

The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P < 0.00001). Genotype ApoE ɛ4/ɛ4 and ɛ4/ɛ3 have statistically significant association with AD as well (ɛ4/ɛ4: OR = 11.76, 95% CI = 6.38-21.47, P < 0.00001; ɛ4/ɛ3: OR = 3.08, 95% CI = 2.57-3.69, P < 0.00001). Furthermore, the frequency of the ApoE ɛ3 is lower in AD than that in the health controls, and the difference of ɛ3 allele is also statistically significant (OR = 0.42, 95% CI = 0.37-0.47, P < 0.00001). No significant heterogeneity was observed among all studies. This meta-analysis suggests that the subject with at least one ApoE ɛ4 allele has higher risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

Two separate pathways for d-lactate oxidation by Saccharomyces cerevisiae mitochondria which differ in energy production and carrier involvement.

PubMed

Pallotta, Maria Luigia; Valenti, Daniela; Iacovino, Michelina; Passarella, Salvatore

2004-02-15

In this work we looked at whether and how mitochondria isolated from Saccharomyces cerevisiae (SCM) oxidize d-lactate. We found that: (1). externally added d-lactate causes oxygen uptake by SCM with P/O ratio equal to 1.5; in the presence of antimycin A (AA), P/O ratio was 1.8, differently in the presence of the non-penetrant alpha-cyanocinnamate (alpha-CCN-) no P/O ratio could be measured. Consistently, mitochondrial electrical membrane potential (deltapsi) generation was found, due to externally added d-lactate in the presence of antimycin A, but not of alpha-CCN-. (2). SCM oxidize d-lactate in two different manners: (i). via inner membrane d-lactate dehydrogenase which leads to d-lactate oxidation without driving deltapsi generation and ATP synthesis and (ii). via the matrix d-lactate dehydrogenase, which drives deltapsi generation and ATP synthesis by using taken up d-lactate. (3). Pyruvate newly synthesised in the mitochondrial matrix is exported via the novel d-lactate/pyruvate antiporter. d-Lactate/pyruvate antiport proved to regulate the rate of pyruvate efflux in vitro. (4). The existence of the d-lactate/H+ symporter is also proposed as shown by mitochondrial swelling. The d-lactate carriers and d-lactate dehydrogenases could account for the removal of the toxic methylglyoxal from cytosol, as well as for the d-lactate-dependent gluconeogenesis.

Synthesis, Bioconjugation and Stability Studies of [18 F] Ethenesulfonyl Fluoride.

PubMed

Zhang, Bo; Pascali, Giancarlo; Wyatt, Naomi; Matesic, Lidia; Klenner, Mitchell A; Sia, Tiffany R; Guastella, Adam J; Massi, Massimiliano; Robinson, Andrea J; Fraser, Benjamin H

2018-06-20

Fluorine-18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [ 18 F] ethenesulfonylfluoride ([ 18 F] ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [ 18 F] ESF was optimised using a microfluidic reactor under both carrier-added (c.a.) and no-carrier-added (n.c.a.) conditions, affording, in a straightforward procedure, 30-50% radiochemical yield (RCY) for c.a. [ 18 F] ESF and 60-70% RCY for n.c.a. [ 18 F] ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [ 18 F] ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging. This article is protected by copyright. All rights reserved.

Temperature dependence of exciton and charge carrier dynamics in organic thin films

NASA Astrophysics Data System (ADS)

Platt, A. D.; Kendrick, M. J.; Loth, M.; Anthony, J. E.; Ostroverkhova, O.

2011-12-01

We report on physical mechanisms behind the temperature-dependent optical absorption, photoluminescence (PL), and photoconductivity in spin-coated films of a functionalized anthradithiophene (ADT) derivative, ADT-triethylsilylethynyl (TES)-F, and its composites with C60 and another ADT derivative, ADT-TIPS-CN. Measurements of absorption and PL spectra, PL lifetimes, and transient photocurrent were performed at temperatures between 98 and 300 K as a function of applied electric field. In pristine ADT-TES-F films, absorptive and emissive species were identified to be disordered H aggregates whose properties are affected by static and dynamic disorder. The exciton bandwidths were ≤0.06 and ˜0.115 eV for absorptive and emissive aggregates, respectively, indicative of higher disorder in the emissive species. The exciton in the latter was found to be delocalized over approximately four to five molecules. The PL properties were significantly modified upon adding a guest molecule to the ADT-TES-F host. In ADT-TES-F/C60 composites, the PL was considerably quenched due to photoinduced electron transfer from ADT-TES-F to C60, while in ADT-TES-F/ADT-TIPS-CN blends, the PL was dominated by emission from an exciplex formed between ADT-TES-F and ADT-TIPS-CN molecules. In all materials, the PL quantum yield dramatically decreased as the temperature increased due to thermally activated nonradiative recombination. Considerable electric-field-induced PL quenching was observed at low temperatures at electric fields above ˜105 V/cm due to tunneling into dark states. No significant contribution of ADT-TES-F emissive exciton dissociation to transient photocurrent was observed. In all materials, charge carriers were photogenerated at sub-500-ps time scales, limited by the laser pulse width, with temperature- and electric-field-independent photogeneration efficiency. In ADT-TES-F/C60 (2%) composites, the photogeneration efficiency was a factor of 2-3 higher than that in pristine ADT-TES-F films. In ADT-TES-F/ADT-TIPS-CN (2%) blends, an additional charge carrier photogeneration component was observed at room temperature at time scales of ˜20 ns due to exciplex dissociation. At ˜0.5-5 ns after photoexcitation, the carriers propagated via thermally and electric-field-activated hopping with an activation energy of ˜0.025 eV. At time scales longer than ˜5 ns, charge transport of carriers that are not frozen in traps proceeded through tunneling via isoenergetic sites.

R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family

PubMed Central

Korvatska, Olena; Leverenz, James B.; Jayadev, Suman; McMillan, Pamela; Kurtz, Irina; Guo, Xindi; Rumbaugh, Malia; Matsushita, Mark; Girirajan, Santhosh; Dorschner, Michael O.; Kiianitsa, Kostantin; Yu, Chang-En; Brkanac, Zoran; Garden, Gwenn A.; Raskind, Wendy H.; Bird, Thomas D.

2016-01-01

Importance The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. Objective To investigate a large family with late-onset AD (LOAD), in which R47H cosegregated with 75% of cases. Design, Setting, and Participants This study includes genetic and pathologic studies of families with LOAD from 1985 to 2014. A total of 131 families with LOAD (751 individuals) were included from the University of Washington Alzheimer Disease Research Center. To identify LOAD genes/risk factors in the LOAD123 family with 21 affected members and 12 autopsies, we sequenced 4 exomes. Candidate variants were tested for cosegregation with the disease. TREM2 R47H was genotyped in an additional 130 families with LOAD. We performed clinical and neuropathological assessments of patients with and without R47H and evaluated the variant's effect on brain pathology, cellular morphology, and expression of microglial markers. Main Outcomes and Measures We assessed the effect of TREM2 genotype on age at onset and disease duration. We compared Braak and Consortium to Establish a Registry for Alzheimer's Disease scores, presence of α-synuclein and TAR DNA-binding protein 43 aggregates, and additional vascular or Parkinson pathology in TREM2 R47H carriers vs noncarriers. Microglial activation was assessed by quantitative immunohistochemistry and morphometry. Results Twelve of 16 patients with AD in the LOAD123 family carried R47H. Eleven patients with dementia had apolipoprotein E 4 (ApoE4) and R47H genotypes. We also found a rare missense variant, D353N, in a nominated AD risk gene, unc-5 homolog C (UNC5C), in 5 affected individuals in the LOAD123 family. R47H carriers demonstrated a shortened disease duration (mean [SD], 6.7 [2.8] vs 11.1 [6.6] years; 2-tailed t test; P = .04) and more frequent α-synucleinopathy. The panmicroglial marker ionized calcium-binding adapter molecule 1 was decreased in all AD cases and the decrease was most pronounced in R47H carriers (mean [SD], in the hilus: 0.114 [0.13] for R47H_AD vs 0.574 [0.26] for control individuals; 2-tailed t test; P = .005 and vs 0.465 [0.32] for AD; P = .02; in frontal cortex gray matter: 0.006 [0.004] for R47H_AD vs 0.016 [0.01] for AD; P = .04 and vs 0.033 [0.013] for control individuals; P < .001). Major histocompatibility complex class II, a marker of microglial activation, was increased in all patients with AD (AD: 2.5, R47H_AD: 2.7, and control: 1.0; P < .01). Conclusions and Relevance Our results demonstrate a complex genetic landscape of LOAD, even in a single pedigree with an apparent autosomal dominant pattern of inheritance. ApoE4, TREM2 R47H, and rare variants in other genes, such as UNC5C D353N, are likely responsible for the notable occurrence of AD in this family. Our findings support the role of the TREM2 receptor in microglial clearance of aggregation-prone proteins that is compromised in R47H carriers and may accelerate the course of disease. PMID:26076170

From Common to Rare Variants: The Genetic Component of Alzheimer Disease.

PubMed

Nicolas, Gaël; Charbonnier, Camille; Campion, Dominique

2016-01-01

Alzheimer disease (AD) is a remarkable example of genetic heterogeneity. Extremely rare variants in the APP, PSEN1, or PSEN2 genes, or duplications of the APP gene cause autosomal dominant forms, generally with complete penetrance by the age of 65 years. Nonautosomal dominant forms are considered as a complex disorder with a high genetic component, whatever the age of onset. Although genetically heterogeneous, AD is defined by the same neuropathological criteria in all configurations. According to the amyloid cascade hypothesis, the Aβ peptide, which aggregates in AD brains, is a key player. APP, PSEN1, or PSEN2 gene mutations increase the production of more aggregation-prone forms of the Aβ peptide, triggering the pathological process. Several risk factors identified in association studies hit genes involved in Aβ production/secretion, aggregation, clearance, or toxicity. Among them, the APOE ε4 allele is a rare example of a common allele with a large effect size, the ORs ranging from 4 to 11-14 for heterozygous and homozygous carriers, respectively. In addition, genome-wide association studies have identified more than two dozen loci with a weak but significant association, the OR of the at-risk allele ranging from 1.08 to 1.30. Recently, the use of massive parallel sequencing has enabled the analysis of rare variants in a genome-wide manner. Two rare variants have been nominally associated with AD risk or protection (TREM2 p.R47H, MAF approximately 0.002, OR approximately 4 and APP p.A673T, MAF approximately 0.0005, OR approximately 0.2). Association analyses at the gene level identified rare loss-of-function and missense, predicted damaging, variants (MAF <0.01) in the SORL1 and ABCA7 genes associated with a moderate relative risk (OR approximately 5 and approximately 2.8, respectively). Although the latter analyses revealed association signals with moderately rare variants by collapsing them, the power to detect genes hit by extremely rare variants is still limited. An alternative approach is to consider the de novo paradigm, stating that de novo variants may contribute to AD genetics in sporadic patients. Here, we critically review AD genetics reports with a special focus on rare variants. © 2016 S. Karger AG, Basel.

Rapid startup and high rate nitrogen removal from anaerobic sludge digester liquor using a SNAP process.

PubMed

Qiao, Sen; Nishiyama, Takashi; Fujii, Tatsuo; Bhatti, Zafar; Furukawa, Kenji

2012-02-01

In this study, a single-stage autotrophic nitrogen removal reactor, packed with a novel acrylic fiber biomass carrier material (Biofix), was applied for nitrogen removal from sludge digester liquor. For rapid start-up, conventional activated sludge was added to the reactor soon after the attachment of anammox biomass on the Biofix carriers, which allowed conventional activated sludge to form a protective layer of biofilm around the anammox biomass. The Nitrogen removal efficiency reached 75% within 1 week at a nitrogen loading rate of 0.46 kg-N/m(3)/day for synthetic wastewater treatment. By the end of the synthetic wastewater treatment period, the maximum nitrogen removal rate had increased to 0.92 kg-N/m(3)/day at a nitrogen loading rate of 1.0 kg-N/m(3)/day. High nitrogen removal rate was also achieved during the actual raw digester liquor treatment with the highest nitrogen removal rate being 0.83 kg-N/m(3)/day at a nitrogen loading rate of 0.93 kg-N/m(3)/day. The thick biofilm on Biofix carriers allowed anammox bacteria to survive under high DO concentration of 5-6 mg/l resulting in stable and high nitrogen removal performance. FISH and CLSM analysis demonstrated that anammox bacteria coexisted and surrounded by ammonium oxidizing bacteria.

Tungsten-188/carrier-free rhenium-188 perrhenic acid generator system

DOEpatents

Knapp, Jr., Furn F.; Lisic, Edward C.; Mirzadeh, Saed; Callahan, Alvin P.

1993-01-01

A generator system for providing a carrier-free radioisotope in the form of an acid comprises a chromatography column in tandem fluid connection with an ion exchange column, the chromatography column containing a charge of a radioactive parent isotope. The chromatography column, charged with a parent isotope, is eluted with an alkali metal salt solution to generate the radioisotope in the form of an intermediate solution, which is passed through the ion-exchange column to convert the radioisotope to a carrier-free acid form.

Tungsten-188/carrier-free rhenium-188 perrhenic acid generator system

DOEpatents

Knapp, F.F. Jr.; Lisic, E.C.; Mirzadeh, S.; Callahan, A.P.

1993-02-16

A generator system for providing a carrier-free radioisotope in the form of an acid comprises a chromatography column in tandem fluid connection with an ion exchange column, the chromatography column containing a charge of a radioactive parent isotope. The chromatography column, charged with a parent isotope, is eluted with an alkali metal salt solution to generate the radioisotope in the form of an intermediate solution, which is passed through the ion-exchange column to convert the radioisotope to a carrier-free acid form.

Tungsten-188/carrier-free rhenium-188 perrhenic acid generator system

DOEpatents

Knapp, Jr., Furn F.; Lisic, Edward C.; Mirzadeh, Saed; Callahan, Alvin P.

1994-01-01

A generator system for providing a carrier-free radioisotope in the form of an acid comprises a chromatography column in tandem fluid connection with an ion exchange column, the chromatography column containing a charge of a radioactive parent isotope. The chromatography column, charged with a parent isotope, is eluted with an alkali metal salt solution to generate the radioisotope in the form of an intermediate solution, which is passed through the ion-exchange column to convert the radioisotope to a carrier-free acid form.

CATEGORICAL AND CORRELATIONAL ANALYSES OF BASELINE FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IMAGES FROM THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI)

PubMed Central

Langbaum, Jessica B.S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Alexander, Gene E.; Foster, Norman L.; Weiner, Michael W.; Koeppe, Robert A.; Jagust, William J.; Reiman, Eric M.

2010-01-01

In mostly small single-center studies, Alzheimer’s disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) ε4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia. PMID:19349228

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Maladaptive decision making and substance use outcomes in high-risk individuals: preliminary evidence for the role of 5-HTTLPR variation.

PubMed

O'Brien, Jessica W; Lichenstein, Sarah D; Hill, Shirley Y

2014-07-01

Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes. Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86). HR offspring showed poorer performance overall on the IGT and especially poor performance on the final trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no significant COMT by Risk interaction. Significantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was significantly associated with an earlier age at SUD onset. This is the first study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefits during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood.

Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding.

PubMed

Zinn, K R; Chaudhuri, T R; Cheng, T P; Morris, J S; Meyer, W A

1994-02-01

Positron emission tomography offers advantages for radioimmunodiagnosis of cancer but requires radionuclides of appropriate half-life that have high specific activity and high radio-purity. This work was designed to develop a viable method to produce and purify 64Cu, which has high specific activity, for positron emission tomography. 64Cu was produced at the University of Missouri Research Reactor by the nuclear reaction, 64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially designed boron nitrite lined container, which minimized thermal neutron reactions during irradiation. A new two-step procedure was developed to chemically separate the no-carrier-added 64Cu from the zinc metal target. 64Cu recovery for 24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold. Zinc radionuclides and non-radioactive zinc were separated successfully from the 64Cu. The new separation technique was fast (2 hours total time) and highly efficient for removing the zinc. The zinc separation factor for this technique averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after separation. Thus far, the highest 64Cu specific activity at end of irradiation was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs. The boron-lined irradiation container has sufficient capacity for 75-fold larger-sized zinc targets (up to 45 g). The new separation technique was excellent for separating 64Cu, which appears to be a radionuclide with great potential for positron emission tomography.

Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers.

PubMed

Gold, Gabriel; Blouin, Jean-Louis; Herrmann, François R; Michon, Agnès; Mulligan, Reinhild; Duriaux Saïl, Geneviève; Bouras, Constantin; Giannakopoulos, Panteleimon; Antonarakis, Stylianos E

2003-05-15

Alzheimer disease (AD) is characterized neuropathologically by neurofibrillary tangles and senile plaques. A key component of plaques is A beta, a polypeptide derived from A beta-precursor protein (APP) through proteolytic cleavage catalyzed by beta and gamma-secretase. We hypothesized that sequence variation in genes BACE1 (on chromosome 11q23.3) and BACE2 (on chromosome 21q22.3), which encode two closely related proteases that seem to act as the APP beta-secretase, may represent a genetic risk factor for AD. We analyzed the frequencies of single nucleotide polymorphisms (SNPs) in BACE1 and BACE2 genes in a community-based sample of 96 individuals with late-onset AD and 170 controls selected randomly among residents of the same community. The genotype data in both study groups did not demonstrate any association between AD and BACE1 or BACE2. After stratification for APOE status, however, an association between a BACE1 polymorphism located within codon V262 and AD in APOE epsilon 4 carriers was observed (P = 0.03). We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone. Copyright 2003 Wiley-Liss, Inc.

DISSOLUTION OF LANTHANUM FLUORIDE PRECIPITATES

DOEpatents

Fries, B.A.

1959-11-10

A plutonium separatory ore concentration procedure involving the use of a fluoride type of carrier is presented. An improvement is given in the derivation step in the process for plutonium recovery by carrier precipitation of plutonium values from solution with a lanthanum fluoride carrier precipitate and subsequent derivation from the resulting plutonium bearing carrier precipitate of an aqueous acidic plutonium-containing solution. The carrier precipitate is contacted with a concentrated aqueous solution of potassium carbonate to effect dissolution therein of at least a part of the precipitate, including the plutonium values. Any remaining precipitate is separated from the resulting solution and dissolves in an aqueous solution containing at least 20% by weight of potassium carbonate. The reacting solutions are combined, and an alkali metal hydroxide added to a concentration of at least 2N to precipitate lanthanum hydroxide concomitantly carrying plutonium values.

78 FR 46319 - Polyethylene Retail Carrier Bags From Taiwan: Initiation of Anti-Circumvention Inquiry on...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...\\ The petitioners claim that there is no commercial justification for not completing the PRCB production process at the place of manufacture and instead locating the final minor finishing operation in the United... in the production process, i.e., cutting-to- size the merchandise, sealing the bag on one end to form...

Writing in Multimodal Texts: A Social Semiotic Account of Designs for Learning

ERIC Educational Resources Information Center

Bezemer, Jeff; Kress, Gunther

2008-01-01

Frequently writing is now no longer the central mode of representation in learning materials--textbooks, Web-based resources, teacher-produced materials. Still (as well as moving) images are increasingly prominent as carriers of meaning. Uses and forms of writing have undergone profound changes over the last decades, which calls for a social,…

76 FR 4994 - Agency Information Collection: Activity Under OMB Review; Report of Traffic and Capacity...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

...] Agency Information Collection: Activity Under OMB Review; Report of Traffic and Capacity Statistics--The... need for and usefulness of DOT requiring U.S. and foreign air carriers to file traffic and capacity... Title: Report of Traffic and Capacity Statistics--The T-100 System. Form No.: Schedules T-100 and T-100...

Amplitude modulation detection with concurrent frequency modulation.

PubMed

Nagaraj, Naveen K

2016-09-01

Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterization.

PubMed

Li, Shu; Yu, Tao; Tian, Yiwei; McCoy, Colin P; Jones, David S; Andrews, Gavin P

2016-09-06

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

Functionalized Nanoparticles and Nanostructures as Carriers for Organic Corrosion Inhibitors

DTIC Science & Technology

2009-02-01

TDA Research Inc.  Wheat Ridge, CO 80033 www.tda.com Clearwater Beach FL February 2-5, 2009 Report Documentation Page Form ApprovedOMB No. 0704-0188...S) AND ADDRESS(ES) TDA Research Inc, Wheat Ridge,CO,80033 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND...DTL-24441 Rust /corrosion removed (in bottom half of panel) to look for undergrowth No corrosion undergrowth, clean scribe Coating scraped to look for

Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.

PubMed

Liu, Chia-Chen; Liu, Chia-Chan; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun

2013-02-01

Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.

Apolipoprotein E and Alzheimer disease: risk, mechanisms, and therapy

PubMed Central

Liu, Chia-Chen; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun

2013-01-01

Apolipoprotein E (ApoE) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk for cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. ApoE–lipoproteins bind to several cell-surface receptors to deliver lipids and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. ApoE isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on ApoE in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different ApoE isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link ApoE4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting ApoE. PMID:23296339

Preparation and photo-catalytic activities of FeOOH/ZnO/MMT composite

NASA Astrophysics Data System (ADS)

Zhou, Yao; Liu, Fusheng; Yu, Shitao

2015-11-01

Montmorillonite (MMT) was used as the carrier for synthesis of FeOOH and FeOOH/ZnO nano-material. FeOOH and FeOOH/ZnO were synthesized by the aqueous solutions of Fe(NO3)3-HNO3 and Zn(NO3)2-NaOH/Fe(NO3)3-HNO3 with the carrier of montmorillonite respectively. Transmission electron-microscopy (TEM) and X-ray diffraction (XRD) were used to study the morphology form and structure of the nano-materials. TEM was also used to demonstrate that FeOOH/ZnO can be formed with the appropriate interface. According to UV-vis absorption spectra, FeOOH/ZnO has a better response to visible light than FeOOH and ZnO, which indicates there is some coupling effect between FeOOH and ZnO. Pentachlorophenol (PCP) was used as a representative organic pollutant to evaluate the photo-catalytic efficiency of the FeOOH/ZnO and FeOOH catalysts in visible light (λ > 400 nm). The photo-catalytic efficiency of FeOOH/ZnO/MMT is better than FeOOH/MMT. According to FTIR, changes of pH and TOC, the degradation mechanism was also discussed. PCP was degraded to aromatic ketone and chloro-hydrocarbon compounds and then to H2O, CO2 and HCl.

Missense mutation (E150K) of rhodopsin in autosomal recessive retinitis pigmentosa

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

Orth, U.; Oehlmann, R.; Gal, A.

1994-09-01

Missense or nonsense mutations of the rhodopsin gene have been implied in the pathogenesis of at least 3 different traits; autosomal dominant retinitis pigmentosa (adRP), congenital stationary night blindness (CSNB), and autosomal recessive retinitis pigmentosa (arRP). For the latter, a single patient has been reported with a nonsense mutation at codon 249 on both alleles. Heterozygous carriers of missense mutations of rhodopsin develop either adRP or CSNB depending on the particular amino acid substitution. Four of the 9 siblings from a consanguineous marriage in southern India were reported the have arRP. Mutational screening and sequencing of the rhodopsin gene revealedmore » a G-to-A transition of the first nucleotide at codon 150 in exon II, which alters glutamate to lysine. The E150K mutation was present in the 4 patients in homozygous form, whereas the parents and 2 of the siblings were heterozygotes. Two-point analysis produced a Zmax=3.46 at theta=0.00. Two unaffected siblings who are heterozygotes for the E150K mutation underwent a thorough ophthalmological and psychophysical examination. No clinical abnormalities were found although these individuals were over forty, whereas the onset of RP in their affected siblings was in the second decade. Collectively, both the genetic and clinical findings strongly suggest that the E150K mutation of rhodopsin is recessive in this family. Glu150 forms part of the CD cytoplasmic loop of rhodopsin, which has been implicated in the binding and activation of transducin. We speculate that E150K leads to RP because the mutant protein may be incapable of activating transducin. It is tempting to speculate that, in addition to mutations in the genes for rhodopsin and the {beta}-subunit of PDE, mutations in the genes for transducin may also result in arRP.« less

Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease.

PubMed

Watabe-Rudolph, M; Song, Z; Lausser, L; Schnack, C; Begus-Nahrmann, Y; Scheithauer, M-O; Rettinger, G; Otto, M; Tumani, H; Thal, D R; Attems, J; Jellinger, K A; Kestler, H A; von Arnim, C A F; Rudolph, K L

2012-02-21

DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (β-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.

In-situ generation of carrier gases for scientific analyses on Mars

NASA Technical Reports Server (NTRS)

Finn, J. E.; Sridhar, K. R.

1997-01-01

The search for useful raw materials on planetary surfaces will involve various scientific analyses of soil and rock samples. The devices performing these measurements often require inert carrier gases for moving analytes and purging instrumentation. At present, the carrier or sweep gas must be carried from Earth in a compressed gas cylinder, and so the supply of this depletable resource sets a hard limit on the (flexible) life span of the experiment. If a suitable carrier gas could be produced in-situ, then the scientific return of exploration missions could be extended and enhanced greatly. Many more samples could be analyzed, long-ranging rovers could have independent gas supplies, and designs could have added flexibility with respect to gas consumption.

49 CFR Appendix B to Part 1035 - Contract Terms and Conditions

Code of Federal Regulations, 2011 CFR

2011-10-01

... any loss thereof or damage thereto, except as hereinafter provided. (b) No carrier or party in... of the carrier by water. (b) No such carrier by water shall be liable for any loss or damage... supplied, no such carrier shall be liable for any loss or damage resulting from the perils of the lakes...

49 CFR Appendix B to Part 1035 - Contract Terms and Conditions

Code of Federal Regulations, 2014 CFR

2014-10-01

... any loss thereof or damage thereto, except as hereinafter provided. (b) No carrier or party in... of the carrier by water. (b) No such carrier by water shall be liable for any loss or damage... supplied, no such carrier shall be liable for any loss or damage resulting from the perils of the lakes...

49 CFR Appendix B to Part 1035 - Contract Terms and Conditions

Code of Federal Regulations, 2010 CFR

2010-10-01

... any loss thereof or damage thereto, except as hereinafter provided. (b) No carrier or party in... of the carrier by water. (b) No such carrier by water shall be liable for any loss or damage... supplied, no such carrier shall be liable for any loss or damage resulting from the perils of the lakes...

19 CFR 102.20 - Specific rules by tariff classification.

Code of Federal Regulations, 2013 CFR

2013-04-01

... bonds are formed between the fragmented molecules and/or added elements so that one or more of the... between the fragmented molecules and/or added elements so that one or more of the original bonds no longer... requirements of these rules by reason of a change from one classification to another merely as the result of...

Morphology Development During Deposition in OPV Low Band Gap Polymer:Bis-Fullerene Heterojunctions: Effect of a Second Solvent

NASA Astrophysics Data System (ADS)

Chen, Huipeng; Hsiao, Yu-Che; Hu, Bin; Dadmun, Mark

2014-03-01

Polymer based bulk-heterojunction solar cells, based on blends of conjugated polymers and fullerenes are one potential option for low cost renewable power generation. One way to improve power conversion efficiency (PCE) of this cell is to increase the open-circuit voltage (Voc) . It has been reported that replacing PCBM with bis-adduct fullerenes (i.e. ICBA) significantly improves Voc and PCE in P3HT device. However, for the most promising low band-gap polymer (LBP) system, replacing PCBM with ICBA gives very poor short-circuit current (Jsc) and PCE although Voc is significantly improved. As Jsc and PCE strongly depend on the morphology, we therefore tried to optimize the morphology of as-cast LBP/ICBA mixture by adding a second solvent with varying solubility to LBP and ICBA to the deposition solution. The results show that there is no change of LBP ordering by adding the second solvent regardless of its solubility. The morphology of all the as-cast samples is then determined by neutron scattering. A homogenous dispersion of ICBA in LBP is found in the sample where the second solvent is selective to LBP, giving poor PCE. Aggregates of ICBA are formed in those samples where the second solvent is selective to ICBA. The resultant morphology improves PCE by up to 246%. A quantitative analysis of neutron data shows that the interfacial area between ICBA aggregates and LBP/ICBA mixed phase is improved in these samples, which appears to facilitate charge transport and reduce the recombination of free charge carriers.

The neuropsychology of normal aging and preclinical Alzheimer’s disease

PubMed Central

Caselli, Richard J.; Locke, Dona E.C.; Dueck, Amylou C.; Knopman, David S.; Woodruff, Bryan K.; Hoffman-Snyder, Charlene; Rademakers, Rosa; Fleisher, Adam S.; Reiman, Eric M.

2013-01-01

Background An NIA-sponsored workgroup on preclinical Alzheimer’s disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods 71 apolipoprotein E (APOE) e4 homozygotes (HMZ), 194 e3/4 heterozygotes (HTZ), and 356 e4 noncarriers (NC) aged 21–87 years who were cognitively healthy underwent neuropsychological testing every two years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results There was a significant effect of age on all cognitive domains in both APOE e4 carriers and NC. A significant effect of APOE e4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross sectional comparisons did not discriminate the groups. Conclusions While cognitive aging patterns are similar in APOE e4 carriers and NC, preclinical AD is characterized by a significant e4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory sensitive measures and longitudinal design. PMID:23541188

The neuropsychology of normal aging and preclinical Alzheimer's disease.

PubMed

Caselli, Richard J; Locke, Dona E C; Dueck, Amylou C; Knopman, David S; Woodruff, Bryan K; Hoffman-Snyder, Charlene; Rademakers, Rosa; Fleisher, Adam S; Reiman, Eric M

2014-01-01

A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Aβ amyloid, cognition, and APOE genotype in healthy older adults.

PubMed

Lim, Yen Ying; Ellis, Kathryn A; Ames, David; Darby, David; Harrington, Karra; Martins, Ralph N; Masters, Colin L; Rowe, Christopher; Savage, Greg; Szoeke, Cassandra; Villemagne, Victor L; Maruff, Paul

2013-09-01

Only one study has investigated the relationship between cerebral β-amyloid (Aβ), apolipoprotein E (APOE) ε4 genotype, and cognition. Although significant relationships between cerebral Aβ and cognition were observed in ε4 carriers but not noncarriers, the magnitude of this relationship was not reported. Further, when demographic variables were controlled, the influence of APOE ε4 on the relationship between cerebral Aβ and cognition dissipated. In 144 healthy older adults who had undergone amyloid scanning and APOE ε4 genotyping in the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Flagship Study of Ageing, correlations were conducted to determine the magnitude of relationship between cerebral Aβ and cognition in ε4 carriers and noncarriers. Fisher's Z was used to compare these correlations and Cohen's q determined the magnitude of difference between correlations. Cerebral Aβ was significantly associated with tasks of visual and verbal episodic memory in APOE ε4 carriers. This association was not observed in ε4 noncarriers. The relationship between cerebral Aβ and episodic memory in ε4 carriers was significantly different from that in ε4 noncarriers, and the magnitude of this difference was small to moderate. In APOE ε 4 carriers, there is a moderate negative relationship between cerebral Aβ and episodic memory. This suggests that increased cerebral Aβ may signify the onset of preclinical AD, especially in healthy older adults who are genetically at risk for AD. Copyright © 2013 The Alzheimer's Association. All rights reserved.

Engineering cyanobacteria for direct biofuel production from CO2.

PubMed

Savakis, Philipp; Hellingwerf, Klaas J

2015-06-01

For a sustainable future of our society it is essential to close the global carbon cycle. Oxidised forms of carbon, in particular CO2, can be used to synthesise energy-rich organic molecules. Engineered cyanobacteria have attracted attention as catalysts for the direct conversion of CO2 into reduced fuel compounds. Proof of principle for this approach has been provided for a vast range of commodity chemicals, mostly energy carriers, such as short chain and medium chain alcohols. More recently, research has focused on the photosynthetic production of compounds with higher added value, most notably terpenoids. Below we review the recent developments that have improved the state-of-the-art of this approach and speculate on future developments. Copyright © 2014 Elsevier Ltd. All rights reserved.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

Development of diagnostics in the search of an explanation for toxic airline syndrome 1

PubMed Central

Schopfer, Lawrence M.; Furlong, Clement E.; Lockridge, Oksana

2010-01-01

Toxic airline syndrome is assumed to be caused by exposure to tri-cresyl phosphate, an additive in engine lubricants and hydraulic fluids, which is activated to the toxic 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP). At present there is no laboratory evidence to support intoxication of airline crew by CBDP. Our goal was to develop methods for testing in vivo exposure by identifying and characterizing biomarkers. Mass spectrometry was used to study the reaction of CBDP with human albumin, free tyrosine, and human butyrylcholinesterase. Human albumin made a covalent bond with CBDP, adding a mass of 170 to tyrosine 411 to yield the ortho-cresyl phosphotyrosine derivative. Human butyrylcholinesterase made a covalent bond with CBDP on serine 198 to yield 5 adducts with added masses of 80, 108, 156, 170, and 186. The most abundant adduct had an added mass of 80 from phosphate (HPO3), a surprising result since no pesticide or nerve agent is known to yield phosphorylated serine with an added mass of 80. The next most abundant adduct had an added mass of 170 to form ortho-cresyl phosphoserine. It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry. PMID:20447373

Tungsten-188/carrier-free rhenium-188 perrhenic acid generator system

DOEpatents

Knapp, F.F. Jr.; Lisic, E.C.; Mirzadeh, S.; Callahan, A.P.

1994-01-04

A generator system has been invented for providing a carrier-free radioisotope in the form of an acid comprises a chromatography column in tandem fluid connection with an ion exchange column, the chromatography column containing a charge of a radioactive parent isotope. The chromatography column, charged with a parent isotope, is eluted with an alkali metal salt solution to generate the radioisotope in the form of an intermediate solution, which is passed through the ion-exchange column to convert the radioisotope to a carrier-free acid form. 1 figure.

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease

PubMed Central

Troesch, Barbara; Weber, Peter; Mohajeri, M. Hasan

2016-01-01

Alzheimer’s disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or modulated neurotransmission. This seems to favor the development of hallmarks of AD particularly when combined with increased oxidative stress e.g., in apolipoprotein E (ApoE) ε4 carriers. However, as these effects can be compensated at least partially by adequate intakes of B-vitamins, achieving optimal B-vitamin status for the general population should be a public health priority. PMID:27973419

Longitudinal MRI findings from the vitamin E and Donepezil treatment study for MCI

PubMed Central

Jack, Clifford R.; Petersen, Ronald C.; Grundman, Michael; Jin, Shelia; Gamst, Anthony; Ward, Chadwick P.; Sencakova, Drahomira; Doody, Rachelle S.; Thal, Leon J.

2009-01-01

The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans. Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE ∈4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE ∈4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p < 0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI. PMID:17452062

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

PubMed

Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

2017-06-01

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

DPLL implementation in carrier acquisition and tracking for burst DS-CDMA receivers.

PubMed

Guan, Yun-feng; Zhang, Zhao-yang; Lai, Li-feng

2003-01-01

This paper presents the architectures, algorithms, and implementation considerations of the digital phase locked loop (DPLL) used for burst-mode packet DS-CDMA receivers. As we know, carrier offset is a rather challenging problem in CDMA system. According to different applications, different DPLL forms should be adopted to correct different maximum carrier offset in CDMA systems. One classical DPLL and two novel DPLL forms are discussed in the paper. The acquisition range of carrier offset can be widened by using the two novel DPLL forms without any performance degradation such as longer acquisition time or larger variance of the phase error. The maximum acquisition range is 1/(4T), where T is the symbol period. The design can be implemented by FPGA directly.

76 FR 8620 - Airworthiness Directives; Pratt & Whitney JT8D-209, -217, -217A, -217C, and -219 Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... inspection AD 97-17-04R1, and to allow automatic eddy current inspection per engine manual Section 72-33-31.... That AD currently requires revisions to the engine manufacturer's time limits section (TLS) to include... modifies the TLS of the manufacturer's engine manual and an air carrier's approved continuous airworthiness...

Open-loop radio science with a suppressed-carrier signal

NASA Technical Reports Server (NTRS)

Greenhall, C. A.

1980-01-01

When a suppressed-carrier signal is squared, the carrier reappears in doubled form. An open-loop receiver can be used to deliver a recording of a band-limited waveform containing this carrier, whose amplitude and phase can be tracked by the radio science experimenter.

The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort.

PubMed

Caroli, A; Frisoni, G B

2010-08-01

The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarker, individual values were Z-transformed and plotted against ADAS-cog scores, and sigmoid and linear fits were compared. For most biomarkers the sigmoid model fitted data significantly better than the linear model. Abeta 1-42 time course followed a steep curve, stabilizing early in the disease course. CSF tau and hippocampal volume changed later showing similar monotonous trends, reflecting disease progression. Hippocampal loss trend was steeper and occurred earlier in time in APOE epsilon4 carriers than in non-carriers. FDG-PET started changing early in time and likely followed a linear decline. In conclusion, this study provides the first evidence in favor of the dynamic biomarker model which has recently been proposed. 2010 Elsevier Inc. All rights reserved.

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

PubMed Central

Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.

2013-01-01

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels. PMID:24011543

Thin-target excitation functions and optimisation of NCA 64Cu and 66,67Ga production by deuteron induced nuclear reactions on natural zinc target, for radiometabolic therapy and for PET

NASA Astrophysics Data System (ADS)

Groppi, F.; Bonardi, M. L.; Birattari, C.; Gini, L.; Mainardi, C.; Menapace, E.; Abbas, K.; Holzwarth, U.; Stroosnijder, R. M. F.

2004-01-01

A novel method for production of No-Carrier-Added 64Cu and 66,67Ga has been developed, based on reactions induced by deuterons up to 19 MeV on Zn target. HPGe and beta (by LSC) spectrometries proved very effective to determine radionuclidic purity of 64Cu and 66,67Ga fractions. Experimental specific activity for 64Cu was measured by ET-AAS and was of the order of 700 MBq · μg -1. Radiochemical yields for 64Cu and 66,67Ga were >80% and >99%.

Shuttle Endeavour Mated to 747 SCA Takeoff for Delivery to Kennedy Space Center, Florida

NASA Image and Video Library

1991-05-02

NASA's 747 Shuttle Carrier Aircraft No. 911, with the space shuttle orbiter Endeavour securely mounted atop its fuselage, begins the ferry flight from Rockwell's Plant 42 at Palmdale, California, where the orbiter was built, to the Kennedy Space Center, Florida. At Kennedy, the space vehicle was processed and launched on orbital mission STS-49, which landed at NASA's Ames-Dryden Flight Research Facility (later redesignated Dryden Flight Research Center), Edwards, California, 16 May 1992. NASA 911, the second modified 747 that went into service in November 1990, has special support struts atop the fuselage and internal strengthening to accommodate the added weight of the orbiters.

Expression of holo and apo forms of spinach acyl carrier protein-I in leaves of transgenic tobacco plants.

PubMed Central

Post-Beittenmiller, M A; Schmid, K M; Ohlrogge, J B

1989-01-01

Acyl carrier protein (ACP) is a chloroplast-localized cofactor of fatty acid synthesis, desaturation, and acyl transfer. We have transformed tobacco with a chimeric gene consisting of the tobacco ribulose-1,5-bisphosphate carboxylase promoter and transit peptide and the sequence encoding the mature spinach ACP-I. Spinach ACP-I was expressed in the transformed plants at levels twofold to threefold higher than the endogenous tobacco ACPs as determined by protein immunoblots and assays of ACP in leaf extracts. In addition to these elevated levels of the holo form, there were high levels of apoACP-I, a form lacking the 4'-phosphopantetheine prosthetic group and not previously detected in vivo. The mature forms of both apoACP-I and holoACP-I were located in the chloroplasts, indicating that the transit peptide was cleaved and that attachment of the prosthetic group was not required for uptake into the plastid. There were also significant levels of spinach acyl-ACP-I, demonstrating that spinach ACP-I participated in tobacco fatty acid metabolism. Lipid analyses of the transformed plants indicated that the increased ACP levels caused no significant alterations in leaf lipid biosynthesis. PMID:2535529

Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3α-HSD type 2 (17β-HSD type 5), moderates the subjective effects of alcohol.

PubMed

Milivojevic, Verica; Feinn, Richard; Kranzler, Henry R; Covault, Jonathan

2014-09-01

Animal models suggest that neuroactive steroids contribute to alcohol's acute effects. We previously reported that a common nonsynonymous polymorphism, AKR1C3 2 in the gene encoding the enzyme 3α-HSD2/17β-HSD5, and a synonymous single nucleotide polymorphism (SNP), rs248793, in SRD5A1, which encodes 5α-reductase, were associated with alcohol dependence (AD). The aim of the study was to investigate whether these polymorphisms moderate subjective effects of alcohol in humans and whether AKR1C3 2 affects neuroactive steroid synthesis. Sixty-five Caucasian men (34 lighter and 31 heavier drinkers; mean age 26.2 years) participated in a double-blind laboratory study where they consumed drinks containing no ethanol or 0.8 g/kg of ethanol. Breath alcohol, heart rate (HR), and self-reported alcohol effects were measured at 40-min intervals, and genotype was examined as a moderator of alcohol's effects. Levels of the neuroactive steroid 5α-androstane-3α,17β-diol and its precursors, 3α,5α-androsterone and dihydrotestosterone, were measured at study entry using GC/MS. Initially, carriers of the AD-protective AKR1C3 2 G allele had higher levels of 5α-androstane-3α,17β-diol relative to the precursor 3α,5α-androsterone than C allele homozygotes. AKR1C3 2 G allele carriers exhibited greater increases in heart rate and stimulant and sedative effects of alcohol than C allele homozygotes. The genotype effects on sedation were observed only in heavier drinkers. The only effect of the SRD5A1 SNP was to moderate HR. There were no interactive effects of the two SNPs. The observed effects of variation in a gene encoding a neuroactive steroid biosynthetic enzyme on the rate of 17β-reduction of androsterone relative to androstanediol and on alcohol's sedative effects may help to explain the association of AKR1C3 2 with AD.

Variation in AKR1C3, which Encodes the Neuroactive Steroid Synthetic Enzyme 3α-HSD Type 2 (17β-HSD Type 5), Moderates the Subjective Effects of Alcohol

PubMed Central

Milivojevic, Verica; Feinn, Richard; Kranzler, Henry R.; Covault, Jonathan

2014-01-01

Rationale Animal models suggest that neuroactive steroids contribute to alcohol’s acute effects. We previously reported that a common non-synonymous polymorphism, AKR1C3*2 in the gene encoding the enzyme 3α-HSD2/17β-HSD5 and a synonymous SNP, rs248793, in SRD5A1, which encodes 5α-reductase, were associated with alcohol dependence (AD). Objectives To investigate whether these polymorphisms moderate subjective effects of alcohol in humans and whether AKR1C3*2 affects neuroactive steroid synthesis. Methods 65 Caucasian men (34 lighter and 31 heavier drinkers; mean age 26.2 y) participated in a double-blind laboratory study where they consumed drinks containing no ethanol or 0.8 g/kg of ethanol. Breath alcohol, heart rate (HR), and self-reported alcohol effects were measured at 40-min intervals and genotype was examined as a moderator of alcohol’s effects. Levels of the neuroactive steroid 5α-androstane-3α,17β-diol and its precursors, 3α,5α-androsterone and dihydrotestosterone, were measured at study entry using GC/MS. Results Initially, carriers of the AD-protective AK1C3*2 G-allele had higher levels of 5α-androstane-3α,17β-diol relative to the precursor 3α,5α-androsterone than C-allele homozygotes. AKR1C3*2 G-allele carriers exhibited greater increases in heart rate and stimulant and sedative effects of alcohol than C-allele homozygotes. The genotype effects on sedation were observed only in heavier drinkers. The only effect of the SRD5A1 SNP was to moderate HR. There were no interactive effects of the two SNPs. Conclusions The observed effects of variation in a gene encoding a neuroactive steroid biosynthetic enzyme on the rate of 17p–reduction of androsterone relative to androstanediol and on alcohol’s sedative effects may help to explain the association of AKR1C3*2 with AD. PMID:24838369

Carrier-mediated transport of riboflavin in the rat colon.

PubMed

Yuasa, H; Hirobe, M; Tomei, S; Watanabe, J

2000-03-01

Carriers involved in riboflavin transport have generally been presumed to be localized in the upper small intestine. However, using a closed loop technique, we found that in the rat colon the absorption of riboflavin could be significantly reduced by raising the concentration from 0.1 to 200 microM and by adding lumiflavin, an analogue of riboflavin. These results suggest that saturable transport by the carrier that is specific for riboflavin and analogues may also be involved in riboflavin absorption in the colon. At the lower concentration of 0.1 microM, carrier-mediated transport was suggested to prevail, compared with passive transport, both in the colon and the small intestine. Furthermore, carrier-mediated transport in the colon was comparable with that in the small intestine. This study is the first to suggest carrier-mediated riboflavin transport in the colon. Although the riboflavin transport system in the colon needs to be subjected to more detailed investigation of its transport functions and role in riboflavin absorption after oral administration, it would be of interest to explore potential use of this carrier as a system for drug delivery.

Introducing correlations into carrier transport simulations of disordered materials through seeded nucleation: impact on density of states, carrier mobility, and carrier statistics

NASA Astrophysics Data System (ADS)

Brown, J. S.; Shaheen, S. E.

2018-04-01

Disorder in organic semiconductors has made it challenging to achieve performance gains; this is a result of the many competing and often nuanced mechanisms effecting charge transport. In this article, we attempt to illuminate one of these mechanisms in the hopes of aiding experimentalists in exceeding current performance thresholds. Using a heuristic exponential function, energetic correlation has been added to the Gaussian disorder model (GDM). The new model is grounded in the concept that energetic correlations can arise in materials without strong dipoles or dopants, but may be a result of an incomplete crystal formation process. The proposed correlation has been used to explain the exponential tail states often observed in these materials; it is also better able to capture the carrier mobility field dependence, commonly known as the Poole-Frenkel dependence, when compared to the GDM. Investigation of simulated current transients shows that the exponential tail states do not necessitate Montroll and Scher fits. Montroll and Scher fits occur in the form of two distinct power law curves that share a common constant in their exponent; they are clearly observed as linear lines when the current transient is plotted using a log-log scale. Typically, these fits have been found appropriate for describing amorphous silicon and other disordered materials which display exponential tail states. Furthermore, we observe the proposed correlation function leads to domains of energetically similar sites separated by boundaries where the site energies exhibit stochastic deviation. These boundary sites are found to be the source of the extended exponential tail states, and are responsible for high charge visitation frequency, which may be associated with the molecular turnover number and ultimately the material stability.

Introducing correlations into carrier transport simulations of disordered materials through seeded nucleation: impact on density of states, carrier mobility, and carrier statistics.

PubMed

Brown, J S; Shaheen, S E

2018-04-04

Disorder in organic semiconductors has made it challenging to achieve performance gains; this is a result of the many competing and often nuanced mechanisms effecting charge transport. In this article, we attempt to illuminate one of these mechanisms in the hopes of aiding experimentalists in exceeding current performance thresholds. Using a heuristic exponential function, energetic correlation has been added to the Gaussian disorder model (GDM). The new model is grounded in the concept that energetic correlations can arise in materials without strong dipoles or dopants, but may be a result of an incomplete crystal formation process. The proposed correlation has been used to explain the exponential tail states often observed in these materials; it is also better able to capture the carrier mobility field dependence, commonly known as the Poole-Frenkel dependence, when compared to the GDM. Investigation of simulated current transients shows that the exponential tail states do not necessitate Montroll and Scher fits. Montroll and Scher fits occur in the form of two distinct power law curves that share a common constant in their exponent; they are clearly observed as linear lines when the current transient is plotted using a log-log scale. Typically, these fits have been found appropriate for describing amorphous silicon and other disordered materials which display exponential tail states. Furthermore, we observe the proposed correlation function leads to domains of energetically similar sites separated by boundaries where the site energies exhibit stochastic deviation. These boundary sites are found to be the source of the extended exponential tail states, and are responsible for high charge visitation frequency, which may be associated with the molecular turnover number and ultimately the material stability.

CSR: Constrained Selfish Routing in Ad-Hoc Networks

NASA Astrophysics Data System (ADS)

Bassem, Christine; Bestavros, Azer

Routing protocols for ad-hoc networks assume that the nodes forming the network are either under a single authority, or else that they would be altruistically forwarding data for other nodes with no expectation of a return. These assumptions are unrealistic since in ad-hoc networks, nodes are likely to be autonomous and rational (selfish), and thus unwilling to help unless they have an incentive to do so. Providing such incentives is an important aspect that should be considered when designing ad-hoc routing protocols. In this paper, we propose a dynamic, decentralized routing protocol for ad-hoc networks that provides incentives in the form of payments to intermediate nodes used to forward data for others. In our Constrained Selfish Routing (CSR) protocol, game-theoretic approaches are used to calculate payments (incentives) that ensure both the truthfulness of participating nodes and the fairness of the CSR protocol. We show through simulations that CSR is an energy efficient protocol and that it provides lower communication overhead in the best and average cases compared to existing approaches.

49 CFR 385.603 - Application.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Special Rules for New Entrant Non-North America-Domiciled Carriers § 385.603 Application. Link to an... Transportation (USDOT) Registration by Non-North America-Domiciled Motor Carriers; (2) Form MCS-150—Motor Carrier...

49 CFR 385.603 - Application.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Special Rules for New Entrant Non-North America-Domiciled Carriers § 385.603 Application. Link to an... Transportation (USDOT) Registration by Non-North America-Domiciled Motor Carriers; (2) Form MCS-150—Motor Carrier...

A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy.

PubMed

Milillo, Annamaria; La Carpia, Francesca; Costanzi, Stefano; D'Urbano, Vanessa; Martini, Maurizio; Lanuti, Paola; Vischini, Gisella; Larocca, Luigi M; Marchisio, Marco; Miscia, Sebastiano; Amoroso, Antonio; Gurrieri, Fiorella; Sangiorgi, Eugenio

2015-12-01

IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In ~5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.

78 FR 38341 - Federal Acquisition Regulation; Information Collection; Preaward Survey Forms (Standard Forms...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... Contractor Accounting System Respondents: 708. Responses annually: 1. Total Responses: 708. Hours per... contractor responsibility in each case. B. Annual Reporting Burden There are no Governmentwide systems for... Procurement Data System (FPDS) ad hoc report was completed identifying that in Fiscal Year (FY) 2012 an...

Prevalence of precore-defective mutant of hepatitis B virus in HBV carriers.

PubMed

Niitsuma, H; Ishii, M; Saito, Y; Miura, M; Kobayashi, K; Ohori, H; Toyota, T

1995-08-01

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

The Tim9p–Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier

PubMed Central

Curran, Sean P.; Leuenberger, Danielle; Oppliger, Wolfgang; Koehler, Carla M.

2002-01-01

The soluble Tim9p–Tim10p (Tim, translocase of inner membrane) complex of the mitochondrial intermembrane space mediates the import of the carrier proteins and is a component of the TIM22 import system. The mechanism by which the Tim9p–Tim10p complex assembles and binds the carriers is not well understood, but previous studies have proposed that the conserved cysteine residues in the ‘twin CX3C’ motif coordinate zinc and potentially generate a zinc-finger-like structure that binds to the matrix loops of the carrier proteins. Here we have purified the native and recombinant Tim9p–Tim10p complex, and show that both complexes resemble each other and consist of three Tim9p and three Tim10p. Results from inductively coupled plasma–mass spectrometry studies failed to detect zinc in the Tim9p–Tim10p complex. Instead, the cysteine residues seemingly formed disulfide linkages. The Tim9p–Tim10p complex bound specifically to the transmembrane domains of the ADP/ATP carrier, but had no affinity for Tim23p, an inner membrane protein that is inserted via the TIM22 complex. The chaperone-like Tim9p–Tim10p complex thus may prevent aggregation of the unfolded carrier proteins in the aqueous intermembrane space. PMID:11867522

Transparent ceramics and methods of preparation thereof

DOEpatents

Hollingsworth, Joel P.; Kuntz, Joshua D.; Seeley, Zachary M.; Soules, Thomas F.

2012-12-25

A method for forming a transparent ceramic preform in one embodiment includes forming a suspension of oxide particles in a solvent, wherein the suspension includes a dispersant, with the proviso that the suspension does not include a gelling agent; and uniformly curing the suspension for forming a preform of gelled suspension. A method according to another embodiment includes creating a mixture of inorganic particles, a solvent and a dispersant, the inorganic particles having a mean diameter of less than about 2000 nm; agitating the mixture; adding the mixture to a mold; and curing the mixture in the mold for gelling the mixture, with the proviso that no gelling agent is added to the mixture.

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : third quarter : [2009

DOT National Transportation Integrated Search

2009-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : second quarter : [2013

DOT National Transportation Integrated Search

2013-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : second quarter : [2012

DOT National Transportation Integrated Search

2012-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : fourth quarter : [2011

DOT National Transportation Integrated Search

2011-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : fourth quarter : [2013

DOT National Transportation Integrated Search

2013-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : first quarter : [2012

DOT National Transportation Integrated Search

2012-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : third quarter : [2010

DOT National Transportation Integrated Search

2010-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : first quarter : [2011

DOT National Transportation Integrated Search

2011-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : third quarter : [2008

DOT National Transportation Integrated Search

2008-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : first quarter : [2013

DOT National Transportation Integrated Search

2013-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : second quarter : [2010

DOT National Transportation Integrated Search

2010-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : first quarter : [2010

DOT National Transportation Integrated Search

2010-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : first quarter : [2014

DOT National Transportation Integrated Search

2014-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : first quarter : [2009

DOT National Transportation Integrated Search

2009-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : fourth quarter : [2010

DOT National Transportation Integrated Search

2010-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : third quarter : [2011

DOT National Transportation Integrated Search

2011-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : third quarter : [2013

DOT National Transportation Integrated Search

2013-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : second quarter : [2011

DOT National Transportation Integrated Search

2011-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : fourth quarter : [2008

DOT National Transportation Integrated Search

2008-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : third quarter : [2012

DOT National Transportation Integrated Search

2012-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : fourth quarter : [2009

DOT National Transportation Integrated Search

2009-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of US Air Carriers : fourth quarter : [2012

DOT National Transportation Integrated Search

2012-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : second quarter : [2009

DOT National Transportation Integrated Search

2009-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

Data Bank 10 - Form 41 Financial Schedules of U.S. Air Carriers : second quarter : [2008

DOT National Transportation Integrated Search

2008-01-01

This CD presents financial data for large certificated U.S. carriers. Schedule B-1 presents the balance sheets of the carrier's accounting reports. Schedules P-1 and P-6 contain profit and loss data (income and expense items) for the carrier's operat...

No more CKY two-forms in the NHEK

NASA Astrophysics Data System (ADS)

Mitsuka, Yoshihiro; Moutsopoulos, George

2012-02-01

We show that in the near-horizon limit of a Kerr-NUT-AdS black hole, the space of conformal Killing-Yano two-forms does not enhance and remains of dimension 2. The same holds for an analogous polar limit in the case of extremal NUT charge. We also derive the conformal Killing-Yano p-form equation for any background in an arbitrary dimension in the form of parallel transport.

Improved synthesis of no-carrier-added p-[124I]iodo-L-phenylalanine and p-[131I]iodo-L-phenylalanine for nuclear medicine applications in malignant gliomas.

PubMed

Israel, Ina; Brandau, Wolfgang; Farmakis, Georgios; Samnick, Samuel

2008-04-01

This work describes the synthesis and the tumor affinity testing of no-carrier-added (n.c.a.) p-[(124)I]iodo-L-phenyalanine ([(124)I]IPA) and n.c.a. p-[(131)I]iodo-l-phenyalanine ([(131)I]IPA) as radiopharmaceuticals for imaging brain tumors with PET and for radionuclid-based therapy, respectively. Parameters for labeling were optimized with regard to the amount of precursor, temperature and time. Thereafter, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were investigated in rat F98 glioma and in primary human A1207 and HOM-T3868 glioblastoma cells in vitro, followed by an in vivo evaluation in CD1 nu/nu mice engrafted with human glioblastoma. No-carrier-added [(124)I]IPA and n.c.a. [(131)I]IPA were obtained in 90+/-6% radiochemical yield and >99% radiochemical purity by iododestannylation of N-Boc-4-(tri-n-butylstannyl)-L-phenylalanine methylester in the presence of chloramine-T, followed by hydrolysis of the protecting groups. The total synthesis time, including the HPLC separation and pharmacological formulation, was less than 60 min and compatible with a clinical routine production. Both amino acid tracers accumulated intensively in rat and in human glioma cells. The radioactivity incorporation in tumor cells following a 15-min incubation at 37 degrees C/pH 7.4 varied from 25% to 42% of the total loaded activity per 10(6) tumor cells (296-540 cpm/1000 cells). Inhibition experiments confirmed that n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were taken up into tumor by the sodium-independent L- and ASC-type transporters. Biodistribution and whole-body imaging by a gamma-camera and a PET scanner demonstrated a high targeting level and a prolonged retention of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA within the xenotransplanted human glioblastoma and a primarily renal excretion. However, an accurate delineation of the tumors in mice was not possible by our imaging systems. Radioactivity accumulation in the thyroid and in the stomach as a secondary indication of deiodination was less than 1% of the injected dose at 24h p.i., confirming the high in vivo stability of the radiopharmaceuticals. In conclusion, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA are new promising radiopharmaceuticals, which can now be prepared in high radiochemical yields and high purity for widespread clinical applications. The specific and high-level targeting of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA to glioma cells in vitro and to glioblastoma engrafts in vivo encourages further in vivo validations to ascertain their clinical potential as agent for imaging and quantitation of gliomas with PET, and for radionuclid-based therapy, respectively.

Amyloid-beta immunotherapy: the hope for Alzheimer disease?

PubMed

Barrera-Ocampo, Alvaro; Lopera, Francisco

2016-12-30

Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.

Amyloid-beta immunotherapy: the hope for Alzheimer disease?

PubMed Central

2016-01-01

Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials. PMID:28293044

Hot-Carrier Immunity of Polycrystalline Silicon Thin Film Transistors Using Silicon Oxynitride Gate Dielectric Formed with Plasma-Enhanced Chemical Vapor Deposition

NASA Astrophysics Data System (ADS)

Kunii, Masafumi

2009-11-01

An analysis is presented of the hot-carrier degradation in a polycrystalline silicon (poly-Si) thin film transistor (TFT) with a silicon oxynitride gate dielectric formed with plasma-enhanced chemical vapor deposition. An introduction of silicon oxynitride into a gate dielectric significantly improves hot-carrier immunity even under the severe stressing mode of drain avalanche hot carriers. To compensate the initial negative shift of threshold voltage for TFTs with a silicon oxynitride gate dielectric, high-pressure water vapor annealing (HWA) is applied. A comparison of TFTs with and without HWA reveals that the improvement in hot-carrier immunity is mainly attributed to the introduction of Si≡N bonds into a gate dielectric.

A Compatible Hardware/Software Reliability Prediction Model.

DTIC Science & Technology

1981-07-22

machines. In particular, he was interested in the following problem: assu me that one has a collection of connected elements computing and transmitting...software reliability prediction model is desirable, the findings about the Weibull distribution are intriguing. After collecting failure data from several...capacitor, some of the added charge carriers are collected by the capacitor. If the added charge is sufficiently large, the information stored is changed

Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia

PubMed Central

Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L.; Tijms, Betty M.; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle

2015-01-01

IMPORTANCE Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOEε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOEgenotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia. PMID:25988462

Effect of precursor concentration and spray pyrolysis temperature upon hydroxyapatite particle size and density.

PubMed

Cho, Jung Sang; Lee, Jeong-Cheol; Rhee, Sang-Hoon

2016-02-01

In the synthesis of hydroxyapatite powders by spray pyrolysis, control of the particle size was investigated by varying the initial concentration of the precursor solution and the pyrolysis temperature. Calcium phosphate solutions (Ca/P ratio of 1.67) with a range of concentrations from 0.1 to 2.0 mol/L were prepared by dissolving calcium nitrate tetrahydrate and diammonium hydrogen phosphate in deionized water and subsequently adding nitric acid. Hydroxyapatite powders were then synthesized by spray pyrolysis at 900°C and at 1500°C, using these calcium phosphate precursor solutions, under the fixed carrier gas flow rate of 10 L/min. The particle size decreased as the precursor concentration decreased and the spray pyrolysis temperature increased. Sinterability tests conducted at 1100°C for 1 h showed that the smaller and denser the particles were, the higher the relative densities were of sintered hydroxyapatite disks formed from these particles. The practical implication of these results is that highly sinterable small and dense hydroxyapatite particles can be synthesized by means of spray pyrolysis using a low-concentration precursor solution and a high pyrolysis temperature under a fixed carrier gas flow rate. © 2015 Wiley Periodicals, Inc.

Spray-dried chestnut extract containing Lactobacillus rhamnosus cells as novel ingredient for a probiotic chestnut mousse.

PubMed

Romano, A; Blaiotta, G; Di Cerbo, A; Coppola, R; Masi, P; Aponte, M

2014-06-01

Consumers' demand for innovative probiotic products has recently increased. In previous studies, chestnuts were evaluated as substrate for the growth of lactobacilli and chestnut extract was found to enhance acid tolerance of probiotic strains. The main objectives of this study were to evaluate the suitability of chestnut extract as carrier for spray drying of two probiotic Lactobacillus rhamnosus strains and to develop a probiotic food chestnut based. The optimal settings for the spray-drying processes were defined and the loads of undamaged cells in the dried powders were quantified. Spray-dried cultures were incorporated into an anhydrous basis for chestnut mousse developed ad hoc. In this form, viable cells remained stable over 10(8) CFU g(-1) during a 3 months long storage at 15°C. Sensorial analysis did not highlighted significant differences (P < 0·05) in preference between probiotic-supplemented and control mousses. Results suggest that chestnut mousse, a food product naturally rich in antioxidant compounds, may represent an excellent carrier for probiotics delivering. To authors' knowledge, this is the first information on the survival of lactobacilli in an anhydrous basis for dessert. © 2014 The Society for Applied Microbiology.

Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells.

PubMed

Dorier, M; Brun, E; Veronesi, G; Barreau, F; Pernet-Gallay, K; Desvergne, C; Rabilloud, T; Carapito, C; Herlin-Boime, N; Carrière, M

2015-04-28

TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients.

10 CFR 40.23 - General license for carriers of transient shipments of natural uranium other than in the form of...

Code of Federal Regulations, 2012 CFR

2012-01-01

... natural uranium other than in the form of ore or ore residue. 40.23 Section 40.23 Energy NUCLEAR... carriers of transient shipments of natural uranium other than in the form of ore or ore residue. (a) A... than in the form of ore or ore residue, in amounts exceeding 500 kilograms. (b)(1) Persons generally...

10 CFR 40.23 - General license for carriers of transient shipments of natural uranium other than in the form of...

Code of Federal Regulations, 2011 CFR

2011-01-01

... natural uranium other than in the form of ore or ore residue. 40.23 Section 40.23 Energy NUCLEAR... carriers of transient shipments of natural uranium other than in the form of ore or ore residue. (a) A... than in the form of ore or ore residue, in amounts exceeding 500 kilograms. (b)(1) Persons generally...

10 CFR 40.23 - General license for carriers of transient shipments of natural uranium other than in the form of...

Code of Federal Regulations, 2013 CFR

2013-01-01

... natural uranium other than in the form of ore or ore residue. 40.23 Section 40.23 Energy NUCLEAR... carriers of transient shipments of natural uranium other than in the form of ore or ore residue. (a) A... than in the form of ore or ore residue, in amounts exceeding 500 kilograms. (b)(1) Persons generally...

10 CFR 40.23 - General license for carriers of transient shipments of natural uranium other than in the form of...

Code of Federal Regulations, 2014 CFR

2014-01-01

... natural uranium other than in the form of ore or ore residue. 40.23 Section 40.23 Energy NUCLEAR... carriers of transient shipments of natural uranium other than in the form of ore or ore residue. (a) A... than in the form of ore or ore residue, in amounts exceeding 500 kilograms. (b)(1) Persons generally...

Ultrafast Interlayer Electron Transfer in Incommensurate Transition Metal Dichalcogenide Homobilayers.

PubMed

Li, Yuanyuan; Cui, Qiannan; Ceballos, Frank; Lane, Samuel D; Qi, Zeming; Zhao, Hui

2017-11-08

Two-dimensional materials, such as graphene, transition metal dichalcogenides, and phosphorene, can be used to construct van der Waals multilayer structures. This approach has shown potentials to produce new materials that combine novel properties of the participating individual layers. One key requirement for effectively harnessing emergent properties of these materials is electronic connection of the involved atomic layers through efficient interlayer charge or energy transfer. Recently, ultrafast charge transfer on a time scale shorter than 100 fs has been observed in several van der Waals bilayer heterostructures formed by two different materials. However, information on the transfer between two atomic layers of the same type is rare. Because these homobilayers are essential elements in constructing multilayer structures with desired optoelectronic properties, efficient interlayer transfer is highly desired. Here we show that electron transfer between two monolayers of MoSe 2 occurs on a picosecond time scale. Even faster transfer was observed in homobilayers of WS 2 and WSe 2 . The samples were fabricated by manually stacking two exfoliated monolayer flakes. By adding a graphene layer as a fast carrier recombination channel for one of the two monolayers, the transfer of the photoexcited carriers from the populated to the drained monolayers was time-resolved by femtosecond transient absorption measurements. The observed efficient interlayer carrier transfer indicates that such homobilayers can be used in van der Waals multilayers to enhance their optical absorption without significantly compromising the interlayer transport performance. Our results also provide valuable information for understanding interlayer charge transfer in heterostructures.

1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease.

PubMed

Joe, Elizabeth; Medina, Luis D; Ringman, John M; O'Neill, Joseph

2018-06-16

1 H magnetic resonance spectroscopy (MRS) can reveal changes in brain biochemistry in vivo in humans and has been applied to late onset Alzheimer disease (AD). Carriers of mutations for autosomal dominant Alzheimer disease (ADAD) may show changes in levels of metabolites prior to the onset of clinical symptoms. Proton MR spectra were acquired at 1.5 T for 16 cognitively asymptomatic or mildly symptomatic mutation carriers (CDR < 1) and 11 non-carriers as part of a comprehensive cross-sectional study of preclinical ADAD. Levels of N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA), glutamate/glutamine (Glx), creatine/phosphocreate (Cr), choline (Cho), and myo-inositol (mI) in the left and right anterior cingulate and midline posterior cingulate and precuneus were compared between mutation carriers (MCs) and non-carriers (NCs) using multivariate analysis of variance with age as a covariate. Among MCs, correlations between metabolite levels and time until expected age of dementia diagnosis were calculated. MCs had significantly lower levels of NAA and Glx in the left pregenual anterior cingulate cortex, and lower levels of NAA and higher levels of mI and Cho in the precuneus compared to NCs. Increased levels of mI were seen in these regions in association with increased proximity to expected age of dementia onset. MRS shows effects of ADAD similar to those seen in late onset AD even during the preclinical period including lower levels of NAA and higher levels of mI. These indices of neuronal and glial dysfunction might serve as surrogate outcome measures in prevention studies of putative disease-modifying agents.

Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

PubMed

Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

2015-03-13

As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

Third trimester fetal heart rate predicts phenotype and mutation burden in the type 1 long QT syndrome.

PubMed

Winbo, Annika; Fosdal, Inger; Lindh, Maria; Diamant, Ulla-Britt; Persson, Johan; Wettrell, Göran; Rydberg, Annika

2015-08-01

Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=-0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (-10 beats per minute per added mutation; P<1.0×10(-23)). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted -7 beats per minute, P<0.0001. In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. © 2015 American Heart Association, Inc.

Radiation-tolerant imaging device

DOEpatents

Colella, N.J.; Kimbrough, J.R.

1996-11-19

A barrier at a uniform depth for an entire wafer is used to produce imaging devices less susceptible to noise pulses produced by the passage of ionizing radiation. The barrier prevents charge created in the bulk silicon of a CCD detector or a semiconductor logic or memory device from entering the collection volume of each pixel in the imaging device. The charge barrier is a physical barrier, a potential barrier, or a combination of both. The physical barrier is formed by an SiO{sub 2} insulator. The potential barrier is formed by increasing the concentration of majority carriers (holes) to combine with the electron`s generated by the ionizing radiation. A manufacturer of CCD imaging devices can produce radiation-tolerant devices by merely changing the wafer type fed into his process stream from a standard wafer to one possessing a barrier beneath its surface, thus introducing a very small added cost to his production cost. An effective barrier type is an SiO{sub 2} layer. 7 figs.

Radiation-tolerant imaging device

DOEpatents

Colella, Nicholas J.; Kimbrough, Joseph R.

1996-01-01

A barrier at a uniform depth for an entire wafer is used to produce imaging devices less susceptible to noise pulses produced by the passage of ionizing radiation. The barrier prevents charge created in the bulk silicon of a CCD detector or a semiconductor logic or memory device from entering the collection volume of each pixel in the imaging device. The charge barrier is a physical barrier, a potential barrier, or a combination of both. The physical barrier is formed by an SiO.sub.2 insulator. The potential barrier is formed by increasing the concentration of majority carriers (holes) to combine with the electron's generated by the ionizing radiation. A manufacturer of CCD imaging devices can produce radiation-tolerant devices by merely changing the wafer type fed into his process stream from a standard wafer to one possessing a barrier beneath its surface, thus introducing a very small added cost to his production cost. An effective barrier type is an SiO.sub.2 layer.

PLUTONIUM CARRIER METATHESIS WITH ORGANIC REAGENT

DOEpatents

Thompson, S.G.

1958-07-01

A method is described for converting a plutonium containing bismuth phosphate carrier precipitate Into a compositton more readily soluble in acid. The method consists of dissolving the bismuth phosphate precipitate in an aqueous solution of alkali metal hydroxide, and adding one of a certaia group of organic compounds, e.g., polyhydric alcohols or a-hydrorycarboxylic acids. The mixture is then heated causiing formation of a bismuth hydroxide precipitate containing plutonium which may be readily dissolved in nitric acid for further processing.

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

NASA Astrophysics Data System (ADS)

Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

2013-04-01

We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

Association between enzymatic and non-enzymatic antioxidant defense mechanism with apolipoprotein E genotypes in Alzheimer disease.

PubMed

Kharrazi, Hadi; Vaisi-Raygani, Asad; Rahimi, Zohreh; Tavilani, Haidar; Aminian, Mahdi; Pourmotabbed, Tayebeh

2008-08-01

There are evidence suggesting that APOE-varepsilon4 allele play an important role in the pathogenesis of Alzheimer's disease (AD) by reducing peripheral levels and activities of a broad spectrum of nonenzymatic and enzymatic antioxidants systems. However, the link between APOE genotype, oxidative stress, and AD has yet to be established. In this study we examined whether antioxidant defense mechanism exacerbates the risk of AD in individual carrying APOE-varepsilon4 allele in a population from Tehran, Iran. We determined the enzymatic activities of the erythrocyte Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and serum level of total antioxidant status(TAS) in various APOE genotypes in 91 patients with AD and 91 healthy subjects as control group (age and sex-matched). The results showed that the TAS level and the activities of enzymatic antioxidants CAT and GSH-Px were significantly lower and the SOD activity was significantly higher in AD patients compared to controls. The AD patients with APOE-varepsilon4 allele genotype had significantly lower serum TAS concentration and lower erythrocytes GSH-Px and CAT activities (p=0.001) but significantly higher erythrocytes Cu-Zn SOD activity (p=0.001) than the non-APOE-varepsilon4 carrier AD and the control group. In addition, the association observed between the factors involved in an antioxidant defense mechanism and APOE-varepsilon4 allele in AD increased with age of the subjects. These data indicate that the reduced serum level of TAS and activity of CAT, GSH-Px and increased SOD exacerbate the risk of AD in individuals carrying APOE-varepsilon4 allele. The reduced antioxidants defense in APOE-varepsilon4 allele carrier may contribute to beta-amyloidosis. This effect, however, is more pronounced in the AD patients older than 75 years of age. This suggests that a therapeutic modality should be considered for these subjects.

Comparison of ionic and non-ionic drug release from multi-membrane spherical aerogels.

PubMed

Veronovski, Anja; Knez, Zeljko; Novak, Zoran

2013-09-15

The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol-gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba(2+) and Ca(2+) metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca(2+) for cross-linking. However, retarded theophylline release was only obtained by using Ba(2+) for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of diagnostics in the search for an explanation of aerotoxic syndrome.

PubMed

Schopfer, Lawrence M; Furlong, Clement E; Lockridge, Oksana

2010-09-01

Aerotoxic syndrome is assumed to be caused by exposure to tricresyl phosphate, an additive in engine lubricants and hydraulic fluids that is activated to the toxic 2-(ortho-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP). Currently, there is no laboratory evidence to support intoxication of airline crew members by CBDP. Our goal was to develop methods for testing in vivo exposure by identifying and characterizing biomarkers. Mass spectrometry was used to study the reaction of CBDP with human albumin, free tyrosine, and human butyrylcholinesterase. Human albumin made a covalent bond with CBDP, adding a mass of 170amu to Tyr411 to yield the o-cresyl phosphotyrosine derivative. Human butyrylcholinesterase made a covalent bond with CBDP on Ser198 to yield five adducts with added masses of 80, 108, 156, 170, and 186amu. The most abundant adduct had an added mass of 80amu from phosphate (HPO(3)), a surprising result given that no pesticide or nerve agent is known to yield phosphorylated serine with an added mass of 80amu. The next most abundant adduct had an added mass of 170amu to form o-cresyl phosphoserine. It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry. 2010 Elsevier Inc. All rights reserved.

Phenotypic similarities between late-onset autosomal dominant and sporadic Alzheimer disease: A single-family case-control study

PubMed Central

Day, Gregory S; Musiek, Erik S; Roe, Catherine M; Norton, Joanne; Goate, Alison M; Cruchaga, Carlos; Cairns, Nigel J; Morris, John C

2016-01-01

Importance The “amyloid hypothesis” posits that disrupted amyloid-beta (Aβ) homeostasis initiates the pathological process resulting in Alzheimer disease (AD). Autosomal dominant Alzheimer disease (ADAD) has an early symptomatic onset and is caused by single gene mutations that result in overproduction of Aβ42. To the extent that “sporadic” late-onset Alzheimer disease (LOAD) also results from dysregulated Aβ42, the clinical phenotypes of ADAD and LOAD should be similar when controlling for the effects of age. Objective To use a family with late-onset ADAD caused by a presenilin 1 (PSEN1) mutation to mitigate the potential confound of age when comparing ADAD and LOAD. Design Case-control study of a family with late-onset ADAD and individuals with histopathologically-proven LOAD. Setting The Knight Alzheimer Disease Research Center, Washington University, St Louis, and other National Institutes of Aging-funded Alzheimer Disease Centers in the United States. Participants Ten PSEN1 A79V mutation carriers from multiple generations of a family with late-onset ADAD (median age-at-onset, 75.0 [63–77] years) and 12 noncarrier family members, followed at the Knight Alzheimer Disease Research Center (1985–2015); and 1115 individuals with neuropathologically confirmed LOAD (median age-at-onset, 74.0 [60–101] years) from the National Alzheimer Coordinating Center database (09/2005-12/14). Main Outcome and Measure Planned comparison of clinical characteristics between cohorts, including age at symptomatic onset, associated symptoms and signs, rates of progression, and disease duration. Results Seven (70%) mutation carriers developed AD dementia, while three are yet asymptomatic in their 7th and 8th decades of life. No differences were observed between mutation carriers and individuals with LOAD concerning age at symptomatic onset, presenting symptoms and duration, and rate of progression of dementia. Early emergence of comorbid hallucinations and delusions were observed in 57% of individuals with ADAD versus 19% of individuals with LOAD (p=.03). Three of twelve (25%) noncarriers from the PSEN1 A79V family are potential phenocopies as they also developed AD dementia (median age at onset=76.0 years). Conclusions and Relevance In this family, the amyloidogenic PSEN1 A79V mutation recapitulates the clinical attributes of LOAD. Previously reported clinical phenotypic differences between individuals with ADAD and LOAD may reflect age- or mutation-dependent effects. PMID:27454811

Internal transmission coefficient in charges carrier generation layer of graphene/Si based solar cell device

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

Rosikhin, Ahmad, E-mail: a.rosikhin86@yahoo.co.id; Winata, Toto, E-mail: toto@fi.itb.ac.id

2016-04-19

Internal transmission profile in charges carrier generation layer of graphene/Si based solar cell has been explored theoretically. Photovoltaic device was constructed from graphene/Si heterojunction forming a multilayer stuck with Si as generation layer. The graphene/Si sheet was layered on ITO/glass wafer then coated by Al forming Ohmic contact with Si. Photon incident propagate from glass substrate to metal electrode and assumed that there is no transmission in Al layer. The wavelength range spectra used in this calculation was 200 – 1000 nm. It found that transmission intensity in the generation layer show non-linear behavior and partitioned by few areas which relatedmore » with excitation process. According to this information, it may to optimize the photons absorption to create more excitation process by inserting appropriate material to enhance optical properties in certain wavelength spectra because of the exciton generation is strongly influenced by photon absorption.« less

Inspection and Analysis of Failed Transmissions

DTIC Science & Technology

2009-01-01

ABNORMAL WEAR FRONT PUMP NO ABNORMAL DETERIORATION OR WEAR, 60% PHOSPHATE COATING REMAINING ON PUMP GEAR TEETH CARRIERS AND GEARS NO ABNORMAL DETERIORATION...PHOSPHATE COATING REMAINING ON PUMP GEAR TEETH CARRIERS AND GEARS NO ABNORMAL DETERIORATION OR WEAR, SOME POLISHING ON GEAR TEETH SEALS SOFT AND PLIABLE...FRONT PUMP NO ABNORMAL DETERIORATION OR WEAR, ALL PHOSPHATE COATING REMAINING ON PUMP GEAR TEETH CARRIERS AND GEARS NO ABNORMAL DETERIORATION OR WEAR

Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease.

PubMed

Paquette, Martine; Saavedra, Yascara Grisel Luna; Poirier, Judes; Théroux, Louise; Dea, Doris; Baass, Alexis; Dufour, Robert

2018-03-01

Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD. A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study. Fifty-four (6.2%) participants carried the R46L mutation, whereas 226 (26.2%) participants carried the InsLEU mutation. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD.

KSC-08pd3239

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, the Orbital Replacement Unit Carrier, or ORUC, is lifted from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. In the foreground is the Super Lightweight Interchangeable Carrier, or SLIC. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

78 FR 66801 - Motor Carrier Safety Advisory Committee; Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee; Charter Renewal AGENCY: Federal Motor Carrier Safety... and recommendations on motor carrier safety programs and motor carrier safety regulations through a...

A critical tyrosine residue determines the uncoupling protein-like activity of the yeast mitochondrial oxaloacetate carrier.

PubMed

Luévano-Martínez, Luis A; Barba-Ostria, Carlos; Araiza-Olivera, Daniela; Chiquete-Félix, Natalia; Guerrero-Castillo, Sergio; Rial, Eduardo; Georgellis, Dimitris; Uribe-Carvajal, Salvador

2012-04-01

The mitochondrial Oac (oxaloacetate carrier) found in some fungi and plants catalyses the uptake of oxaloacetate, malonate and sulfate. Despite their sequence similarity, transport specificity varies considerably between Oacs. Indeed, whereas ScOac (Saccharomyces cerevisiae Oac) is a specific anion-proton symporter, the YlOac (Yarrowia lipolytica Oac) has the added ability to transport protons, behaving as a UCP (uncoupling protein). Significantly, we identified two amino acid changes at the matrix gate of YlOac and ScOac, tyrosine to phenylalanine and methionine to leucine. We studied the role of these amino acids by expressing both wild-type and specifically mutated Oacs in an Oac-null S. cerevisiae strain. No phenotype could be associated with the methionine to leucine substitution, whereas UCP-like activity was dependent on the presence of the tyrosine residue normally expressed in the YlOac, i.e. Tyr-ScOac mediated proton transport, whereas Phe-YlOac lost its protonophoric activity. These findings indicate that the UCP-like activity of YlOac is determined by the tyrosine residue at position 146.

Binding assessment of two arachidonic-based synthetic derivatives of adrenalin with β-lactoglobulin: Molecular modeling and chemometrics approach.

PubMed

Gholami, S; Bordbar, A K; Akvan, N; Parastar, H; Fani, N; Gretskaya, N M; Bezuglov, V V; Haertlé, T

2015-12-01

A computational approach to predict the main binding modes of two adrenalin derivatives, arachidonoyl adrenalin (AA-AD) and arachidonoyl noradrenalin (AA-NOR) with the β-lactoglubuline (BLG) as a nano-milk protein carrier is presented and assessed by comparison to the UV-Vis absorption spectroscopic data using chemometric analysis. Analysis of the spectral data matrices by using the multivariate curve resolution-alternating least squares (MCR-ALS) algorithm led to the pure concentration calculation and spectral profiles resolution of the chemical constituents and the apparent equilibrium constants computation. The negative values of entropy and enthalpy changes for both compound indicated the essential role of hydrogen bonding and van der Waals interactions as main driving forces in stabilizing protein-ligand complex. Computational studies predicted that both derivatives are situated in the calyx pose and remained in that pose during the whole time of simulation with no any significant protein structural changes which pointed that the BLG could be considered as a suitable carrier for these catecholamine compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

PubMed

Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

2004-09-01

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

78 FR 67799 - Qualification, Service, and Use of Crewmembers and Aircraft Dispatchers

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

...This final rule revises the training requirements for pilots in air carrier operations. The regulations enhance air carrier pilot training programs by emphasizing the development of pilots' manual handling skills and adding safety-critical tasks such as recovery from stall and upset. The final rule also requires enhanced runway safety training and pilot monitoring training to be incorporated into existing requirements for scenario-based flight training and requires air carriers to implement remedial training programs for pilots. The FAA expects these changes to contribute to a reduction in aviation accidents. Additionally, the final rule revises recordkeeping requirements for communications between the flightcrew and dispatch; ensures that personnel identified as flight attendants have completed flight attendant training and qualification requirements; provides civil enforcement authority for making fraudulent statements; and, provides a number of conforming and technical changes to existing air carrier crewmember training and qualification requirements. The final rule also includes provisions that provide opportunities for air carriers to modify training program requirements for flightcrew members when the air carrier operates multiple aircraft types with similar design and flight handling characteristics.

Improved electrical properties of n-type SiGe alloys

NASA Technical Reports Server (NTRS)

Scoville, A. N.; Bajgar, Clara; Vandersande, Jan; Fleurial, Jean-Pierre

1992-01-01

The effect of changes in the carrier concentration and mobility for heavily doped n-type SiGe on the electrical power factor has been investigated. It has been shown that power factors of 37-40 microV/cm-K-squared can be achieved with carrier concentrations of 2.0 - 2.5 x 10 exp 20/cu cm and mobilities of 38-40 sq cm/V-sec. Many samples with suitable carrier concentration do not have high mobilities and some rationale for this behavior is presented. Initial results are presented on fabrication of n-type samples from ultrafine powders. The emphasis in this work is to achieve thermal conductivity reductions by adding inert particles to scatter midfrequency phonons.

On supersymmetric AdS6 solutions in 10 and 11 dimensions

NASA Astrophysics Data System (ADS)

Gutowski, J.; Papadopoulos, G.

2017-12-01

We prove a non-existence theorem for smooth, supersymmetric, warped AdS 6 solutions with connected, compact without boundary internal space in D = 11 and (massive) IIA supergravities. In IIB supergravity we show that if such AdS 6 solutions exist, then the NSNS and RR 3-form fluxes must be linearly independent and certain spinor bilinears must be appropriately restricted. Moreover we demonstrate that the internal space admits an so(3) action which leaves all the fields invariant and for smooth solutions the principal orbits must have co-dimension two. We also describe the topology and geometry of internal spaces that admit such a so(3) action and show that there are no solutions for which the internal space has topology F × S 2, where F is an oriented surface.

GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.

PubMed

Lieberman, Richard; Kranzler, Henry R; Joshi, Pujan; Shin, Dong-Guk; Covault, Jonathan

2015-09-01

Genetic variation in a region of chromosome 4p12 that includes the GABAA subunit gene GABRA2 has been reproducibly associated with alcohol dependence (AD). However, the molecular mechanisms underlying the association are unknown. This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system. We examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction and next-generation RNA sequencing. mRNA expression in adult human brain was examined using the BrainCloud and BRAINEAC data sets. We found significantly lower levels of GABRA2 mRNA in neural cell cultures derived from rs279858*C-allele carriers. Levels of GABRA2 RNA were correlated with those of the other 3 chromosome 4p12 GABAA genes, but not other neural genes. Cluster analysis based on the relative RNA levels of the 4 chromosome 4p12 GABAA genes identified 2 distinct clusters of cell lines, a low-expression cluster associated with rs279858*C-allele carriers and a high-expression cluster enriched for the rs279858*T/T genotype. In contrast, there was no association of genotype with chromosome 4p12 GABAA gene expression in postmortem adult cortex in either the BrainCloud or BRAINEAC data sets. AD-associated variation in GABRA2 is associated with differential expression of the entire cluster of GABAA subunit genes on chromosome 4p12 in human iPSC-derived neural cell cultures. The absence of a parallel effect in postmortem human adult brain samples suggests that AD-associated genotype effects on GABAA expression, although not present in mature cortex, could have effects on regulation of the chromosome 4p12 GABAA cluster during neural development. Copyright © 2015 by the Research Society on Alcoholism.

Paving the way to personalized medicine: production of some theragnostic radionuclides at Brookhaven National Laboratory

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

Srivastava S. C.

2011-06-06

This paper introduces a relatively novel paradigm that involves specific individual radionuclides or radionuclide pairs that have emissions that allow pre-therapy low-dose imaging plus higher-dose therapy in the same patient. We have made an attempt to sort out and organize a number of such theragnostic radionuclides and radionuclide pairs that may potentially bring us closer to the age-long dream of personalized medicine for performing tailored low-dose molecular imaging (SPECT/CT or PET/CT) to provide the necessary pre-therapy information on biodistribution, dosimetry, the limiting or critical organ or tissue, and the maximum tolerated dose (MTD), etc. If the imaging results then warrantmore » it, it would be possible to perform higher-dose targeted molecular therapy in the same patient with the same radiopharmaceutical. A major problem that remains yet to be fully resolved is the lack of availability, in sufficient quantities, of a majority of the best candidate theragnostic radionuclides in a no-carrier-added (NCA) form. A brief description of the recently developed new or modified methods at BNL for the production of four theragnostic radionuclides, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer therapy are described.« less

High Specific Activity Tritium-Labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A High Affinity 5-HT2A Receptor-Selective Agonist Radioligand

PubMed Central

Nichols, David E.; Frescas, Stewart P.; Chemel, Benjamin R.; Rehder, Kenneth S.; Zhong, Desong; Lewin, Anita H.

2009-01-01

The title compound ([3H]INBMeO) was prepared by an O,O-dimethylation reaction of a t-BOC protected diphenolic precursor using no carrier added tritiated iodomethane in DMF with K2CO3. Removal of the t-BOC protecting group and purification by HPLC afforded an overall yield of 43%, with a radiochemical purity of 99% and specific activity of 164 Ci/mmol. The new radioligand was suitable for labeling human 5-HT2A receptors in two heterologous cell lines and had about 20-fold higher affinity than [3H]ketanserin. PMID:18468904

Shuttle Endeavour Mated to 747 SCA Taxi to Runway for Delivery to Kennedy Space Center, Florida

NASA Image and Video Library

1991-05-02

NASA's 747 Shuttle Carrier Aircraft No. 911, with the space shuttle orbiter Endeavour securely mounted atop its fuselage, taxies to the runway to begin the ferry flight from Rockwell's Plant 42 at Palmdale, California, where the orbiter was built, to the Kennedy Space Center, Florida. At Kennedy, the space vehicle was processed and launched on orbital mission STS-49, which landed at NASA's Ames-Dryden Flight Research Facility (later redesignated Dryden Flight Research Center), Edwards, California, 16 May 1992. NASA 911, the second modified 747 that went into service in November 1990, has special support struts atop the fuselage and internal strengthening to accommodate the added weight of the orbiters.

No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols

DOEpatents

Shiue, Chyng-Yann; Wolf, Alfred P.; Bai, Lan-Qin; Teng, Ren-Tui

1989-01-01

There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.

Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease

PubMed Central

Reiman, Eric M.; Chen, Kewei; Liu, Xiaofen; Bandy, Daniel; Yu, Meixiang; Lee, Wendy; Ayutyanont, Napatkamon; Keppler, Jennifer; Reeder, Stephanie A.; Langbaum, Jessica B. S.; Alexander, Gene E.; Klunk, William E.; Mathis, Chester A.; Price, Julie C.; Aizenstein, Howard J.; DeKosky, Steven T.; Caselli, Richard J.

2009-01-01

Fibrillar amyloid-beta (Aβ) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar Aβ burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar Aβ burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) ε4 allele. The 8 ε4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Aβ was significantly associated with APOE ε4 carrier status and ε4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Aβ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Aβ, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Aβ imaging in primary prevention trials. PMID:19346482

Benchmarking Customer Service Practices of Air Cargo Carriers: A Case Study Approach

DTIC Science & Technology

1994-09-01

customer toll free hotlines, comment and complaint analysis, and consumer advisory panels (Zemke and Schaaf, 1989:31-34). The correct use of any or all of... customer service criteria. The research also provides a host of customer service criteria that the researchers find important to most consumers . Bhote...AD-A285 014 DTIC ELECI’E SEP 2 9 1994 kOF4 * BENCHMARKING CUSTOMER SERVICE -, PRACTICES OF AIR CARGO CARRIERS: A CASE STUDY APPROACH THESIS Patrick D

Lumen claims of the STERRAD 100NX sterilizer: testing performance limits when processing equipment containing long, narrow lumens.

PubMed

Diab-Elschahawi, Magda; Blacky, Alexander; Bachhofner, Nicole; Koller, Walter

2011-11-01

According to manufacturers information, the STERRAD 100NX sterilizer-a low temperature H(2)O(2) gas plasma sterilizer-can adequately process single channel stainless steel lumens with an inside diameter of 0.7 mm or larger and a maximum length of 500 mm using standard cycle sterilizing conditions. The aim of this study was to qualify the performance of this H(2)O(2) gas plasma sterilizer under different experimental settings representing worst case conditions. Inoculated carriers were placed at the midpoint position of specified lumens and then submitted to flex scope sterilizing conditions. To simulate insufficient cleaning or crystalline residues, we added organic and inorganic challenges to our inoculated carriers. For experiments done with unchallenged carriers, quantitative analysis reached a log(10) reduction rate of ≥5.71, whereas qualitative results showed no growth in 24 out of 30 biologic indicators tested using flex scope half cycle conditions. Any additional kind of challenge significantly impaired the sterilization outcome. The findings of our current study emphasize the importance of a thorough validated cleaning of medical devices as well as timing for cleaning and decontamination before being exposed to the H(2)O(2) sterilization process and, furthermore, the need for strict adherence to manufacturer's recommendations. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Traumatic Brain Injury History is Associated with Earlier Age of Onset of Alzheimer Disease

PubMed Central

LoBue, Christian; Wadsworth, Hannah; Wilmoth, Kristin; Clem, Matthew; Hart, John; Womack, Kyle B.; Didehbani, Nyaz; Lacritz, Laura H.; Rossetti, Heidi C.; Cullum, C. Munro

2016-01-01

Objective This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender. Method Participants with a clinical diagnosis of AD (n=7625) were obtained from the National Alzheimer’s Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs TBI-) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset. Results Estimated AD onset differed by TBI history and Apoe4 independently (p’s <.001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI- group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p = .34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (MDifference = 2.8 & 2.7 years, respectively). These results remained unchanged when stratified by gender. Conclusions History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear. PMID:27855547

Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine carriers for Coxsackievirus A16 and Enterovirus 71.

PubMed

Zhang, Chao; Yang, Yong; Chi, Yudan; Yin, Jieyun; Yan, Lijun; Ku, Zhiqiang; Liu, Qingwei; Huang, Zhong; Zhou, Dongming

2015-09-22

Hand, foot and mouth disease (HFMD) is a major public health concern in Asia; more efficient vaccines against HFMD are urgently required. Adenoviral (Ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. Here, we describe a novel bivalent vaccine for HFMD based on the hexon-modified, E1-deleted chimpanzee adenovirus serotype 68 (AdC68). The novel vaccine candidate was generated by incorporating the neutralising epitope of Coxsackievirus A16 (CA16), PEP71, into hypervariable region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71), sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results demonstrated that these two epitopes were well presented on the virion surface and had high affinity towards specific antibodies, and VP1 of EV71 was also significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68 elicited neutralising antibodies against both CA16 and EV71, which conferred protection to suckling mice against a lethal challenge of CA16 and EV71. In summary, this study demonstrates that the hexon-modified AdC68 may represent a promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display platform for other pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Longitudinal Changes in Serum Glucose Levels are Associated with Metabolic Changes in Alzheimer's Disease Related Brain Regions.

PubMed

Burns, Christine M; Kaszniak, Alfred W; Chen, Kewei; Lee, Wendy; Bandy, Daniel J; Caselli, Richard J; Reiman, Eric M

2018-01-01

The association between longitudinal changes in serum glucose level and longitudinal changes in [18F] Fluorodeoxyglucose-PET (FDG PET) measurements of Alzheimer's disease (AD) risk are unknown. To investigate whether variation in serum glucose levels across time are associated with changes in FDG PET measurements of cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). Participants are a subset of a prospective cohort study investigating FDG PET, apolipoprotein E (APOE) ɛ4, and risk for AD which includes data from baseline, interim, and follow up visits over 4.4±1.0-years. An automated brain-mapping algorithm was utilized to characterize and compare associations between longitudinal changes in serum glucose levels and longitudinal changes in rCMRgl. This study included 80 adults aged 61.5±5 years, including 38 carriers and 42 non-carriers of the APOE ɛ4 allele. Longitudinal increases in serum glucose levels were associated with longitudinal CMRgl decline in the vicinity of parietotemporal, precuneus/posterior cingulate, and prefrontal brain regions preferentially affected by AD (p < 0.05, corrected for multiple comparisons). Findings remained significant when controlled for APOE ɛ4 status and baseline and advancing age. Additional studies are needed to clarify and confirm the relationship between longitudinal changes in peripheral glucose and FDG PET measurements of AD risk. Future findings will set the stage on the use of FDG PET in the evaluation of possible interventions that target risk factors for the development of AD.

Sex Differences in Risk for Alzheimer's Disease Related to Neurotrophin Gene Polymorphisms: The Cache County Memory Study.

PubMed

Matyi, Joshua; Tschanz, JoAnn T; Rattinger, Gail B; Sanders, Chelsea; Vernon, Elizabeth K; Corcoran, Chris; Kauwe, John S K; Buhusi, Mona

2017-11-09

Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex differences in risk. We examined four single-nucleotide polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415, rs2289656, rs2072446) and risk for AD by sex in a population-based sample of older adults. Three thousand four hundred and ninety-nine individuals without dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female] underwent dementia screening and assessment over four triennial waves. Cox regression was used to examine time to AD or right censoring for each SNP. Female carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93, 95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61% lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level significance (p = .07). The association between certain neurotrophin gene polymorphisms and AD differs by sex and may explain inconsistent findings in the literature. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

75 FR 61128 - Polyethylene Retail Carrier Bags From Malaysia: Final Results of Antidumping Duty Administrative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... INFORMATION CONTACT: Jerrold Freeman or Yang Chun, AD/CVD Operations, Office 5, Import Administration... establishments, e.g., grocery, drug, convenience, department, specialty retail, discount stores, and restaurants...

76 FR 12700 - Polyethylene Retail Carrier Bags From Thailand: Final Results of Antidumping Duty Administrative...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Richard Rimlinger, AD/CVD Operations, Office 5, Import Administration, International Trade Administration... stores, and restaurants, to their customers to package and carry their purchased products. The scope of...

78 FR 50376 - Polyethylene Retail Carrier Bags From Thailand: Final Results of Antidumping Duty Administrative...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... INFORMATION CONTACT: Dmitry Vladimirov or Minoo Hatten, AD/ CVD Operations, Office 1, Import Administration... establishments, e.g., grocery, drug, convenience, department, specialty retail, discount stores, and restaurants...

Sex modifies the APOE-related risk of developing Alzheimer disease.

PubMed

Altmann, Andre; Tian, Lu; Henderson, Victor W; Greicius, Michael D

2014-04-01

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer's Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis. © 2014 American Neurological Association.

Prevalence of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon.

PubMed

El Ariss, Abdel Badih; Younes, Mohamad; Matar, Jad; Berjaoui, Zeina

2016-01-01

The objective of this study was to assess the prevalence, gender differences, and time trends of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon, as well as to highlight the importance of screening for Sickle Cell Trait carriers in this population. Another objective was to describe a new screening technique for Sickle Cell Trait carriers. This was a retrospective cohort study carried out at a private laboratory in the Southern Suburb of Beirut, Lebanon between 2002 and 2014. The sickling test was carried out for each patient using two methods: the classical "sodium metabisulfite sickling test", and the new "sickling test method" used in the private lab. As a confirmatory test, hemoglobin electrophoresis was run on a random sample of 223 cases which were found to be positive using the two sickling tests. A total of 899 cases were found to be positive for the sickle cell trait out of 184,105 subjects screened during the 12-year period, prevalence = 0.49% (95% CI: 0.46 - 0.52). Among the total sample, females were found to have higher prevalence, where no time trend over the studied period was noted. The haemoglobin electrophoresis method confirmed the results of this new sickling test technique among the random sample of the 223 cases. We found that the prevalence of sickle cell trait is lower as compared to other Arab countries, higher in females, with no significant time trend. The sickle cell test was found to be an accurate, simple and cheap test that could be easily added as a requirement for the pre-marital testing to screen for Sickle Cell Trait carriers.

Prevalence of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon

PubMed Central

El Ariss, Abdel Badih; Younes, Mohamad; Matar, Jad; Berjaoui, Zeina

2016-01-01

Objective The objective of this study was to assess the prevalence, gender differences, and time trends of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon, as well as to highlight the importance of screening for Sickle Cell Trait carriers in this population. Another objective was to describe a new screening technique for Sickle Cell Trait carriers. Methods This was a retrospective cohort study carried out at a private laboratory in the Southern Suburb of Beirut, Lebanon between 2002 and 2014. The sickling test was carried out for each patient using two methods: the classical “sodium metabisulfite sickling test”, and the new “sickling test method” used in the private lab. As a confirmatory test, hemoglobin electrophoresis was run on a random sample of 223 cases which were found to be positive using the two sickling tests. Results A total of 899 cases were found to be positive for the sickle cell trait out of 184,105 subjects screened during the 12-year period, prevalence = 0.49% (95% CI: 0.46 – 0.52). Among the total sample, females were found to have higher prevalence, where no time trend over the studied period was noted. The haemoglobin electrophoresis method confirmed the results of this new sickling test technique among the random sample of the 223 cases. Conclusion We found that the prevalence of sickle cell trait is lower as compared to other Arab countries, higher in females, with no significant time trend. The sickle cell test was found to be an accurate, simple and cheap test that could be easily added as a requirement for the pre-marital testing to screen for Sickle Cell Trait carriers. PMID:26977274

Experience from start-ups of the first ANITA Mox plants.

PubMed

Christensson, M; Ekström, S; Andersson Chan, A; Le Vaillant, E; Lemaire, R

2013-01-01

ANITA™ Mox is a new one-stage deammonification Moving-Bed Biofilm Reactor (MBBR) developed for partial nitrification to nitrite and autotrophic N-removal from N-rich effluents. This deammonification process offers many advantages such as dramatically reduced oxygen requirements, no chemical oxygen demand requirement, lower sludge production, no pre-treatment or requirement of chemicals and thereby being an energy and cost efficient nitrogen removal process. An innovative seeding strategy, the 'BioFarm concept', has been developed in order to decrease the start-up time of new ANITA Mox installations. New ANITA Mox installations are started with typically 3-15% of the added carriers being from the 'BioFarm', with already established anammox biofilm, the rest being new carriers. The first ANITA Mox plant, started up in 2010 at Sjölunda wastewater treatment plant (WWTP) in Malmö, Sweden, proved this seeding concept, reaching an ammonium removal rate of 1.2 kgN/m³ d and approximately 90% ammonia removal within 4 months from start-up. This first ANITA Mox plant is also the BioFarm used for forthcoming installations. Typical features of this first installation were low energy consumption, 1.5 kW/NH4-N-removed, low N₂O emissions, <1% of the reduced nitrogen and a very stable and robust process towards variations in loads and process conditions. The second ANITA Mox plant, started up at Sundets WWTP in Växjö, Sweden, reached full capacity with more than 90% ammonia removal within 2 months from start-up. By applying a nitrogen loading strategy to the reactor that matches the capacity of the seeding carriers, more than 80% nitrogen removal could be obtained throughout the start-up period.

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis.

PubMed

Adams, Crystal

2016-02-18

The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads.

40 CFR 180.930 - Inert ingredients applied to animals; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... clay Solid diluent, carrier Barium sulfate (CAS Reg. No. 7727-43-7) Carrier, density control agent...-Difluoroethane (CAS Reg. No. 75-37-6) For aerosol pesticide formulations used for insect control in food- and... tris-12-hydroxystearate Flow control agent Graphite Solid diluent, carrier n-Hexyl alcohol (CAS Reg. No...

Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency.

PubMed

Nagasaka, Hironori; Yorifuji, Tohru; Egawa, Hiroto; Inui, Ayano; Fujisawa, Tomoo; Komatsu, Haruki; Tsukahara, Hirokazu; Uemoto, Shinji; Inomata, Yukihiro

2013-07-01

Urea cycle deficient patients with prominent hyperammonemic often exhibit abnormal production of nitric oxide (NO), which reduces vascular tone, along with amino acid abnormalities. However, information related to the metabolic changes in heterozygotes of ornithine transcarbamylase deficiency (OTCD) lacking overt hyperammonemia is quite limited. We examined vascular mediators and amino acids in non-hyperammonemic heterozygotes. Twenty-four heterozygous OTCD adult females without hyperammonemic bouts, defined as non-hyperammonemic carriers, were enrolled. We measured blood amino acids constituting urea cycle and nitric oxide (NO) cycle. Blood concentrations of nitrate/nitrite (NOx) as stable NO-metabolites, asymmetric dimethylarginine (ADMA) inhibiting NO synthesis, and endothelin-1 (ET-1) raising vascular tone were also determined. NOx concentrations were significantly lower in non-hyperammonemic carriers (p < 0.01). However, ADMA and ET-1 levels in this group were comparable to those in the age-matched control group. Arginine and citrulline levels were also significantly lower in non-hyperammonemic carriers than in controls (p < 0.01). Of the 24 non-hyperammonemic carriers, 10 often developed headaches. Their daily NOx and arginine levels were significantly lower than those in headache-free carriers (p < 0.05). In three carriers receiving oral l-arginine, blood NOx concentrations were significantly higher. In two of those three, the occurrence of headaches was decreased. These results suggest that NO cycle coupling with the urea cycle is altered substantially even in non-hyperammonemic OTCD carriers, predisposing them to headaches. Copyright © 2013 Elsevier Inc. All rights reserved.

The X linked recessive form of XY gonadal dysgenesis with a high incidence of gonadal germ cell tumours: clinical and genetic studies.

PubMed

Mann, J R; Corkery, J J; Fisher, H J; Cameron, A H; Mayerová, A; Wolf, U; Kennaugh, A A; Woolley, V

1983-08-01

Five phenotypic females in one family had the genotype 46,XY and all had gonadal germ cell tumours. Studies of the family pedigree suggest that this form of XY gonadal dysgenesis is inherited in an X linked recessive manner. G banding of elongated metaphase chromosomes from two subjects with XY gonadal dysgenesis and a female carrier showed no aberrations of the X chromosome. The titres of H-Y antigen in three girls with XY gonadal dysgenesis were in the male control range. Thus it appears that, in the X linked form, XY gonadal dysgenesis may be caused by a point deletion or mutation of a gene on the X chromosome, which controls the gonad specific receptor for the H-Y antigen. Studies of Xg blood groups were uninformative about linkage of Xg with the X borne gene causing the XY gonadal dysgenesis. Dermatoglyphic studies in the girls with XY gonadal dysgenesis and female carriers revealed high a-b palmar ridge counts and a tendency for the A mainline to terminate in the thenar area. Both of these features have been described in patients with Turner's syndrome.

THERMAL INSULATION SYSTEMS

NASA Technical Reports Server (NTRS)

Augustynowicz, Stanislaw D. (Inventor); Fesmire, James E. (Inventor)

2005-01-01

Thermal insulation systems and with methods of their production. The thermal insulation systems incorporate at least one reflection layer and at least one spacer layer in an alternating pattern. Each spacer layer includes a fill layer and a carrier layer. The fill layer may be separate from the carrier layer, or it may be a part of the carrier layer, i.e., mechanically injected into the carrier layer or chemically formed in the carrier layer. Fill layers contain a powder having a high surface area and low bulk density. Movement of powder within a fill layer is restricted by electrostatic effects with the reflection layer combined with the presence of a carrier layer, or by containing the powder in the carrier layer. The powder in the spacer layer may be compressed from its bulk density. The thermal insulation systems may further contain an outer casing. Thermal insulation systems may further include strips and seams to form a matrix of sections. Such sections serve to limit loss of powder from a fill layer to a single section and reduce heat losses along the reflection layer.

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

PubMed Central

van den Broek, Alexandra J; de Ruiter, Karen; van 't Veer, Laura J; Tollenaar, Rob A E M; van Leeuwen, Flora E; Verhoef, Senno; Schmidt, Marjanka K

2015-01-01

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a ‘triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria. PMID:25138101

Preclinical cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers in Swedish familial Alzheimer's disease.

PubMed

Thordardottir, Steinunn; Ståhlbom, Anne Kinhult; Ferreira, Daniel; Almkvist, Ove; Westman, Eric; Zetterberg, Henrik; Eriksdotter, Maria; Blennow, Kaj; Graff, Caroline

2015-01-01

It is currently believed that therapeutic interventions will be most effective when introduced at the preclinical stage of Alzheimer's disease (AD). This underlines the importance of biomarkers to detect AD pathology in vivo before clinical disease onset. To examine the evolution of cerebrospinal fluid (CSF) biomarker and brain structure changes in the preclinical phase of familial AD. The study included members from four Swedish families at risk for carrying an APPswe, APParc, PSEN1 H163Y, or PSEN1 I143T mutation. Magnetic resonance imaging (MRI) scans were obtained from 13 mutation carriers (MC) and 20 non-carriers (NC) and analyzed using vertex-based analyses of cortical thickness and volume. CSF was collected from 10 MC and 12 NC from familial AD families and analyzed for Aβ42, total tau (T-tau) and phospho-tau (P-tau). The MC had significantly lower levels of CSF Aβ42 and higher levels T-tau and P-tau than the NC. There was a trend for a decrease in Aβ42 15-20 years before expected onset of clinical symptoms, while increasing T-tau and P-tau was not found until close to the expected clinical onset. The MC had decreased volume on MRI in the left precuneus, superior temporal gyrus, and fusiform gyrus. Aberrant biomarker levels in CSF as well as regional brain atrophy are present in preclinical familial AD, several years before the expected onset of clinical symptoms.

Ordering Molecular Genetic Tests and Reporting Results

PubMed Central

Lubin, Ira M.; Caggana, Michele; Constantin, Carolyn; Gross, Susan J.; Lyon, Elaine; Pagon, Roberta A.; Trotter, Tracy L.; Wilson, Jean Amos; McGovern, Margaret M.

2008-01-01

Previous studies have suggested that patient care may be compromised as a consequence of poor communication between clinicians and laboratory professionals in cases in which molecular genetic test results are reported. To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms. We found instances in which result reports for simulated diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis. Similarly, reports based on simulated scenarios for carrier testing were problematic when no mutations were identified, and the patient's race/ethnicity and family history were not discussed in reference to residual risk of disease. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency. These findings are reviewed in light of what efforts should be taken to improve the quality of test-ordering and result-reporting practices. PMID:18669879

Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks.

PubMed

Didic, Mira; Felician, Olivier; Gour, Natalina; Bernard, Rafaelle; Pécheux, Christophe; Mundler, Olivier; Ceccaldi, Mathieu; Guedj, Eric

2015-09-01

The ε4 allele of the apolipoprotein E (APO-E4) gene, a genetic risk factor for Alzheimer's disease (AD), also modulates brain metabolism and function in healthy subjects. The aim of the present study was to explore cerebral metabolism using FDG PET in healthy APO-E4 carriers by comparing cognitively normal APO-E4 carriers to noncarriers and to assess if patterns of metabolism are correlated with performance on cognitive tasks. Moreover, metabolic connectivity patterns were established in order to assess if the organization of neural networks is influenced by genetic factors. Whole-brain PET statistical analysis was performed at voxel-level using SPM8 with a threshold of p < 0.005, corrected for volume, with age, gender and level of education as nuisance variables. Significant hypometabolism between APO-E4 carriers (n = 11) and noncarriers (n = 30) was first determined. Mean metabolic values with clinical/neuropsychological data were extracted at the individual level, and correlations were searched using Spearman's rank test in the whole group. To evaluate metabolic connectivity from metabolic cluster(s) previously identified in the intergroup comparison, voxel-wise interregional correlation analysis (IRCA) was performed between groups of subjects. APO-E4 carriers had reduced metabolism within the left anterior medial temporal lobe (MTL), where neuropathological changes first appear in AD, including the entorhinal and perirhinal cortices. A correlation between metabolism in this area and performance on the DMS48 (delayed matching to sample-48 items) was found, in line with converging evidence involving the perirhinal cortex in object-based memory. Finally, a voxel-wise IRCA revealed stronger metabolic connectivity of the MTL cluster with neocortical frontoparietal regions in carriers than in noncarriers, suggesting compensatory metabolic networks. Exploring cerebral metabolism using FDG PET can contribute to a better understanding of the influence of genetic factors on cerebral metabolism at both the local and network levels leading to phenotypical variations of the healthy brain and selective vulnerability.

Monitoring nitrite and nitrate residues in frankfurters during processing and storage.

PubMed

Pérez-Rodríguez, M L; Bosch-Bosch, N; Garciá-Mata, M

1996-09-01

Frankfurter-type sausages were prepared in a pilot plant with different concentrations of NaNO(2) (75, 125 or 250 ppm) combined or not with 200 ppm KNO(3). A meat system, free of curing agents, was also used as control. Nitrite and nitrate levels were tested in various processing steps and over 120 days storage at 3 °C of the vacuum-packaged frankfurters. Little influence of the originally added nitrite level on the amount of nitrate formed was observed. Important losses of nitrite and nitrate were due to cooking. Thereafter about 50% of the nitrite added initially remained in this form in all samples (39, 59 and 146 ppm, respectively) and between 10 and 15% as nitrate. When only nitrate was initially added, formation of nitrite after cooking was observed (maximum level 43 ppm NaNO(2)). Formulations prepared with both nitrate and nitrite showed no significant differences (p < 0.01) respect to their nitrite or nitrate counterparts. A good correlation among nitrite and nitrate levels and storage time was showed by multiple linear regression analysis. It is concluded that the use of nitrate in combination with nitrite in cooked meat products seems to have little technological significance and adds to the total body burden of nitrite.

Genetic association between Alzheimer disease and the alpha-synuclein gene.

PubMed

Matsubara, M; Yamagata, H; Kamino, K; Nomura, T; Kohara, K; Kondo, I; Miki, T

2001-01-01

alpha-Synuclein has been isolated as a component of amyloid in addition to the major A beta peptide in Alzheimer disease (AD). However, there are conflicting reports regarding the association of alpha-synuclein gene polymorphism with AD. Using a novel and common polymorphism in intron 3, we examined the relationship between AD and alpha-synuclein and apolipoprotein E (ApoE) genes in 183 Japanese AD patients and 210 controls. Carriers of the alpha-synuclein deletion (D) allele had a 2.2-fold increased risk of developing AD than noncarriers in women. The odds ratio for the ApoE epsilon 4 and the alpha-synuclein D allele was 11.4 in women. The results showed that the alpha-synuclein gene is associated with sporadic AD in women, independent of ApoE epsilon 4 status. Copyright 2001 S. Karger AG, Basel

Analysis of Soldier Radio Waveform Performance in Operational Test

DTIC Science & Technology

2015-05-01

different frequencies based on carrier, uplink/downlink, and generation. In general, 2G and 3G cellular phones operate at 850 MHz uplink, and 1,900 MHz...spectrum management that may not be operationally feasible. These issues are not unique to SRW, but rather have plagued the mobile ad-hoc network... mobile ad-hoc network (MANET), enabling communication through a self-configuring, infrastructure-less network of mobile nodes. In the SS domain, these

Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

PubMed

Shamash, Jana; Rienstein, Shlomit; Wolf-Reznik, Haike; Pras, Elon; Dekel, Michal; Litmanovitch, Talia; Brengauz, Masha; Goldman, Boleslav; Yonath, Hagith; Dor, Jehoshua; Levron, Jacob; Aviram-Goldring, Ayala

2011-01-01

Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

47 CFR 64.2500 - Prohibited agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) MISCELLANEOUS... Prohibited agreements. (a) No common carrier shall enter into any contract, written or oral, that would in...) No common carrier shall enter into or enforce any contract, written or oral, that would in any way...

75 FR 23670 - Polyethylene Retail Carrier Bags from the Socialist Republic of Vietnam: Countervailing Duty Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... Calvert or Jun Jack Zhao, AD/CVD Operations, Office 6, Import Administration, International Trade..., convenience, department, specialty retail, discount stores, and restaurants to their customers to package and...

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

Gao, Ruili; Lu, Fachuang; Zhu, Yimin

Linking lignin model compounds to carrier proteins is required either to raise antibodies to them or to structurally screen antibodies raised against lignins or models. This paper describes a flexible method to link phenolic compounds of interest to cationic bovine serum albumin (cBSA) without interfering with their important structural features. With the guaiacylglycerol- β-guaiacyl ether dimer, for example, the linking was accomplished in 89% yield with the number of dimers per carrier protein being as high as 50; NMR experiments on a 15N- and 13C-labeled conjugation product indicated that 13 dimers were added to the native lysine residues and themore » remainder (~37) to the amine moieties on the ethylenediamine linkers added to BSA; ~32% of the available primary amine groups on cBSA were therefore conjugated to the hapten. As a result, this loading is suitable for attempting to raise new antibodies to plant lignins and for screening.« less

Occurrence of the malate-aspartate shuttle in various tumor types.

PubMed

Greenhouse, W V; Lehninger, A L

1976-04-01

The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.

KSC-08pd3240

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, workers watch as the Orbital Replacement Unit Carrier, or ORUC, is lowered from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. In the foreground is the Super Lightweight Interchangeable Carrier, or SLIC. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

Improvement of the butanol production selectivity and butanol to acetone ratio (B:A) by addition of electron carriers in the batch culture of a new local isolate of Clostridium acetobutylicum YM1.

PubMed

Nasser Al-Shorgani, Najeeb Kaid; Kalil, Mohd Sahaid; Wan Yusoff, Wan Mohtar; Shukor, Hafiza; Hamid, Aidil Abdul

2015-12-01

Improvement in the butanol production selectivity or enhanced butanol:acetone ratio (B:A) is desirable in acetone-butanol-ethanol (ABE) fermentation by Clostridium strains. In this study, artificial electron carriers were added to the fermentation medium of a new isolate of Clostridium acetobutylicum YM1 in order to improve the butanol yield and B:A ratio. The results revealed that medium supplementation with electron carriers changed the metabolism flux of electron and carbon in ABE fermentation by YM1. A decrease in acetone production, which subsequently improved the B:A ratio, was observed. Further improvement in the butanol production and B:A ratios were obtained when the fermentation medium was supplemented with butyric acid. The maximum butanol production (18.20 ± 1.38 g/L) was gained when a combination of methyl red and butyric acid was added. Although the addition of benzyl viologen (0.1 mM) and butyric acid resulted in high a B:A ratio of 16:1 (800% increment compared with the conventional 2:1 ratio), the addition of benzyl viologen to the culture after 4 h resulted in the production of 18.05 g/L butanol. Manipulating the metabolic flux to butanol through the addition of electron carriers could become an alternative strategy to achieve higher butanol productivity and improve the B:A ratio. Copyright © 2015 Elsevier Ltd. All rights reserved.

Longitudinal patterns of semantic and episodic memory in frontotemporal lobar degeneration and Alzheimer's disease.

PubMed

Xie, Sharon X; Libon, David J; Wang, Xingmei; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Khan, Alea; Chatterjee, Anjan; Coslett, H Branch; Hurtig, Howard I; Liang, Tsao-Wei; Grossman, Murray

2010-03-01

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer's disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype.

14 CFR 205.4 - Filing of evidence of insurance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... commuter air carriers and air taxi operators, and OST Form 6411 for foreign air carriers, including Canadian air taxi operators. The Department may return the certificate or self-insurance plan to the... Headquarters, AAL-230, 222 West 7th Avenue, Box 14, Anchorage, Alaska 99513. For Canadian air taxis, the forms...

14 CFR 205.4 - Filing of evidence of insurance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... commuter air carriers and air taxi operators, and OST Form 6411 for foreign air carriers, including Canadian air taxi operators. The Department may return the certificate or self-insurance plan to the... Headquarters, AAL-230, 222 West 7th Avenue, Box 14, Anchorage, Alaska 99513. For Canadian air taxis, the forms...

Mitochondrial carrier family inventory of Trypanosoma brucei brucei: Identification, expression and subcellular localisation.

PubMed

Colasante, Claudia; Peña Diaz, P; Clayton, Christine; Voncken, Frank

2009-10-01

The mitochondrial carrier family (MCF) is a group of structurally conserved proteins that mediate the transport of a wide range of metabolic intermediates across the mitochondrial inner membrane. In this paper, an overview of the mitochondrial carrier proteins (MCPs) of the early-branching kinetoplastid parasite Trypanosoma brucei brucei is presented. Sequence analysis and phylogenetic reconstruction gave insight into the evolution and conservation of the 24 identified TbMCPs; for most of these, putative transport functions could be predicted. Comparison of the kinetoplastid MCP inventory to those previously reported for other eukaryotes revealed remarkable deviations: T. b. brucei lacks genes encoding some prototypical MCF members, such as the citrate carrier and uncoupling proteins. The in vivo expression of the identified TbMCPs in the two replicating life-cycle forms of T. b. brucei, the bloodstream-form and procyclic-form, was quantitatively assessed at the mRNA level by Northern blot analysis. Immunolocalisation studies confirmed that majority of the 24 identified TbMCPs is found in the mitochondrion of procyclic-form T. b. brucei.

A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

PubMed

Athan, E S; Williamson, J; Ciappa, A; Santana, V; Romas, S N; Lee, J H; Rondon, H; Lantigua, R A; Medrano, M; Torres, M; Arawaka, S; Rogaeva, E; Song, Y Q; Sato, C; Kawarai, T; Fafel, K C; Boss, M A; Seltzer, W K; Stern, Y; St George-Hyslop, P; Tycko, B; Mayeux, R

2001-11-14

Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.

Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity

PubMed Central

Scaria, Puthupparampil V.; Jones, David S.; Barnafo, Emma; Fischer, Elizabeth R.; Anderson, Charles; MacDonald, Nicholas J.; Lambert, Lynn; Rausch, Kelly M.; Narum, David L.

2017-01-01

Chemical conjugation of polysaccharide to carrier proteins has been a successful strategy to generate potent vaccines against bacterial pathogens. We developed a similar approach for poorly immunogenic malaria protein antigens. Our lead candidates in clinical trials are the malaria transmission blocking vaccine antigens, Pfs25 and Pfs230D1, individually conjugated to the carrier protein Exoprotein A (EPA) through thioether chemistry. These conjugates form nanoparticles that show enhanced immunogenicity compared to unconjugated antigens. In this study, we examined the broad applicability of this technology as a vaccine development platform, by comparing the immunogenicity of conjugates prepared by four different chemistries using different malaria antigens (PfCSP, Pfs25 and Pfs230D1), and carriers such as EPA, TT and CRM197. Several conjugates were synthesized using thioether, amide, ADH and glutaraldehyde chemistries, characterized for average molecular weight and molecular weight distribution, and evaluated in mice for humoral immunogenicity. Conjugates made with the different chemistries, or with different carriers, showed no significant difference in immunogenicity towards the conjugated antigens. Since particle size can influence immunogenicity, we tested conjugates with different average size in the range of 16–73 nm diameter, and observed greater immunogenicity of smaller particles, with significant differences between 16 and 73 nm particles. These results demonstrate the multiple options with respect to carriers and chemistries that are available for protein-protein conjugate vaccine development. PMID:29281708

75 FR 29384 - Motor Carrier Safety Advisory Committee Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-25

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2010-0143] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee meeting. SUMMARY: FMCSA...

Membrane-targeted strategies for modulating APP and Aβ-mediated toxicity

PubMed Central

Price, Katherine A; Crouch, Peter J; Donnelly, Paul S; Masters, Colin L; White, Anthony R; Curtain, Cyril C

2009-01-01

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by numerous pathological features including the accumulation of neurotoxic amyloid-β (Aβ) peptide. There is currently no effective therapy for AD, but the development of therapeutic strategies that target the cell membrane is gaining increased interest. The amyloid precursor protein (APP) from which Aβ is formed is a membrane-bound protein, and Aβ production and toxicity are both membrane mediated events. This review describes the critical role of cell membranes in AD with particular emphasis on how the composition and structure of the membrane and its specialized regions may influence toxic or benign Aβ/APP pathways in AD. The putative role of copper (Cu) in AD is also discussed, and we highlight how targeting the cell membrane with Cu complexes has therapeutic potential in AD. PMID:19278455

Reactivity Control of Rhodium Cluster Ions by Alloying with Tantalum Atoms.

PubMed

Mafuné, Fumitaka; Tawaraya, Yuki; Kudoh, Satoshi

2016-02-18

Gas phase, bielement rhodium and tantalum clusters, RhnTam(+) (n + m = 6), were prepared by the double laser ablation of Rh and Ta rods in He carrier gas. The clusters were introduced into a reaction gas cell filled with nitric oxide (NO) diluted with He and were subjected to collisions with NO and He at room temperature. The product species were observed by mass spectrometry, demonstrating that the NO molecules were sequentially adsorbed on the RhnTam(+) clusters to form RhnTam(+)NxOx (x = 1, 2, 3, ...) species. In addition, oxide clusters, RhnTam(+)O2, were also observed, suggesting that the NO molecules were dissociatively adsorbed on the cluster, the N atoms migrated on the surface to form N2, and the N2 molecules were released from RhnTam(+)N2O2. The reactivity, leading to oxide formation, was composition dependent: oxide clusters were dominantly formed for the bielement clusters containing both Rh and Ta atoms, whereas such clusters were hardly formed for the single-element Rhn(+) and Tam(+) clusters. DFT calculations indicated that the Ta atoms induce dissociation of NO on the clusters by lowering the dissociation energy, whereas the Rh atoms enable release of N2 by lowering the binding energy of the N atoms on the clusters.

Peroxy radical measurements with NCAR's chemical amplifier

NASA Technical Reports Server (NTRS)

Cantrell, Christopher; Shetter, Richard; Calvert, Jack G.

1994-01-01

The present NCAR instrument for HO2/RO2 measurements has been described previously. It is based on the reactions involving HO2, RO2, and HO radicals with CO and NO. Since (HO2) + (RO2) + (HO) is much greater than (HO) for most atmospheres, it is useful as a peroxy radical detector. Operation of the instrument depends on the creation of a chemical chain reaction which is initiated as HO2 and RO2 radicals in ambient air encounter added NO gas; this forms an NO2 molecule and an HO or RO radical: HO2(RO2) + NO yields HO(RO) + NO2. RO radicals react relatively efficiently with O2 to form an HO2 radical, and subsequently an HO-radical, by reaction with NO. CO gas added to the reaction chamber during part of the operating cycle, recycles the HO to HO2; HO + CO (+O2) yields HO2 + CO2. The reaction sequence may form several hundred NO2 molecules per HO2 (RO2) originally present, before chain termination occurs. The added CO is replaced by N2 addition periodically so that the chain reaction is suppressed, and a 'blank' signal resulting from NO2, O3 and possibly other NO2-forming species (non-chain processes) in ambient air is recorded. The difference between the signal with and without CO is proportional to the peroxy radical concentration. The NO2 produced is monitored using a sensitive luminol chemiluminescence detector system. In the NCAR instrument the length of the amplification chain is determined using a stable source of HO2 radicals (H2O2 thermal decomposition); the ratio of the signal seen with CO present to that with N2 present gives the sensitivity of the instrument to HO2 (molecules of NO2 formed/peroxy radical). The instrument is automated to carry out in hourly repeated cycles: (1) chain length determination; (2) NO2 calibration; and (3) linearity check on the response of signals. One minute averages of signals are normally recorded. The sensitivity of the instrument to detect peroxy radicals is in the pptv range. The present instrument has operated continuously (24 hr/day) in the field studies which extended over a period of several weeks. The major advantages of this instrument are as follows: (1) its relative simplicity; (2) low power requirements; and (3) its rapid response to all types of peroxy radicals--HO2, CH3O2 and the higher alkyl and acyl peroxy radicals; however not all RO2 species generate HO2 radicals with perfect efficiency and hence have somewhat lower response/molecule than HO2 radicals.

KSC-08pd3237

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, the Super Lightweight Interchangeable Carrier, or SLIC, is placed on a work platform after its return to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

78 FR 17751 - Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Meeting of Motor Carrier Safety Advisory Committee...

76 FR 32390 - Motor Carrier Safety Advisory Committee Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... Measurement System (SafeStat), CSMS quantifies the on-road safety performance of carriers to identify... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety...

Analysis of Energy Efficiencies and Source Tradespace in an A2/Ad Seabase-to-Shore Operation With an Asymmetric Threat

DTIC Science & Technology

2016-12-01

i REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1...Unclassified 20. LIMITATION OF ABSTRACT UU NSN 7540-01-280-5500 Standard Form 298 (Rev. 2-89) Prescribed by ANSI Std. 239-18 ii THIS PAGE...Table 23. Form Factor Ranking Calculations ..........................................................265 Table 24. Cost Ranking Calculation

76 FR 6688 - Land Border Carrier Initiative Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-08

... [Docket No. USCBP-2006-0132; CBP Dec. No. 11-04] RIN 1651-AA68 Land Border Carrier Initiative Program... Carrier Initiative Program (LBCIP). The LBCIP was established as a voluntary industry partnership program... Initiative Program (LBCIP) was established as a CBP-industry partnership regulatory program enlisting the...

A case study of haemoglobinopathy screening in the Netherlands: witnessing the past, lessons for the future

PubMed Central

Jans, Suze M.P.J.; van El, Carla G.; Houwaart, Eddy S.; Westerman, Marjan J.; Janssens, Rien J.P.A.; Lagro-Janssen, Antoinette L.M.; Plass, Anne Marie C.; Cornel, Martina C.

2011-01-01

Objectives. In 2007 neonatal screening (NNS) was expanded to include screening for sickle cell disease (SCD) and beta-thalassaemia. Up until that year no formal recommendations for haemoglobinopathy (carrier) screening existed in the Netherlands. Although it has been subject to debate in the past, preconceptional and prenatal haemoglobinopathy carrier screening are not part of routine healthcare in the Netherlands. This study aimed to explore the decision-making process of the past: why was the introduction of a screening programme for haemoglobinopathy considered to be untimely, and did ethnicity play a role given the history in other countries surrounding the introduction of haemoglobinopathy screening? Design. A witness seminar was organised, inviting key figures to discuss the decision-making process concerning haemoglobinopathy screening in the Netherlands, thereby adding new perspectives on past events. The transcript was content-analysed. Results. The subject of haemoglobinopathy screening first appeared in the 1970s. As opposed to a long history of neglect of African-American health in the United States, the heritage of the Second World War influenced the decision-making process in the Netherlands. As a consequence, registration of ethnicity surfaced as an impeding factor. However, overall, official Dutch screening policy was restrained regarding reproductive issues caused by fear of eugenics. In the 1990s haemoglobinopathy screening was found to be ‘not opportune’ due to low prevalence, lack of knowledge and fear of stigmatisation. Currently the registration of ethnicity remains on the political agenda, but still proves to be a sensitive subject. Discussion. Carrier screening in general never appeared high on the policy agenda. Registration of ethnicity remains sensitive caused by the current political climate. Complexities related to carrier screening are a challenge in Dutch healthcare. Whether carrier screening will be considered a valuable complementary strategy in the Netherlands, depends partly on participation of representatives of high-risk groups in policy making. PMID:21819310

APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study.

PubMed

Allard, Joanne S; Ntekim, Oyonumo; Johnson, Steven P; Ngwa, Julius S; Bond, Vernon; Pinder, Dynell; Gillum, Richard F; Fungwe, Thomas V; Kwagyan, John; Obisesan, Thomas O

2017-01-01

Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO 2 Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO 2 Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects.

PubMed

Arancibia, Sergio; Del Campo, Miguel; Nova, Esteban; Salazar, Fabián; Becker, María Inés

2012-03-01

Hemocyanins, which boost the immune system of mammals, have been used as carrier-adjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding interdisciplinary health care teams: using simulation design processes from the Air Carrier Advanced Qualification Program to identify and train critical teamwork skills.

PubMed

Hamman, William R; Beaudin-Seiler, Beth M; Beaubien, Jeffrey M

2010-09-01

In the report "Five Years After 'To Err is Human' ", it was noted that "the combination of complexity, professional fragmentation, and a tradition of individualism, enhanced by a well-entrenched hierarchical authority structure and diffuse accountability, forms a daunting barrier to creating the habits and beliefs of common purpose, teamwork, and individual accountability for successful interdependence that a safe culture requires". Training physicians, nurses, and other professionals to work in teams is a concept that has been promoted by many patient safety experts. However the model of teamwork in healthcare is diffusely defined, no clear performance metrics have been established, and the use of simulation to train teams has been suboptimal. This paper reports on the first three years of work performed in the Michigan Economic Development Corporation (MEDC) Tri-Corridor life science grant to apply concepts and processes of simulation design that were developed in the air carrier industry to understand and train healthcare teams. This work has been monitored by the American Academy for the Advancement of Science (AAA) and is based on concepts designed in the Advanced Qualification Program (AQP) from the air carrier industry, which trains and assesses teamwork skills in the same manner as technical skills. This grant has formed the foundation for the Center of Excellence for Simulation Education and Research (CESR).

Formation of Ozonic Compound and Used as Therapeutic Agent in Medicine

NASA Astrophysics Data System (ADS)

Zhu, Lei; Ye, Chunyong; Min, Xinmin

2018-03-01

It has some encouraging results to use ozone in medicine. However, as ozone is usually in gas state, unstable and strong oxidability, it is difficult to be stored and used commonly. Ozone, ethylene, acrylic acid and the ozonic compounds were calculated to study the interaction between ozone and carrier material to form ozonide. The stability of the ozonide, or the bond strength between ozone and ions of carrier are controlled felicitously to release ozone from the ozonide with proper velocity. Ozone antimicrobial has been composed on the above principle. It can be used conveniently, especially for common families. There are some characteristics of ozone antimicrobial or ozone, such as universal applicability, efficiency and rapidity, security, strong penetrability, no drug resistance and sterilization and treatment simultaneity.

Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology.

PubMed

Calderón-Garcidueñas, Lilian; González-Maciel, Angélica; Reynoso-Robles, Rafael; Kulesza, Randy J; Mukherjee, Partha S; Torres-Jardón, Ricardo; Rönkkö, Topi; Doty, Richard L

2018-06-20

There is growing evidence that air pollution is a risk factor for a number of neurodegenerative diseases, most notably Alzheimer's (AD) and Parkinson's (PD). It is generally assumed that the pathology of these diseases arises only later in life and commonly begins within olfactory eloquent pathways prior to the onset of the classical clinical symptoms. The present study demonstrates that chronic exposure to high levels of air pollution results in AD- and PD-related pathology within the olfactory bulbs of children and relatively young adults ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6-13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM 2.5 ) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control. Copyright © 2018 Elsevier Inc. All rights reserved.

Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials.

PubMed

Liu, Enchi; Schmidt, Mark E; Margolin, Richard; Sperling, Reisa; Koeppe, Robert; Mason, Neale S; Klunk, William E; Mathis, Chester A; Salloway, Stephen; Fox, Nick C; Hill, Derek L; Les, Andrea S; Collins, Peter; Gregg, Keith M; Di, Jianing; Lu, Yuan; Tudor, I Cristina; Wyman, Bradley T; Booth, Kevin; Broome, Stephanie; Yuen, Eric; Grundman, Michael; Brashear, H Robert

2015-08-25

To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using (11)C-Pittsburgh compound B ((11)C-PiB)-PET. Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an (11)C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in (11)C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = -0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = -0.068; p = 0.027; 1.0 mg/kg vs placebo δ = -0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. The (11)C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. © 2015 American Academy of Neurology.

Effectiveness evaluation of STOL transport operations (phase 2). [computer simulation program of commercial short haul aircraft operations

NASA Technical Reports Server (NTRS)

Welp, D. W.; Brown, R. A.; Ullman, D. G.; Kuhner, M. B.

1974-01-01

A computer simulation program which models a commercial short-haul aircraft operating in the civil air system was developed. The purpose of the program is to evaluate the effect of a given aircraft avionics capability on the ability of the aircraft to perform on-time carrier operations. The program outputs consist primarily of those quantities which can be used to determine direct operating costs. These include: (1) schedule reliability or delays, (2) repairs/replacements, (3) fuel consumption, and (4) cancellations. More comprehensive models of the terminal area environment were added and a simulation of an existing airline operation was conducted to obtain a form of model verification. The capability of the program to provide comparative results (sensitivity analysis) was then demonstrated by modifying the aircraft avionics capability for additional computer simulations.

Are Aβ and Its Derivatives Causative Agents or Innocent Bystanders in AD?

PubMed Central

Robakis, Nikolaos K.

2010-01-01

Alzheimer's disease (AD) is characterized by neurodegeneration in neocortical regions of the brain. Currently, Aβ-based theories, including amyloid depositions and soluble Aβ, form the basis of most therapeutic approaches to AD. It remains unclear, however, whether Aβ and its derivatives are the primary causative agents of neuronal loss in AD. Reported studies show no significant correlations between brain amyloid depositions and either degree of dementia or loss of neurons, and brain amyloid loads similar to AD are often found in normal individuals. Furthermore, behavioral abnormalities in animal models overexpressing amyloid precursor protein seem independent of amyloid depositions. Soluble Aβ theories propose toxic Aβ42 or its oligomers as the agents that promote cell death in AD. Aβ peptides, however, are normal components of human serum and CSF, and it is unclear under what conditions these peptides become toxic. Presently, there is little evidence of disease-associated abnormalities in soluble Aβ and no toxic oligomers specific to AD have been found. That familial AD mutations of amyloid precursor protein, PS1 and PS2 promote neurodegeneration suggests the biological functions of these proteins play critical roles in neuronal survival. Evidence shows that the PS/γ-secretase system promotes production of peptides involved in cell surface-to-nucleus signaling and gene expression, providing support for the hypothesis that familial AD mutations may contribute to neurodegeneration by inhibiting PS-dependent signaling pathways. PMID:20160455

Binderless fiberboard from two different types of fiber furnishes

Treesearch

Otto Suchsland; George Woodson; Charles W. McMillin

1985-01-01

Fiber furnishes from two commercial processes were used to make experimental hardboards by all four possible methods: wet formed (pressed dry and wet), and dry formed (pressed dry and wet). Since no adhesives were added, all bonding was due to natural agents. Results of mechanical and physical testing of the hardboards indicated that high quality hardboard can be made...

Do methicillin resistant staphylococcus (MRSA) carrier patients influence MRSA infection more than MRSA-carrier medical officers and MRSA-carrier family?

PubMed

Dilogo, Ismail H; Arya, Abikara; Phedy; Loho, Tony

2013-07-01

to determine the rate of MRSA-carrier among patients, family members and health care providers, and the association between MRSA-carrier family members and health care providers on MRSA infection patient after orthopaedic surgery. this is a cross-sectional analytical study. Samples were taken consecutively during December 2010 to December 2011, consisting of postoperative patients infected with MRSA, attending family members, and the medical officers with history of contact with the patient. Swab culture were taken from nasal and axilla of all subjects. The incidence of MRSA infection, and MRSA-carrier on the patient, family members and medical officers were presented descriptively, while their association with MRSA infection was statistically tested using Fischer exact test. during the study period, there were 759 surgeries, with 4 (0.5%) patients were identified to have MRSA infection. Of these four cases, 48 subjects were enrolled. The rate of MRSA-carrier among patients, family and health care providers were 50%, 25% and 0% respectively. There were no significant association between MRSA and the rates of MRSA-carrier on the family member or health care providers. the incidence of MRSA infection, MRSA-carrier patient, MRSA-carrier health care providers, and family member carrier were 0.5%, 50%, 0%, and 25% respectively. No significant association found between MRSA-carrier on the family member or health care providers and MRSA infection patient. There were no MRSA infection found on the health care provider.

Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer's disease.

PubMed

Chang, Chiung-Chih; Chang, Ya-Ting; Huang, Chi-Wei; Tsai, Shih-Jen; Hsu, Shih-Wei; Huang, Shu-Hua; Lee, Chen-Chang; Chang, Wen-Neng; Lui, Chun-Chung; Lien, Chia-Yi

2018-02-08

Alzheimer's disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores. Gray matter structural covariance networks (SCNs) were constructed in 104 patients with AD using T1-weighted magnetic resonance imaging with seed-based correlation analysis. The patients were stratified into two genotype groups on the basis of Bcl-2 expression (G carriers, n = 76; A homozygotes, n = 28). Four SCNs characteristic of AD were constructed from seeds in the default mode network, salience network, and executive control network, and cognitive test scores served as the major outcome factor. For the G carriers, influences of the SCNs were observed mostly in the default mode network, of which the peak clusters anchored by the posterior cingulate cortex seed determined the cognitive test scores. In contrast, genetic influences in the A homozygotes were found mainly in the executive control network, and both the dorsolateral prefrontal cortex seed and the interconnected peak clusters were correlated with the clinical scores. Despite a small number of cases, the A homozygotes showed greater covariance strength than the G carriers among all four SCNs. Our results suggest that the Bcl-2 rs956572 polymorphism is associated with different strengths of structural covariance in AD that determine clinical outcomes. The greater covariance strength in the four SCNs shown in the A homozygotes suggests that different Bcl-2 polymorphisms play different modulatory roles.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

PubMed Central

Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

2011-01-01

Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype. PMID:21791467

Butyrylcholinesterase K and Apolipoprotein E-ɛ4 Reduce the Age of Onset of Alzheimer's Disease, Accelerate Cognitive Decline, and Modulate Donepezil Response in Mild Cognitively Impaired Subjects.

PubMed

De Beaumont, Louis; Pelleieux, Sandra; Lamarre-Théroux, Louise; Dea, Doris; Poirier, Judes

2016-10-04

Genetic heterogeneity in amnestic mild cognitively impaired (aMCI) subjects could lead to variations in progression rates and response to cholinomimetic agents. Together with the apolipoprotein E4 (APOE-ɛ4) gene, butyrylcholinesterase (BCHE) has become recently one of the few Alzheimer's disease (AD) susceptibility genes with distinct pharmacogenomic properties. To validate candidate genes (APOE/BCHE) which display associations with age of onset of AD and donepezil efficacy in aMCI subjects. Using the Petersen et al. (2005) study on vitamin E and donepezil efficacy in aMCI, we contrasted the effects of BCHE and APOE variants on donepezil drug response using the Alzheimer's Disease Assessment Score-Cognition (ADAS-Cog) scale. Independently, we assessed the effects of APOE/BCHE genotypes on age of onset and cortical choline acetyltransferase activity in autopsy-confirmed AD and age-matched control subjects. Statistical analyses revealed a significant earlier age of onset in AD for APOE-ɛ4, BCHE-K*, and APOE-ɛ4/BCHE-K* carriers. Among the carriers of APOE-ɛ4 and BCHE-K*, the benefit of donepezil was evident at the end of the three-year follow-up. The responder's pharmacogenomic profile is consistent with reduced brain cholinergic activity measured in APOE-ɛ4 and BCHE-K* positive subjects. APOE-ɛ4 and BCHE-K* positive subjects display an earlier age of onset of AD, an accelerated cognitive decline and a greater cognitive benefits to donepezil therapy. These results clearly emphasize the necessity of monitoring potential pharmacogenomic effects in this population of subjects, and suggest enrichment strategies for secondary prevention trials involving prodromal AD subjects.

Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

PubMed

Mandecka, Monika; Budziszewska, Magdalena; Barczak, Anna; Pepłońska, Beata; Chodakowska-Żebrowska, Małgorzata; Filipek-Gliszczyńska, Anna; Nesteruk, Marta; Styczyńska, Maria; Barcikowska, Maria; Gabryelewicz, Tomasz

2016-07-29

In the course of Alzheimer's disease (AD), early pathological changes in the brain start decades before any clinical manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer's dementia (AD-D), together with the relationships between the biomarkers, an APOE ɛ4 presence, and a verbal episodic memory performance. We included 252 patients from the memory clinic with a diagnosis of SCD (n = 85), MCI (n = 87), and AD-D (n = 80). A verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly lower levels of Aβ1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE ɛ4 carriers, who had lower levels of Aβ1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly higher in the APOE ɛ4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole study samples was predicted by age, Aβ1-42, and the T-tau CSF biomarkers, but not by the APOE genotyping.

76 FR 29169 - Requirements for Intermodal Equipment Providers and for Motor Carriers and Drivers Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... No. FMCSA-2005-23315] RIN 2126-AB37 Requirements for Intermodal Equipment Providers and for Motor Carriers and Drivers Operating Intermodal Equipment AGENCY: Federal Motor Carrier Safety Administration... driver- vehicle inspection report (DVIR) on an item of intermodal equipment (IME) when no damage, defects...

Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis.

PubMed

Benitez, Bruno A; Sands, Mark S

2017-07-24

Mutations in the co- chaperone protein, CSPα, cause an autosomal dominant, adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of CSPα function exclusively at the synapse fails to explain the autophagy-lysosome pathway (ALP) dysfunction in cells from AD-ANCL patients. Here, we demonstrate unexpectedly that primary dermal fibroblasts from pre-symptomatic mutation carriers recapitulate in vitro features found in the brains of AD-ANCL patients including auto-fluorescent storage material (AFSM) accumulation, CSPα aggregates, increased levels of lysosomal proteins and lysosome enzyme activities. AFSM accumulation correlates with CSPα aggregation and both are susceptible to pharmacological modulation of ALP function. In addition, we demonstrate that endogenous CSPα is present in the lysosome-enriched fractions and co-localizes with lysosome markers in soma, neurites and synaptic boutons. Overexpression of CSPα wild-type (WT) decreases lysotracker signal, secreted lysosomal enzymes and SNAP23-mediated lysosome exocytosis. CSPα WT, mutant and aggregated CSPα are degraded mainly by the ALP but this disease-causing mutation exhibits a faster rate of degradation. Co-expression of both WT and mutant CSPα cause a block in the fusion of autophagosomes/lysosomes. Our data suggest that aggregation-dependent perturbation of ALP function is a relevant pathogenic mechanism for AD-ANCL and supports the use of AFSM or CSPα aggregation as biomarkers for drug screening purposes.

Effect of rivastigmine or memantine add-on therapy is affected by butyrylcholinesterase genotype in patients with probable Alzheimer's disease.

PubMed

Han, Hyun Jeong; Kwon, Jay C; Kim, Jung Eun; Kim, Shin Gyeom; Park, Jong-Moo; Park, Kyung Won; Park, Key Chung; Park, Kee Hyung; Moon, So Young; Seo, Sang Won; Choi, Seong Hye; Cho, Soo-Jin

2015-01-01

The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene. To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene. A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score. BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E ε 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables. The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E ε 4.

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

Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [ 11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiBmore » SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.« less

Application of a MRI based index to longitudinal atrophy change in Alzheimer disease, mild cognitive impairment and healthy older individuals in the AddNeuroMed cohort

PubMed Central

Aguilar, Carlos; Muehlboeck, J-Sebastian; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Wahlund, Lars-Olof; Simmons, Andrew; Westman, Eric

2014-01-01

Cross sectional studies of patients at risk of developing Alzheimer disease (AD) have identified several brain regions known to be prone to degeneration suitable as biomarkers, including hippocampal, ventricular, and whole brain volume. The aim of this study was to longitudinally evaluate an index based on morphometric measures derived from MRI data that could be used for classification of AD and healthy control subjects, as well as prediction of conversion from mild cognitive impairment (MCI) to AD. Patients originated from the AddNeuroMed project at baseline (119 AD, 119 MCI, 110 controls (CTL)) and 1-year follow-up (62 AD, 73 MCI, 79 CTL). Data consisted of 3D T1-weighted MR images, demographics, MMSE, ADAS-Cog, CERAD and CDR scores, and APOE e4 status. We computed an index using a multivariate classification model (AD vs. CTL), using orthogonal partial least squares to latent structures (OPLS). Sensitivity, specificity and AUC were determined. Performance of the classifier (AD vs. CTL) was high at baseline (10-fold cross-validation, 84% sensitivity, 91% specificity, 0.93 AUC) and at 1-year follow-up (92% sensitivity, 74% specificity, 0.93 AUC). Predictions of conversion from MCI to AD were good at baseline (77% of MCI converters) and at follow-up (91% of MCI converters). MCI carriers of the APOE e4 allele manifested more atrophy and presented a faster cognitive decline when compared to non-carriers. The derived index demonstrated a steady increase in atrophy over time, yielding higher accuracy in prediction at the time of clinical conversion. Neuropsychological tests appeared less sensitive to changes over time. However, taking the average of the two time points yielded better correlation between the index and cognitive scores as opposed to using cross-sectional data only. Thus, multivariate classification seemed to detect patterns of AD changes before conversion from MCI to AD and including longitudinal information is of great importance. PMID:25071554

Enzyme immobilization techniques on poly(glycidyl methacrylate-co-ethylene dimethacrylate) carrier with penicillin amidase as model.

PubMed

Drobník, J; Saudek, V; Svec, F; Kálal, J; Vojtísek, V; Bárta, M

1979-08-01

Two types of bead-form macroporous carriers based on glycidyl methacrylate with ethylene dimethacrylate copolymers were used for the immobilization of penicillin amidase either directly or after chemical modification. Direct binding through oxirane groups, which is equally efficient at pH 4.2 and 7, is relatively slow and brings about an activity loss at low enzyme concentrations. The most efficient immobilization was achieved on glutaraldehyde-activated amino carrier, irrespective of whether the amino groups were formed by ammonia or 1,6-diaminohexane treatment of the original oxirane carrier. Hydrazine treatment gave lower immobilization yields. The same is true of the azide method independent of the length of the spacer. Most enzyme activity was preserved by coupling the carbodiimide-activated enzyme to the carrier with alkyl or arylamino groups at the end of a longer substituent. Immobilization on diazo-modified carrier gave average results. Rapid immobilization by a lysine-modified phosgene-treated carrier resulted in an activity loss. It is suggested that multipoint and very tight attachment of the enzyme molecule to the matrix decreased the activity. The immobilized activity is quite stable in solution and very stable upon lyophilization with sucrose.

Mathematical models utilized in the retrieval of displacement information encoded in fringe patterns

NASA Astrophysics Data System (ADS)

Sciammarella, Cesar A.; Lamberti, Luciano

2016-02-01

All the techniques that measure displacements, whether in the range of visible optics or any other form of field methods, require the presence of a carrier signal. A carrier signal is a wave form modulated (modified) by an input, deformation of the medium. A carrier is tagged to the medium under analysis and deforms with the medium. The wave form must be known both in the unmodulated and the modulated conditions. There are two basic mathematical models that can be utilized to decode the information contained in the carrier, phase modulation or frequency modulation, both are closely connected. Basic problems connected to the detection and recovery of displacement information that are common to all optical techniques will be analyzed in this paper, focusing on the general theory common to all the methods independently of the type of signal utilized. The aspects discussed are those that have practical impact in the process of data gathering and data processing.

Changes in Physical Activity Following a Genetic-Based Internet-Delivered Personalized Intervention: Randomized Controlled Trial (Food4Me)

PubMed Central

Livingstone, Katherine M; Fallaize, Rosalind; Kolossa, Silvia; Hallmann, Jacqueline; San-Cristobal, Rodrigo; Navas-Carretero, Santiago; O'Donovan, Clare B; Woolhead, Clara; Forster, Hannah; Moschonis, George; Lambrinou, Christina-Paulina; Surwillo, Agnieszka; Godlewska, Magdalena; Hoonhout, Jettie; Goris, Annelies; Macready, Anna L; Walsh, Marianne C; Gibney, Eileen R; Brennan, Lorraine; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Lovegrove, Julie A; Martinez, J Alfredo; Daniel, Hannelore; Gibney, Michael J; Mathers, John C; Saris, Wim HM

2016-01-01

Background There is evidence that physical activity (PA) can attenuate the influence of the fat mass- and obesity-associated (FTO) genotype on the risk to develop obesity. However, whether providing personalized information on FTO genotype leads to changes in PA is unknown. Objective The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention. Methods The single nucleotide polymorphism (SNP) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study, a four-arm, Web-based randomized controlled trial (RCT) in 7 European countries on the effects of personalized advice on nutrition and PA. PA was measured objectively using a TracmorD accelerometer and was self-reported using the Baecke questionnaire at baseline and 6 months. Differences in baseline PA variables between risk (AA and AT genotypes) and nonrisk (TT genotype) carriers were tested using multiple linear regression. Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA, by including an interaction term in the model: disclosure (yes/no) × FTO risk (yes/no). Results At baseline, data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes, respectively. There were no significant differences in objectively measured or self-reported baseline PA between risk and nonrisk carriers. A total of 807 (72.05%) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline. Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention. Attrition was higher in nonrisk participants for whom genotype was disclosed (P=.01) compared with their at-risk counterparts. Conclusions No association between baseline PA and FTO risk genotype was observed. There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention. Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change. Trial Registration ClinicalTrials.gov NCT01530139; http://clinicaltrials.gov/show/NCT01530139 (Archived by WebCite at: http://www.webcitation.org/6XII1QwHz) PMID:26851191

Changes in Physical Activity Following a Genetic-Based Internet-Delivered Personalized Intervention: Randomized Controlled Trial (Food4Me).

PubMed

Marsaux, Cyril F M; Celis-Morales, Carlos; Livingstone, Katherine M; Fallaize, Rosalind; Kolossa, Silvia; Hallmann, Jacqueline; San-Cristobal, Rodrigo; Navas-Carretero, Santiago; O'Donovan, Clare B; Woolhead, Clara; Forster, Hannah; Moschonis, George; Lambrinou, Christina-Paulina; Surwillo, Agnieszka; Godlewska, Magdalena; Hoonhout, Jettie; Goris, Annelies; Macready, Anna L; Walsh, Marianne C; Gibney, Eileen R; Brennan, Lorraine; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Lovegrove, Julie A; Martinez, J Alfredo; Daniel, Hannelore; Gibney, Michael J; Mathers, John C; Saris, Wim H M

2016-02-05

There is evidence that physical activity (PA) can attenuate the influence of the fat mass- and obesity-associated (FTO) genotype on the risk to develop obesity. However, whether providing personalized information on FTO genotype leads to changes in PA is unknown. The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention. The single nucleotide polymorphism (SNP) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study, a four-arm, Web-based randomized controlled trial (RCT) in 7 European countries on the effects of personalized advice on nutrition and PA. PA was measured objectively using a TracmorD accelerometer and was self-reported using the Baecke questionnaire at baseline and 6 months. Differences in baseline PA variables between risk (AA and AT genotypes) and nonrisk (TT genotype) carriers were tested using multiple linear regression. Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA, by including an interaction term in the model: disclosure (yes/no) × FTO risk (yes/no). At baseline, data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes, respectively. There were no significant differences in objectively measured or self-reported baseline PA between risk and nonrisk carriers. A total of 807 (72.05%) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline. Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention. Attrition was higher in nonrisk participants for whom genotype was disclosed (P=.01) compared with their at-risk counterparts. No association between baseline PA and FTO risk genotype was observed. There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention. Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change. ClinicalTrials.gov NCT01530139; http://clinicaltrials.gov/show/NCT01530139 (Archived by WebCite at: http://www.webcitation.org/6XII1QwHz).

Geomagnetic paleointensity between 1300 and 1750 A.D. derived from a bread oven floor sequence in Lübeck, Germany

NASA Astrophysics Data System (ADS)

Schnepp, Elisabeth; Lanos, Philippe; Chauvin, Annick

2009-08-01

Geomagnetic paleointensities have been determined from a single archaeological site in Lübeck, Germany, where a sequence of 25 bread oven floors has been preserved in a bakery from medieval times until today. Age dating confines the time interval from about 1300 A.D. to about 1750 A.D. Paleomagnetic directions have been published from each oven floor and are updated here. The specimens have very stable directions and no or only weak secondary components. The oven floor material was characterized rock magnetically using Thellier viscosity indices, median destructive field values, Curie point determinations, and hysteresis measurements. Magnetic carriers are mixtures of SD, PSD, and minor MD magnetite and/or maghemite together with small amounts of hematite. Paleointensity was measured from selected specimens with the double-heating Thellier method including pTRM checks and determination of TRM anisotropy tensors. Corrections for anisotropy as well as for cooling rate turned out to be unnecessary. Ninety-two percent of the Thellier experiments passed the assigned acceptance criteria and provided four to six reliable paleointensity estimates per oven floor. Mean paleointensity values derived from 22 oven floors show maxima in the 15th and early 17th centuries A.D., followed by a decrease of paleointensity of about 20% until 1750 A.D. Together with the directions the record represents about 450 years of full vector secular variation. The results compare well with historical models of the Earth's magnetic field as well as with a selected high-quality paleointensity data set for western and central Europe.

Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion

PubMed Central

Alagdar, Gada Sulaiman A.; Oo, May Kyaw; Sengupta, Pinaki; Mandal, Uttam Kumar; Jaffri, Julian Md.; Chatterjee, Bappaditya

2017-01-01

Background and Objective: One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier. Methods: Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties. Results: SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent. Conclusion: The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form. PMID:29184827

75 FR 38978 - Polyethylene Retail Carrier Bags From the People's Republic of China, Malaysia, and Thailand...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-07

... Date: July 7, 2010. FOR FURTHER INFORMATION CONTACT: Dustin Ross or Minoo Hatten, AD/CVD Operations... stores, and restaurants, to their customers to package and carry their purchased products. The scopes of...

Microbial community and removal of nitrogen via the addition of a carrier in a pilot-scale duckweed-based wastewater treatment system.

PubMed

Zhao, Yonggui; Fang, Yang; Jin, Yanling; Huang, Jun; Ma, Xinrong; He, Kaize; He, Zhiming; Wang, Feng; Zhao, Hai

2015-03-01

Carriers were added to a pilot-scale duckweed-based (Lemna japonica 0223) wastewater treatment system to immobilize and enhance microorganisms. This system and another parallel duckweed system without carriers were operated for 1.5 years. The results indicated the addition of the carrier did not significantly affect the growth and composition of duckweed, the recovery of total nitrogen (TN), total phosphorus (TP) and CO2 or the removal of TP. However, it significantly improved the removal efficiency of TN and NH4(+)-N (by 19.97% and 15.02%, respectively). The use of 454 pyrosequencing revealed large differences of the microbial communities between the different components within a system and similarities within the same components between the two systems. The carrier biofilm had the highest bacterial diversity and relative abundance of nitrifying bacteria (3%) and denitrifying bacteria (24% of Rhodocyclaceae), which improved nitrogen removal of the system. An efficient N-removal duckweed system with enhanced microorganisms was established. Copyright © 2014 Elsevier Ltd. All rights reserved.

Variability of age at onset in siblings with familial Alzheimer disease.

PubMed

Gómez-Tortosa, Estrella; Barquero, M Sagrario; Barón, Manuel; Sainz, M Jose; Manzano, Sagrario; Payno, Maria; Ros, Raquel; Almaraz, Carmen; Gómez-Garré, Pilar; Jiménez-Escrig, Adriano

2007-12-01

Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects. To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD. Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain. Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype. Maternal transmission of AD was significantly more frequent than paternal transmission (P < .001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (< or =5 years) or high (>5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO. There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

The theory, design, and operation of the suppressed carrier data-aided tracking receiver

NASA Technical Reports Server (NTRS)

Simon, M. K.; Springett, J. C.

1973-01-01

A viable, efficient, and easily mechanized carrier regenerating receiver for use in suppressed carrier-tracking system is described. The receiver referred to as a data-aided receiver (DAR) incorporates a data-aided loop (DAL) which provides the required carrier reference signal. The DAL employs the principle of decision feedback and as such is more efficient than other forms of suppressed carrier-tracking loops. The analysis, design, and implementation of the DAR are covered in detail. Performance comparisons and mechanization tradeoffs are made, wherever possible, with discrete carrier systems and other suppressed carrier systems presently in use. Experimental performance verification is given throughout in support of the theory presented.

Poly β-cyclodextrin/TPdye nanomicelle-based two-photon nanoprobe for caspase-3 activation imaging in live cells and tissues.

PubMed

Yan, Huijuan; He, Leiliang; Zhao, Wenjie; Li, Jishan; Xiao, Yue; Yang, Ronghua; Tan, Weihong

2014-11-18

Two-photon excitation (TPE) with near-infrared (NIR) photons as the excitation source has important advantages over conventional one-photon excitation (OPE) in the field of biomedical imaging. β-cyclodextrin polymer (βCDP)-based two-photon absorption (TPA) fluorescent nanomicelle exhibits desirable two-photon-sensitized fluorescence properties, high photostability, high cell-permeability and excellent biocompatibility. By combination of the nanostructured two-photon dye (TPdye)/βCDP nanomicelle with the TPE technique, herein we have designed a TPdye/βCDP nanomicelle-based TPA fluorescent nanoconjugate for enzymatic activity assay in biological fluids, live cells and tissues. This sensing system is composed of a trans-4-[p-(N,N-diethylamino)styryl]-N-methylpyridinium iodide (DEASPI)/βCDP nanomicelle as TPA fluorophore and carrier vehicle for delivery of a specific peptide sequence to live cell through fast endocytosis, and an adamantine (Ad)-GRRRDEVDK-BHQ2 (black hole quencher 2) peptide (denoted as Ad-DEVD-BHQ2) anchored on the DEASPI/βCDP nanomicelle's surface to form TPA DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate by the βCD/Ad host-guest inclusion strategy. Successful in vitro and in vivo enzymatic activities assay of caspase-3 was demonstrated with this sensing strategy. Our results reveal that this DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate not only is a robust, sensitive and selective sensor for quantitative assay of caspase-3 in the complex biological environment but also can be efficiently delivered into live cells as well as tissues and act as a "signal-on" fluorescent biosensor for specific, high-contrast imaging of enzymatic activities. This DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated disease progression. Moreover, our design also provides a methodology model scheme for development of future TPdye/βCDP nanomicelle-based two-photon fluorescent probes for in vitro or in vivo determination of biological or biologically relevant species.

Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease

PubMed Central

Abdel Moneim, Ahmed E.

2015-01-01

Alzheimer's disease (AD) is the most common form of dementia characterized by progressive loss of memory and other cognitive functions among older people. Senile plaques and neurofibrillary tangles are the most hallmarks lesions in the brain of AD in addition to neurons loss. Accumulating evidence has shown that oxidative stress–induced damage may play an important role in the initiation and progression of AD pathogenesis. Redox impairment occurs when there is an imbalance between the production and quenching of free radicals from oxygen species. These reactive oxygen species augment the formation and aggregation of amyloid-β and tau protein hyperphosphorylation and vice versa. Currently, there is no available treatments can modify the disease. However, wide varieties of antioxidants show promise to delay or prevent the symptoms of AD and may help in treating the disease. In this review, the role of oxidative stress in AD pathogenesis and the common used antioxidant therapies for AD will summarize. PMID:25817254

Effects of metabolic pathway precursors and polydimethylsiloxane (PDMS) on poly-(gamma)-glutamic acid production by Bacillus subtilis BL53.

PubMed

de Cesaro, Alessandra; da Silva, Suse Botelho; Ayub, Marco Antônio Záchia

2014-09-01

The aims of this study were to evaluate the effects of the addition of metabolic precursors and polydimethylsiloxane (PDMS) as an oxygen carrier to cultures of Bacillus subtilis BL53 during the production of γ-PGA. Kinetics analyses of cultivations of different media showed that B. subtilis BL53 is an exogenous glutamic acid-dependent strain. When the metabolic pathway precursors of γ-PGA synthesis, L-glutamine and a-ketoglutaric acid, were added to the culture medium, production of the biopolymer was increased by 20 % considering the medium without these precursors. The addition of 10 % of the oxygen carrier PDMS to cultures caused a two-fold increase in the volumetric oxygen mass transfer coefficient (kLa), improving γ-PGA production and productivity. Finally, bioreactor cultures of B. subtilis BL53 adopting the combination of optimized medium E, added of glutamine, α-ketoglutaric acid, and PDMS, showed a productivity of 1 g L(-1) h(-1) of g-PGA after only 24 h of cultivation. Results of this study suggest that the use of metabolic pathway precursors glutamine and a-ketolgutaric acid, combined with the addition of PDMS as an oxygen carrier in bioreactors, can improve γ-PGA production and productivity by Bacillus strains .

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis

PubMed Central

2016-01-01

Background The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. Objective This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. Methods A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug’s risks and side effects or of a “major statement” identifying the drug’s major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of “fair balance,” the FDA’s requirement that prescription drug ads balance information relating to the drug’s risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Results Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug’s risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. Conclusions In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads. PMID:26892749

Method of making electrodes for electrochemical cell

DOEpatents

Kaun, Thomas D.; Kilsdonk, Dennis J.

1983-01-01

A method of making an electrode for an electrochemical cell in which particulate electrode-active material is mixed with a liquid organic carrier chemically inert with respect to the electrode-active material, mixing the liquid carrier to form an extrudable slurry. The liquid carrier is present in an amount of from about 10 to about 50 percent by volume of the slurry, and then the carrier is removed from the slurry leaving the electrode-active material.

No differences in brain microstructure between young KIBRA-C carriers and non-carriers.

PubMed

Hu, Li; Xu, Qunxing; Li, Jizhen; Wang, Feifei; Xu, Xinghua; Sun, Zhiyuan; Ma, Xiangxing; Liu, Yong; Wang, Qing; Wang, Dawei

2018-01-02

KIBRA rs17070145 polymorphism is associated with variations in memory function and the microstructure of related brain areas. Diffusion kurtosis imaging (DKI) as an extension of diffusion tensor imaging that can provide more information about changes in microstructure, based on the idea that water diffusion in biological tissues is heterogeneous due to structural hindrance and restriction. We used DKI to explore the relationship between KIBRA gene polymorphism and brain microstructure in young adults. We recruited 100 healthy young volunteers, including 53 TT carriers and 47 C allele carriers. No differences were detected between the TT homozygotes and C-allele carriers for any diffusion and kurtosis parameter. These results indicate KIBRA rs17070145 polymorphism likely has little or no effect on brain microstructure in young adults.

Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

PubMed Central

Abbasi, Sana; Paul, Arghya; Shao, Wei; Prakash, Satya

2012-01-01

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs. PMID:22187654

A stable Fe{sup III}-Fe{sup IV} replacement of tyrosyl radical in a class I ribonucleotide reductase

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

Voevodskaya, N.; Lendzian, F.; Graeslund, A.

2005-05-20

Ribonucleotide reductase (RNR) of Chlamydia trachomatis is a class I RNR enzyme composed of two homodimeric components, proteins R1 and R2. In class I RNR, R1 has the substrate binding site, whereas R2 has a diferric site and normally in its active form a stable tyrosyl free radical. C. trachomatis RNR is unusual, because its R2 component has a phenylalanine in the place of the radical carrier tyrosine. Replacing the tyrosyl radical, a paramagnetic Fe{sup III}-Fe{sup IV} species (species X, normally a transient intermediate in the process leading to radical formation) may provide the oxidation equivalent needed to start themore » catalytic process via long range electron transfer from the active site in R1. Here EPR spectroscopy shows that in C. trachomatis RNR, species X can become essentially stable when formed in a complete RNR (R1/R2/substrate) complex, adding further weight to the possible role of this species X in the catalytic reaction.« less

Analysis of a gas-liquid film plasma reactor for organic compound oxidation.

PubMed

Hsieh, Kevin; Wang, Huijuan; Locke, Bruce R

2016-11-05

A pulsed electrical discharge plasma formed in a tubular reactor with flowing argon carrier gas and a liquid water film was analyzed using methylene blue as a liquid phase hydroxyl radical scavenger and simultaneous measurements of hydrogen peroxide formation. The effects of liquid flow rate, liquid conductivity, concentration of dye, and the addition of ferrous ion on dye decoloration and degradation were determined. Higher liquid flow rates and concentrations of dye resulted in less decoloration percentages and hydrogen peroxide formation due to initial liquid conductivity effects and lower residence times in the reactor. The highest decoloration energy yield of dye found in these studies was 5.2g/kWh when using the higher liquid flow rate and adding the catalyst. The non-homogeneous nature of the plasma discharge favors the production of hydrogen peroxide in the plasma-liquid interface over the chemical oxidation of the organic in the bulk liquid phase and post-plasma reactions with the Fenton catalyst lead to complete utilization of the plasma-formed hydrogen peroxide. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving the AOAC use-dilution method by establishing a minimum log density value for test microbes on inoculated carriers.

PubMed

Tomasino, Stephen F; Pines, Rebecca M; Hamilton, Martin A

2009-01-01

The AOAC Use-Dilution methods, 955.14 (Salmonella enterica), 955.15 (Staphylococcus aureus), and 964.02 (Pseudomonas aeruginosa), are used to measure the efficacy of disinfectants on hard inanimate surfaces. The methods do not provide procedures to assess log density of the test microbe on inoculated penicylinders (carrier counts). Without a method to measure and monitor carrier counts, the associated efficacy data may not be reliable and repeatable. This report provides a standardized procedure to address this method deficiency. Based on carrier count data collected by four laboratories over an 8 year period, a minimum log density value is proposed to qualify the test results. Carrier count data were collected concurrently with 242 Use-Dilution tests. The tests were conducted on products bearing claims against P. aeruginosa and S. aureus with and without an organic soil load (OSL) added to the inoculum (as specified on the product label claim). Six carriers were assayed per test for a total of 1452 carriers. All 242 mean log densities were at least 6.0 (geometric mean of 1.0 x 10(6) CFU/carrier). The mean log densities did not exceed 7.5 (geometric mean of 3.2 x 10(7) CFU/carrier). For all microbes and OSL treatments, the mean log density (+/- SEM) was 6.7 (+/- 0.07) per carrier (a geometric mean of 5.39 x 10(6) CFU/carrier). The mean log density for six carriers per test showed good repeatability (0.29) and reproducibility (0.32). A minimum mean log density of 6.0 is proposed as a validity requirement for S. aureus and P. aeruginosa. The minimum level provides for the potential inherent variability that may be experienced by a wide range of laboratories and the slight effect due to the addition of an OSL. A follow-up report is planned to present data to support the carrier count procedure and carrier counts for S. enterica.

Selecting appropriate forms of nitrogen fertilizer to enhance soil arsenic removal by Pteris vittata: a new approach in phytoremediation.

PubMed

Liao, Xiao-Yong; Chen, Tong-Bin; Xiao, Xi-Yuan; Xie, Hua; Yan, Xiu-Lan; Zhai, Li-Mei; Wu, Bin

2007-01-01

Certain plant species have been shown to vigorously accumulate some metals from soil, and thus represent promising and effective remediation alternatives. In order to select the optimum forms of nitrogen (N) fertilizers for the arsenic (As) hyperaccumulator, Pteris vittata L., to maximize As extraction, five forms of N were added individually to different treatments to study the effect of N forms on As uptake of the plants under soil culture in a greenhouse. Although shoot As concentration tended to decrease and As translocation from root to shoot was inhibited, overall As accumulation was greater due to higher biomass when N fertilizer was added. Arsenic accumulation in plants with N fertilization was 100-300% more than in the plants without N fertilization. There were obvious differences in plant biomass and As accumulation among the N forms, i.e., NH4HCO3, (NH4)2S04, Ca(NO3)2, KNO3, urea. The total As accumulation in the plants grown in As-supplied soil, under different forms of N fertilizer, decreased as NH4HCO3>(NH4)2S04 > urea > Ca(NO3)2 >KNO3>CK. The plants treated with N and As accumulated up to 5.3-7.97 mg As/pot and removed 3.7-5.5% As from the soils, compared to approximately 2.3% of As removal in the control. NH4+ -N was apparently more effective than other N fertilizers in stimulating As removal when soil was supplied with As at initiation. No significant differences in available As were found among different forms of N fertilizer after phytoremediation. It is concluded that NH4+ -N was the preferable fertilizer for P. vittata to maximize As removal.

Studies on stercuia gum formulations in the form of osmotic core tablet for colon-specific drug delivery of azathioprine.

PubMed

Nath, Bipul; Nath, Lila Kanta

2013-01-01

The purpose of this research is to evaluate Sterculia urens gum as a carrier for a colon-targeted drug delivery system. Microflora degradation studies of Sterculia gum was conducted in phosphate-buffered saline pH 7.4 containing rat caecal medium under an anaerobic environment. Solubility, swelling index, viscosity, and pH of the polymer solution were determined. Different formulation aspects considered were gum concentration (10-40%) and concentration of citric acid (10-30%) on the swelling index and in-vitro dissolution release. The results of the isothermal stress testing showed that there is no degradation of samples of model drug, azathioprine, the drug polymer mixture, and the core tablet excipients. Differential scanning calorimetry and Fourier transform infrared spectroscopy study proved the compatibility of the drug with Sterculia gum and other tablet excipients. Microflora degradation study revealed that Sterculia gum can be used as tablet excipient for drug release in the colonic region by utilizing the action of enterobacteria. The swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the mixed film coating under colonic microflora-activated environment. Sterculia gum gives premature drug release in the upper gastrointestinal tract without enteric coating and may not reach the colonic region. Sterculia gum as a colon-targeting carrier is possible via double-layer coating with chitosan/Eudragit RLPO (ammonio-methacrylate copolymer) mixed blend as well as enteric polymers, which would provide acid as well as intestinal resistance but undergo enzymatic degradation once reaching the colon. The aim of the research is to evaluate wheather Sterculia urens, which is a polysaccharide, is suitable as a carrier for colonic delivery of drugs acting locally in the colon. Sterculia gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent, and as a controlled release polymer. Sterculia gum falls under the category of a polysaccharide and is yet to be evaluated as a carrier for colonic delivery of drugs. First the susceptibility of the polysaccharide gum in rat caecal microflora was investigated because true polysaccharides are degraded by the action of normal colonic bacteria. Bacterial degradation of the gum in the colonic environment was confirmed by adding a small quantity of the gum in rat caecal content mixed with phosphate-buffered saline pH 7.4 under an anaerobic environment. Solubility, swelling index, viscosity, and pH of the polymer solution were determined. Different formulation aspects considered were gum concentration (10-40%), concentration of citric acid (10-30%) on swelling index, and in vitro dissolution behavior. Isothermal stress testing was done to determine that there was no degradation of the model drug, azathioprine, with Sterculia gum excipient mixtures under stressed conditions. Differential scanning calorimetry and Fourier transform infrared spectroscopy study proved the compatibility of the drug with Sterculia gum and other tablet excipients. Microflora degradation study revealed that Sterculia gum is digested by the colonic microflora and therefore can be used as a tablet excipient for drug release in the colonic region utilizing the microflora degradation mechanism. Sterculia gum gives premature drug release in the upper gastrointestinal tract without enteric coating and may not reach the colonic region. Sterculia gum as colon-targeting carrier is possible via double-layer coating with chitosan/Eudragit RLPO (ammonio-methacrylate copolymer) and Eudragit L100 polymers, which would provide acid as well as intestinal resistance but undergo enzymatic degradation once reaching the colon.

Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells

NASA Astrophysics Data System (ADS)

Dorier, M.; Brun, E.; Veronesi, G.; Barreau, F.; Pernet-Gallay, K.; Desvergne, C.; Rabilloud, T.; Carapito, C.; Herlin-Boime, N.; Carrière, M.

2015-04-01

TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients.TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients. Electronic supplementary information (ESI) available: Nanoparticle physico-chemical characterization: size distribution in exposure medium, as measured by DLS (Fig. S1), and X-ray diffraction patterns of A12 and R20 (Fig. S2); characterization of the protein corona on A12 and R20 (Table S1-S4 and experimental). See DOI: 10.1039/c5nr00505a

Surface Warfare: A Total Force. Volume 19. Number 4, July/August 1994

DTIC Science & Technology

1994-08-01

USS Puget Sound (AD 38) (AOE 1) Support USS Grasp (ARS 51) Combat Logistics (med/small) USS Mauna Lea (AE 22) COMINEWARCOM: Repair USS Acadia (AD 42...structure is Operational Reserve Carrier ( ORC ). When USS John being shaped to expand this role. In the recently P. Eznnedy (CV 67) joins the NRF in...A typical Aegis engagement sequence begins as a engineer and test the fought in the waters of Port RoyalAegis Combat System. Sound and on the adjacent

Awareness of Emerging Wireless Technologies: Ad-hoc and Personal Area Networks Standards and Emerging Technologies (Sensibilisation a l’emergence des technologies sans fil: technologies emergeantes et normes de reseaux personnels et ad-hoc)

DTIC Science & Technology

2007-04-01

for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data...Control Organization NRL Navy Research Laboratory nrtPS Non-real- time Polling Services OFDM Orthogonal frequency division multiplex OFDMA...Routeur IDentifier RTG RTO Task Group RTO Research & Technology Organization rtPS Real- time Polling Services SC Single-carrier modulation

SCAVENGER AND PROCESS OF SCAVENGING

DOEpatents

Olson, C.M.

1960-04-26

Carrier precipitation processes are given for the separation and recovery of plutonium from aqueous acidic solutions containing plutonium and fission products. Bismuth phosphate is precipitated in the acidic solution while plutonlum is maintained in the hexavalent oxidation state. Preformed, uncalcined, granular titanium dioxide is then added to the solution and the fission product-carrying bismuth phosphate and titanium dioxide are separated from the resulting mixture. Fluosilicic acid, which dissolves any remaining titanium dioxide particles, is then added to the purified plutonium-containing solution.

Adding Design Elements to Improve Time Series Designs: No Child Left behind as an Example of Causal Pattern-Matching

ERIC Educational Resources Information Center

Wong, Manyee; Cook, Thomas D.; Steiner, Peter M.

2015-01-01

Some form of a short interrupted time series (ITS) is often used to evaluate state and national programs. An ITS design with a single treatment group assumes that the pretest functional form can be validly estimated and extrapolated into the postintervention period where it provides a valid counterfactual. This assumption is problematic. Ambiguous…

[Effect of penicillin and the habitat medium in the body of bacterial carriers on the intercellular bonds in populations of the meningococcus and pertussis microbe].

PubMed

Vysotskiĭ, V V; Smirnova-Mutusheva, M A; Efimova, O G; Bakulina, N A

1983-04-01

The relationship of the bacterial cells in populations and their adhesion activity is at present one of the research priorities in microbiological studies. The stimulating effect of penicillin on the development of morphologically different intercellular bonds (IB) in populations of the pertussis causative agent and first of all derivatives or evaginates of the cell wall membranes was observed. Morphologically similar systems and polytubular IB were detected in populations of meningococcal strains isolated from carriers having no signs of the disease. Correlation between the after-effect of penicillin and the presence of the causative agent in bacterial carriers was shown. Unknown systems of interlacing tubular structures not directly bound with the cells, the walls of which were single contour membranes were determined in the meningococcal populations treated with penicillin. IB were observed in the population in the form of transpopulation cords. Morphologically different IB playing the role of specialized organelles might be considered as factors of the functional unity of the bacterial population as a multicellular system.

ACOG Committee Opinion No. 660 Summary: Family Building Through Gestational Surrogacy.

PubMed

Ryan, Ginny L

2016-03-01

Gestational surrogacy is an increasingly common form of family building that can allow individuals or a couple to become parents despite circumstances in which carrying a pregnancy is biologically impossible or medically contraindicated. The practice of gestational surrogacy involves a woman known as a gestational carrier who agrees to bear a genetically unrelated child with the help of assisted reproductive technologies for an individual or couple who intend(s) to be the legal and rearing parent(s), referred to as the intended parent(s). Obstetrician-gynecologists may become involved in gestational surrogacy through caring for the gestational carrier or by caring for the intended parent(s). Although gestational surrogacy increases options for family building, this treatment also involves ethical, medical, psychosocial, and legal complexities that must be taken into account to minimize risks of adverse outcomes for the gestational carrier, intended parent(s), and resulting children. The purpose of this document is to provide an overview of gestational surrogacy and to describe the ethical responsibilities for obstetrician-gynecologists who take part in the care of women who participate in these arrangements.

ACOG Committee Opinion No. 660: Family Building Through Gestational Surrogacy.

PubMed

2016-03-01

Gestational surrogacy is an increasingly common form of family building that can allow individuals or a couple to become parents despite circumstances in which carrying a pregnancy is biologically impossible or medically contraindicated. The practice of gestational surrogacy involves a woman known as a gestational carrier who agrees to bear a genetically unrelated child with the help of assisted reproductive technologies for an individual or couple who intend(s) to be the legal and rearing parent(s), referred to as the intended parent(s). Obstetrician-gynecologists may become involved in gestational surrogacy through caring for the gestational carrier or by caring for the intended parent(s). Although gestational surrogacy increases options for family building, this treatment also involves ethical, medical, psychosocial, and legal complexities that must be taken into account to minimize risks of adverse outcomes for the gestational carrier, intended parent(s), and resulting children. The purpose of this document is to provide an overview of gestational surrogacy and to describe the ethical responsibilities for obstetrician-gynecologists who take part in the care of women who participate in these arrangements.

KSC-08pd3234

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. – In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, the Super Lightweight Interchangeable Carrier, or SLIC, is removed from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

KSC-08pd3242

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, workers secure the Orbital Replacement Unit Carrier, or ORUC, onto a stand after it was returned back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

KSC-08pd3238

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, the Orbital Replacement Unit Carrier, or ORUC, is removed from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

KSC-08pd3236

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, workers remove the Super Lightweight Interchangeable Carrier, or SLIC, from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

KSC-08pd3241

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, workers position the Orbital Replacement Unit Carrier, or ORUC, onto a stand after it was returned back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

KSC-08pd3235

NASA Image and Video Library

2008-10-16

CAPE CANAVERAL, Fla. - In the Payload Hazardous Servicing Facility, or PHSF, at NASA's Kennedy Space Center in Florida, the Super Lightweight Interchangeable Carrier, or SLIC, is lifted from the payload canister which transported the Hubble Space Telescope equipment back to the clean room from Launch Pad 39A. The payload for Hubble servicing mission 4 comprises four carriers holding various equipment for the mission. In the PHSF, the carriers will be stored until a new target launch date in 2009 can be set for Atlantis’ STS-125 mission. Atlantis’ October target launch date was delayed after a device on board Hubble, used in the storage and transmission of science data to Earth, shut down on Sept. 27. Replacing the broken device will be added to Atlantis’ servicing mission to the telescope. Photo credit: NASA/Jim Grossmann

[11C]metaraminol, a false neurotransmitter: preparation, metabolite studies and positron emission tomography examination in monkey.

PubMed

Någren, K; Halldin, C; Swahn, C G; Suhara, T; Farde, L

1996-04-01

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.

DEMONSTRATION BULLETIN: THE DEHYDRO-TECH CORP. CARVER-GREENFIELD PROCESS

EPA Science Inventory

The Carver-Greenfield (C-G) Process (Figure 1) is a physical process that separates hazardous oil-soluble organic contaminants from sludges, soils, and non-aqueous liquids. The process involves adding to the waste a "carrier" oil, which removes hazardous organics from contamin...

21 CFR 131.115 - Concentrated milk.

Code of Federal Regulations, 2014 CFR

2014-04-01

... be homogenized. (b) Vitamin addition (Optional). If added, vitamin D shall be present in such... manufacturing practice. (c) Optional ingredients. The following safe and suitable optional ingredients may be used: (1) Carrier for vitamin D. (2) Characterizing flavoring ingredients, with or without coloring, as...

Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective.

PubMed

Ahmad, Javed; Akhter, Sohail; Rizwanullah, Md; Khan, Mohammad Ahmed; Pigeon, Lucie; Addo, Richard T; Greig, Nigel H; Midoux, Patrick; Pichon, Chantal; Kamal, Mohammad Amjad

2017-01-01

Alzheimer's disease (AD), a cognitive dysfunction/dementia state amongst the elders is characterized by irreversible neurodegeneration due to varied pathophysiology. Up till now, anti-AD drugs having different pharmacology have been developed and used in clinic. Yet, these medications are not curative and only lowering the AD associated symptoms. Improvement in treatment outcome required drug targeting across the blood-brain barrier (BBB) to the central nervous system (CNS) in optimal therapeutic concentration. Nanotechnology based diagnostic tools, drug carriers and theranostics offer highly sensitive molecular detection, effective drug targeting and their combination. Over the past decade, significant works have been done in this area and we have seen very remarkable outocome in AD therapy. Various nanoparticles from organic and inorganic nanomaterial category have successfully been investigated against AD. This paper discussed the role of nanoparticles in early detection of AD, effective drug targeting to brain and theranostic (diagnosis and therapy) approaches in AD's management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

77 FR 60507 - Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Meeting of Compliance, Safety...

49 CFR 392.80 - Prohibition against texting.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS DRIVING OF COMMERCIAL MOTOR... driver shall engage in texting while driving. (b) Motor Carriers. No motor carrier shall allow or require...

Feedback Form for the ADS Abstract Service

Science.gov Websites

ADS Feedback Form for the ADS Abstract Service Please use this form to report bugs or send comments to the ADS Abstract Project. Thank you for your feedback. ❉ Required field Your Name: ❉ Your E

14 CFR 121.590 - Use of certificated land airports in the United States.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF TRANSPORTATION (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND...) of this section, or unless authorized by the Administrator under 49 U.S.C. 44706(c), no air carrier and no pilot being used by an air carrier may operate, in the conduct of a domestic type operation...

14 CFR 121.590 - Use of certificated land airports in the United States.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF TRANSPORTATION (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND...) of this section, or unless authorized by the Administrator under 49 U.S.C. 44706(c), no air carrier and no pilot being used by an air carrier may operate, in the conduct of a domestic type operation...

Influence of ethanol vapor addition on the surface modification of polyethylene in a dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Van Deynse, Annick; Morent, Rino; Leys, Christophe; De Geyter, Nathalie

2017-10-01

In this paper, ethanol vapor up to 50% is added to an argon, air or nitrogen dielectric barrier discharge at medium pressure to profoundly investigate the effect of ethanol addition on the surface modification of low density polyethylene (LDPE). Water contact angle (WCA) and X-ray photoelectron spectroscopy (XPS) measurements show that the ethanol vapor addition effect on the LDPE surface depends on the used carrier gas. Adding ethanol to an argon plasma has no significant effect on the wettability nor on the chemical composition of LDPE compared to a pure argon plasma treatment. Ethanol addition does however slightly increase the LDPE surface roughness. Addition of small amounts of ethanol vapor to an air plasma makes it possible to incorporate additional nitrogen and oxygen groups on the LDPE surface, resulting in an extra decrease of 11% in WCA value. Moreover, the LDPE surface roughness is slightly increased due to the ethanol vapor addition. The most significant effect of ethanol addition is however observed when nitrogen is used as carrier gas. After an N2/2% ethanol plasma treatment, an 85% reduction in WCA value to 8.5° is found compared to a pure N2 plasma treatment. This very hydrophilic LDPE surface is obtained due to a significantly high incorporation of oxygen and nitrogen groups on the surface with an O/C and N/C ratio reaching 32% and 53% respectively. FTIR measurements also reveal that the observed extremely high wettability of LDPE is not the result of plasma activation but is due to plasma polymerization effects occurring on the surface resulting into the deposition of a plasma polymer containing ketones, amides as well as Cdbnd N groups. In addition, ageing studies have also been conducted and these studies reveal that for all carrier gases, ethanol addition to the discharge gas significantly suppresses the ageing effect. All the above mentioned conclusions therefore indicate that ethanol vapor based plasmas can be an excellent tool to increase the surface energy of polymers.

Ordering molecular genetic tests and reporting results: practices in laboratory and clinical settings.

PubMed

Lubin, Ira M; Caggana, Michele; Constantin, Carolyn; Gross, Susan J; Lyon, Elaine; Pagon, Roberta A; Trotter, Tracy L; Wilson, Jean Amos; McGovern, Margaret M

2008-09-01

Previous studies have suggested that patient care may be compromised as a consequence of poor communication between clinicians and laboratory professionals in cases in which molecular genetic test results are reported. To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms. We found instances in which result reports for simulated diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis. Similarly, reports based on simulated scenarios for carrier testing were problematic when no mutations were identified, and the patient's race/ethnicity and family history were not discussed in reference to residual risk of disease. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency. These findings are reviewed in light of what efforts should be taken to improve the quality of test-ordering and result-reporting practices.

49 CFR 390.19 - Motor carrier, hazardous material shipper, and intermodal equipment provider identification reports.

Code of Federal Regulations, 2011 CFR

2011-10-01

... file a Motor Carrier Identification Report, Form MCS-150. (2) A motor carrier conducting operations in... this section at the following times: (1) Before it begins operations; and (2) Every 24 months, according to the following schedule: USDOT numberending in Must file by last day of 1 January. 2 February. 3...

49 CFR 390.19 - Motor carrier, hazardous material shipper, and intermodal equipment provider identification reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... file a Motor Carrier Identification Report, Form MCS-150. (2) A motor carrier conducting operations in... this section at the following times: (1) Before it begins operations; and (2) Every 24 months, according to the following schedule: USDOT numberending in Must file by last day of 1 January. 2 February. 3...

Modular multi-element high energy particle detector

DOEpatents

Coon, D.D.; Elliott, J.P.

1990-01-02

Multi-element high energy particle detector modules comprise a planar heavy metal carrier of tungsten alloy with planar detector units uniformly distributed over one planar surface. The detector units are secured to the heavy metal carrier by electrically conductive adhesive so that the carrier serves as a common ground. The other surface of each planar detector unit is electrically connected to a feedthrough electrical terminal extending through the carrier for front or rear readout. The feedthrough electrical terminals comprise sockets at one face of the carrier and mating pins projecting from the other face, so that any number of modules may be plugged together to create a stack of modules of any desired number of radiation lengths. The detector units each comprise four, preferably rectangular, p-i-n diode chips arranged around the associated feedthrough terminal to form a square detector unit providing at least 90% detector element coverage of the carrier. Integral spacers projecting from the carriers extend at least partially along the boundaries between detector units to space the p-i-n diode chips from adjacent carriers in a stack. The spacers along the perimeters of the modules are one-half the width of the interior spacers so that when stacks of modules are arranged side by side to form a large array of any size or shape, distribution of the detector units is uniform over the entire array. 5 figs.

Modular multi-element high energy particle detector

DOEpatents

Coon, Darryl D.; Elliott, John P.

1990-01-02

Multi-element high energy particle detector modules comprise a planar heavy metal carrier of tungsten alloy with planar detector units uniformly distributed over one planar surface. The detector units are secured to the heavy metal carrier by electrically conductive adhesive so that the carrier serves as a common ground. The other surface of each planar detector unit is electrically connected to a feedthrough electrical terminal extending through the carrier for front or rear readout. The feedthrough electrical terminals comprise sockets at one face of the carrier and mating pins porjecting from the other face, so that any number of modules may be plugged together to create a stack of modules of any desired number of radiation lengths. The detector units each comprise four, preferably rectangular, p-i-n diode chips arranged around the associated feedthrough terminal to form a square detector unit providing at least 90% detector element coverage of the carrier. Integral spacers projecting from the carriers extend at least partially along the boundaries between detector units to space the p-i-n diode chips from adjacent carriers in a stack. The spacers along the perimeters of the modules are one-half the width of the interior spacers so that when stacks of modules are arranged side by side to form a large array of any size or shape, distribution of the detector units is uniform over the entire array.

No genetic effect of {alpha}{sub 1}-antichymotrypsin in Alzheimer disease

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

Haines, J.L.; Pritchard, M.L.; Saunders, A.M.

1996-04-01

Alzheimer disease (AD) is the most common neurodegenerative disorder for individuals over the age of 40.AD has a complex etiology, and it is likely that multiple genes, acting independently and/or interacting, affect the risk of developing AD. Several genes involved with AD have been described already, but only the APOE gene on chromosome 19q has been shown to affect the risk of the common late onset form of AD. {alpha}{sub 1}-Antichymotrypsin (AACT) is a major component of the amyloid plaques found in the brains of AD patients, and an allele in its gene has been proposed to increase the riskmore » of developing AD when also associated with the APOE-4 allele. We have examined the role of this AACT polymorphism in a large set of families and sporadic cases, and do not see any effect, either alone or in combination with the APOE-4 allele. 18 refs., 3 tabs.« less

Are Abeta and its derivatives causative agents or innocent bystanders in AD?

PubMed

Robakis, Nikolaos K

2010-01-01

Alzheimer's disease (AD) is characterized by neurodegeneration in neocortical regions of the brain. Currently, Abeta-based theories, including amyloid depositions and soluble Abeta, form the basis of most therapeutic approaches to AD. It remains unclear, however, whether Abeta and its derivatives are the primary causative agents of neuronal loss in AD. Reported studies show no significant correlations between brain amyloid depositions and either degree of dementia or loss of neurons, and brain amyloid loads similar to AD are often found in normal individuals. Furthermore, behavioral abnormalities in animal models overexpressing amyloid precursor protein seem independent of amyloid depositions. Soluble Abeta theories propose toxic Abeta42 or its oligomers as the agents that promote cell death in AD. Abeta peptides, however, are normal components of human serum and CSF, and it is unclear under what conditions these peptides become toxic. Presently, there is little evidence of disease-associated abnormalities in soluble Abeta and no toxic oligomers specific to AD have been found. That familial AD mutations of amyloid precursor protein, PS1 and PS2 promote neurodegeneration suggests the biological functions of these proteins play critical roles in neuronal survival. Evidence shows that the PS/gamma-secretase system promotes production of peptides involved in cell surface-to-nucleus signaling and gene expression, providing support for the hypothesis that familial AD mutations may contribute to neurodegeneration by inhibiting PS-dependent signaling pathways. Copyright 2010 S. Karger AG, Basel.

Evaluation of Varying Biochars as Carrier Materials for Bacterial Soil Inoculants

NASA Astrophysics Data System (ADS)

Hale, Lauren; Crowley, David

2014-05-01

The incorporation of biochar into agricultural soils for carbon sequestration and improved soil fertility creates an opportunity to simultaneously deliver plant-growth promoting rhizobacteria (PGPR). Many characteristics of biochar materials indicate that these particles could be conducive as inoculum carriers. This could provide a value-added component for biochar marketing and has an advantage over traditional carrier materials, which can be unsustainable or expensive to produce. Here, we assessed the suitability of 10 biochar types, made from 5 feedstocks at 2 pyrolysis temperatures (300°C and 600°C), to serve as carriers for 2 model PGPR strains, Enterobacter cloacae UW5 and Pseudomonas putida UW4. All biochars were characterized based on BET specific surface area, C-N content, pH, EC, and their abilities to adsorb bacterial cells from a liquid inoculum. Further studies incorporated qPCR to quantify the survival of inoculants after introduction into soils via biochar carriers. The biochars that performed well were further assayed for their influence on PGPR traits, 1-aminocyclopropane-1-carboxylate (ACC) deaminase and auxin production. Peat and vermiculite served as traditional carrier materials to which we compared the biochars. Our findings indicated that biochars varied in their interactions with our model PGPR strains. Based on our analysis several biochar types were able to serve as carriers which were as good, if not better than, the traditional carrier materials. Future work should seek to assess shelf life and varying inoculation methods for the biochar-inoculant complexes.