Measurement of the membrane dipole electric field in DMPC vesicles using vibrational shifts of p-cyanophenylalanine and molecular dynamics simulations.

PubMed

Shrestha, Rebika; Cardenas, Alfredo E; Elber, Ron; Webb, Lauren J

2015-02-19

The magnitude of the membrane dipole field was measured using vibrational Stark effect (VSE) shifts of nitrile oscillators placed on the unnatural amino acid p-cyanophenylalanine (p-CN-Phe) added to a peptide sequence at four unique positions. These peptides, which were based on a repeating alanine-leucine motif, intercalated into small unilamellar DMPC vesicles which formed an α-helix as confirmed by circular dichroic (CD) spectroscopy. Molecular dynamics simulations of the membrane-intercalated helix containing two of the nitrile probes, one near the headgroup region of the lipid (αLAX(25)) and one buried in the interior of the bilayer (αLAX(16)), were used to examine the structure of the nitrile with respect to the membrane normal, the assumed direction of the dipole field, by quantifying both a small tilt of the helix in the bilayer and conformational rotation of the p-CN-Phe side chain at steady state. Vibrational absorption energies of the nitrile oscillator at each position showed a systematic blue shift as the nitrile was stepped toward the membrane interior; for several different concentrations of peptide, the absorption energy of the nitrile located in the middle of the bilayer was ∼3 cm(-1) greater than that of the nitrile closest to the surface of the membrane. Taken together, the measured VSE shifts and nitrile orientations within the membrane resulted in an absolute magnitude of 8-11 MV/cm for the dipole field, at the high end of the range of possible values that have been accumulated from a variety of indirect measurements. Implications for this are discussed.

Growth Mechanism of Lipid-Based Nanodiscs -- a Model Membrane for Studying Kinetics of Particle Coalescence

NASA Astrophysics Data System (ADS)

Nieh, Mu-Ping; Dizon, Anthony; Li, Ming; Hu, Andrew; Fan, Tai-Hsi

2012-02-01

Lipid-based nanodiscs composed of long- and short- chain lipids [namely, dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG) and dihexanoyl phosphatidylcholine (DHPC)] constantly form at high lipid concentrations and at low temperatures (i.e., below the melting transition temperature of DMPC, TM). The initial size of these nanodiscs (at high total lipid concentration, CL> 20 wt.%) is relatively uniform and of similar dimension (according to dynamic light scattering and small angle neutron scattering experiments), seemingly independent of thermal history. Upon dilution, the nanodiscs slowly coalesce and grow in size with time irreversibly. Our preliminary result shows that the growth rate strongly depends on several parameters such as charge density, CL and temperature. We have also found that the nanodisc coalescence is a reaction limit instead of diffusion limit process through a time-resolved study.

Oriented 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine/ganglioside membranes: a Fourier transform infrared attenuated total reflection spectroscopic study. Band assignments; orientational, hydrational, and phase behavior; and effects of Ca2+ binding.

PubMed

Müller, E; Giehl, A; Schwarzmann, G; Sandhoff, K; Blume, A

1996-09-01

Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy was used to elucidate the hydration behavior and molecular order of phospholipid/ganglioside bilayers. We examined dry and hydrated films of the gangliosides GM1, deacetyl-GM1, lyso-GM1, deacetyllyso-GM1, and GM3 and oriented mixed films of these gangliosides with 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) using polarized light. Analysis of the amide I frequencies reveals that the amide groups are involved in intermolecular interactions via hydrogen bonds of varying strengths. The tilt angle of the acyl chains of the lipids in mixed films was determined as a function of ganglioside structure. Deacetylation of the sialic acid in the headgroup has a stronger influence on the tilt angle than the removal of the ganglioside fatty acid. The phase behavior was examined by FTIR ATR spectroscopy and by differential scanning calorimetry (DSC) measurements on lipid suspensions. At the same molar concentration, lyso-gangliosides have less effect on changes of transition temperature compared to the double-chain analogs. Distinct differences in the amide band shapes were observed between mixtures with lyso-gangliosides and normal double-chain gangliosides. Determined from the dicroic ratio RATR, the orientation of the COO- group in all DMPC/ganglioside mixtures was found to be relatively fixed with respect to the membrane normal. In 4:1 mixtures of DMPC with GM1 and deacetyl-GM1, the binding of Ca2+ leads to a slight decrease in chain tilt in the gel phase, probably caused by a dehydration of the membrane-water interface. In mixtures of DMPC with GM3 and deacetyl-lyso-GM1, a slight increase in chain tilt is observed. The chain tilt in DMPC/lyso-GM1 mixtures is unchanged. Analysis of the COO- band reveals that Ca2+ does not bind to the carboxylate group of the sialic acid of GM1 and deacetyl-GM1, the mixtures in which a decrease in chain tilt was observed. Binding to the sialic acid was

Measurement of the Membrane Dipole Electric Field in DMPC Vesicles Using Vibrational Shifts of p-Cyanophenylalanine and Molecular Dynamics Simulations

PubMed Central

Shrestha, Rebika; Cardenas, Alfredo E.; Elber, Ron; Webb, Lauren J.

2015-01-01

The magnitude of the membrane dipole field was measured using vibrational Stark effect (VSE) shifts of nitrile oscillators placed on the unnatural amino acid p-cyanophenylalanine (p-CN-Phe) added to a peptide sequence at four unique positions. These peptides, which were based on a repeating alanine-leucine motif, intercalated into small unilamellar DMPC vesicles which formed an α-helix as confirmed by circular dichroic (CD) spectroscopy. Molecular dynamics simulations of the membrane-intercalated helix containing two of the nitrile probes, one near the head-group region of the lipid (αLAX(25)) and one buried in the interior of the bilayer (αLAX(16)), were used to examine the structure of the nitrile with respect to the membrane normal, the assumed direction the dipole field, by quantifying both a small tilt of the helix in the bilayer and conformational rotation of the p-CN-Phe side chain at steady-state. Vibrational absorption energies of the nitrile oscillator at each position showed a systematic blue shift as the nitrile was stepped towards the membrane interior; for several different concentrations of peptide, the absorption energy of the nitrile located in the middle of the bilayer was ~3 cm−1 greater than that of the nitrile closest to the surface of the membrane. Taken together, the measured VSE shifts and nitrile orientations within the membrane resulted in a value of 8 – 11 MV/cm for the dipole field, at the high end of the range of possible values that have been accumulated from a variety of indirect measurements. Implications for this are discussed. PMID:25602635

Direct comparison of elastic incoherent neutron scattering experiments with molecular dynamics simulations of DMPC phase transitions.

PubMed

Aoun, Bachir; Pellegrini, Eric; Trapp, Marcus; Natali, Francesca; Cantù, Laura; Brocca, Paola; Gerelli, Yuri; Demé, Bruno; Marek Koza, Michael; Johnson, Mark; Peters, Judith

2016-04-01

Neutron scattering techniques have been employed to investigate 1,2-dimyristoyl-sn -glycero-3-phosphocholine (DMPC) membranes in the form of multilamellar vesicles (MLVs) and deposited, stacked multilamellar-bilayers (MLBs), covering transitions from the gel to the liquid phase. Neutron diffraction was used to characterise the samples in terms of transition temperatures, whereas elastic incoherent neutron scattering (EINS) demonstrates that the dynamics on the sub-macromolecular length-scale and pico- to nano-second time-scale are correlated with the structural transitions through a discontinuity in the observed elastic intensities and the derived mean square displacements. Molecular dynamics simulations have been performed in parallel focussing on the length-, time- and temperature-scales of the neutron experiments. They correctly reproduce the structural features of the main gel-liquid phase transition. Particular emphasis is placed on the dynamical amplitudes derived from experiment and simulations. Two methods are used to analyse the experimental data and mean square displacements. They agree within a factor of 2 irrespective of the probed time-scale, i.e. the instrument utilized. Mean square displacements computed from simulations show a comparable level of agreement with the experimental values, albeit, the best match with the two methods varies for the two instruments. Consequently, experiments and simulations together give a consistent picture of the structural and dynamical aspects of the main lipid transition and provide a basis for future, theoretical modelling of dynamics and phase behaviour in membranes. The need for more detailed analytical models is pointed out by the remaining variation of the dynamical amplitudes derived in two different ways from experiments on the one hand and simulations on the other.

Reconciling Differences between Lipid Transfer in Free-Standing and Solid Supported Membranes: A Time-Resolved Small-Angle Neutron Scattering Study.

PubMed

Wah, Benny; Breidigan, Jeffrey M; Adams, Joseph; Horbal, Piotr; Garg, Sumit; Porcar, Lionel; Perez-Salas, Ursula

2017-04-11

Maintaining compositional lipid gradients across membranes in animal cells is essential to biological function, but what is the energetic cost to maintain these differences? It has long been recognized that studying the passive movement of lipids in membranes can provide insight into this toll. Confusingly the reported values of inter- and, particularly, intra-lipid transport rates of lipids in membranes show significant differences. To overcome this difficulty, biases introduced by experimental approaches have to be identified. The present study addresses the difference in the reported intramembrane transport rates of dimyristoylphosphatidylcholine (DMPC) on flat solid supports (fast flipping) and in curved free-standing membranes (slow flipping). Two possible scenarios are potentially at play: one is the difference in curvature of the membranes studied and the other the presence (or not) of the support. Using DMPC vesicles and DMPC supported membranes on silica nanoparticles of different radii, we found that an increase in curvature (from a diameter of 30 nm to a diameter of 100 nm) does not change the rates significantly, differing only by factors of order ∼1. Additionally, we found that the exchange rates of DMPC in supported membranes are similar to the ones in vesicles. And as previously reported, we found that the activation energies for exchange on free-standing and supported membranes are similar (84 and 78 kJ/mol, respectively). However, DMPC's flip-flop rates increase significantly when in a supported membrane, surpassing the exchange rates and no longer limiting the exchange process. Although the presence of holes or cracks in supported membranes explains the occurrence of fast lipid flip-flop in many studies, in defect-free supported membranes we find that fast flip-flop is driven by the surface's induced disorder of the bilayer's acyl chain packing as evidenced from their broad melting temperature behavior.

Effect of phloretin on the binding of 1-anilino-8-naphtalene sulfonate (ANS) to 1,2-Dimyristoyl-sn-glycero-3-phosphocoline (DMPC) vesicles in the gel and liquid-crystalline state.

PubMed

Cutró, Andrea C; Montich, Guillermo; Roveri, Oscar A

2015-02-01

Phloretin is a known modifier of the internal dipole potential of lipid membranes. We studied the interaction of phloretin with model lipid membranes and how it influences the membrane dipole organization using ANS as fluorescent probe. The fluorescence increase observed when ANS binds to DMPC liposomes in gel phase (13 °C) was 2.5 times larger in the presence of phloretin. This effect was due to an increase in ANS affinity, which can be related to the known capability of phloretin in decreasing the dipole potential. Conversely, when the experiments were carried out at 33 °C (liquid crystalline phase), phloretin completely inhibited the increase in ANS fluorescence. In addition, phloretin only affected the electrical properties of the membrane in the gel phase, whereas it modifies structural ones in the liquid-crystalline state. We postulate that phloretin was bound only to the DMPC interface in the gel phase decreasing the surface negative charge density without modifying the structural properties of the ANS binding sites. In the liquid-crystalline phase instead, it increased the accessibility of water to the ANS binding sites decreasing the intrinsic affinity and the fluorescence quantum yield of ANS.

Small RNA and A-to-I Editing in Autism Spectrum Disorders

NASA Astrophysics Data System (ADS)

Eran, Alal

One in every 88 children is diagnosed with Autism Spectrum Disorders (ASDs), a set of neurodevelopmental conditions characterized by social impairments, communication deficits, and repetitive behavior. ASDs have a substantial genetic component, but the specific cause of most cases remains unknown. Understanding gene-environment interactions underlying ASD is essential for improving early diagnosis and identifying critical targets for intervention and prevention. Towards this goal, we surveyed adenosine-to-inosine (A-to-I) RNA editing in autistic brains. A-to-I editing is an epigenetic mechanism that fine-tunes synaptic function in response to environmental stimuli, shown to modulate complex behavior in animals. We used ultradeep sequencing to quantify A-to-I receding of candidate synaptic genes in postmortem cerebella from individuals with ASD and neurotypical controls. We found unexpectedly wide distributions of human A-to-I editing levels, whose extremes were consistently populated by individuals with ASD. We correlated A-to-I editing with isoform usage, identified clusters of correlated sites, and examined differential editing patterns. Importantly, we found that individuals with ASD commonly use a dysfunctional form of the editing enzyme ADARB1. We next profiled small RNAs thought to regulate A-to-I editing, which originate from one of the most commonly altered loci in ASD, 15q11. Deep targeted sequencing of SNORD115 and SNORD116 transcripts enabled their high-resolution detection in human brains, and revealed a strong gender bias underlying their expression. The consistent 2-fold upregulation of 15q11 small RNAs in male vs. female cerebella could be important in delineating the role of this locus in ASD, a male dominant disorder. Overall, these studies provide an accurate population-level view of small RNA and A-to-I editing in human cerebella, and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism

Experimental Acquisitions with ^125I on a Small Animal SPECT Device*

NASA Astrophysics Data System (ADS)

Knott, Kevin; Welsh, Robert E.; Bradley, Eric L.; Saha, Margaret S.; Kross, Brian; Majewski, Stan; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Wojcik, Randolph

2001-04-01

We have performed single photon emission computed tomography (SPECT) studies on a small animal scanning system for which the detector employed position sensitive phototubes (125 mm dia. Hamamatsu R3292 and 18 x 18 mm Hamamatsu M-64) coupled to pixelated scintillators CsI(Tl) and CsI(Na) Phantom acquisitions were used to investigate the effects of angular sampling and scan time on reconstructed image quality and noise. Results from these studies will be described and extended to in vivo studies with small animals. *Supported in part by the Thomas F. and Kate Miller Jeffress Trust, the Department of Energy, The American Diabetes Association, The National Science Foundation, the Howard Hughes Foundation and the Virginia Commonwealth Health Research Board.

The heterogeneity statistic I(2) can be biased in small meta-analyses.

PubMed

von Hippel, Paul T

2015-04-14

Estimated effects vary across studies, partly because of random sampling error and partly because of heterogeneity. In meta-analysis, the fraction of variance that is due to heterogeneity is estimated by the statistic I(2). We calculate the bias of I(2), focusing on the situation where the number of studies in the meta-analysis is small. Small meta-analyses are common; in the Cochrane Library, the median number of studies per meta-analysis is 7 or fewer. We use Mathematica software to calculate the expectation and bias of I(2). I(2) has a substantial bias when the number of studies is small. The bias is positive when the true fraction of heterogeneity is small, but the bias is typically negative when the true fraction of heterogeneity is large. For example, with 7 studies and no true heterogeneity, I(2) will overestimate heterogeneity by an average of 12 percentage points, but with 7 studies and 80 percent true heterogeneity, I(2) can underestimate heterogeneity by an average of 28 percentage points. Biases of 12-28 percentage points are not trivial when one considers that, in the Cochrane Library, the median I(2) estimate is 21 percent. The point estimate I(2) should be interpreted cautiously when a meta-analysis has few studies. In small meta-analyses, confidence intervals should supplement or replace the biased point estimate I(2).

The Consequences of Metric Conversion for Small Manufacturers. Volume I. Summary Report.

DTIC Science & Technology

1982-02-08

RP4 Unlimited IS SUPPLEMENTARY NOTIES I0. KEY WORDS (CNOUS -e~o side NE DIlee... 0ed Idnŕh’ OF WOO~ 11011161) Metrication, Small business , costs...benefited from the conversion except to keep the business of their customers that convert to metric. Metric conversion for small manufacturers is neither... small manufacturprs as a routine aspect of doing business . UJNCLASS IFIED UCVUITY CLASIFICATION OF THIS PA66EVt" " tt*O COATES§i~ S1r’"-’q T I p E L E

Effects of gramicidin-A on the adsorption of phospholipids to the air–water interface

PubMed Central

Biswas, Samares C.; Rananavare, Shankar B.; Hall, Stephen B.

2012-01-01

Prior studies suggest that the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of the lipids in pulmonary surfactant to an air–water interface by stabilizing a negatively curved rate-limiting structure that is intermediate between bilayer vesicles and the surface film. This model predicts that other peptides capable of stabilizing negative curvature should also promote lipid adsorption. Previous reports have shown that under appropriate conditions, gramicidin-A (GrA) induces dioleoyl phosphatidylcholine (DOPC), but not dimyristoyl phosphatidylcholine (DMPC), to form the negatively curved hexagonal-II (HII) phase. The studies reported here determined if GrA would produce the same effects on adsorption of DMPC and DOPC that the hydrophobic surfactant proteins have on the surfactant lipids. Small angle X-ray scattering and 31P-nuclear magnetic resonance confirmed that at the particular conditions used to study adsorption, GrA induced DOPC to form the HII phase, but DMPC remained lamellar. Measurements of surface tension showed that GrA in vesicles produced a general increase in the rate of adsorption for both phospholipids. When restricted to the interface, however, in preexisting films, GrA with DOPC, but not with DMPC, replicated the ability of the surfactant proteins to promote adsorption of vesicles containing only the lipids. The correlation between the structural and functional effects of GrA with the two phospholipids, and the similar effects on adsorption of GrA with DOPC and the hydrophobic surfactant proteins with the surfactant lipids fit with the model in which SP-B and SP-C facilitate adsorption by stabilizing a rate-limiting intermediate with negative curvature. PMID:16242116

Cavitation characteristics of a small centrifugal pump in He I and He II

NASA Technical Reports Server (NTRS)

Ludtke, P. R.; Daney, D. E.

1988-01-01

The cavitation characteristics of a small preinduced centrifugal pump operating in He I and He II over the temperature range 1.8-4.2 K are presented. The pump and close-coupled induction motor operate immersed in liquid helium. A six-blade propeller inducer and a three-blade screw inducer were both tested. With this pump configuration using either inducer, there is a tremendous difference between the cavitation characteristics of He I and He II. The net positive suction head requirements for this pump with the screw inducer could not be determined for He I, but it is less than -100 mm and, depending on flow rate, ranges between 35 and 165 mm for He II.

The gene coding for small ribosomal subunit RNA in the basidiomycete Ustilago maydis contains a group I intron.

PubMed Central

De Wachter, R; Neefs, J M; Goris, A; Van de Peer, Y

1992-01-01

The nucleotide sequence of the gene coding for small ribosomal subunit RNA in the basidiomycete Ustilago maydis was determined. It revealed the presence of a group I intron with a length of 411 nucleotides. This is the third occurrence of such an intron discovered in a small subunit rRNA gene encoded by a eukaryotic nuclear genome. The other two occurrences are in Pneumocystis carinii, a fungus of uncertain taxonomic status, and Ankistrodesmus stipitatus, a green alga. The nucleotides of the conserved core structure of 101 group I intron sequences present in different genes and genome types were aligned and their evolutionary relatedness was examined. This revealed a cluster including all group I introns hitherto found in eukaryotic nuclear genes coding for small and large subunit rRNAs. A secondary structure model was designed for the area of the Ustilago maydis small ribosomal subunit RNA precursor where the intron is situated. It shows that the internal guide sequence pairing with the intron boundaries fits between two helices of the small subunit rRNA, and that minimal rearrangement of base pairs suffices to achieve the definitive secondary structure of the 18S rRNA upon splicing. PMID:1561081

Facilitating Personal Transformations in Small Groups: Part I.

ERIC Educational Resources Information Center

Boyd, Robert D.

1989-01-01

Describes personal transformation in small groups method that employs Matrix Model as its operational structure in Part I of two-part article. Describes method's reliance on metaphors and nature and manner in which they are employed. Defines personal transformation within framework of analytical psychology. (Author/CM)

Influence of ceramide on the internal structure and hydration of the phospholipid bilayer studied by neutron and X-ray scattering

NASA Astrophysics Data System (ADS)

Kiselev, M. A.; Zemlyanaya, E. V.; Ryabova, N. Y.; Hauss, T.; Almasy, L.; Funari, S. S.; Zbytovska, J.; Lombardo, D.

2014-07-01

Small angle neutron scattering (SANS), neutron diffraction and X-ray powder diffraction were used to investigate influence of N-stearoyl phytosphingosine (CER[NP]) and α-hydroxy- N-stearoyl phytosphingosine (CER[AP]) on the internal structure and hydration of DMPC membrane in fully and partly hydrated states at T = 30 °C. Application of Fourier analysis for diffraction data and model calculations for the SANS data evidence that addition of both CER[NP] and CER[AP] in small concentrations promotes significant changes in the organization of DMPC bilayers, such as the increase of the hydrophobic core region. SANS data evidence a decrease in the average radius and polydispersity of the vesicles that can be ascribed to hydrogen bonds interactions that favor tight lipid packing with a compact, more rigid character.

Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates

DOE PAGES

Xia, Yan; Li, Ming; Charubin, Kamil; ...

2015-11-05

In this paper, we report on studies of lipid transfer rates between different morphology nanoparticles and lipids with different length acyl chains. The lipid transfer rate of dimyristoylphosphatidylcholine (di-C 14, DMPC) in discoidal “bicelles” (0.156 h –1) is 2 orders of magnitude greater than that of DMPC vesicles (ULVs) (1.1 × 10 –3 h –1). For both bicellar and ULV morphologies, increasing the acyl chain length by two carbons [going from di-C 14 DMPC to di-C 16, dipalmitoylphosphatidylcholine (DPPC)] causes lipid transfer rates to decrease by more than 2 orders of magnitude. Results from small angle neutron scattering (SANS), differentialmore » scanning calorimetry (DSC), and fluorescence correlation spectroscopy (FCS) are in good agreement. Finally, the present studies highlight the importance of lipid dynamic processes taking place in different morphology biomimetic membranes.« less

Effect of antimicrobial peptide on dynamics of phosphocholine membrane: role of cholesterol and physical state of bilayer

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

Sharma, Veerendra K.; Mamontov, Eugene; Anunciado, Divina B.

Antimicrobial peptides are universal in all forms of life and are well known for their strong interaction with the cell membrane. This makes them a popular target for investigation of peptide-lipid interactions. Here we report the effect of melittin, an important antimicrobial peptide, on the dynamics of membranes based on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid in both the solid gel and fluid phases. To probe the phase transition, elastic neutron intensity temperature scans have been carried out on DMPC-based unilamellar vesicles (ULV) with and without melittin. We have found that addition of a small amount (0.2 mol%) melittin eliminates the steep fallmore » in the elastic intensity at 296 K associated with the solid gel to fluid phase transition, which is observed for pure DMPC vesicles. Quasielastic neutron scattering (QENS) experiments have been carried out on DMPC ULV in the solid gel and fluid phases with and without 0.2 mol % melittin. The data analysis invariably shows the presence of lateral and internal motions of the DMPC molecule. We found that melittin does have a profound effect on the dynamics of lipid molecules, especially on the lateral motion, and affects it in a different way, depending on the phase of the bilayers. In the solid gel phase, it acts as a plasticizer, enhancing the lateral motion of DMPC. However, in the fluid phase it acts as a stiffening agent, restricting the lateral motion of the lipid molecules. These observations are consistent with the mean squared displacements extracted from the elastic intensity temperature scans. Cholesterol is a vital component of eukaryotic membrane, which is a natural target for melittin. To investigate the effect of melittin on vesicles supplemented with cholesterol, QENS experiments have also been carried out on DMPC ULV with 20 mol% cholesterol in the presence and absence of 0.2 mol% melittin. Remarkably, the effects of melittin on the membrane dynamics disappear in the presence

Effect of antimicrobial peptide on dynamics of phosphocholine membrane: role of cholesterol and physical state of bilayer

DOE PAGES

Sharma, Veerendra K.; Mamontov, Eugene; Anunciado, Divina B.; ...

2015-06-24

Antimicrobial peptides are universal in all forms of life and are well known for their strong interaction with the cell membrane. This makes them a popular target for investigation of peptide-lipid interactions. Here we report the effect of melittin, an important antimicrobial peptide, on the dynamics of membranes based on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid in both the solid gel and fluid phases. To probe the phase transition, elastic neutron intensity temperature scans have been carried out on DMPC-based unilamellar vesicles (ULV) with and without melittin. We have found that addition of a small amount (0.2 mol%) melittin eliminates the steep fallmore » in the elastic intensity at 296 K associated with the solid gel to fluid phase transition, which is observed for pure DMPC vesicles. Quasielastic neutron scattering (QENS) experiments have been carried out on DMPC ULV in the solid gel and fluid phases with and without 0.2 mol % melittin. The data analysis invariably shows the presence of lateral and internal motions of the DMPC molecule. We found that melittin does have a profound effect on the dynamics of lipid molecules, especially on the lateral motion, and affects it in a different way, depending on the phase of the bilayers. In the solid gel phase, it acts as a plasticizer, enhancing the lateral motion of DMPC. However, in the fluid phase it acts as a stiffening agent, restricting the lateral motion of the lipid molecules. These observations are consistent with the mean squared displacements extracted from the elastic intensity temperature scans. Cholesterol is a vital component of eukaryotic membrane, which is a natural target for melittin. To investigate the effect of melittin on vesicles supplemented with cholesterol, QENS experiments have also been carried out on DMPC ULV with 20 mol% cholesterol in the presence and absence of 0.2 mol% melittin. Remarkably, the effects of melittin on the membrane dynamics disappear in the presence

Multivariate Analysis of Mixed Lipid Aggregate Phase Transitions Monitored Using Raman Spectroscopy.

PubMed

Neal, Sharon L

2018-01-01

The phase behavior of aqueous 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC)/1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) mixtures between 8.0 ℃ and 41.0 ℃ were monitored using Raman spectroscopy. Temperature-dependent Raman matrices were assembled from series of spectra and subjected to multivariate analysis. The consensus of pseudo-rank estimation results is that seven to eight components account for the temperature-dependent changes observed in the spectra. The spectra and temperature response profiles of the mixture components were resolved by applying a variant of the non-negative matrix factorization (NMF) algorithm described by Lee and Seung (1999). The rotational ambiguity of the data matrix was reduced by augmenting the original temperature-dependent spectral matrix with its cumulative counterpart, i.e., the matrix formed by successive integration of the spectra across the temperature index (columns). Successive rounds of constrained NMF were used to isolate component spectra from a significant fluorescence background. Five major components exhibiting varying degrees of gel and liquid crystalline lipid character were resolved. Hydrogen-bonded water networks exhibiting varying degrees of organization are associated with the lipid components. Spectral parameters were computed to compare the chain conformation, packing, and hydration indicated by the resolved spectra. Based on spectral features and relative amounts of the components observed, four components reflect long chain lipid response. The fifth component could reflect the response of the short chain lipid, DHPC, but there were no definitive spectral features confirming this assignment. A minor component of uncertain assignment that exhibits a striking response to the DMPC pre-transition and chain melting transition also was recovered. While none of the spectra resolved exhibit features unequivocally attributable to a specific aggregate morphology or step in the gelation process

31P NMR and AFM studies on the destabilization of cell and model membranes by the major bovine seminal plasma protein, PDC-109.

PubMed

Damai, Rajani S; Sankhala, Rajeshwer S; Anbazhagan, Veerappan; Swamy, Musti J

2010-11-01

The effect of PDC-109 binding to dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) and supported membranes was investigated by (31)P NMR spectroscopy and atomic force microscopy. Additionally, the effect of cholesterol on the binding of PDC-109 to phosphatidylcholine (PC) membranes was studied. Binding of PDC-109 to MLVs of DMPC and DPPG induced the formation of an isotropic signal in their (31)P NMR spectra, which increased with increasing protein/lipid ratio and temperature, consistent with protein-induced disruption of the MLVs and the formation of small unilamellar vesicles or micelles but not inverse hexagonal or cubic phases. Incorporation of cholesterol in the DMPC MLVs afforded a partial stabilization of the lamellar structure, consistent with previous reports of membrane stabilization by cholesterol. AFM results are consistent with the above findings and show that addition of PDC-109 leads to a complete breakdown of PC membranes. The fraction of isotropic signal in (31)P NMR spectra of DPPG in the presence of PDC-109 was less than that of DMPC under similar conditions, suggesting a significantly higher affinity of the protein for PC. Confocal microscopic studies showed that addition of PDC-109 to human erythrocytes results in a disruption of the plasma membrane and release of hemoglobin into the solution, which was dependent on the protein concentration and incubation time.

Lessons from isolable nickel(I) precursor complexes for small molecule activation.

PubMed

Yao, Shenglai; Driess, Matthias

2012-02-21

Small-molecule activation by transition metals is essential to numerous organic transformations, both biological and industrial. Creating useful metal-mediated activation systems often depends on stabilizing the metal with uncommon low oxidation states and low coordination numbers. This provides a redox-active metal center with vacant coordination sites well suited for interacting with small molecules. Monovalent nickel species, with their d(9) electronic configuration, are moderately strong one-electron reducing agents that are synthetically attractive if they can be isolated. They represent suitable reagents for closing the knowledge gap in nickel-mediated activation of small molecules. Recently, the first strikingly stable dinuclear β-diketiminate nickel(I) precursor complexes were synthesized, proving to be suitable promoters for small-molecule binding and activation. They have led to many unprecedented nickel complexes bearing activated small molecules in different reduction stages. In this Account, we describe selected achievements in the activation of nitrous oxide (N(2)O), O(2), the heavier chalcogens (S, Se, and Te), and white phosphorus (P(4)) through this β-diketiminatonickel(I) precursor species. We emphasize the reductive activation of O(2), owing to its promise in oxidation processes. The one-electron-reduced O(2) activation product, that is, the corresponding β-diketiminato-supported Ni-O(2) complex, is a genuine superoxonickel(II) complex, representing an important intermediate in the early stages of O(2) activation. It selectively acts as an oxygen-atom transfer agent, hydrogen-atom scavenger, or both towards exogenous organic substrates to yield oxidation products. The one-electron reduction of the superoxonickel(II) moiety was examined by using elemental potassium, β-diketiminatozinc(II) chloride, and β-diketiminatoiron(I) complexes, affording the first heterobimetallic complexes featuring a [NiO(2)M] subunit (M is K, Zn, or Fe). Through

Targeting Mycobacterium tuberculosis Topoisomerase I by Small-Molecule Inhibitors

PubMed Central

Godbole, Adwait Anand; Ahmed, Wareed; Bhat, Rajeshwari Subray; Bradley, Erin K.; Ekins, Sean

2014-01-01

We describe inhibition of Mycobacterium tuberculosis topoisomerase I (MttopoI), an essential mycobacterial enzyme, by two related compounds, imipramine and norclomipramine, of which imipramine is clinically used as an antidepressant. These molecules showed growth inhibition of both Mycobacterium smegmatis and M. tuberculosis cells. The mechanism of action of these two molecules was investigated by analyzing the individual steps of the topoisomerase I (topoI) reaction cycle. The compounds stimulated cleavage, thereby perturbing the cleavage-religation equilibrium. Consequently, these molecules inhibited the growth of the cells overexpressing topoI at a low MIC. Docking of the molecules on the MttopoI model suggested that they bind near the metal binding site of the enzyme. The DNA relaxation activity of the metal binding mutants harboring mutations in the DxDxE motif was differentially affected by the molecules, suggesting that the metal coordinating residues contribute to the interaction of the enzyme with the drug. Taken together, the results highlight the potential of these small molecules, which poison the M. tuberculosis and M. smegmatis topoisomerase I, as leads for the development of improved molecules to combat mycobacterial infections. Moreover, targeting metal coordination in topoisomerases might be a general strategy to develop new lead molecules. PMID:25534741

Maxwell displacement current allows to study structural changes of gramicidin A in monolayers at the air-water interface.

PubMed

Vitovic, Pavol; Weis, Martin; Tomcík, Pavol; Cirák, Július; Hianik, Tibor

2007-05-01

We applied methods of measurement Maxwell displacement current (MDC) pressure-area isotherms and dipole potential for analysis of the properties of gramicidin A (gA) and mixed gA/DMPC monolayers at an air-water interface. The MDC method allowed us to observe the kinetics of formation of secondary structure of gA in monolayers at an air-water interface. We showed, that secondary structure starts to form at rather low area per molecule at which gA monolayers are in gaseous state. Changes of the MDC during compression can be attributed to the reorientation of dipole moments in a gA double helix at area 7 nm(2)/molecule, followed by the formation of intertwined double helix of gA. The properties of gA in mixed monolayers depend on the molar fraction of gA/DMPC. At higher molar fractions of gA (around 0.5) the shape of the changes of dipole moment of mixed monolayer was similar to that for pure gA. The analysis of excess free energy in a gel (18( ) degrees C) and in a liquid-crystalline phase (28( ) degrees C) allowed us to show influence of the monolayer structural state on the interaction between gA and the phospholipids. In a gel state and at the gA/DMPC molar ratio below 0.17 the aggregates of gA were formed, while above this molar ratio gA interacts favorably with DMPC. In contrast, for DMPC in a liquid-crystalline state aggregation of gA was observed for all molar fractions studied. The effect of formation ordered structures between gA and DMPC is more pronounced at low temperatures.

A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug's biological activity.

PubMed

Alves, Ana Catarina; Ribeiro, Daniela; Horta, Miguel; Lima, José L F C; Nunes, Cláudia; Reis, Salette

2017-08-01

Daunorubicin is extensively used in chemotherapy for diverse types of cancer. Over the years, evidence has suggested that the mechanisms by which daunorubicin causes cytotoxic effects are also associated with interactions at the membrane level. The aim of the present work was to study the interplay between daunorubicin and mimetic membrane models composed of different ratios of 1,2-dimyristoyl- sn -glycero- 3 -phosphocholine (DMPC), sphingomyelin (SM) and cholesterol (Chol). Several biophysical parameters were assessed using liposomes as mimetic model membranes. Thereby, the ability of daunorubicin to partition into lipid bilayers, its apparent location within the membrane and its effect on membrane fluidity were investigated. The results showed that daunorubicin has higher affinity for lipid bilayers composed of DMPC, followed by DMPC : SM, DMPC : Chol and lastly by DMPC : SM : Chol. The addition of SM or Chol into DMPC membranes not only increases the complexity of the model membrane but also decreases its fluidity, which, in turn, reduces the amount of anticancer drug that can partition into these mimetic models. Fluorescence quenching studies suggest a broad distribution of the drug across the bilayer thickness, with a preferential location in the phospholipid tails. The gathered data support that daunorubicin permeates all types of membranes to different degrees, interacts with phospholipids through electrostatic and hydrophobic bonds and causes alterations in the biophysical properties of the bilayers, namely in membrane fluidity. In fact, a decrease in membrane fluidity can be observed in the acyl region of the phospholipids. Ultimately, such outcomes can be correlated with daunorubicin's biological action, where membrane structure and lipid composition have an important role. In fact, the results indicate that the intercalation of daunorubicin between the phospholipids can also take place in rigid domains, such as rafts that are known to be involved in

The NST observation of a small loop eruption in He I D3 line on 2016 May 30

NASA Astrophysics Data System (ADS)

Kim, Yeon-Han; Xu, Yan; Bong, Su-Chan; Lim, Eunkyung; Yang, Heesu; Park, Young-Deuk; Yurchyshyn, Vasyl B.; Ahn, Kwangsu; Goode, Philip R.

2017-08-01

Since the He I D3 line has a unique response to a flare impact on the low solar atmosphere, it can be a powerful diagnostic tool for energy transport processes. In order to obtain comprehensive data sets for studying solar flare activities in D3 spectral line, we performed observations for several days using the 1.6m New Solar Telescope of Big Bear Solar Observatory (BBSO) in 2015 and 2016, equipped with the He I D3 filter, the photospheric broadband filter, and Near IR imaging spectrograph (NIRIS). On 2016 May 30, we observed a small loop eruption in He I D3 images associated with a B class brightening, which is occurred around 17:10 UT in a small active region, and dynamic variations of photospheric features in G-band images. Accordingly, the cause of the loop eruption can be magnetic reconnection driven by photospheric plasma motions. In this presentation, we will give the observation results and the interpretation.

77 FR 11618 - Solutions Capital I, L.P.; Notice Seeking Exemption Under the Small Business Investment Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... SMALL BUSINESS ADMINISTRATION [License No. 03/03-0247] Solutions Capital I, L.P.; Notice Seeking Exemption Under the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Solutions Capital I, L.P., 1100 Wilson Blvd., Suite 3000, Arlington, VA 22209, a Federal Licensee under the...

PARTITIONING OF PERFLUOROOCTANOATE INTO PHOSPHATIDYLCHOLINE BILAYERS IS CHAIN LENGTH-INDEPENDENT

PubMed Central

Xie, Wei; Bothun, Geoffrey D.; Lehmler, Hans-Joachim

2010-01-01

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature Tm while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA’s effect on the on Tm and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC and DSPC liposomes at 37°C in the DLS experiments, which suggests that PFOA partitions more readily into bilayers in the fluid phase. These findings suggest that PFOA’s effect on the phase behavior of phosphatidylcholines depends on the cooperativity and state (i.e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios > 1, which suggests the formation of mixed PFOA-lipid micelles. PMID:20096277

A Small as Possible

NASA Technical Reports Server (NTRS)

Tibbitts, Scott

2003-01-01

This story begins with a bit of serendipity: I was on a trip to see a Shuttle launch and I happened to sit next to a guy who was in charge of batteries for Space Systems/Loral. He told me that they needed to create a new battery bypass switch, the device that takes a battery out of commission if it goes bad. After discussing the conversation back at my company, we decided that we could create the switch. We contacted the folks at Loral and they said, 'Okay, let s see what you can come up with. We need it as small as possible.' We asked, 'How small?' They said, 'We need it as small as you can possibly make it.'

A Phase 1 Trial of an Immune Checkpoint Inhibitor plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer

DTIC Science & Technology

2017-10-01

with Inoperable Stage I Non-Small Cell Lung Cancer PRINCIPAL INVESTIGATOR: Karen Kelly, MD CONTRACTING ORGANIZATION: University of California...Inhibitor plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer 5b. GRANT NUMBER W81XWH-15-2-0063...immune checkpoint inhibitor MPDL3280A (atezolizumab) in early stage inoperable non-small cell lung cancer . The trial is comprised of a traditional 3 + 3

40 CFR 62.15400 - When must I submit a title V permit application for my existing small municipal waste combustion...

Code of Federal Regulations, 2013 CFR

2013-07-01

... application for my existing small municipal waste combustion unit? 62.15400 Section 62.15400 Protection of... Combustion Units Constructed on or Before August 30, 1999 Title V Requirements § 62.15400 When must I submit a title V permit application for my existing small municipal waste combustion unit? (a) You must...

40 CFR 62.15400 - When must I submit a title V permit application for my existing small municipal waste combustion...

Code of Federal Regulations, 2012 CFR

2012-07-01

... application for my existing small municipal waste combustion unit? 62.15400 Section 62.15400 Protection of... Combustion Units Constructed on or Before August 30, 1999 Title V Requirements § 62.15400 When must I submit a title V permit application for my existing small municipal waste combustion unit? (a) You must...

40 CFR 62.15400 - When must I submit a title V permit application for my existing small municipal waste combustion...

Code of Federal Regulations, 2014 CFR

2014-07-01

... application for my existing small municipal waste combustion unit? 62.15400 Section 62.15400 Protection of... Combustion Units Constructed on or Before August 30, 1999 Title V Requirements § 62.15400 When must I submit a title V permit application for my existing small municipal waste combustion unit? (a) You must...

40 CFR 62.15400 - When must I submit a title V permit application for my existing small municipal waste combustion...

Code of Federal Regulations, 2010 CFR

2010-07-01

... application for my existing small municipal waste combustion unit? 62.15400 Section 62.15400 Protection of... Combustion Units Constructed on or Before August 30, 1999 Title V Requirements § 62.15400 When must I submit a title V permit application for my existing small municipal waste combustion unit? (a) You must...

40 CFR 62.15400 - When must I submit a title V permit application for my existing small municipal waste combustion...

Code of Federal Regulations, 2011 CFR

2011-07-01

... application for my existing small municipal waste combustion unit? 62.15400 Section 62.15400 Protection of... Combustion Units Constructed on or Before August 30, 1999 Title V Requirements § 62.15400 When must I submit a title V permit application for my existing small municipal waste combustion unit? (a) You must...

40 CFR Table 2 to Subpart Bbbb of... - Model Rule-Class I Emission Limits for Existing Small Municipal Waste Combustion Units a

Code of Federal Regulations, 2014 CFR

2014-07-01

... Existing Small Municipal Waste Combustion Units a 2 Table 2 to Subpart BBBB of Part 60 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... Part 60—Model Rule—Class I Emission Limits for Existing Small Municipal Waste Combustion Units a For...

40 CFR Table 2 to Subpart Bbbb of... - Model Rule-Class I Emission Limits for Existing Small Municipal Waste Combustion Units a

Code of Federal Regulations, 2012 CFR

2012-07-01

... Existing Small Municipal Waste Combustion Units a 2 Table 2 to Subpart BBBB of Part 60 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... Part 60—Model Rule—Class I Emission Limits for Existing Small Municipal Waste Combustion Units a For...

40 CFR Table 2 to Subpart Bbbb of... - Model Rule-Class I Emission Limits for Existing Small Municipal Waste Combustion Units a

Code of Federal Regulations, 2013 CFR

2013-07-01

... Existing Small Municipal Waste Combustion Units a 2 Table 2 to Subpart BBBB of Part 60 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... Part 60—Model Rule—Class I Emission Limits for Existing Small Municipal Waste Combustion Units a For...

40 CFR Table 2 to Subpart Bbbb of... - Model Rule-Class I Emission Limits for Existing Small Municipal Waste Combustion Units a

Code of Federal Regulations, 2010 CFR

2010-07-01

... Existing Small Municipal Waste Combustion Units a 2 Table 2 to Subpart BBBB of Part 60 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... Part 60—Model Rule—Class I Emission Limits for Existing Small Municipal Waste Combustion Units a For...

40 CFR Table 2 to Subpart Bbbb of... - Model Rule-Class I Emission Limits for Existing Small Municipal Waste Combustion Units a

Code of Federal Regulations, 2011 CFR

2011-07-01

... Existing Small Municipal Waste Combustion Units a 2 Table 2 to Subpart BBBB of Part 60 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... Part 60—Model Rule—Class I Emission Limits for Existing Small Municipal Waste Combustion Units a For...

Correlation of membrane binding and hydrophobicity to the chaperone-like activity of PDC-109, the major protein of bovine seminal plasma.

PubMed

Sankhala, Rajeshwer S; Damai, Rajani S; Swamy, Musti J

2011-03-08

The major protein of bovine seminal plasma, PDC-109 binds to choline phospholipids present on the sperm plasma membrane upon ejaculation and plays a crucial role in the subsequent events leading to fertilization. PDC-109 also shares significant similarities with small heat shock proteins and exhibits chaperone-like activity (CLA). Although the polydisperse nature of this protein has been shown to be important for its CLA, knowledge of other factors responsible for such an activity is scarce. Since surface exposure of hydrophobic residues is known to be an important factor which modulates the CLA of chaperone proteins, in the present study we have probed the surface hydrophobicity of PDC-109 using bisANS and ANS. Further, effect of phospholipids on the structure and chaperone-like activity of PDC-109 was studied. Presence of DMPC was found to increase the CLA of PDC-109 significantly, which could be due to the considerable exposure of hydrophobic regions on the lipid-protein recombinants, which can interact productively with the nonnative structures of target proteins, resulting in their protection. However, inclusion of DMPG instead of DMPC did not significantly alter the CLA of PDC-109, which could be due to the lower specificity of PDC-109 for DMPG as compared to DMPC. Cholesterol incorporation into DMPC membranes led to a decrease in the CLA of PDC-109-lipid recombinants, which could be attributed to reduced accessibility of hydrophobic surfaces to the substrate protein(s). These results underscore the relevance of phospholipid binding and hydrophobicity to the chaperone-like activity of PDC-109.

Correlation of Membrane Binding and Hydrophobicity to the Chaperone-Like Activity of PDC-109, the Major Protein of Bovine Seminal Plasma

PubMed Central

Sankhala, Rajeshwer S.; Damai, Rajani S.; Swamy, Musti J.

2011-01-01

The major protein of bovine seminal plasma, PDC-109 binds to choline phospholipids present on the sperm plasma membrane upon ejaculation and plays a crucial role in the subsequent events leading to fertilization. PDC-109 also shares significant similarities with small heat shock proteins and exhibits chaperone-like activity (CLA). Although the polydisperse nature of this protein has been shown to be important for its CLA, knowledge of other factors responsible for such an activity is scarce. Since surface exposure of hydrophobic residues is known to be an important factor which modulates the CLA of chaperone proteins, in the present study we have probed the surface hydrophobicity of PDC-109 using bisANS and ANS. Further, effect of phospholipids on the structure and chaperone-like activity of PDC-109 was studied. Presence of DMPC was found to increase the CLA of PDC-109 significantly, which could be due to the considerable exposure of hydrophobic regions on the lipid-protein recombinants, which can interact productively with the nonnative structures of target proteins, resulting in their protection. However, inclusion of DMPG instead of DMPC did not significantly alter the CLA of PDC-109, which could be due to the lower specificity of PDC-109 for DMPG as compared to DMPC. Cholesterol incorporation into DMPC membranes led to a decrease in the CLA of PDC-109-lipid recombinants, which could be attributed to reduced accessibility of hydrophobic surfaces to the substrate protein(s). These results underscore the relevance of phospholipid binding and hydrophobicity to the chaperone-like activity of PDC-109. PMID:21408153

High Bypass Turbofan Component Development. Amendment I. Small Fan Redesign.

DTIC Science & Technology

1980-02-01

A0A89 67 BENRAL EECTRIC CO LYNN MA AIRCRAFT ENGINE GROUP P’S 21 5 HIGH BYPASS TURBOFAN COMPONENT DEVELOPMENT. AMENDMENT I. SMALL -ETC(U) FEB 80 H...Weldon Aircraft Engine Group S General Electric Co. Lynn, Massachusetts 01910 0 February 1980 DTC Technical Report AF.AL-TR-80-2011 Final Report for...LARRY W.4ILL, CAPT, USAF ERIK W. LINDNER, TAM Project Engineer Special Engines Performance Branch Performance Branch Turbine Engine Division FOR THE

Effectiveness of local therapy for stage I non-small-cell lung cancer in nonagenarians.

PubMed

Arnold, Brian N; Thomas, Daniel C; Rosen, Joshua E; Salazar, Michelle C; Detterbeck, Frank C; Blasberg, Justin D; Boffa, Daniel J; Kim, Anthony W

2017-09-01

Stage I non-small-cell lung cancer is potentially curable, yet older patients undergo treatment at lower rates than younger patients. This analysis sought to describe the treatment outcomes of nonagenarians with stage I non-small-cell lung cancer to better guide treatment decisions in this population. The National Cancer DataBase was queried for patients age ≥90 years old with stage I non-small-cell lung cancer (tumors ≤4 cm). Patients were divided into 3 groups: local therapy, other therapy, or no treatment. The primary outcomes were 5-year overall and relative survival. Of the 616 patients identified, 33% (202) were treated with local therapy, 34% (207) were treated with other therapy, and 34% (207) underwent no treatment. Compared with local therapy, overall mortality was significantly higher with no treatment (hazard ratio 2.50, 95% confidence interval, 1.95-3.21) and other therapy (hazard ratio 1.43, 95% confidence interval, 1.11-1.83). The 5-year relative survival was 81% for local therapy, 49% for other therapy, and 32% for no treatment (P < .0001). Nonagenarians managed with local therapy for stage I non-small-cell lung cancer (tumors ≤4 cm) have better overall survival than those receiving other therapy or no treatment and should be considered for treatment with either operation or stereotactic body radiation therapy if able to tolerate treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 32230 - Solutions Capital I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

... SMALL BUSINESS ADMINISTRATION [License No. 03/03-0247] Solutions Capital I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Solutions Capital I, L.P., 1100 Wilson Blvd., Suite 3000, Arlington, VA 22209, a Federal...

Acemetacin-phosphatidylcholine interactions are determined by the drug ionization state.

PubMed

Pereira-Leite, Catarina; Nunes, Cláudia; Grahl, Débora; Bozelli, José C; Schreier, Shirley; Kamma-Lorger, Christina S; Cuccovia, Iolanda M; Reis, Salette

2018-05-17

Gastrointestinal (GI) toxicity is a major drawback of the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAIDs topical actions on the protective phospholipid layers of the GI mucosa seem to be a central toxicity mechanism of these pharmaceuticals. This work describes the interactions of acemetacin, a commercialized NSAID, with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at pH 3.0, 5.0, and 7.4. This pH range was chosen to mimic the pH gradient found in the gastric mucosa, and to ultimately gain insights into the mechanisms underlying the acemetacin-induced gastric toxicity. Various experimental techniques were combined to characterize the partitioning of acemetacin in DMPC bilayers, and its effects on the phase transition behavior, as well as the structure and dynamics of DMPC bilayers. The acemetacin-DMPC interactions were clearly pH-dependent. The neutral (protonated) form of acemetacin had more affinity for the DMPC bilayer than the negatively charged form. Due to the higher affinity of neutral acemetacin, the drug effects on the phase transition and the structure and dynamics of the DMPC bilayer were more pronounced at lower pH values. In general, acemetacin decreased the temperature and the cooperativity of the lipid phase transition and induced changes in the packing and dynamics of the DMPC bilayer. These results support the hypothesis that acemetacin-induced gastric toxicity may be related to its effects on the protective phospholipid layers of the mucosal barrier.

77 FR 23229 - Submission for OMB Review; Small Business Innovation Research (SBIR) Program-Phase I-Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

....133). This is in response to Public Law 106- 554, the ``Small Business Reauthorization Act of [[Page... DEPARTMENT OF EDUCATION Submission for OMB Review; Small Business Innovation Research (SBIR) Program--Phase I--Grant Application Package SUMMARY: This application package invites small business...

Small Business Innovation Research. Abstracts of Phase I awards, 1999

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

None

1999-12-01

This booklet presents technical abstracts of Phase I awards made in Fiscal Year (FY) 1999 under the DOE Small Business Innovation Research (SBIR) program. SBIR research explores innovative concepts in important technological and scientific areas that can lead to valuable new technology and products. The work described in the abstracts is novel, high-risk research, but the benefits will also be potentially high if the objectives are met. Brief comments on the potential applications, as described by the awardee, are given after each abstract. Individuals and organizations, including venture capital and larger industrial firms, with an interest in the research describedmore » in any of the abstracts are encouraged to contact the appropriate small business directly.« less

Cholesterol-diethylenetriaminepentaacetate complexed with thulium ions integrated into bicelles to increase their magnetic alignability.

PubMed

Liebi, Marianne; Kuster, Simon; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Walde, Peter; Windhab, Erich J

2013-11-27

Lanthanides have been used for several decades to increase the magnetic alignability of bicelles. DMPE-DTPA (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylenetriaminepentaacetate) is commonly applied to anchor the lanthanides into the bicelles. However, because DMPE-DTPA has the tendency to accumulate at the highly curved edge region of the bicelles and if located there does not contribute to the magnetic orientation energy, we have tested cholesterol-DTPA complexed with thulium ions (Tm(3+)) as an alternative chelator to increase the magnetic alignability. Differential scanning calorimetric (DSC) measurements indicate the successful integration of cholesterol-DTPA into a DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) bilayer. Cryo transmission electron microscopy and small-angle neutron scattering (SANS) measurements show that the disklike structure, that is, bicelles, is maintained if cholesterol-DTPA·Tm(3+) is integrated into a mixture of DMPC, cholesterol, and DMPE-DTPA·Tm(3+). The size of the bicelles is increased compared to the size of the bicelles obtained from mixtures without cholesterol-DTPA·Tm(3+). Magnetic-field-induced birefringence and SANS measurements in a magnetic field show that with addition of cholesterol-DTPA·Tm(3+) the magnetic alignability of these bicelles is significantly increased compared to bicelles composed of DMPC, cholesterol, and DMPE-DTPA·Tm(3+) only.

Small Business Management. Part I, A Suggested Course Outline.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Continuing Education Curriculum Development.

In this curriculum guide on small business management, lessons (including specific course content and teaching suggestions) are developed around general traits and practices conducive to success in small businesses, loans and other sources of capital, budgeting and planning, recordkeeping, marketing and selling, advertising and sales promotion,…

Characterization of a small CsI(Na)-WSF-SiPM gamma camera prototype using 99mTc

NASA Astrophysics Data System (ADS)

Castro, I. F.; Soares, A. J.; Moutinho, L. M.; Ferreira, M. A.; Ferreira, R.; Combo, A.; Muchacho, F.; Veloso, J. F. C. A.

2013-03-01

A small field of view gamma camera is being developed, aiming for applications in scintimammography, sentinel lymph node detection or small animal imaging and research. The proposed wavelength-shifting fibre (WSF) gamma camera consists of two perpendicular sets of WSFs covering both sides of a CsI(Na) crystal, such that the fibres positioned at the bottom of the crystal provide the x coordinate and the ones on top the y coordinate of the gamma photon interaction point. The 2D position is given by highly sensitive photodetectors reading out each WSF and the energy information is provided by PMTs that cover the full detector area. This concept has the advantage of using N+N instead of N × N photodetectors to cover an identical imaging area, and is being applied using for the first time SiPMs. Previous studies carried out with 57Co have proved the feasibility of this concept using SiPM readout. In this work, we present experimental results from true 2D image acquisitions with a 10+10 SiPMs prototype, i.e. 10 × 10 mm2, using a parallel-hole collimator and different samples filled with 99mTc solution. The performance of the small prototype in these conditions is evaluated through the characterization of different gamma camera parameters, such as energy and spatial resolution. Ongoing advances towards a larger prototype of 100+100 SiPMs (10 × 10 cm2) are also presented.

Things I Wish They Had Told Me: Advice From a Newly Tenured Faculty Member From a Small, Liberal Arts College

NASA Astrophysics Data System (ADS)

Sheldon, Peter

2002-04-01

I followed a relatively unique path to tenure. I knew I wanted to teach at a small, liberal arts college, so I chose to “post-doc” as a visiting faculty member instead of doing research. I continued to do research as I taught, but teaching was the main focus. I feel that the path that I followed, the opportunities for research and having found tremendously effective mentors in my three years as a visiting faculty member put me in the perfect position to find the job I wanted. I am now in the fourth year of my first tenure-track job, and find myself with tenure. Randolph-Macon Woman’s College is a nationally ranked liberal arts college in central VA with 720 students. The Department of Physics and Astronomy offers both a BA and a BS in physics, and in struggling to stay alive with only two faculty members, I have actually managed to keep going with a few research and grant opportunities. I hope that my experiences will strike a chord with some of the audience, and my experiences can help others to decide what is and what is not important to them in the finding and holding of a faculty job. Other topics that could be covered include juggling responsibilities, seeking grants, dealing with colleagues, interacting with students, and learning to teach.

Polarization-modulated FTIR spectroscopy of lipid/gramicidin monolayers at the air/water interface.

PubMed Central

Ulrich, W P; Vogel, H

1999-01-01

Monolayers of gramicidin A, pure and in mixtures with dimyristoylphosphatidylcholine (DMPC), were studied in situ at the air/H2O and air/D2O interfaces by polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Simulations of the entire set of amide I absorption modes were also performed, using complete parameter sets for different conformations based on published normal mode calculations. The structure of gramicidin A in the DMPC monolayer could clearly be assigned to a beta6.3 helix. Quantitative analysis of the amide I bands revealed that film pressures of up to 25-30 mN/m the helix tilt angle from the vertical in the pure gramicidin A layer exceeded 60 degrees. A marked dependence of the peptide orientation on the applied surface pressure was observed for the mixed lipid-peptide monolayers. At low pressure the helix lay flat on the surface, whereas at high pressures the helix was oriented almost parallel to the surface normal. PMID:10049344

75 FR 45178 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... SMALL BUSINESS ADMINISTRATION Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners SBIC I, L.P., 300 W. 6th Street, Suite 2250, Austin, TX 78701, a Federal...

76 FR 76475 - Tregaron Opportunity Fund I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-07

... SMALL BUSINESS ADMINISTRATION [License No. 09/09-0463] Tregaron Opportunity Fund I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Tregaron Opportunity Fund I, L.P., 540 University Avenue, Suite 250, Palo Alto, CA...

Small Business Innovation Research GRC Phase I, Phase II, and Post-Phase II Opportunity Assessment for 2015

NASA Technical Reports Server (NTRS)

Nguyen, Hung D.; Steele, Gynelle C.

2016-01-01

This report outlines the 2015 Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) Phase I, Phase II, and Post-Phase II opportunity contract award results associated with NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD) for NASA Glenn Research Center. The report also highlights the number of Phase I, Phase II, and Post-Phase II contracts awarded by mission directorate. The 2015 Phase I contract awards to companies in Ohio and their corresponding technologies are also discussed.

Superparamagnetic iron oxide nanoparticles modified with dimyristoylphosphatidylcholine and their distribution in the brain after injection in the rat substantia nigra.

PubMed

Su, Lichao; Zhang, Baolin; Huang, Yinping; Zhang, Hao; Xu, Qin; Tan, Jie

2017-12-01

The subcellular distributions of nanoparticles in the brain are important for their biological application. We synthesized and characterized the superparamagnetic iron oxide nanoparticles (SPIONs) modified with poly (ethylene glycol) (PEG) and polyethylenimine (PEI) (PEG/PEI-SPIONs), and with dimyristoylphosphatidylcholine (DMPC) (DMPC-SPIONs). The nanoparticles were unilaterally injected into the left substantia nigra of rat brains. The distributions of the nanoparticles in the left brains of the rats were examined by ICP-OES (inductively coupled plasma optical emission spectrometer) and TEM (transmission electron microscopy) at 24h after the injection. Iron was found in the olfactory bulb, temporal lobe, frontal cortex, thalamus and brain stem at 24h after the injection of DMPC-SPIONs and PEG/PEI-SPIONs. In the rat substantia nigra, most DMPC-SPIONs were distributed in and on the myelin sheath around axons or on cell membranes, some were in cells. As a comparison, less iron was found in the rat brains at 24h after the injection of PEG/PEI-SPIONs. Our experiments suggest DMPC modification on SPIONs be a safe and effective method for increasing SPIONs distribution on the cell membranes. This work is encouraging for further study on using DMPC-SPIONs for efficient drug delivery or for deep brain stimulation of neurons in a magnetic field. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

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

Mamontov, Eugene; Tyagi, M.; Qian, Shuo

Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature nomore » longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.« less

Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

DOE PAGES

Mamontov, Eugene; Tyagi, M.; Qian, Shuo; ...

2016-05-27

Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature nomore » longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.« less

40 CFR 60.1565 - What subcategories of small municipal waste combustion units must I include in my State plan?

Code of Federal Regulations, 2014 CFR

2014-07-01

... waste combustion units must I include in my State plan? 60.1565 Section 60.1565 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... of small municipal waste combustion units must I include in my State plan? This subpart specifies...

40 CFR 60.1565 - What subcategories of small municipal waste combustion units must I include in my State plan?

Code of Federal Regulations, 2011 CFR

2011-07-01

... waste combustion units must I include in my State plan? 60.1565 Section 60.1565 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... of small municipal waste combustion units must I include in my State plan? This subpart specifies...

40 CFR 60.1565 - What subcategories of small municipal waste combustion units must I include in my State plan?

Code of Federal Regulations, 2012 CFR

2012-07-01

... waste combustion units must I include in my State plan? 60.1565 Section 60.1565 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... of small municipal waste combustion units must I include in my State plan? This subpart specifies...

40 CFR 60.1565 - What subcategories of small municipal waste combustion units must I include in my State plan?

Code of Federal Regulations, 2013 CFR

2013-07-01

... waste combustion units must I include in my State plan? 60.1565 Section 60.1565 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... of small municipal waste combustion units must I include in my State plan? This subpart specifies...

40 CFR 60.1565 - What subcategories of small municipal waste combustion units must I include in my State plan?

Code of Federal Regulations, 2010 CFR

2010-07-01

... waste combustion units must I include in my State plan? 60.1565 Section 60.1565 Protection of... NEW STATIONARY SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion... of small municipal waste combustion units must I include in my State plan? This subpart specifies...

77 FR 42353 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners SBIC I, L.P., 300 West 6th Street, Suite 2250...

76 FR 619 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners, SBIC I, L.P., 300 W. 6th Street, Suite 2250...

76 FR 68803 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... SMALL BUSINESS ADMINISTRATION [License No. 06/06-0335] Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners, SBIC I, L.P., 300 W. 6th Street, Suite 2250...

Incidence of hypothyroidism following small doses of /sup 131/I in the treatment of Graves' disease

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

McCullagh, F.P.; Jelden, G.L.; Rodriguez-Antunez, A.

1976-09-01

In a group of 147 patients treated with /sup 131/I in doses of 3.0 millicuries or less for Graves' disease, the incidence of hypothyroidism was calculated 10 to 17 years after treatment. This paper emphasizes the frequency of hypothyroidism after treatment with /sup 131/I in small doses, if sufficient time lapse is considered.

Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery

ClinicalTrials.gov

2018-04-27

EGFR (Epidermal Growth Factor Receptor) Exon 19 Deletion Mutation; EGFR NP_005219.2:p.L858R; EGFR NP_005219.2:p.T790M; Stage I Non-Small Cell Lung Cancer AJCC (American Joint Committee on Cancer) v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Data decomposition method for parallel polygon rasterization considering load balancing

NASA Astrophysics Data System (ADS)

Zhou, Chen; Chen, Zhenjie; Liu, Yongxue; Li, Feixue; Cheng, Liang; Zhu, A.-xing; Li, Manchun

2015-12-01

It is essential to adopt parallel computing technology to rapidly rasterize massive polygon data. In parallel rasterization, it is difficult to design an effective data decomposition method. Conventional methods ignore load balancing of polygon complexity in parallel rasterization and thus fail to achieve high parallel efficiency. In this paper, a novel data decomposition method based on polygon complexity (DMPC) is proposed. First, four factors that possibly affect the rasterization efficiency were investigated. Then, a metric represented by the boundary number and raster pixel number in the minimum bounding rectangle was developed to calculate the complexity of each polygon. Using this metric, polygons were rationally allocated according to the polygon complexity, and each process could achieve balanced loads of polygon complexity. To validate the efficiency of DMPC, it was used to parallelize different polygon rasterization algorithms and tested on different datasets. Experimental results showed that DMPC could effectively parallelize polygon rasterization algorithms. Furthermore, the implemented parallel algorithms with DMPC could achieve good speedup ratios of at least 15.69 and generally outperformed conventional decomposition methods in terms of parallel efficiency and load balancing. In addition, the results showed that DMPC exhibited consistently better performance for different spatial distributions of polygons.

Investigating new activators for small-bandgap LaX3 (X = Br, I) scintillators

NASA Astrophysics Data System (ADS)

Rutstrom, Daniel; Collette, Robyn; Stand, Luis; Loyd, Matthew; Wu, Yuntao; Koschan, Merry; Melcher, Charles L.; Zhuravleva, Mariya

2018-02-01

Luminescence and scintillation properties of Bi3+, Sb3+, and Eu2+-doped LaI3 and LaBr3 were explored. Out of the three dopants investigated, Eu2+ was the most promising new activator for small-bandgap LaX3 (X = Br, I) and was further studied in the mixed-halide LaBr3-xIx. Crystals were grown from the melt using the vertical Bridgman method. LaBr3:Eu2+ 0.5% (mol) had the most favorable scintillation properties with a light output of 43,000 ph/MeV and 6% energy resolution at 662 keV. Performance of LaBr3-xIx:Eu2+ worsened for most samples as iodide concentration was increased. Room-temperature scintillation of LaI3:Eu2+ 0.1% and 0.5% was observed and is the first case of room-temperature emission reported for doped LaI3.

Angiotensin-Converting Enzyme I/D Polymorphism and Preeclampsia Risk: Evidence of Small-Study Bias

PubMed Central

Serrano, Norma C; Díaz, Luis A; Páez, Maria C; Mesa, Clara M; Cifuentes, Rodrigo; Monterrosa, Alvaro; González, Adriana; Smeeth, Liam; Hingorani, Aroon D; Casas, Juan P

2006-01-01

Background Inappropriate activation of the renin–angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks. Methods and Findings A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR = 0.95 [95% CI, 0.81–1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR = 0.90 [95% CI, 0.77–1.06]) and using other genetic models of inheritance. A meta-analysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07–1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased. Conclusions It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of

A General Method for Assessing the Origin of Interstellar Small Bodies: The Case of 1I/2017 U1 (‘Oumuamua)

NASA Astrophysics Data System (ADS)

Zuluaga, Jorge I.; Sánchez-Hernández, Oscar; Sucerquia, Mario; Ferrín, Ignacio

2018-06-01

With the advent of more and deeper sky surveys, the discovery of interstellar small objects entering into the solar system has been finally possible. In 2017 October 19, using observations of the Pan-STARRS survey, a fast moving object, now officially named 1I/2017 U1 (‘Oumuamua), was discovered in a heliocentric unbound trajectory, suggesting an interstellar origin. Assessing the provenance of interstellar small objects is key for understanding their distribution, spatial density, and the processes responsible for their ejection from planetary systems. However, their peculiar trajectories place a limit on the number of observations available to determine a precise orbit. As a result, when its position is propagated ∼105–106 years backward in time, small errors in orbital elements become large uncertainties in position in the interstellar space. In this paper we present a general method for assigning probabilities to nearby stars of being the parent system of an observed interstellar object. We describe the method in detail and apply it for assessing the origin of ‘Oumuamua. A preliminary list of potential progenitors and their corresponding probabilities is provided. In the future, when further information about the object and/or the nearby stars be refined, the probabilities computed with our method can be updated. We provide all the data and codes we developed for this purpose in the form of an open source C/C++/Python package, iWander, which is publicly available at http://github.com/seap-udea/iWander.

Stereotactic Body Radiation Therapy Followed by Surgery in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer

ClinicalTrials.gov

2017-12-28

Stage I Non-Small Cell Lung Cancer AJCC v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Thermal stabilization of bicelles by a bile-salt-derived detergent: a combined ³¹P and ²H nuclear magnetic resonance study.

PubMed

Morales, Hannah Hazel; Saleem, Qasim; Macdonald, Peter M

2014-12-23

The properties of bicelles composed of mixtures of long-chain lipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG), stabilized by zwitterionic bile salt analogue 3-[(3-cholamidopropyl)dimethyl-d6-ammonio]-2-hydroxy-1-propanesulfonate (CHAPSO-d6), deuterated at both amino methyls, were investigated by a combination of (31)P and (2)H NMR, focusing on the behavior of CHAPSO as a function of temperature. For compositions of molar ratio q = [DMPC + DMPG]/[CHAPSO] = 3, R = [DMPG]/[DMPC + DMPG] = 0, 0.01 and 0.10 and lipid concentration CL = 25 wt % lipid at temperatures of between 30 and 60 °C, magnetic alignment was readily achieved as assessed via both (31)P NMR of the phospholipids and (2)H NMR of CHAPSO-d6. Increasing temperature yielded higher values for the chemical shift anisotropy of the former and the quadrupole splitting of the latter, consistent with the progressive migration of CHAPSO from edge regions into planar regions of the bicellar assemblies. However, relative to dihexadecyl phosphatidylcholine (DHPC), CHAPSO exhibited lower miscibility with DMPC, although the presence of DMPG enhanced this miscibility. At 65 °C, thermal instability became evident in the appearance of a separate isotropic component in both (31)P and (2)H NMR spectra. This isotropic phase was CHAPSO-enriched but less so as a function of increasing DMPG. These findings indicate that the enhanced thermal stability of CHAPSO- versus DHPC-containing bicelles arises from a combination of the larger surface area that edge CHAPSO is able to mask, mole for mole, and its relative preference for edge regions, plus, possibly, specific interactions with DMPG.

Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer.

PubMed

Kim, Soo-Yeon; Lee, Sang-Jin; Kim, Jin-Ki; Choi, Han-Gon; Lim, Soo-Jeong

2017-01-01

Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus-liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation.

Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer

PubMed Central

Kim, Soo-Yeon; Lee, Sang-Jin; Kim, Jin-Ki; Choi, Han-Gon; Lim, Soo-Jeong

2017-01-01

Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation. PMID:29070949

76 FR 35263 - Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... SMALL BUSINESS ADMINISTRATION [License No. 02/72-0625] Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is... 107.730, Financings Which Constitute Conflicts of Interest of the Small Business Administration (``SBA...

Changes in lipid bilayer structure caused by the helix-to-sheet transition of an HIV-1 gp41 fusion peptide derivative

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

Heller, William T.; Rai, Durgesh K.

HIV-1, like other enveloped viruses, undergoes fusion with the cell membrane to infect it. Viral coat proteins are thought to bind the virus to the membrane and actively fuse the viral and cellular membranes together. The actual molecular mechanism of fusion is challenging to visualize, resulting in the use of model systems. In this paper, the bilayer curvature modifying properties of a synthetic variant of the HIV-1 gp41 fusion peptide with lipid bilayer vesicles composed of a mixture of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) were studied. In 7:3 DMPC:DMPS vesicles made with deuterium-labeled DMPC, the peptide was observedmore » to undergo a concentration-dependent conformational transition between an α-helix and an antiparallel β-sheet. Through the use of small-angle neutron scattering (SANS) and selective deuterium labeling, it was revealed that conformational transition of the peptide is also accompanied by a transition in the structure of the lipid bilayer. In addition to changes in the distribution of the lipid between the leaflets of the vesicle, the SANS data are consistent with two regions having different thicknesses. Finally, of the two different bilayer structures, the one corresponding to the smaller area fraction, being ~8% of the vesicle area, is much thicker than the remainder of the vesicle, which suggests that there are regions of localized negative curvature similar to what takes place at the point of contact between two membranes immediately preceding fusion.« less

Changes in lipid bilayer structure caused by the helix-to-sheet transition of an HIV-1 gp41 fusion peptide derivative

DOE PAGES

Heller, William T.; Rai, Durgesh K.

2017-01-16

HIV-1, like other enveloped viruses, undergoes fusion with the cell membrane to infect it. Viral coat proteins are thought to bind the virus to the membrane and actively fuse the viral and cellular membranes together. The actual molecular mechanism of fusion is challenging to visualize, resulting in the use of model systems. In this paper, the bilayer curvature modifying properties of a synthetic variant of the HIV-1 gp41 fusion peptide with lipid bilayer vesicles composed of a mixture of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) were studied. In 7:3 DMPC:DMPS vesicles made with deuterium-labeled DMPC, the peptide was observedmore » to undergo a concentration-dependent conformational transition between an α-helix and an antiparallel β-sheet. Through the use of small-angle neutron scattering (SANS) and selective deuterium labeling, it was revealed that conformational transition of the peptide is also accompanied by a transition in the structure of the lipid bilayer. In addition to changes in the distribution of the lipid between the leaflets of the vesicle, the SANS data are consistent with two regions having different thicknesses. Finally, of the two different bilayer structures, the one corresponding to the smaller area fraction, being ~8% of the vesicle area, is much thicker than the remainder of the vesicle, which suggests that there are regions of localized negative curvature similar to what takes place at the point of contact between two membranes immediately preceding fusion.« less

Preparation of pancreatic β-cells from human iPS cells with small molecules

PubMed Central

2012-01-01

Human induced pluripotent stem (iPS) cells obtained from patients are expected to be a useful source for cell transplantation therapy, because many patients (including those with type 1 diabetes and severe type 2 diabetes) are on waiting lists for transplantation for a long time due to the shortage of donors. At present, many concerns related to clinical application of human iPS cells have been raised, but rapid development of methods for the establishment, culture, and standardization of iPS cells will lead autologous cell therapy to be realistic sooner or later. However, establishment of a method for preparing some of desired cell types is still challenging. Regarding pancreatic β-cells, there have been many reports about differentiation of these cells from human embryonic stem (ES)/iPS cells, but a protocol for clinical application has still not been established. Since there is clear proof that cell transplantation therapy is effective for diabetes based on the results of clinical islet transplantation, pancreatic β-cells prepared from human iPS cells are considered likely to be effective for reducing the burden on patients. In this article, the current status of procedures for preparing pancreatic β-cells from human ES/iPS cells, including effective use of small molecules, is summarized, and some of the problems that still need to be overcome are discussed. PMID:22722666

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation

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

Urra, Félix A., E-mail: felix.urra@qf.uchile.cl; Córdova-Delgado, Miguel; Lapier, Michel

2016-01-15

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cellmore » line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3{sub ADP}), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells. - Highlights: • Small changes on a hydroquinone scaffold modify the action on OXPHOS of

Metric Issues for Small Business.

DTIC Science & Technology

1981-08-01

time, it seems that small business is meeting the problens (f ()ijutarv, metric conversion within its own resources ( manager ",a1, t, ,’bral, an...AD-AI07 861 UNITED STATES METRIC BOARD ARLINGTON VA FIG 5/3 METRIC ISSUES FOR SMALL BUSINESS . (U) UNCASIF AUG a I EHEHEi-17i i/ll/l///i//,° i MENNEN...METRIC ISSUES FOR SMALL BUSINESS EXECUTIVE SUMMARY DTIC ifELECT A This o@~ant )u enapo.I fW pu~~w Z. Ias ,!W% si~ts La-i UNITED STATES METRIC BOARD

Are Subject Small Clauses Really Small Clauses?

ERIC Educational Resources Information Center

Kubo, Miori

1993-01-01

This paper discusses the ongoing debate over small clauses concerning the structure of the verb phrase in "I consider Bill smart." It is demonstrated that the subject constituent in question is not a small clause, but a Noun Phrase (NP), following Noun (N). It is shown that some peculiar phenomena under the small clause analysis are…

40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL... operator of a small MS4, am I regulated under the NPDES storm water program? (a) Unless you qualify for a... a petition to the NPDES permitting authority to require an NPDES permit for your discharge of storm...

40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL... operator of a small MS4, am I regulated under the NPDES storm water program? (a) Unless you qualify for a... a petition to the NPDES permitting authority to require an NPDES permit for your discharge of storm...

40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL... operator of a small MS4, am I regulated under the NPDES storm water program? (a) Unless you qualify for a... a petition to the NPDES permitting authority to require an NPDES permit for your discharge of storm...

40 CFR 62.15030 - What are my obligations under this subpart if I reduce my small municipal waste combustion unit's...

Code of Federal Regulations, 2014 CFR

2014-07-01

... subpart if I reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons... POLLUTANTS Federal Plan Requirements for Small Municipal Waste Combustion Units Constructed on or Before... reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons per day? If...

40 CFR 62.15030 - What are my obligations under this subpart if I reduce my small municipal waste combustion unit's...

Code of Federal Regulations, 2012 CFR

2012-07-01

... subpart if I reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons... POLLUTANTS Federal Plan Requirements for Small Municipal Waste Combustion Units Constructed on or Before... reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons per day? If...

40 CFR 62.15030 - What are my obligations under this subpart if I reduce my small municipal waste combustion unit's...

Code of Federal Regulations, 2010 CFR

2010-07-01

... subpart if I reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons... POLLUTANTS Federal Plan Requirements for Small Municipal Waste Combustion Units Constructed on or Before... reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons per day? If...

40 CFR 62.15030 - What are my obligations under this subpart if I reduce my small municipal waste combustion unit's...

Code of Federal Regulations, 2013 CFR

2013-07-01

... subpart if I reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons... POLLUTANTS Federal Plan Requirements for Small Municipal Waste Combustion Units Constructed on or Before... reduce my small municipal waste combustion unit's combustion capacity to less than 35 tons per day? If...

Can NO-indomethacin counteract the topical gastric toxicity induced by indomethacin interactions with phospholipid bilayers?

PubMed

Pereira-Leite, Catarina; Nunes, Cláudia; Bozelli, José C; Schreier, Shirley; Kamma-Lorger, Christina S; Cuccovia, Iolanda M; Reis, Salette

2018-05-23

Nitric oxide (NO)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) have been developed to overcome the gastrointestinal and cardiovascular toxicity of NSAIDs, by chemically associating a NO-releasing moiety with commercial NSAIDs. Since increasing evidence supports that NSAIDs toxicity is related to their topical actions in membrane lipids, this work aims to evaluate the impact of adding a NO-releasing moiety to parent NSAIDs regarding their effect on lipid bilayers. Thus, the interactions of NO-indomethacin and indomethacin (parent drug) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers were described herein at pH 3.0 and 7.4. Diverse experimental techniques were combined to characterize the partitioning and location of drugs in DMPC bilayers, and to analyze their effect on the lipid phase transition and the bilayer structure and dynamics. The partitioning of NO-indomethacin into DMPC bilayers was similar to that of charged indomethacin and smaller than that of neutral indomethacin. Both drugs were found to insert the DMPC bilayer and the membrane location of indomethacin was pH-dependent. NO-indomethacin and indomethacin induced a decrease of the main phase transition temperature of DMPC. The effect of these drugs on the bilayer structure and dynamics was dependent on diverse factors, namely drug ionization state, drug:lipid molar ratio, temperature and lipid phase. It is noteworthy that NO-indomethacin induced more pronounced alterations in the biophysical properties of DMPC bilayers than indomethacin, considering equivalent membrane concentrations. Such modifications may have in vivo implications, particularly in the gastric mucosa, where NO-NSAIDs-induced changes in the protective properties of phospholipid layers may contribute to the occurrence of adverse effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Wetting properties of phospholipid dispersion on tunable hydrophobic SiO2-glass plates.

PubMed

Alexandrova, Lidia; Karakashev, Stoyan I; Grigorov, L; Phan, Chi M; Smoukov, Stoyan K

2015-06-01

We study the wetting properties of very small droplets of salty aqueous suspensions of unilamellar liposomes of DMPC (dimyristoylphosphatidylcholine), situated on SiO2-glass surfaces with different levels of hydrophobicity. We evaluated two different measures of hydrophobicity of solid surfaces - receding contact angles and the thickness of wetting films trapped between an air bubble and the solid surface at different levels of hydrophobicity. We established a good correlation between methods which differ significantly in measurement difficulty and experimental setup. We also reveal details of the mechanism of wetting of different surfaces by the DMPC liposome suspension. Hydrophilic surfaces with water contact angles in the range of 0° to 35° are readily hydrophobized by the liposomes and only showed corresponding contact angles in the range 27°-43°. For same range of surface hydrophobicities, there was a clear reduction of the thickness of the wetting films between the surface and a bubble, reaching a minimum in the 35°-40° range. At higher levels of hydrophobicity both pure water and the liposome suspension show similar contact angles, and the thickness of wetting films between a bubble and those surfaces increases in parallel. Our analysis showed that the only force able to stabilize the film under these experimental conditions is steric repulsion. The latter suggests that nanobubbles adsorbed on hydrophobic parts of the surface, and coated with a DMPC layer, may be the cause of the 40-70 nm thickness of wetting films we observe. Copyright © 2014 Elsevier B.V. All rights reserved.

40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false As an operator of a small MS4, am I regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EPA ADMINISTERED PERMIT PROGRAMS: THE NATIONAL POLLUTANT DISCHARGE ELIMINATION SYSTEM Permit...

40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false As an operator of a small MS4, am I regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EPA ADMINISTERED PERMIT PROGRAMS: THE NATIONAL POLLUTANT DISCHARGE ELIMINATION SYSTEM Permit...

Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

ClinicalTrials.gov

2017-10-10

Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

PubMed

Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

2014-10-16

Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

Novel Small Molecule Therapeutics for Sickle Cell Disease: Nitric Oxide, Carbon Monoxide, Nitrite, and Apolipoprotein A-I

PubMed Central

Kato, Gregory J.

2009-01-01

A hemolysis-linked subphenotype of sickle cell disease (SCD), characterized by pulmonary hypertension, stroke, priapism and leg ulcers, is associated with decreased nitric oxide bioavailability and vasculopathy. Vasculopathy appears to have a multifactorial etiology, including mechanisms primarily that involve deficient nitric oxide (NO) signaling, but also involving altered function of NO synthase related to substrate availability and cooperating factors such as apolipoproteins. Improved understanding of the vascular pathophysiology of SCD has led to new vascular targets for translational research in SCD. This growing vascular therapeutics field in SCD is complementary to the ongoing efforts to reduce the morbidity of vaso-occlusive pain crisis. This presentation will review the current biology and translational clinical development of novel small molecules targeting sickle cell vasculopathy. Strategies targeting the heme-oxygenase-carbon monoxide pathway, the arginine-NO synthase-cGMP-phosphodiesterase 5 pathway, the nitrate-nitrite-NO pathway, and the apolipoprotein A-I pathways will be reviewed. In this context, current clinical trials of inhaled NO, CO, nitrite, sildenafil and apoA-I mimetics will be discussed. PMID:19074079

78 FR 32293 - VPC SBIC I, LP, License No. 05/05 0308; Notice Seeking Exemption Under Section 312 of the Small...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... SMALL BUSINESS ADMINISTRATION VPC SBIC I, LP, License No. 05/05 0308; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given..., Financings which Constitute Conflicts of Interest of the Small Business Administration (``SBA'') Rules and...

Interactions of the local anesthetic tetracaine with membranes containing phosphatidylcholine and cholesterol: a /sup 2/H NMR study

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

Auger, M.; Jarrell, H.C.; Smith, I.C.P.

1988-06-28

The interactions of local anesthetic tetracaine with multilamellar dispersions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol have been investigated by deuterium nuclear magnetic resonance of specifically deuteriated tetracaines, DMPC and cholesterol. Experiments were performed at pH 5.5, when the anesthetic is primarily charged, and at pH 9.5, when it is primarily uncharged. The partition coefficients of the anesthetic in the membrane have been measured at both pH values for phosphatidylcholine bilayers with and without cholesterol. The higher partition coefficients obtained at pH 9.5 reflect the hydrophobic interactions between the uncharged form of the anesthetic and the hydrocarbon region of the bilayer. Themore » lower partition coefficients for the DMPC/cholesterol system at both pH values suggest that cholesterol, which increases the order of the lipid chains, decreases the solubility of tetracaine into the bilayer. For phosphatidylcholine bilayers, it has been proposed that the charged tetracaine at low pH is located mostly at the phospholipid headgroup level while the uncharged tetracaine intercalates more deeply into the bilayer. The present study suggests that the location of tetracaine in the cholesterol-containing system is different from that in pure phosphatidylcholine bilayers: the anesthetic sits higher in the membrane. An increase in temperature results in a deeper penetration of the anesthetic into the bilayer. Moreover, the incorporation of the anesthetic into DMPC bilayers with or without cholesterol results in a reduction of the lipid order parameters both in the plateau and in the tail regions of the acyl chains, this effect being greater with the charged form of the anesthetic.« less

DETAILED ABUNDANCES OF STARS WITH SMALL PLANETS DISCOVERED BY KEPLER. I. THE FIRST SAMPLE

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

Schuler, Simon C.; Vaz, Zachary A.; Santrich, Orlando J. Katime

2015-12-10

We present newly derived stellar parameters and the detailed abundances of 19 elements of seven stars with small planets discovered by NASA's Kepler Mission. Each star, save one, has at least one planet with a radius ≤1.6 R{sub ⊕}, suggesting a primarily rocky composition. The stellar parameters and abundances are derived from high signal-to-noise ratio, high-resolution echelle spectroscopy obtained with the 10 m Keck I telescope and High Resolution Echelle Spectrometer using standard spectroscopic techniques. The metallicities of the seven stars range from −0.32 to +0.13 dex, with an average metallicity that is subsolar, supporting previous suggestions that, unlike Jupiter-typemore » giant planets, small planets do not form preferentially around metal-rich stars. The abundances of elements other than iron are in line with a population of Galactic disk stars, and despite our modest sample size, we find hints that the compositions of stars with small planets are similar to stars without known planets and with Neptune-size planets, but not to those of stars with giant planets. This suggests that the formation of small planets does not require exceptional host-star compositions and that small planets may be ubiquitous in the Galaxy. We compare our derived abundances (which have typical uncertainties of ≲0.04 dex) to the condensation temperature of the elements; a correlation between the two has been suggested as a possible signature of rocky planet formation. None of the stars demonstrate the putative rocky planet signature, despite at least three of the stars having rocky planets estimated to contain enough refractory material to produce the signature, if real. More detailed abundance analyses of stars known to host small planets are needed to verify our results and place ever more stringent constraints on planet formation models.« less

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro.

PubMed

Yoshino, Hironori; Iwabuchi, Miyu; Kazama, Yuka; Furukawa, Maho; Kashiwakura, Ikuo

2018-04-01

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro

PubMed Central

Yoshino, Hironori; Iwabuchi, Miyu; Kazama, Yuka; Furukawa, Maho; Kashiwakura, Ikuo

2018-01-01

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis. PMID:29541243

SmallSats, Iodine Propulsion Technology, Applications to Low-Cost Lunar Missions, and the Iodine Satellite (iSAT) Project

NASA Technical Reports Server (NTRS)

Dankanich, John W.

2014-01-01

Closing Remarks: ?(1) SmallSats hold significant potential for future low cost high value missions; (2) Propulsion remains a key limiting capability for SmallSats that Iodine can address: High ISP * Density for volume constrained spacecraft; Indefinite quiescence, unpressurized and non-hazardous as a secondary payload; (3) Iodine enables MicroSat and SmallSat maneuverability: Enables transfer into high value orbits, constellation deployment and deorbit; (4) Iodine may enable a new class of planetary and exploration class missions: Enables GTO launched secondary spacecraft to transit to the moon, asteroids, and other interplanetary destinations for approximately 150 million dollars full life cycle cost including the launch; (5) ESPA based OTVs are also volume constrained and a shift from xenon to iodine can significantly increase the transfer vehicle change in volume capability including transfers from GTO to a range of Lunar Orbits; (6) The iSAT project is a fast pace high value iodine Hall technology demonstration mission: Partnership with NASA GRC and NASA MSFC with industry partner - Busek; (7) The iSAT mission is an approved project with PDR in November of 2014 and is targeting a flight opportunity in FY17.

Contract Financing for Small Business

DTIC Science & Technology

1981-11-01

problem. Small business contractors devote considerable management attention to operating capital and cash flow. Small business contractors are keenly...CONTRACT FINANCING 0FOR SMALL BUSINESS November 1981 -s Paul R. McClenon Prepared pursuant to Department of Defense Contract No. MDA903-81-C-0166...34 i 12 17046 DistIbufios Unlimted !I CONTRACT FINANCING FOR SMALL BUSINESS EXECUTIVE SUMMHARY To perform effectively on a contract, a firm needs

Effect of α-Tocopherol on the Microscopic Dynamics of Dimyristoylphosphatidylcholine Membrane

DOE PAGES

Sharma, V. K.; Mamontov, E.; Tyagi, M.; ...

2015-12-16

Vitamin E behaves as an antioxidant and is well known for its protective properties of the lipid membrane. The most biologically active form of vitamin E in the human organism is α-tocopherol (aToc). Recently (Marquardt, D.; et al. J. Am. Chem. Soc. 2014, 136, 203₋210) it has been shown that aToc resides near the center of dimyristoylphosphatidylcholine (DMPC) bilayer, which is in stark contrast with other PC membranes, where aToc is located near the lipid₋water interface. Here we report an unusual effect of this exceptional location of aToc on the dynamical behavior of DMPC membrane probed by incoherent elastic andmore » quasielastic neutron scattering. For pure DMPC vesicles, elastic scan data show two step-like drops in the elastic intensity at 288 and 297 K, which correspond to the pre- and main phase transitions, respectively. However, inclusion of aToc into DMPC membrane inhibits the step-like elastic intensity drops, indicating a significant impact of aToc on the phase behavior of the membrane. This observation is supported by our differential scanning calorimetry data, which shows that inclusion of aToc leads to a significant broadening of the main phase transition peak, whereas the peak corresponding to the pretransition disappears. We have performed quasielastic neutron scattering (QENS) measurements on DMPC vesicles with various concentrations of aToc at 280, 293, and 310 K. We have found that aToc affects both the lateral diffusion and the internal motions of the lipid molecules. Below the main phase transition temperature inclusion of aToc accelerates both the lateral and the internal lipid motions. On the other hand, above the main phase transition temperature the addition of aToc restricts only the internal motion, without a significant influence on the lateral motion. To conclude, our results support the finding that the location of aToc in DMPC membrane is deep within the bilayer.« less

Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine.

PubMed

Vaghadia, H; McLeod, D H; Mitchell, G W; Merrick, P M; Chilvers, C R

1997-01-01

A randomized, single-blind trial of two spinal anesthetic solutions for outpatient laparoscopy was conducted to compare intraoperative conditions and postoperative recovery. Thirty women (ASA physical status I and II) were assigned to one of two groups. Group I patients received a small-dose hypobaric solution of 1% lidocaine 25 mg made up to 3 mL by the addition of fentanyl 25 micrograms. Group II patients received a conventional-dose hyperbaric solution of 5% lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10% dextrose. All patients received 500 mL of crystalloid preloading. Spinal anesthesia was performed at L2-3 or L3-4 with a 27-gauge Quincke point needle. Surgery commenced when the level of sensory anesthesia reached T-6. Intraoperative hypotension requiring treatment with ephedrine occurred in 54% of Group II patients but not in any Group I patients. Median (range) time for full motor recovery was 50 (0-95) min in Group I patients compared to 90 (50-120) min in Group II patients (P = 0.0005). Sensory recovery also occurred faster in Group I patients (100 +/- 22 min) compared with Group II patients (140 +/- 27 min, P = 0.0001). Postoperative headache occurred in 38% of all patients and 70% of these were postural in nature. Oral analgesia was the only treatment required. Spinal anesthesia did not result in a significant incidence of postoperative backache. On follow-up, 96% said they found spinal needle insertion acceptable, 93% found surgery comfortable, and 90% said they would request spinal anesthesia for laparoscopy in future. Overall, this study found spinal anesthesia for outpatient laparoscopy to have high patient acceptance and a comparable complication rate to other studies. The small-dose hypobaric lidocaine-fentanyl technique has advantages over conventional-dose hyperbaric lidocaine of no hypotension and faster recovery.

Cofilin and DNase I affect the conformation of the small domain of actin.

PubMed Central

Dedova, Irina V; Dedov, Vadim N; Nosworthy, Neil J; Hambly, Brett D; dos Remedios, Cris G

2002-01-01

Cofilin binding induces an allosteric conformational change in subdomain 2 of actin, reducing the distance between probes attached to Gln-41 (subdomain 2) and Cys-374 (subdomain 1) from 34.4 to 31.4 A (pH 6.8) as demonstrated by fluorescence energy transfer spectroscopy. This effect was slightly less pronounced at pH 8.0. In contrast, binding of DNase I increased this distance (35.5 A), a change that was not pH-sensitive. Although DNase I-induced changes in the distance along the small domain of actin were modest, a significantly larger change (38.2 A) was observed when the ternary complex of cofilin-actin-DNase I was formed. Saturation binding of cofilin prevents pyrene fluorescence enhancement normally associated with actin polymerization. Changes in the emission and excitation spectra of pyrene-F actin in the presence of cofilin indicate that subdomain 1 (near Cys-374) assumes a G-like conformation. Thus, the enhancement of pyrene fluorescence does not correspond to the extent of actin polymerization in the presence of cofilin. The structural changes in G and F actin induced by these actin-binding proteins may be important for understanding the mechanism regulating the G-actin pool in cells. PMID:12023237

Small-Gap Flows

DTIC Science & Technology

1984-04-01

I TV N 4 NAVAL ARCIETUR & OFFSHORE ENGINEERING SMALL- GAP FLOWSti E 0.TUCK01 REPORT NO- M!AOL 34-1 CONTRACT NJU1-𔃾-K-0026 APRIL 1984 let.? UNIVERSMn...34’OF CALIFORNIA# BERKELEY, CA 5.1720 ft (45 642-141 SMALL- GAP FLOWS BY E. 0. TUCK REPORT No. NAUE 84-1 CONTRACT N00014-84-K-OU26 APRIL i984...34small- gap " theme.Chapters 1-4 were originally presented in the form of a lecture series in the Department of Naval Architecture and Offshore

Characterization of the Structure and Membrane Interaction of the Antimicrobial Peptides Aurein 2.2 and 2.3 from Australian Southern Bell Frogs

PubMed Central

Pan, Yeang-Ling; Cheng, John T.-J.; Hale, John; Pan, Jinhe; Hancock, Robert E. W.; Straus, Suzana K.

2007-01-01

The structure and membrane interaction of the antimicrobial peptide aurein 2.2 (GLFDIVKKVVGALGSL-CONH2), aurein 2.3 (GLFDIVKKVVGAIGSL-CONH2), both from Litoria aurea, and a carboxy C-terminal analog of aurein 2.3 (GLFDIVKKVVGAIGSL-COOH) were studied to determine which features of this class of peptides are key to activity. Circular dichroism and solution-state NMR data indicate that all three peptides adopt an α-helical structure in the presence of trifluoroethanol or lipids such as 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and a 1:1 mixture of DMPC and 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG). Oriented circular dichroism was used to determine the orientation of the peptides in lipid bilayers over a range of concentrations (peptide/lipid molar ratios (P/L) = 1:15–1:120) in DMPC and 1:1 DMPC/DMPG, in the liquid crystalline state. The results demonstrate that in DMPC all three peptides are surface adsorbed over a range of low peptide concentrations but insert into the bilayers at high peptide concentrations. This finding is corroborated by 31P-solid-state NMR data of the three peptides in DMPC, which shows that at high peptide concentrations the peptides perturb the membrane. Oriented circular dichroism data of the aurein peptides in 1:1 DMPC/DMPG, on the other hand, show that the peptides with amidated C-termini readily insert into the membrane bilayers over the concentration range studied (P/L = 1:15–1:120), whereas the aurein 2.3 peptide with a carboxy C-terminus inserts at a threshold concentration of P/L* between 1:80 and 1:120. Overall, the data presented here suggest that all three peptides studied interact with phosphatidylcholine membranes in a manner which is similar to aurein 1.2 and citropin 1.1, as reported in the literature, with no correlation to the reported activity. On the other hand, both aurein 2.2 and aurein 2.3 behave similarly in phosphatidylcholine/phosphatidylglycerol (PC/PG) membranes, whereas aurein 2

Characterization of the structure and membrane interaction of the antimicrobial peptides aurein 2.2 and 2.3 from Australian southern bell frogs.

PubMed

Pan, Yeang-Ling; Cheng, John T-J; Hale, John; Pan, Jinhe; Hancock, Robert E W; Straus, Suzana K

2007-04-15

The structure and membrane interaction of the antimicrobial peptide aurein 2.2 (GLFDIVKKVVGALGSL-CONH(2)), aurein 2.3 (GLFDIVKKVVGAIGSL-CONH(2)), both from Litoria aurea, and a carboxy C-terminal analog of aurein 2.3 (GLFDIVKKVVGAIGSL-COOH) were studied to determine which features of this class of peptides are key to activity. Circular dichroism and solution-state NMR data indicate that all three peptides adopt an alpha-helical structure in the presence of trifluoroethanol or lipids such as 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and a 1:1 mixture of DMPC and 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG). Oriented circular dichroism was used to determine the orientation of the peptides in lipid bilayers over a range of concentrations (peptide/lipid molar ratios (P/L) = 1:15-1:120) in DMPC and 1:1 DMPC/DMPG, in the liquid crystalline state. The results demonstrate that in DMPC all three peptides are surface adsorbed over a range of low peptide concentrations but insert into the bilayers at high peptide concentrations. This finding is corroborated by (31)P-solid-state NMR data of the three peptides in DMPC, which shows that at high peptide concentrations the peptides perturb the membrane. Oriented circular dichroism data of the aurein peptides in 1:1 DMPC/DMPG, on the other hand, show that the peptides with amidated C-termini readily insert into the membrane bilayers over the concentration range studied (P/L = 1:15-1:120), whereas the aurein 2.3 peptide with a carboxy C-terminus inserts at a threshold concentration of P/L* between 1:80 and 1:120. Overall, the data presented here suggest that all three peptides studied interact with phosphatidylcholine membranes in a manner which is similar to aurein 1.2 and citropin 1.1, as reported in the literature, with no correlation to the reported activity. On the other hand, both aurein 2.2 and aurein 2.3 behave similarly in phosphatidylcholine/phosphatidylglycerol (PC/PG) membranes, whereas aurein

40 CFR Table 2 to Subpart Jjj of... - Class I Emission Limits for Existing Small Municipal Waste Combustion Limits

Code of Federal Regulations, 2010 CFR

2010-07-01

... Small Municipal Waste Combustion Limits 2 Table 2 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 2 Table 2 to Subpart JJJ of Part 62—Class I Emission Limits for Existing Small Municipal Waste Combustion Limits ER31JA03.006...

40 CFR Table 2 to Subpart Jjj of... - Class I Emission Limits for Existing Small Municipal Waste Combustion Limits

Code of Federal Regulations, 2013 CFR

2013-07-01

... Small Municipal Waste Combustion Limits 2 Table 2 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 2 Table 2 to Subpart JJJ of Part 62—Class I Emission Limits for Existing Small Municipal Waste Combustion Limits ER31JA03.006...

40 CFR Table 2 to Subpart Jjj of... - Class I Emission Limits for Existing Small Municipal Waste Combustion Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... Small Municipal Waste Combustion Limits 2 Table 2 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 2 Table 2 to Subpart JJJ of Part 62—Class I Emission Limits for Existing Small Municipal Waste Combustion Limits ER31JA03.006...

40 CFR Table 2 to Subpart Jjj of... - Class I Emission Limits for Existing Small Municipal Waste Combustion Limits

Code of Federal Regulations, 2012 CFR

2012-07-01

... Small Municipal Waste Combustion Limits 2 Table 2 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 2 Table 2 to Subpart JJJ of Part 62—Class I Emission Limits for Existing Small Municipal Waste Combustion Limits ER31JA03.006...

40 CFR Table 2 to Subpart Jjj of... - Class I Emission Limits for Existing Small Municipal Waste Combustion Limits

Code of Federal Regulations, 2014 CFR

2014-07-01

... Small Municipal Waste Combustion Limits 2 Table 2 to Subpart JJJ of Part 62 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Pt. 62, Subpt. JJJ, Table 2 Table 2 to Subpart JJJ of Part 62—Class I Emission Limits for Existing Small Municipal Waste Combustion Limits ER31JA03.006...

Cd-binding to model membranes

NASA Astrophysics Data System (ADS)

Geszner, R.; Saibene, S.; Butz, T.; Lerf, A.

1990-08-01

The binding of Cd2+ to the model membranes Di-myristoyl L-α-phosphatidic acid (DMPA) and Di-myristoyl L-α-phosphatidylcholine (DMPC) was studied by time differential perturbed angular correlation (TDPAC) on111mCd, via its nuclear quadrupole interaction. Whereas Cd2+ does not bind to the neutral DMPC, it binds to charged DMPA up to a 0.8∶1 Cd/lipid ratio.

New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer.

PubMed

Melloni, G; Gajate, A M S; Sestini, S; Gallivanone, F; Bandiera, A; Landoni, C; Muriana, P; Gianolli, L; Zannini, P

2013-11-01

The recurrence rate for stage I non-small cell lung cancer is high, with 20-40% of patients that relapse after surgery. The aim of this study was to evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) derived parameters, such as standardized uptake value index (SUVindex), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for recurrence in resected stage I non-small cell lung cancer. We retrospectively reviewed 99 resected stage I non-small cell lung cancer patients that were grouped by SUVindex, TLG and MTV above or below their median value. Disease free survival was evaluated as primary end point. The 5-year overall survival and the 5-year disease free survival rates were 62% and 73%, respectively. The median SUVindex, MTL and TLG were 2.73, 2.95 and 9.61, respectively. Patients with low SUVindex, MTV and TLG were more likely to have smaller tumors (p ≤ 0.001). Univariate analysis demonstrated that SUVindex (p = 0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to recurrence showing a better predictive performance than SUVmax (p = 0.031). The 5-year disease free survival rates in patients with low and high SUVindex, MTV and TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate analysis showed that only TLG was an independent prognostic factor (p = 0.014) with a hazard ratio of 4.782. Of the three PET-derived parameters evaluated, TLG seems to be the most accurate in stratifying surgically treated stage I non-small cell lung cancer patients according to their risk of recurrence. Copyright © 2013 Elsevier Ltd. All rights reserved.

Temperature driven annealing of perforations in bicellar model membranes.

PubMed

Nieh, Mu-Ping; Raghunathan, V A; Pabst, Georg; Harroun, Thad; Nagashima, Kazuomi; Morales, Hannah; Katsaras, John; Macdonald, Peter

2011-04-19

Bicellar model membranes composed of 1,2-dimyristoylphosphatidylcholine (DMPC) and 1,2-dihexanoylphosphatidylcholine (DHPC), with a DMPC/DHPC molar ratio of 5, and doped with the negatively charged lipid 1,2-dimyristoylphosphatidylglycerol (DMPG), at DMPG/DMPC molar ratios of 0.02 or 0.1, were examined using small angle neutron scattering (SANS), (31)P NMR, and (1)H pulsed field gradient (PFG) diffusion NMR with the goal of understanding temperature effects on the DHPC-dependent perforations in these self-assembled membrane mimetics. Over the temperature range studied via SANS (300-330 K), these bicellar lipid mixtures exhibited a well-ordered lamellar phase. The interlamellar spacing d increased with increasing temperature, in direct contrast to the decrease in d observed upon increasing temperature with otherwise identical lipid mixtures lacking DHPC. (31)P NMR measurements on magnetically aligned bicellar mixtures of identical composition indicated a progressive migration of DHPC from regions of high curvature into planar regions with increasing temperature, and in accord with the "mixed bicelle model" (Triba, M. N.; Warschawski, D. E.; Devaux, P. E. Biophys. J.2005, 88, 1887-1901). Parallel PFG diffusion NMR measurements of transbilayer water diffusion, where the observed diffusion is dependent on the fractional surface area of lamellar perforations, showed that transbilayer water diffusion decreased with increasing temperature. A model is proposed consistent with the SANS, (31)P NMR, and PFG diffusion NMR data, wherein increasing temperature drives the progressive migration of DHPC out of high-curvature regions, consequently decreasing the fractional volume of lamellar perforations, so that water occupying these perforations redistributes into the interlamellar volume, thereby increasing the interlamellar spacing. © 2011 American Chemical Society

Language Learning Motivation through a Small Lens: A Research Agenda

ERIC Educational Resources Information Center

Ushioda, Ema

2016-01-01

In this paper I propose an agenda for researching language learning motivation "through a small lens", to counteract our tendency in the second language (L2) motivation field to engage with language learning and teaching processes at a rather general level. I argue that by adopting a more sharply focused or contextualized angle of…

Teaching Small Business Management in the UK Part I.

ERIC Educational Resources Information Center

Birley, Sue; Gibb, Allan

1984-01-01

Reviews the key factors influencing small business management education in the United Kingdom, particularly government policies encouraging small business development. Postulates a model based on the career cycle and considers training opportunities for various stages. (SK)

Reconciling Structural and Thermodynamic Predictions Using All-Atom and Coarse-Grain Force Fields: The Case of Charged Oligo-Arginine Translocation into DMPC Bilayers

PubMed Central

2015-01-01

Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide–water and peptide–membrane interactions allow prediction of free energy minima at the bilayer–water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are −2.51, −4.28, and −5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are −0.83, −3.33, and −3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of

Effects of imidazolium-based ionic surfactants on the size and dynamics of phosphatidylcholine bilayers with saturated and unsaturated chains.

PubMed

Lee, Hwankyu

2015-07-01

Imidazolium-based ionic surfactants of different sizes were simulated with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers. Regardless of the phospholipid type, larger surfactants at higher concentrations more significantly insert into the bilayer and increase the bilayer-surface size, in agreement with experiments and previous simulations. Insertion of surfactants only slightly decreases the bilayer thickness, as also observed in experiments. Although the surfactant insertion and its effect on the bilayer size and thickness are similar in different types of bilayers, the volume fractions of surfactants in the bilayer are higher for DMPC bilayers than for POPC and DOPC bilayers. In particular, ionic surfactants with four hydrocarbons yield their volume fractions of 4.6% and 8.7%, respectively, in POPC and DMPC bilayers, in quantitative agreement with experimental values of ∼5% and ∼10%. Also, the inserted surfactants increase the lateral diffusivity of the bilayer, which depends on the bilayer type. These findings indicate that although the surfactant insertion does not depend on the bilayer type, the effects of surfactants on the volume fraction and bilayer dynamics occur more significantly in the DMPC bilayer because of the smaller area per lipid and shorter saturated tails, which helps explain the experimental observations regarding different volume fractions of surfactants in POPC and DMPC bilayers. Copyright © 2015 Elsevier Inc. All rights reserved.

Mature Follow-Up for High-Risk Stage I Non-Small-Cell Lung Carcinoma Treated With Sublobar Resection and Intraoperative Iodine-125 Brachytherapy

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

Colonias, Athanasios, E-mail: acolonia@wpahs.or; Drexel University College of Medicine, Allegheny Campus, Pittsburgh, PA; Betler, James

2011-01-01

Purpose: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative {sup 125}I Vicryl mesh brachytherapy. Methods and Materials: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of {sup 125}I seeds along the resection line. The {sup 125}I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. Results:more » The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm{sup 2} (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. Conclusion: {sup 125}I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.« less

Differential effects of eNOS uncoupling on conduit and small arteries in GTP-cyclohydrolase I-deficient hph-1 mice.

PubMed

d'Uscio, Livius V; Smith, Leslie A; Katusic, Zvonimir S

2011-12-01

In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin (BH(4)) in conduit and small arteries activates compensatory mechanisms designed to protect vascular wall from oxidative stress induced by uncoupling of endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels were reduced in the aortas and small mesenteric arteries of hph-1 mice. However, the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1 aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were significantly enhanced in aortas but not in small mesenteric arteries of hph-1 mice. In contrast to the aorta, protein expression of copper- and zinc-containing superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric arteries of hph-1 mice. Protein expression of catalase was increased in both aortas and small mesenteric arteries of hph-1 mice. Further analysis of endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas. Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the most likely mechanism responsible for phosphorylation of eNOS and elevation of cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is sufficient to protect vascular tissue from increased production of reactive oxygen species generated by uncoupling of eNOS. The results of our study suggest that anatomical origin determines the ability of vessel wall to cope with oxidative stress induced by uncoupling of eNOS.

Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung Cancer.

PubMed

Handa, Yoshinori; Tsutani, Yasuhiro; Tsubokawa, Norifumi; Misumi, Keizo; Hanaki, Hideaki; Miyata, Yoshihiro; Okada, Morihito

2017-12-01

Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n = 60) or basal segment (n = 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p = 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p = 0.080). Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Purchasing a Computer System for the Small Construction Company,

DTIC Science & Technology

1983-06-08

October 1982. . . . . . . .. i. i...< ..- . ,. .-: i. i? ,. . .-- i * i . . . ., r77- 7 *,~ .- -- 36 IBM - International Business Machines...Corporation, "Small Systems Solutions: An Introduction to Business Computing," Pamphlet SC21-5205-0, Atlanta, Georgia, January 1979. International Business Machines...Corporation, "IBM System/34 Introduction," Pamphlet GC21-5153-5, File No. S34-00, Atlanta, Georgia, January 1979. International Business Machines

Chlorine Incorporation in the CH3NH3PbI3 Perovskite: Small Concentration, Big Effect.

PubMed

Quarti, Claudio; Mosconi, Edoardo; Umari, Paolo; De Angelis, Filippo

2017-01-03

The role of chlorine doping in CH 3 NH 3 PbI 3 represents an important open issue in the use of hybrid perovskites for photovoltaic applications. In particular, even if a positive role of chlorine doping on perovskite film formation and on material morphology has been demonstrated, an inherent positive effect on the electronic and photovoltaic properties cannot be excluded. Here we carried out periodic density functional theory and Car-Parrinello molecular dynamics simulations, going down to ∼1% doping, to investigate the effect of chlorine on CH 3 NH 3 PbI 3 . We found that such a small doping has important effects on the dynamics of the crystalline structure, both with respect to the inorganic framework and with respect to the cation libration motion. Together, we observe a dynamic spatial localization of the valence and conduction states in separated spatial material regions, which takes place in the 10 -1 ps time scale and which could be the key to ease of exciton dissociation and, likely, to small charge recombination in hybrid perovskites. Moreover, such localization is enhanced by chlorine doping, demonstrating an inherent positive role of chlorine doping on the electronic properties of this class of materials.

Small Engines Care, Operation, Maintenance and Repair. Volume I.

ERIC Educational Resources Information Center

Turner, J. Howard

Developed by teacher educators and agricultural engineers and tested by vocational agriculture teachers, this reference is for student and teacher use as part of a course on servicing and operating an engine. Content includes: (1) Distinguishing Features of Small Engines, (2) How Small Gasoline Engines Work, (3) Comparing 4-(Stroke)Cycle and…

Detailed Abundances of Stars with Small Planets Discovered by Kepler. I. The First Sample

NASA Astrophysics Data System (ADS)

Schuler, Simon C.; Vaz, Zachary A.; Katime Santrich, Orlando J.; Cunha, Katia; Smith, Verne V.; King, Jeremy R.; Teske, Johanna K.; Ghezzi, Luan; Howell, Steve B.; Isaacson, Howard

2015-12-01

We present newly derived stellar parameters and the detailed abundances of 19 elements of seven stars with small planets discovered by NASA's Kepler Mission. Each star, save one, has at least one planet with a radius ≤1.6 R⊕, suggesting a primarily rocky composition. The stellar parameters and abundances are derived from high signal-to-noise ratio, high-resolution echelle spectroscopy obtained with the 10 m Keck I telescope and High Resolution Echelle Spectrometer using standard spectroscopic techniques. The metallicities of the seven stars range from -0.32 to +0.13 dex, with an average metallicity that is subsolar, supporting previous suggestions that, unlike Jupiter-type giant planets, small planets do not form preferentially around metal-rich stars. The abundances of elements other than iron are in line with a population of Galactic disk stars, and despite our modest sample size, we find hints that the compositions of stars with small planets are similar to stars without known planets and with Neptune-size planets, but not to those of stars with giant planets. This suggests that the formation of small planets does not require exceptional host-star compositions and that small planets may be ubiquitous in the Galaxy. We compare our derived abundances (which have typical uncertainties of ≲0.04 dex) to the condensation temperature of the elements; a correlation between the two has been suggested as a possible signature of rocky planet formation. None of the stars demonstrate the putative rocky planet signature, despite at least three of the stars having rocky planets estimated to contain enough refractory material to produce the signature, if real. More detailed abundance analyses of stars known to host small planets are needed to verify our results and place ever more stringent constraints on planet formation models. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California

Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

ClinicalTrials.gov

2018-03-02

Non-Squamous Non-Small Cell Lung Carcinoma; Stage I Non-Small Cell Lung Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage II Non-Small Cell Lung Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer

Discrete Cu(i) complexes for azide-alkyne annulations of small molecules inside mammalian cells.

PubMed

Miguel-Ávila, Joan; Tomás-Gamasa, María; Olmos, Andrea; Pérez, Pedro J; Mascareñas, José L

2018-02-21

The archetype reaction of "click" chemistry, namely, the copper-promoted azide-alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)-tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of "non-innocent" reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities.

Improving Early Reading Skills in Young Children through an iPad App: Small-Group Instruction and Observational Learning

ERIC Educational Resources Information Center

Chai, Zhen

2017-01-01

This study evaluated the effectiveness of using a researcher-developed iPad app with a 0- to 5-s constant time delay procedure to improve phonological awareness skills of young children with mild developmental delays in a small-group arrangement in a rural public elementary school in Southwest United States. The study was conducted using a…

40 CFR 62.15025 - How do I determine if my small municipal waste combustion unit is covered by an approved and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... municipal waste combustion unit is covered by an approved and effective State or Tribal Plan? 62.15025... Requirements for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of This Subpart § 62.15025 How do I determine if my small municipal waste combustion unit is covered...

40 CFR 62.15025 - How do I determine if my small municipal waste combustion unit is covered by an approved and...

Code of Federal Regulations, 2012 CFR

2012-07-01

... municipal waste combustion unit is covered by an approved and effective State or Tribal Plan? 62.15025... Requirements for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of This Subpart § 62.15025 How do I determine if my small municipal waste combustion unit is covered...

40 CFR 62.15025 - How do I determine if my small municipal waste combustion unit is covered by an approved and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... municipal waste combustion unit is covered by an approved and effective State or Tribal Plan? 62.15025... Requirements for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of This Subpart § 62.15025 How do I determine if my small municipal waste combustion unit is covered...

40 CFR 62.15025 - How do I determine if my small municipal waste combustion unit is covered by an approved and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... municipal waste combustion unit is covered by an approved and effective State or Tribal Plan? 62.15025... Requirements for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of This Subpart § 62.15025 How do I determine if my small municipal waste combustion unit is covered...

40 CFR 62.15025 - How do I determine if my small municipal waste combustion unit is covered by an approved and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... municipal waste combustion unit is covered by an approved and effective State or Tribal Plan? 62.15025... Requirements for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Applicability of This Subpart § 62.15025 How do I determine if my small municipal waste combustion unit is covered...

Proline Kink Angle Distributions for GWALP23 in Lipid Bilayers of Different Thickness†

PubMed Central

Rankenberg, Johanna M.; Vostrikov, Vitaly V.; DuVall, Christopher D.; Greathouse, Denise V.; Koeppe, Roger E.; Grant, Christopher V.; Opella, Stanley J.

2013-01-01

By using selected 2H and 15N labels, we have examined the influence of a central proline residue upon the properties of a defined peptide that spans lipid bilayer membranes by solid-state NMR spectroscopy. For this purpose, GWALP23 (acetyl-GGALW5LALALALALALALW19LAGA-ethanolamide) is a suitable model peptide that employs—for the purpose of interfacial anchoring—only one tryptophan residue on either end of a central alpha-helical core sequence. Because of its systematic behavior in lipid bilayer membranes of differing thickness (see J. Biol. Chem. 285, 31723), we utilize GWALP23 as a well-characterized framework for introducing guest residues within a transmembrane sequence; for example, a central proline yields acetyl-GGALW5LALALAP12ALALALW19LAGA-ethanolamide. We synthesized the GWALP23-P12 with specifically placed 2H and 15N labels for solid-state NMR spectroscopy, and examined the peptide orientation and segmental tilt in oriented DMPC lipid bilayer membranes using combined (2H)-GALA and (15N-1H) high resolution separated local field methods. In DMPC bilayer membranes, the peptide segments N-terminal and C-terminal to the proline are both tilted substantially with respect to the bilayer normal, by about 34° and 29° (± 5°), respectively. While the tilt increases for both segments when proline is present, the range and extent of the individual segment motions are comparable or less than those of the entire GWALP23 peptide in bilayer membranes. In DMPC, the proline induces a kink of about 30° (± 5°), with an apparent helix unwinding or “swivel” angle of about 70°. In DLPC and DOPC, based on 2H NMR data only, the kink angle and swivel angle probability distributions overlap those of DMPC, yet the most probable kink angle appears somewhat smaller than in DMPC. As has been described for GWALP23 itself, the C-terminal helix ends before Ala-21 in the phospholipids DMPC and DLPC, yet remains intact through Ala-21 in DOPC. The dynamics of bilayer

Nanomechanical characterization of phospholipid bilayer islands on flat and porous substrates: a force spectroscopy study.

PubMed

Nussio, Matthew R; Oncins, Gerard; Ridelis, Ingrid; Szili, Endre; Shapter, Joseph G; Sanz, Fausto; Voelcker, Nicolas H

2009-07-30

In this study, we compare for the first time the nanomechanical properties of lipid bilayer islands on flat and porous surfaces. 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayers were deposited on flat (silicon and mica) and porous silicon (pSi) substrate surfaces and examined using atomic force spectroscopy and force volume imaging. Force spectroscopy measurements revealed the effects of the underlying substrate and of the lipid phase on the nanomechanical properties of bilayers islands. For mica and silicon, significant differences in breakthrough force between the center and the edges of bilayer islands were observed for both phospolipids. These differences were more pronounced for DMPC than for DPPC, presumably due to melting effects at the edges of DMPC bilayers. In contrast, bilayer islands deposited on pSi yielded similar breakthrough forces in the central region and along the perimeter of the islands, and those values in turn were similar to those measured along the perimeter of bilayer islands deposited on the flat substrates. The study also demonstrates that pSi is suitable solid support for the formation of pore-spanning phospholipid bilayers with potential applications in transmembrane protein studies, drug delivery, and biosensing.

Quantification of Randomly-methylated-{beta}-cyclodextrin effect on liposome: An ESR study

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

Grammenos, A., E-mail: A.Grammenos@ulg.ac.be; Bahri, M.A.; Guelluy, P.H.

2009-12-04

In the present work, the effect of Randomly-methylated-{beta}-cyclodextrin (Rameb) on the microviscosity of dimyristoyl-L-{alpha} phosphatidylcholine (DMPC) bilayer was investigated using the electron spin resonance (ESR) technique. The ability of Rameb to extract membrane cholesterol was demonstrated. For the first time, the percentage of cholesterol extracted by Rameb from cholesterol doped DMPC bilayer was monitored and quantified throughout a wide Rameb concentration range. The effect of cholesterol on the inner part of the membrane was also investigated using 16-doxyl stearic acid spin label (16-DSA). 16-DSA seems to explore two different membrane domains and report their respective microviscosities. ESR experiments also establishmore » that the presence of 30% of cholesterol in DMPC liposomes suppresses the jump in membrane fluidity at lipids phase-transition temperature (23.9 {sup o}C).« less

VISIR-I: small vessels, least-time nautical routes using wave forecasts

NASA Astrophysics Data System (ADS)

Mannarini, G.; Pinardi, N.; Coppini, G.; Oddo, P.; Iafrati, A.

2015-09-01

A new numerical model for the on-demand computation of optimal ship routes based on sea-state forecasts has been developed. The model, named VISIR (discoVerIng Safe and effIcient Routes) is designed to support decision-makers when planning a marine voyage. The first version of the system, VISIR-I, considers medium and small motor vessels with lengths of up to a few tens of meters and a displacement hull. The model is made up of three components: the route optimization algorithm, the mechanical model of the ship, and the environmental fields. The optimization algorithm is based on a graph-search method with time-dependent edge weights. The algorithm is also able to compute a voluntary ship speed reduction. The ship model accounts for calm water and added wave resistance by making use of just the principal particulars of the vessel as input parameters. The system also checks the optimal route for parametric roll, pure loss of stability, and surfriding/broaching-to hazard conditions. Significant wave height, wave spectrum peak period, and wave direction forecast fields are employed as an input. Examples of VISIR-I routes in the Mediterranean Sea are provided. The optimal route may be longer in terms of miles sailed and yet it is faster and safer than the geodetic route between the same departure and arrival locations. Route diversions result from the safety constraints and the fact that the algorithm takes into account the full temporal evolution and spatial variability of the environmental fields.

Controlling DNA compaction with cationic amphiphiles for efficient delivery systems A step forward towards non-viral Gene Therapy

NASA Astrophysics Data System (ADS)

Savarala, Sushma

The synthesis of pyridinium cationic lipids, their counter-ion exchange, and the transfection of lipoplexes consisting of these lipids with firefly luciferase plasmid DNA (6.7 KDa), into lung, prostate and breast cancer cell lines was investigated. The transfection ability of these newly synthesized compounds was found to be twice as high as DOTAP/cholesterol and Lipofectamine TM (two commercially available successful transfection agents). The compaction of the DNA onto silica (SiO2) nanoparticles was also investigated. For this purpose, it was necessary to study the stability and fusion studies of colloidal systems composed of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), a zwitterionic lipid, and mixtures of DMPC with cationic DMTAP (1,2-dimyristoyl-3-trimethylammonium-propane).

What Makes a Team? The Composition of Small Groups for C.A.I.

ERIC Educational Resources Information Center

Bellows, B. P.

This study examined the task performance and social interaction of young children who used a computer to learn map skills. Specifically, ability and sex were examined in relation to students' achievement on a social studies task and in relation to student interaction in small groups. Subjects were 66 second grade students in 3 different…

Using Micropatterned Lipid Bilayer Arrays to Measure the Effect of Membrane Composition on Merocyanine 540 Binding

PubMed Central

Smith, Kathryn A.; Conboy, John C.

2011-01-01

The lipophilic dye merocyanine 540 (MC540) was used to model small molecule-membrane interactions using micropatterned lipid bilayer arrays (MLBAs) prepared using a 3D Continuous Flow Microspotter (CFM). Fluorescence microscopy was used to monitor MC540 binding to fifteen different bilayer compositions simultaneously. MC540 fluorescence was two times greater for bilayers composed of liquid-crystalline (l.c.) phase lipids (1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)) compared to bilayers in the gel phase (1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)). The effect cholesterol (CHO) had on MC540 binding to the membrane was found to be dependent on the lipid component; cholesterol decreased MC540 bindingin DMPC, DPPC and DSPC bilayers while having little to no effect on the remaining l.c. phase lipids. MC540 fluorescence was also lowered when 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (sodium salt) (DOPS) was incorporated into DOPC bilayers. The increase in the surface charge density appears to decrease the occurrence of highly fluorescent monomers and increase the formation of weakly fluorescent dimers via electrostatic repulsion. This paper demonstrates that MLBAs are a useful tool for preparing high density reproducible bilayer arrays to study small molecule-membrane interactions in a high-throughput manner. PMID:21376014

The Transcriptional Complex Between the BCL2 i-Motif and hnRNP LL Is a Molecular Switch for Control of Gene Expression That Can Be Modulated by Small Molecules

PubMed Central

2015-01-01

In a companion paper (DOI: 10.021/ja410934b) we demonstrate that the C-rich strand of the cis-regulatory element in the BCL2 promoter element is highly dynamic in nature and can form either an i-motif or a flexible hairpin. Under physiological conditions these two secondary DNA structures are found in an equilibrium mixture, which can be shifted by the addition of small molecules that trap out either the i-motif (IMC-48) or the flexible hairpin (IMC-76). In cellular experiments we demonstrate that the addition of these molecules has opposite effects on BCL2 gene expression and furthermore that these effects are antagonistic. In this contribution we have identified a transcriptional factor that recognizes and binds to the BCL2 i-motif to activate transcription. The molecular basis for the recognition of the i-motif by hnRNP LL is determined, and we demonstrate that the protein unfolds the i-motif structure to form a stable single-stranded complex. In subsequent experiments we show that IMC-48 and IMC-76 have opposite, antagonistic effects on the formation of the hnRNP LL–i-motif complex as well as on the transcription factor occupancy at the BCL2 promoter. For the first time we propose that the i-motif acts as a molecular switch that controls gene expression and that small molecules that target the dynamic equilibrium of the i-motif and the flexible hairpin can differentially modulate gene expression. PMID:24559432

Interaction of the major protein from bovine seminal plasma, PDC-109 with phospholipid membranes and soluble ligands investigated by fluorescence approaches.

PubMed

Anbazhagan, V; Damai, Rajani S; Paul, Aniruddha; Swamy, Musti J

2008-06-01

The major protein from bovine seminal plasma, PDC-109 binds selectively to choline phospholipids on the sperm plasma membrane and plays a crucial role in priming spermatozoa for fertilization. The microenvironment and accessibility of tryptophans of PDC-109 in the native state, in the presence of phosphorylcholine (PrC) and phospholipid membranes as well as upon denaturation have been investigated by fluorescence approaches. Quenching of the protein intrinsic fluorescence by different quenchers decreased in the order: acrylamide>succinimide>Cs(+)>I(-). Ligand binding afforded considerable protection from quenching, with shielding efficiencies following the order: dimyristoylphosphatidylcholine (DMPC)>lysophosphatidylcholine (Lyso-PC)>PrC. This has been attributed to a partial penetration of the protein into the DMPC membranes and Lyso-PC micelles, as well as a further stabilization of the binding due to the interaction of PDC-109 with lipid acyl chains and the resulting tightening of the protein structure, leading to a decreased accessibility of the tryptophan residues. Red-edge excitation shift (REES) studies yielded REES values of 4 nm for both native and denatured PDC-109, whereas reduced and denatured protein gave a REES of only 0.5 nm, clearly indicating that the structural and dynamic features of the microenvironment around the tryptophan residues are retained even after denaturation, presumably due to the constraints imposed on the protein structure by disulfide bonds. Upon binding of PDC-109 to DMPC membranes and Lyso-PC micelles the REES values were reduced to 2.5 and 1.0 nm, respectively, which could be due to the penetration of some parts of the protein, especially the segment containing Trp-90 into the membrane interior, where the red-edge effects are considerably reduced.

Pediatric Chiari malformation type I: long-term outcomes following small-bone-window posterior fossa decompression with autologous-fascia duraplasty

PubMed Central

Liu, Hai; Yang, Chenlong; Yang, Jun; Xu, Yulun

2017-01-01

Chiari malformation type I (CM-I) is a common hindbrain disorder that is associated with deformity and elongation of the cerebellar tonsils. Although CM-I occurs in both pediatric and adult patients, its prevalence, clinical features and management in the pediatric population are not well defined. The current study evaluated a consecutive case series of 92 children (38 females and 54 males) who were diagnosed with congenital CM-I. All patients underwent small-bone-window posterior fossa decompression with autologous-fascia duraplasty. Clinical and radiological features were analyzed and long-term follow-up data were recorded. Risk factors associated with clinical outcomes were investigated using comprehensive statistical methods. Out of the 92 children, 11 (12.0%) were asymptomatic. Associated ventricular dilation was observed in 24 children (26.1%) and concomitant syringomyelia was observed in 72 children (78.3%). A total of 44 children (47.8%) showed scoliosis on plain films. Follow-up data (mean duration, 88.6 months) were available for all patients. Syringomyelia was absent or markedly reduced in 56 patients (77.8%). Symptoms were alleviated in 66 patients, remained unchanged in 12 patients and progressed in 3 patients. Statistical analysis indicated that the cerebellar tonsillar descent (CTD) grade, basilar invagination and platybasia influenced the clinical outcome (P<0.05). In conclusion, early recognition and surgical treatment of CM-I in pediatric patients can lead to good outcomes. The current results suggested that small-bone-window posterior fossa decompression with autologous-fascia duraplasty was an effective safe treatment option with a low complication rate. High CTD grade, basilar invagination and platybasia were indicated to be predictors of poor clinical prognosis. PMID:29285106

PACE. A Program for Acquiring Competence in Entrepreneurship. Part I: Getting Ready to Become an Entrepreneur. Unit A: Nature of Small Business. Research and Development Series No. 194 A-1.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the three instructional units in Part I is understanding businesses. Unit A focuses on defining small business.…

Antioxidant capacity of Ugni molinae fruit extract on human erythrocytes: an in vitro study.

PubMed

Suwalsky, Mario; Avello, Marcia

2014-08-01

Ugni molinae is an important source of molecules with strong antioxidant activity widely used as a medicinal plant in Southern Chile-Argentina. Total phenol concentration from its fruit extract was 10.64 ± 0.04 mM gallic acid equivalents. Analysis by means of HPLC/MS indicated the presence of the anthocyanins cyanidin and peonidin, and the flavonol quercitin, all in glycosylated forms. Its antioxidant properties were assessed in human erythrocytes in vitro exposed to HClO oxidative stress. Scanning electron microscopy showed that HClO induced an alteration in erythrocytes from a normal shape to echinocytes; however, this change was highly attenuated in samples containing U. molinae extracts. It also had a tendency in order to reduce the hemolytic effect of HClO. In addition, X-ray diffraction experiments were performed in dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine bilayers, classes of lipids preferentially located in the outer and inner monolayers, respectively, of the human erythrocyte membrane. It was observed that U. molinae only interacted with DMPC. Results by fluorescence spectroscopy on DMPC large unilamellar vesicles and isolated unsealed human erythrocyte membranes also showed that it interacted with the erythrocyte membrane and DMPC. It is possible that the location of U. molinae components into the membrane outer monolayer might hinder the diffusion of HClO and of free radicals into cell membranes and the consequent decrease of the kinetics of free radical reactions.

Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn

PubMed Central

2011-01-01

Background Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). Results Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ± 4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. Conclusions The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways. PMID:22152428

Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer.

PubMed

Zimmermann, Frank B; Geinitz, Hans; Schill, Sabine; Grosu, Anca; Schratzenstaller, Ulrich; Molls, Michael; Jeremic, Branislav

2005-04-01

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only

VEGA, a small launch vehicle

NASA Astrophysics Data System (ADS)

Duret, François; Fabrizi, Antonio

1999-09-01

Several studies have been performed in Europe aiming to promote the full development of a small launch vehicle to put into orbit one ton class spacecrafts. But during the last ten years, the european workforce was mainly oriented towards the qualification of the heavy class ARIANE 5 launch vehicle.Then, due also to lack of visibility on this reduced segment of market, when comparing with the geosatcom market, no proposal was sufficiently attractive to get from the potentially interrested authorities a clear go-ahead, i.e. a financial committment. The situation is now rapidly evolving. Several european states, among them ITALY and FRANCE, are now convinced of the necessity of the availability of such a transportation system, an important argument to promote small missions, using small satellites. Application market will be mainly scientific experiments and earth observation; some telecommunications applications may be also envisaged such as placement of little LEO constellation satellites, or replacement after failure of big LEO constellation satellites. FIAT AVIO and AEROSPATIALE have proposed to their national agencies the development of such a small launch vehicle, named VEGA. The paper presents the story of the industrial proposal, and the present status of the project: Mission spectrum, technical definition, launch service and performance, target development plan and target recurring costs, as well as the industrial organisation for development, procurement, marketing and operations.

The impact of coexisting lung diseases on outcomes in patients with pathological Stage I non-small-cell lung cancer.

PubMed

Tao, Hiroyuki; Onoda, Hideko; Okabe, Kazunori; Matsumoto, Tsuneo

2018-06-01

Cigarette smoking is a well-known cause of interstitial lung disease (ILD), pulmonary emphysema and lung cancer. Coexisting pulmonary disease can affect prognosis in patients with lung cancer. The aim of this study was to determine the influence of pulmonary disease on outcomes in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer. Medical records of 257 patients with a smoking history who underwent surgery for pathological Stage I non-small-cell lung cancer between June 2009 and December 2014 were reviewed. Coexisting ILDs were evaluated using high-resolution computed tomography. The degree of pulmonary emphysema was determined using image analysis software according to the Goddard classification. The impact of clinicopathological factors on outcome was evaluated. Among the 257 patients, ILDs were detected via high-resolution computed tomography in 60 (23.3%) patients; of these, usual interstitial pneumonia (UIP) patterns and non-UIP patterns were seen in 25 (9.7%) and 35 (13.6%) patients, respectively. The degree of pulmonary emphysema was classified as none, mild and moderate and included 50 (19.5%), 162 (63.0%) and 45 (17.5%) patients, respectively. The 5-year overall survival, cancer-specific survival and relapse-free survival were 80.7%, 88.0% and 74.9%, respectively, during a median follow-up period of 50.5 months. In multivariate analysis, the presence of a UIP pattern was shown to be an independent risk factor for poor outcome. The presence of a UIP-pattern ILD on high-resolution computed tomography images was shown to be a risk factor for poor outcome in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer.

Thermocron iButton and iBBat temperature dataloggers emit ultrasound.

PubMed

Willis, Craig K R; Jameson, Joel W; Faure, Paul A; Boyles, Justin G; Brack, Virgil; Cervone, Tom H

2009-10-01

Thermocron iButton dataloggers are widely used to measure thermal microclimates experienced by wild animals. The iBBat is a smaller version of the datalogger, also commercially available, that is used to measure animal skin or core body temperatures when attached externally or surgically implanted. Field observations of bats roosting under a bridge suggested that bats avoided locations with iButtons. A heterodyne bat detector revealed that the dataloggers emitted ultrasound which was detectable from a distance of up to 30 cm. We therefore recorded and quantified the acoustic properties [carrier frequency (Hz) and root mean square sound pressure level (dB SPL)] of iButton and iBBat dataloggers. All units emitted a 32.9 kHz pure tone that was readily picked up with a time expansion bat detector at a distance of 1 cm, and most were detected at a distance of 15 cm. The maximum amplitude of iButton dataloggers was 46.5 dB SPL at 1.0 cm-a level within the range of auditory sensitivity for most small mammals. Wrapping iButtons in plastic insulation severely attenuated the amplitude of ultrasound. Although there was a statistically significant reduction in rates of warming and cooling with insulation, this effect was small and we suggest that insulation may be a viable solution to eliminate unwanted ultrasonic noise in instances when small delays in thermal response dynamics are not a concern. We recommend behavioural studies to assess if the electronic signals emitted by iButtons are disturbing to small mammals.

RNA and DNA interactions with zwitterionic and charged lipid membranes - a DSC and QCM-D study.

PubMed

Michanek, Agnes; Kristen, Nora; Höök, Fredrik; Nylander, Tommy; Sparr, Emma

2010-04-01

The aim of the present study is to establish under which conditions tRNA associates with phospholipid bilayers, and to explore how this interaction influences the lipid bilayer. For this purpose we have studied the association of tRNA or DNA of different sizes and degrees of base pairing with a set of model membrane systems with varying charge densities, composed of zwitterionic phosphatidylcholines (PC) in mixtures with anionic phosphatidylserine (PS) or cationic dioctadecyl-dimethyl-ammoniumbromide (DODAB), and with fluid or solid acyl-chains (oleoyl, myristoyl and palmitoyl). To prove and quantify the attractive interaction between tRNA and model-lipid membrane we used quartz crystal microbalance with dissipation (QCM-D) monitoring to study the tRNA adsorption to deposit phospholipid bilayers from solutions containing monovalent (Na(+)) or divalent (Ca(2+)) cations. The influence of the adsorbed polynucleic acids on the lipid phase transitions and lipid segregation was studied by means of differential scanning calorimetry (DSC). The basic findings are: i) tRNA adsorbs to zwitterionic liquid-crystalline and gel-phase phospholipid bilayers. The interaction is weak and reversible, and cannot be explained only on the basis of electrostatic attraction. ii) The adsorbed amount of tRNA is higher for liquid-crystalline bilayers compared to gel-phase bilayers, while the presence of divalent cations show no significant effect on the tRNA adsorption. iii) The adsorption of tRNA can lead to segregation in the mixed 1,2-dimyristoyl-sn-glycerol-3-phosphatidylcholine (DMPC)-1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) and DMPC-DODAB bilayers, where tRNA is likely excluded from the anionic DMPS-rich domains in the first system, and associated with the cationic DODAB-rich domains in the second system. iv) The addition of shorter polynucleic acids influence the chain melting transition and induce segregation in a mixed DMPC-DMPS system, while larger polynucleic acids do

Peptide stabilized amphotericin B nanodisks

PubMed Central

Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

2007-01-01

Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

A Mobile Robot for Small Object Handling

NASA Astrophysics Data System (ADS)

Fišer, Ondřej; Szűcsová, Hana; Grimmer, Vladimír; Popelka, Jan; Vonásek, Vojtěch; Krajník, Tomáš; Chudoba, Jan

The aim of this paper is to present an intelligent autonomous robot capable of small object manipulation. The design of the robot is influenced mainly by the rules of EUROBOT 09 competition. In this challenge, two robots pick up objects scattered on a planar rectangular playfield and use these elements to build models of Hellenistic temples. This paper describes the robot hardware, i.e. electro-mechanics of the drive, chassis and manipulator, as well as the software, i.e. localization, collision avoidance, motion control and planning algorithms.

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation.

PubMed

Urra, Félix A; Córdova-Delgado, Miguel; Lapier, Michel; Orellana-Manzano, Andrea; Acevedo-Arévalo, Luis; Pessoa-Mahana, Hernán; González-Vivanco, Jaime M; Martínez-Cifuentes, Maximiliano; Ramírez-Rodríguez, Oney; Millas-Vargas, Juan Pablo; Weiss-López, Boris; Pavani, Mario; Ferreira, Jorge; Araya-Maturana, Ramiro

2016-01-15

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3ADP), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells.

Nonlinear gravitational self-force: Field outside a small body

NASA Astrophysics Data System (ADS)

Pound, Adam

2012-10-01

A small extended body moving through an external spacetime gαβ creates a metric perturbation hαβ, which forces the body away from geodesic motion in gαβ. The foundations of this effect, called the gravitational self-force, are now well established, but concrete results have mostly been limited to linear order. Accurately modeling the dynamics of compact binaries requires proceeding to nonlinear orders. To that end, I show how to obtain the metric perturbation outside the body at all orders in a class of generalized wave gauges. In a small buffer region surrounding the body, the form of the perturbation can be found analytically as an expansion for small distances r from a representative worldline. Given only a specification of the body’s multipole moments, the field obtained in the buffer region suffices to find the metric everywhere outside the body via a numerical puncture scheme. Following this procedure at first and second order, I calculate the field in the buffer region around an arbitrarily structured compact body at sufficiently high order in r to numerically implement a second-order puncture scheme, including effects of the body’s spin. I also define nth-order (local) generalizations of the Detweiler-Whiting singular and regular fields and show that in a certain sense, the body can be viewed as a skeleton of multipole moments.

Comparative effectiveness of i-SCAN™ and high-definition white light characterizing small colonic polyps.

PubMed

Chan, Johanna L; Lin, Li; Feiler, Michael; Wolf, Andrew I; Cardona, Diana M; Gellad, Ziad F

2012-11-07

To evaluate accuracy of in vivo diagnosis of adenomatous vs non-adenomatous polyps using i-SCAN digital chromoendoscopy compared with high-definition white light. This is a single-center comparative effectiveness pilot study. Polyps (n = 103) from 75 average-risk adult outpatients undergoing screening or surveillance colonoscopy between December 1, 2010 and April 1, 2011 were evaluated by two participating endoscopists in an academic outpatient endoscopy center. Polyps were evaluated both with high-definition white light and with i-SCAN to make an in vivo prediction of adenomatous vs non-adenomatous pathology. We determined diagnostic characteristics of i-SCAN and high-definition white light, including sensitivity, specificity, and accuracy, with regards to identifying adenomatous vs non-adenomatous polyps. Histopathologic diagnosis was the gold standard comparison. One hundred and three small polyps, detected from forty-three patients, were included in the analysis. The average size of the polyps evaluated in the analysis was 3.7 mm (SD 1.3 mm, range 2 mm to 8 mm). Formal histopathology revealed that 54/103 (52.4%) were adenomas, 26/103 (25.2%) were hyperplastic, and 23/103 (22.3%) were other diagnoses include "lymphoid aggregates", "non-specific colitis," and "no pathologic diagnosis." Overall, the combined accuracy of endoscopists for predicting adenomas was identical between i-SCAN (71.8%, 95%CI: 62.1%-80.3%) and high-definition white light (71.8%, 95%CI: 62.1%-80.3%). However, the accuracy of each endoscopist differed substantially, where endoscopist A demonstrated 63.0% overall accuracy (95%CI: 50.9%-74.0%) as compared with endoscopist B demonstrating 93.3% overall accuracy (95%CI: 77.9%-99.2%), irrespective of imaging modality. Neither endoscopist demonstrated a significant learning effect with i-SCAN during the study. Though endoscopist A increased accuracy using i-SCAN from 59% (95%CI: 42.1%-74.4%) in the first half to 67.6% (95%CI: 49.5%-82.6%) in the

Small-volume potentiometric titrations: EPR investigations of Fe-S cluster N2 in mitochondrial complex I.

PubMed

Wright, John J; Salvadori, Enrico; Bridges, Hannah R; Hirst, Judy; Roessler, Maxie M

2016-09-01

EPR-based potentiometric titrations are a well-established method for determining the reduction potentials of cofactors in large and complex proteins with at least one EPR-active state. However, such titrations require large amounts of protein. Here, we report a new method that requires an order of magnitude less protein than previously described methods, and that provides EPR samples suitable for measurements at both X- and Q-band microwave frequencies. We demonstrate our method by determining the reduction potential of the terminal [4Fe-4S] cluster (N2) in the intramolecular electron-transfer relay in mammalian respiratory complex I. The value determined by our method, E m7 =-158mV, is precise, reproducible, and consistent with previously reported values. Our small-volume potentiometric titration method will facilitate detailed investigations of EPR-active centres in non-abundant and refractory proteins that can only be prepared in small quantities. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

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

Zhang Jian; Yang Fujun; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan

2011-11-15

Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data weremore » combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.« less

Proline kink angle distributions for GWALP23 in lipid bilayers of different thicknesses.

PubMed

Rankenberg, Johanna M; Vostrikov, Vitaly V; DuVall, Christopher D; Greathouse, Denise V; Koeppe, Roger E; Grant, Christopher V; Opella, Stanley J

2012-05-01

By using selected (2)H and (15)N labels, we have examined the influence of a central proline residue on the properties of a defined peptide that spans lipid bilayer membranes by solid-state nuclear magnetic resonance (NMR) spectroscopy. For this purpose, GWALP23 (acetyl-GGALW(5)LALALALALALALW(19)LAGA-ethanolamide) is a suitable model peptide that employs, for the purpose of interfacial anchoring, only one tryptophan residue on either end of a central α-helical core sequence. Because of its systematic behavior in lipid bilayer membranes of differing thicknesses [Vostrikov, V. V., et al. (2010) J. Biol. Chem. 285, 31723-31730], we utilize GWALP23 as a well-characterized framework for introducing guest residues within a transmembrane sequence; for example, a central proline yields acetyl-GGALW(5)LALALAP(12)ALALALW(19)LAGA-ethanolamide. We synthesized GWALP23-P12 with specifically placed (2)H and (15)N labels for solid-state NMR spectroscopy and examined the peptide orientation and segmental tilt in oriented DMPC lipid bilayer membranes using combined (2)H GALA and (15)N-(1)H high-resolution separated local field methods. In DMPC bilayer membranes, the peptide segments N-terminal and C-terminal to the proline are both tilted substantially with respect to the bilayer normal, by ~34 ± 5° and 29 ± 5°, respectively. While the tilt increases for both segments when proline is present, the range and extent of the individual segment motions are comparable to or smaller than those of the entire GWALP23 peptide in bilayer membranes. In DMPC, the proline induces a kink of ~30 ± 5°, with an apparent helix unwinding or "swivel" angle of ~70°. In DLPC and DOPC, on the basis of (2)H NMR data only, the kink angle and swivel angle probability distributions overlap those of DMPC, yet the most probable kink angle appears to be somewhat smaller than in DMPC. As has been described for GWALP23 itself, the C-terminal helix ends before Ala(21) in the phospholipids DMPC and DLPC yet

TerraSAR-X interferometry reveals small-scale deformation associated with the summit eruption of Kilauea Volcano, Hawai‘i

USGS Publications Warehouse

Richter, Nichole; Poland, Michael P.; Lundgren, Paul R.

2013-01-01

On 19 March 2008, a small explosive eruption at the summit of Kīlauea Volcano, Hawai‘i, heralded the formation of a new vent along the east wall of Halema‘uma‘u Crater. In the ensuing years, the vent widened due to collapses of the unstable rim and conduit wall; some collapses impacted an actively circulating lava pond and resulted in small explosive events. We used synthetic aperture radar data collected by the TerraSAR-X satellite, a joint venture between the German Aerospace Center (DLR) and EADS Astrium, to identify and analyze small-scale surface deformation around the new vent during 2008-2012. Lidar data were used to construct a digital elevation model to correct for topographic phase, allowing us to generate differential interferograms with a spatial resolution of about 3 m in Kīlauea's summit area. These interferograms reveal subsidence within about 100 m of the rim of the vent. Small baseline subset time series analysis suggests that the subsidence rate is not constant and, over time, may provide an indication of vent stability and potential for rim and wall collapse -- information with obvious hazard implications. The deformation is not currently detectable by other space- or ground-based techniques.

Integration and Test of Shuttle Small Payloads

NASA Technical Reports Server (NTRS)

Wright, Michael R.

2003-01-01

Recommended approaches for space shuttle small payload integration and test (I&T) are presented. The paper is intended for consideration by developers of shuttle small payloads, including I&T managers, project managers, and system engineers. Examples and lessons learned are presented based on the extensive history of NASA's Hitchhiker project. All aspects of I&T are presented, including: (1) I&T team responsibilities, coordination, and communication; (2) Flight hardware handling practices; (3) Documentation and configuration management; (4) I&T considerations for payload development; (5) I&T at the development facility; (6) Prelaunch operations, transfer, orbiter integration and interface testing; (7) Postflight operations. This paper is of special interest to those payload projects that have small budgets and few resources: that is, the truly faster, cheaper, better projects. All shuttle small payload developers are strongly encouraged to apply these guidelines during I&T planning and ground operations to take full advantage of today's limited resources and to help ensure mission success.

Integration and Test for Small Shuttle Payloads

NASA Technical Reports Server (NTRS)

Wright, Michael R.; Day, John H. (Technical Monitor)

2001-01-01

Recommended approaches for shuttle small payload integration and test (I&T) are presented. The paper is intended for consideration by developers of small shuttle payloads, including I&T managers, project managers, and system engineers. Examples and lessons learned are presented based on the extensive history of the NASA's Hitchhiker project. All aspects of I&T are presented, including: (1) I&T team responsibilities, coordination, and communication; (2) Flight hardware handling practices; (3) Documentation and configuration management; (4) I&T considerations for payload development; (5) I&T at the development facility; (6) Prelaunch operations, transfer, orbiter integration, and interface testing; and (7) Postflight operations. This paper is of special interest to those payload projects which have small budgets and few resources: That is, the truly 'faster, cheaper, better' projects. All shuttle small payload developers are strongly encouraged to apply these guidelines during I&T planning and ground operations to take full advantage of today's limited resources and to help ensure mission success.

Gene-Expression Signature Predicts Postoperative Recurrence in Stage I Non-Small Cell Lung Cancer Patients

PubMed Central

Lu, Yan; Wang, Liang; Liu, Pengyuan; Yang, Ping; You, Ming

2012-01-01

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset −142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = −0.83, P<1e-16) and this signature was validated in four independent datasets with AUC >85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients. PMID:22292069

Photofragment Coincidence Imaging of Small I- (H2O)n Clusters Excited to the Charge-transfer-to-solvent State

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

Neumark, D. E. Szpunar, K. E. Kautzman, A. E. Faulhaber, and D. M.; Kautzman, K.E.; Faulhaber, A.E.

2005-11-09

The photodissociation dynamics of small I{sup -}(H{sub 2}O){sub n} (n = 2-5) clusters excited to their charge-transfer-to-solvent (CTTS) states have been studied using photofragment coincidence imaging. Upon excitation to the CTTS state, two photodissociation channels were observed. The major channel ({approx}90%) is a 2-body process forming neutral I + (H{sub 2}O){sub n} photofragments, and the minor channel is a 3-body process forming I + (H{sub 2}O){sub n-1} + H{sub 2}O fragments. Both process display translational energy (P(E{sub T})) distributions peaking at E{sub T} = 0 with little available energy partitioned into translation. Clusters excited to the detachment continuum rather thanmore » to the CTTS state display the same two channels with similar P(E{sub T}) distributions. The observation of similar P(E{sub T}) distributions from the two sets of experiments suggests that in the CTTS experiments, I atom loss occurs after autodetachment of the excited (I(H{sub 2}O){sub n}{sup -})* cluster, or, less probably, that the presence of the excess electron has little effect on the departing I atom.« less

Interpreting survival data from clinical trials of surgery versus stereotactic body radiation therapy in operable Stage I non-small cell lung cancer patients.

PubMed

Samson, Pamela; Keogan, Kathleen; Crabtree, Traves; Colditz, Graham; Broderick, Stephen; Puri, Varun; Meyers, Bryan

2017-01-01

To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. Clinical Stage I NSCLC patients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLC patients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro effects of benzimidazole/thioether-copper complexes with antitumor activity on human erythrocytes.

PubMed

Suwalsky, Mario; Castillo, Ivan; Sánchez-Eguía, Brenda N; Gallardo, María José; Dukes, Nathan; Santiago-Osorio, Edelmiro; Aguiñiga, Itzen; Rivera-Martínez, Ana R

2018-01-01

Two cytotoxic copper(II) complexes with N-H and N-methylated benzimidazole-derived ligands (Cu-L 1 and Cu-L 1Me ; L 1 =bis(2-methylbenzimidazolyl)(2-methylthioethyl)amine, L 1Me =bis(1-methyl-2-methylbenzimidazolyl)(2-methylthioethyl)amine) were synthesized and exposed to human erythrocytes and molecular models of its membrane. The latter were bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), classes of lipids present in the external and internal moieties of the human red cell membrane, respectively. Scanning electron microscopy (SEM) of erythrocytes incubated with solutions of both Cu(II) complexes showed that they induced morphological changes to the normal cells to echinocytes, and hemolysis at higher concentrations. Real-time observation of the dose-dependent effects of the complexes on live erythrocytes by defocusing microscopy (DM) confirmed SEM results. The formation of echinocytes implied that complex molecules inserted into the outer moiety of the red cell membrane. X-ray diffraction studies on DMPC and DMPE showed that none of these complexes interacted with DMPE and only Cu-L 1 interacted with DMPC. This difference was explained by the fact that Cu-L 1Me complex is more voluminous than Cu-L 1 because it has two additional methyl groups; on the other hand, DMPC molecule has three methyl groups in its bulky terminal amino end. Thus, by steric hindrance Cu-L 1Me molecules cannot intercalate into DMPC bilayer, which besides is present in the gel phase. These results, together with the increased antiproliferative capacity of the N-methylated complex Cu-L 1Me over that of Cu-L 1 are rationalized mainly based on its higher lipophilicity. Copyright © 2017 Elsevier Inc. All rights reserved.

ALS-causing profilin-1-mutant forms a non-native helical structure in membrane environments.

PubMed

Lim, Liangzhong; Kang, Jian; Song, Jianxing

2017-11-01

Despite having physiological functions completely different from superoxide dismutase 1 (SOD1), profilin 1 (PFN1) also carries mutations causing amyotrophic lateral sclerosis (ALS) with a striking similarity to that triggered by SOD1 mutants. Very recently, the C71G-PFN1 has been demonstrated to cause ALS by a gain of toxicity and the acceleration of motor neuron degeneration preceded the accumulation of its aggregates. Here by atomic-resolution NMR determination of conformations and dynamics of WT-PFN1 and C71G-PFN1 in aqueous buffers and in membrane mimetics DMPC/DHPC bicelle and DPC micelle, we deciphered that: 1) the thermodynamic destabilization by C71G transforms PFN1 into coexistence with the unfolded state, which is lacking of any stable tertiary/secondary structures as well as restricted ps-ns backbone motions, thus fundamentally indistinguishable from ALS-causing SOD1 mutants. 2) Most strikingly, while WT-PFN1 only weakly interacts with DMPC/DHPC bicelle without altering the native structure, C71G-PFN1 acquires abnormal capacity in strongly interacting with DMPC/DHPC bicelle and DPC micelle, energetically driven by transforming the highly disordered unfolded state into a non-native helical structure, similar to what has been previously observed on ALS-causing SOD1 mutants. Our results imply that one potential mechanism for C71G-PFN1 to initiate ALS might be the abnormal interaction with membranes as recently established for SOD1 mutants. Copyright © 2017 Elsevier B.V. All rights reserved.

1I/‘Oumuamua as a Tidal Disruption Fragment from a Binary Star System

NASA Astrophysics Data System (ADS)

Ćuk, Matija

2018-01-01

1I/‘Oumuamua is the first known interstellar small body, probably being only about 100 m in size. Against expectations based on comets, ‘Oumuamua does not show any activity and has a very elongated figure, and it also exhibits undamped rotational tumbling. In contrast, ‘Oumuamua’s trajectory indicates that it was moving with the local stars, as expected from a low-velocity ejection from a relatively nearby system. Here, I assume that ‘Oumuamua is typical of 100 m interstellar objects and speculate on its origins. I find that giant planets are relatively inefficient at ejecting small bodies from inner solar systems of main-sequence stars, and that binary systems offer a much better opportunity for ejections of non-volatile bodies. I also conclude that ‘Oumuamua is not a member of a collisional population, which could explain its dramatic difference from small asteroids. I observe that 100 m small bodies are expected to carry little mass in realistic collisional populations and that occasional events, when whole planets are disrupted in catastrophic encounters, may dominate the interstellar population of 100 m fragments. Unlike the Sun or Jupiter, red dwarf stars are very dense and are capable of thoroughly tidally disrupting terrestrial planets. I conclude that ‘Oumuamua may have originated as a fragment from a planet that was tidally disrupted and then ejected by a dense member of a binary system, which could explain its peculiarities.

Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

PubMed

Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

2017-04-01

Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Small RNA profiling in Mycobacterium tuberculosis identifies MrsI as necessary for an anticipatory iron sparing response.

PubMed

Gerrick, Elias R; Barbier, Thibault; Chase, Michael R; Xu, Raylin; François, Josie; Lin, Vincent H; Szucs, Matthew J; Rock, Jeremy M; Ahmad, Rushdy; Tjaden, Brian; Livny, Jonathan; Fortune, Sarah M

2018-06-19

One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated. Here, we performed large-scale sRNA discovery and expression profiling in M. tuberculosis during exposure to five pathogenically relevant stresses. From these data, we identified a subset of sRNAs that are highly induced in multiple stress conditions. We focused on one of these sRNAs, ncRv11846, here renamed mycobacterial regulatory sRNA in iron (MrsI). We characterized the regulon of MrsI and showed in mycobacteria that it regulates one of its targets, bfrA , through a direct binding interaction. MrsI mediates an iron-sparing response that is required for optimal survival of M. tuberculosis under iron-limiting conditions. However, MrsI is induced by multiple host-like stressors, which appear to trigger MrsI as part of an anticipatory response to impending iron deprivation in the macrophage environment. Copyright © 2018 the Author(s). Published by PNAS.

Minding your Own Small Business - An Introductory Curriculum for Small Business Management. Volume I.

ERIC Educational Resources Information Center

Holt, Nancy; And Others

Ten units on the basic knowledge and skills needed to manage a small business are provided in this curriculum guide designed for use with secondary and postsecondary students. Unit topics include forms of businesses, marketing, location, systems and records, promotion, pricing, human relations, financing a business, and effects of business…

Outdoor flocking of quadcopter drones with decentralized model predictive control.

PubMed

Yuan, Quan; Zhan, Jingyuan; Li, Xiang

2017-11-01

In this paper, we present a multi-drone system featured with a decentralized model predictive control (DMPC) flocking algorithm. The drones gather localized information from neighbors and update their velocities using the DMPC flocking algorithm. In the multi-drone system, data packages are transmitted through XBee ® wireless modules in broadcast mode, yielding such an anonymous and decentralized system where all the calculations and controls are completed on an onboard minicomputer of each drone. Each drone is a double-layered agent system with the coordination layer running multi-drone flocking algorithms and the flight control layer navigating the drone, and the final formation of the flock relies on both the communication range and the desired inter-drone distance. We give both numerical simulations and field tests with a flock of five drones, showing that the DMPC flocking algorithm performs well on the presented multi-drone system in both the convergence rate and the ability of tracking a desired path. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

[Small bowel metastasis from breast cancer: a case report].

PubMed

Jo, Don Hyoun; Cheung, Dae Young; Kim, Hyung Keun; Son, Dong Kyun; Chung, Ji Sung; Kim, Jin Il; Park, Soo Heon; Han, Joon Yeol; Kim, Jae Kwang; Chung, Kyu Won

2005-08-01

Breast cancer is a common malignancy in women and frequently metastasizes to various organs such as liver, lung, brain, bone and so on. But metastasis to gastrointestinal tract is rare. We describe a 73-year-old woman with small intestinal metastasis of breast cancer. She was diagnosed as right breast cancer in stage I, received modified radical mastectomy 6 years ago and had been followed up without any evidence of residual disease. During investigation for lower abdominal pain and weight loss of 9 kg, we found a small bowel mass. The histology of the tissue taken from small bowel mass was adenocarcinoma, poorly differentiated. The immunohistochemical stain of this specimen showed 75% positivity of estrogen receptor and 90% positivity of progesterone receptor. This is a case of small bowel metastasis from breast cancer and we report this case with a review of literatures.

VISIR-I: small vessels - least-time nautical routes using wave forecasts

NASA Astrophysics Data System (ADS)

Mannarini, Gianandrea; Pinardi, Nadia; Coppini, Giovanni; Oddo, Paolo; Iafrati, Alessandro

2016-05-01

A new numerical model for the on-demand computation of optimal ship routes based on sea-state forecasts has been developed. The model, named VISIR (discoVerIng Safe and effIcient Routes) is designed to support decision-makers when planning a marine voyage. The first version of the system, VISIR-I, considers medium and small motor vessels with lengths of up to a few tens of metres and a displacement hull. The model is comprised of three components: a route optimization algorithm, a mechanical model of the ship, and a processor of the environmental fields. The optimization algorithm is based on a graph-search method with time-dependent edge weights. The algorithm is also able to compute a voluntary ship speed reduction. The ship model accounts for calm water and added wave resistance by making use of just the principal particulars of the vessel as input parameters. It also checks the optimal route for parametric roll, pure loss of stability, and surfriding/broaching-to hazard conditions. The processor of the environmental fields employs significant wave height, wave spectrum peak period, and wave direction forecast fields as input. The topological issues of coastal navigation (islands, peninsulas, narrow passages) are addressed. Examples of VISIR-I routes in the Mediterranean Sea are provided. The optimal route may be longer in terms of miles sailed and yet it is faster and safer than the geodetic route between the same departure and arrival locations. Time savings up to 2.7 % and route lengthening up to 3.2 % are found for the case studies analysed. However, there is no upper bound for the magnitude of the changes of such route metrics, which especially in case of extreme sea states can be much greater. Route diversions result from the safety constraints and the fact that the algorithm takes into account the full temporal evolution and spatial variability of the environmental fields.

Prognostic value of the frequency of vascular invasion in stage I non-small cell lung cancer.

PubMed

Okada, Satoshi; Mizuguchi, Shinjiro; Izumi, Nobuhiro; Komatsu, Hiroaki; Toda, Michihito; Hara, Kantaro; Okuno, Takahiro; Shibata, Toshihiko; Wanibuchi, Hideki; Nishiyama, Noritoshi

2017-01-01

There is no standard pathological method for determining vessel invasion in lung cancer. Herein, we examine whether vessel invasion can be accurately assessed using hematoxylin-eosin staining alone, and investigate the prognostic impact of the presence and frequency of vessel invasion in lung cancer. Vessel invasion was assessed by hematoxylin-eosin, Victoria blue, and D2-40 in 251 completely resected stage I non-small cell lung cancer patients. Vessel invasion was classified into 3 grades according to the number of invaded vessels. Using hematoxylin-eosin and Victoria blue, vascular invasion was detected in 27 (10.8 %) and 75 (29.9 %) of patients, respectively. Lymphatic permeation was detected in 126 (50.2 %) and 70 (27.9 %) of patients using hematoxylin-eosin and D2-40 staining. Hematoxylin-eosin staining did not accurately detect a high frequency of vessel invasion; only 5 and 21.7 % of high-frequency vascular invasion and lymphatic permeation cases diagnosed with Victoria blue and D2-40 were detected. Multivariate analysis based on elastic stain and immunostaining indicated that plural invasion, a high frequency of vascular invasion (hazard ratio 4.00), and a high frequency of lymphatic permeation (hazard ratio 2.30) were independent predictors of cancer recurrence within 3 years. Likewise, an age ≥70 years, male, and a high frequency of vascular invasion (hazard ratio 3.41) were independent predictors of overall survival. Vascular invasion should be confirmed by elastic stains, and the frequency, not but the presence, of vascular invasion is a powerful independent prognostic factor in completely resected stage I non-small cell lung cancer patients.

The Consequences of Metric Production for Small Manufacturers. Volume II. Case Studies of Large Business-Small Business Interaction,

DTIC Science & Technology

1982-02-08

II 00 CASE STUDIES OF LARGE BUSINESS - SMALL BUSINESS INTERACTION ’C- DTIC. Henry H1. Hitchcock dlELECTE7 Joseph F. Coates Marcy M. Canavan AUGG261982...J wis&omWWS1ARET N W WASIINGTOW. OC NO$I THE CONSEQUENCES OF METRIC PRODUCTION FOR SMALL MANUFACTURERS Volume 11 CASE STUDIES OF LARGE BUSINESS ... SMALL BUSINESS INTERACTION Accesqi~r, For NTIS GRA&t DTIC TAB Unannoun~ced J’htiI’ctof _ Henry H. Hitchcock vi 1ribr i t o aes Joseph F. Coates Avail arid

Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors

PubMed Central

Smith, Aaron L.; Freeman, Sara M.; Stehouwer, Jeffery S.; Inoue, Kiyoshi; Voll, Ronald J.; Young, Larry J.; Goodman, Mark M.

2013-01-01

Compounds 1–4 were synthesized and investigated for selectivity and potency for the oxytocin receptor (OTR) to determine their viability as radioactive ligands. Binding assays determined 1–4 to have high binding affinity for both the human and rodent OTR and also have high selectivity for the human OTR over human vasopressin V1a receptors (V1aR). Inadequate selectivity for OTR over V1aR was found for rodent receptors in all four compounds. The radioactive (C-11, F-18, and I-125) derivatives of 1–4 were synthesized and investigated for use as autoradiography and positron emission tomography (PET) ligands. Receptor autoradiography performed with [125I]1 and [125I]2 on rodent brain slices provided the first small molecule radioligand images of the OTR and V1aR. Biodistribution studies determined [125I]1 and [125I]2 were adequate for in vivo peripheral investigations, but not for central investigations due to low uptake within the brain. A biodistribution study with [18F]3 suggested brain uptake occurred slowly over time. PET imaging studies with [18F]3 and [11C]4 using a rat model provided insufficient uptake in the brain over a 90 and 45 min scan times respectively to merit further investigations in non-human primates. PMID:22425346

TerraSAR-X interferometry reveals small-scale deformation associated with the summit eruption of Kīlauea Volcano, Hawai`i

NASA Astrophysics Data System (ADS)

Richter, Nicole; Poland, Michael P.; Lundgren, Paul R.

2013-04-01

On 19 March 2008, a small explosive eruption at the summit of Kīlauea Volcano, Hawai`i, heralded the formation of a new vent along the east wall of Halema`uma`u Crater. In the ensuing years, the vent widened due to collapses of the unstable rim and conduit wall; some collapses impacted an actively circulating lava pond and resulted in small explosive events. We used synthetic aperture radar data collected by the TerraSAR-X satellite, a joint venture between the German Aerospace Center (DLR) and EADS Astrium, to identify and analyze small-scale surface deformation around the new vent during 2008-2012. Lidar data were used to construct a digital elevation model to correct for topographic phase, allowing us to generate differential interferograms with a spatial resolution of about 3 m in Kīlauea's summit area. These interferograms reveal subsidence within about 100 m of the rim of the vent. Small baseline subset time series analysis suggests that the subsidence rate is not constant and, over time, may provide an indication of vent stability and potential for rim and wall collapse—information with obvious hazard implications. The deformation is not currently detectable by other space- or ground-based techniques.

Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

PubMed Central

Jung, In-Hye; Jung, Jinhong; Cho, Byungchul; Kwak, Jungwon; Je, Hyoung Uk; Choi, Wonsik; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung

2015-01-01

Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID:26157678

Evaluation of the interaction and drug release from alpha,beta-polyaspartamide derivatives to a biomembrane model.

PubMed

Castelli, F; Messina, C; Craparo, E F; Mandracchia, D; Pitarresi, G

2005-01-01

This article reports on a comparative study on the ability of various polymers, containing hydrophilic and/or hydrophobic groups, to interact with a biomembrane model using the differential scanning calorimetry (DSC) technique. Multilamellar vesicles of mixed dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidic acid (DMPA) were chosen as a model of cell membranes. The investigated samples were a water soluble polymer, the alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) and its derivatives partially functionalized with polyethylene glycol (PEG2000) to obtain PHEA-PEG2000, with hexadecylamine (C16) to obtain PHEA-C16, and with both compounds to obtain PHEA-PEG2000-C16. These polymers are potential candidates to prepare drug delivery systems. In particular, some samples give rise to polymeric micelles able to entrap hydrophobic drugs in an aqueous medium. The migration of drug molecules from these micelles to DMPC/DMPA vesicles also has been evaluated by DSC analysis, by using ketoprofen as a model drug.

Small Impact Crater

NASA Technical Reports Server (NTRS)

2005-01-01

22 June 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a small impact crater with a 'butterfly' ejecta pattern. The butterfly pattern results from an oblique impact. Not all oblique impacts result in an elliptical crater, but they can result in a non-radial pattern of ejecta distribution. The two-toned nature of the ejecta -- with dark material near the crater and brighter material further away -- might indicate the nature of subsurface materials. Below the surface, there may be a layer of lighter-toned material, underlain by a layer of darker material. The impact throws these materials out in a pattern that reflects the nature of the underlying layers.

<i>Location neari>: 3.7oN, 348.2oW <i>Image widthi>: 3 km (1.9 mi) <i>Illumination fromi>: lower left <i>Season>: Northern Autumn

Small Schools in the Big City: Neoliberalism, Bureaucracy and the Sustainability of Small by Design Schools in Chicago

ERIC Educational Resources Information Center

Pitluck, Corrin

2010-01-01

Assuming the strength of small by design schools for poor urban students of color to be a settled question, this project attempts to analyze the sustainability of small by design schools in a large, complex urban district. Asking what causes small schools to converge toward or diverge from the small by design model, I analyze three sets of design…

Reversible Lifting of Surface Supported Lipid Bilayers with a Membrane-Spanning Nonionic Triblock Copolymer

DOE PAGES

Hayden, Steven C.; Junghans, Ann; Majewski, Jaroslaw; ...

2017-02-22

Neutron reflectometry was used to monitor structural variations in surface supported DMPC bilayers induced by the addition of Triton X-100, a surfactant commonly used to aid solubilization of membrane proteins, and the co-addition of a membrane spanning non-ionic amphiphilic triblock copolymer, (PEO 117-PPO 47-PE O117, Pluronic F98). Surfactant addition causes slight compression of the bilayer thickness and the creation of a distinct EO layer that increases the hydrophilic layer proximal to the supporting substrate (i.e., a water and EO gap between the lipid bilayer and quartz) to 6.8 ± 0.4 Å. Addition of the triblock copolymer into the DMPC: Tritonmore » X-100 bilayer increases the complexity (broadens) the lipid phase transition, further compresses the bilayer, and continues to expand the proximal hydrophilic layer thickness. The observed structural changes are temperature dependent with transmembrane polymer insertion achieved at 37 °C leading to a compressed membrane thickness of 39.2 ± 0.2 Å and proximal gap of 45.2 ± 0.2 Å. Temperature driven exclusion of the polymer at 15 °C causes partitioning of the polymer into the proximal space generating a large hydrogel cushion 162 ± 16 Å thick. An intermediate gap width (10 – 27 Å) is achieved at room temperature (22 – 25 °C). The temperature-driven changes in the proximal hydrophilic gap dimensions are shown to be reversible but thermal history causes variation in magnitude. Temperature-driven changes in polymer association with a supported lipid bilayer offer a facile means to reversibly control both the membrane characteristics as well as the separation between membrane and solid substrate.« less

Reversible Lifting of Surface Supported Lipid Bilayers with a Membrane-Spanning Nonionic Triblock Copolymer

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

Hayden, Steven C.; Junghans, Ann; Majewski, Jaroslaw

Neutron reflectometry was used to monitor structural variations in surface supported DMPC bilayers induced by the addition of Triton X-100, a surfactant commonly used to aid solubilization of membrane proteins, and the co-addition of a membrane spanning non-ionic amphiphilic triblock copolymer, (PEO 117-PPO 47-PE O117, Pluronic F98). Surfactant addition causes slight compression of the bilayer thickness and the creation of a distinct EO layer that increases the hydrophilic layer proximal to the supporting substrate (i.e., a water and EO gap between the lipid bilayer and quartz) to 6.8 ± 0.4 Å. Addition of the triblock copolymer into the DMPC: Tritonmore » X-100 bilayer increases the complexity (broadens) the lipid phase transition, further compresses the bilayer, and continues to expand the proximal hydrophilic layer thickness. The observed structural changes are temperature dependent with transmembrane polymer insertion achieved at 37 °C leading to a compressed membrane thickness of 39.2 ± 0.2 Å and proximal gap of 45.2 ± 0.2 Å. Temperature driven exclusion of the polymer at 15 °C causes partitioning of the polymer into the proximal space generating a large hydrogel cushion 162 ± 16 Å thick. An intermediate gap width (10 – 27 Å) is achieved at room temperature (22 – 25 °C). The temperature-driven changes in the proximal hydrophilic gap dimensions are shown to be reversible but thermal history causes variation in magnitude. Temperature-driven changes in polymer association with a supported lipid bilayer offer a facile means to reversibly control both the membrane characteristics as well as the separation between membrane and solid substrate.« less

Colour gamut mapping between small and large colour gamuts: Part I. gamut compression.

PubMed

Xu, Lihao; Zhao, Baiyue; Luo, M R

2018-04-30

This paper describes an investigation into the performance of different gamut compression algorithms (GCAs) in different uniform colour spaces (UCSs) between small and large colour gamuts. Gamut mapping is a key component in a colour management system and has drawn much attention in the last two decades. Two new GCAs, i.e. vividness-preserved (VP) and depth-preserved (DP), based on the concepts of 'vividness' and 'depth' are proposed and compared with the other commonly used GCAs with the exception of spatial GCAs since the goal of this study was to develop an algorithm that could be implemented in real time for mobile phone applications. In addition, UCSs including CIELAB, CAM02-UCS, and a newly developed UCS, J z a z b z , were tested to verify how they affect the performance of the GCAs. A psychophysical experiment was conducted and the results showed that one of the newly proposed GCAs, VP, gave the best performance among different GCAs and the J z a z b z is a promising UCS for gamut mapping.

Role of Small Subunit in Mediating Assembly of Red-type Form I Rubisco

PubMed Central

Joshi, Jidnyasa; Mueller-Cajar, Oliver; Tsai, Yi-Chin C.; Hartl, F. Ulrich; Hayer-Hartl, Manajit

2015-01-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme involved in photosynthetic carbon fixation, converting atmospheric CO2 to organic compounds. Form I Rubisco is a cylindrical complex composed of eight large (RbcL) subunits that are capped by four small subunits (RbcS) at the top and four at the bottom. Form I Rubiscos are phylogenetically divided into green- and red-type. Some red-type enzymes have catalytically superior properties. Thus, understanding their folding and assembly is of considerable biotechnological interest. Folding of the green-type RbcL subunits in cyanobacteria is mediated by the GroEL/ES chaperonin system, and assembly to holoenzyme requires specialized chaperones such as RbcX and RAF1. Here, we show that the red-type RbcL subunits in the proteobacterium Rhodobacter sphaeroides also fold with GroEL/ES. However, assembly proceeds in a chaperone-independent manner. We find that the C-terminal β-hairpin extension of red-type RbcS, which is absent in green-type RbcS, is critical for efficient assembly. The β-hairpins of four RbcS subunits form an eight-stranded β-barrel that protrudes into the central solvent channel of the RbcL core complex. The two β-barrels stabilize the complex through multiple interactions with the RbcL subunits. A chimeric green-type RbcS carrying the C-terminal β-hairpin renders the assembly of a cyanobacterial Rubisco independent of RbcX. Our results may facilitate the engineering of crop plants with improved growth properties expressing red-type Rubisco. PMID:25371207

Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

PubMed

Fiorelli, Alfonso; Sagan, Dariusz; Mackiewicz, Lukasz; Cagini, Lucio; Scarnecchia, Elisa; Chiodini, Paolo; Caronia, Francesco Paolo; Puma, Francesco; Santini, Mario; Ragusa, Mark

2015-10-01

To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated. Georg Thieme Verlag KG Stuttgart · New York.

SMALL MAMMAL USE OF MICROHABITAT REVIEWED

EPA Science Inventory

Small mammal microhabitat research has greatly influenced vertebrate community ecologists. There exists a "microhabitat paradigm" that states that sympatry among small mammal species is enabled by differential use of microhabitat (i.e., microhabitat partitioning). However, seve...

The prognostic impact of tumor volume on stage I non-small cell lung cancer.

PubMed

Su, Xiao-Dong; Xie, Hao-Jun; Liu, Qian-Wen; Mo, Yun-Xian; Long, Hao; Rong, Tie-Hua

2017-02-01

The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS. By using 3.046cm 3 and 8.078cm 3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm 3 , 3.046-8.078cm 3 , and>8.078cm 3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively. TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Solvent history dependence of gramicidin A conformations in hydrated lipid bilayers.

PubMed Central

LoGrasso, P V; Moll, F; Cross, T A

1988-01-01

Reconstituted lipid bilayers of dimyristoylphosphatidylcholine (DMPC) and gramicidin A' have been prepared by cosolubilizing gramicidin and DMPC in one of three organic solvent systems followed by vacuum drying and hydration. The conformational state of gramicidin as characterized by 23Na NMR, circular dichroism, and solid state 15N NMR is dependent upon the cosolubilizing solvent system. In particular, two conformational states are described; a state in which Na+ has minimal interactions with the polypeptide, referred to as a nonchannel state, and a state in which Na+ interacts very strongly with the polypeptide, referred to as the channel state. Both of these conformations are intimately associated with the hydrophobic core of the lipid bilayer. Furthermore, both of these states are stable in the bilayer at neutral pH and at a temperature above the bilayer phase transition temperature. These results with gramicidin suggest that the conformation of membrane proteins may be dictated by the conformation before membrane insertion and may be dependent upon the mechanism by which the insertion is accomplished. PMID:2462923

Lymphatic vessel invasion and lymph node metastasis in patients with clinical stage I non-small cell lung cancer.

PubMed

Kang, Du-Young; Lee, Sungsoo

2014-09-01

The aim of this study was to investigate the association between the presence of lymphatic vessel invasion (LVI) in primary tumors and lymph node (LN) metastasis in clinical stage I non-small cell lung cancer (NSCLC) patients. A total of 76 patients who underwent complete resection for clinical stage I adenocarcinoma and squamous cell carcinoma were retrospectively examined. Tumors consisted of 51 cases of adenocarcinoma and 25 cases of squamous cell carcinoma as determined by histology. LN metastasis was detected in 24.4% (19/76) of patients. Factors associated with LN metastasis on univariate analysis included LVI (p < 0.001) and increased tumor dimensions (p < 0.05). Binary logistic regression analysis showed that the presence of LVI (p < 0.001) was the only predictor of LN metastasis. LVI is significantly associated with LN metastasis in patients with clinical stage I NSCLC. These findings may be helpful in determining the most appropriate operative strategy for patients if preoperative detection of LVI becomes feasible. Georg Thieme Verlag KG Stuttgart · New York.

Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

PubMed

Shi, Shiming; Zeng, Zhaochong; Ye, Luxi; Huang, Yan; He, Jian

2017-06-01

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Mesoporous silica for drug delivery: Interactions with model fluorescent lipid vesicles and live cells.

PubMed

Bardhan, Munmun; Majumdar, Anupa; Jana, Sayantan; Ghosh, Tapas; Pal, Uttam; Swarnakar, Snehasikta; Senapati, Dulal

2018-01-01

Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer. The interaction of DPH incorporated DMPC membrane with Fluorescein loaded MSN lead to the release of Fluorescein (Fl) dye from the interior pores of MSN systems. The extent of release of Fl and spatial distribution of the DPH molecule has been explored by monitoring steady-state fluorescence intensity and fluorescence lifetime at physiological condition. To investigate the fate of drug molecule released from MSN, fluorescence anisotropy has been used. The drug delivery efficiency of the MSN as a carrier for doxorubicin (DOX), a fluorescent chemotherapeutic drug, has also been investigated at physiological conditions. The study gives a definite confirmation for high uptake and steady release of DOX in primary oral mucosal non-keratinized squamous cells in comparison to naked DOX treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Small Business Management. Instructor's Manual. Volume I. Third Edition.

ERIC Educational Resources Information Center

Jeanneau, Joseph A.; And Others

The instructor's manual is one of four prepared as a guide in conducting a small Business Management course for American Indians to prepare them for jobs as owners/managers of their own businesses and for management positions with business owned by bonds, cooperatives, and others. The manual contains lesson plans, suggested methodologies, and…

40 CFR Table 3 to Subpart Bbbb of... - Model Rule-Class I Nitrogen Oxides Emission Limits for Existing Small Municipal Waste Combustion...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Emission Limits for Existing Small Municipal Waste Combustion Units a b c 3 Table 3 to Subpart BBBB of Part... Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Pt. 60, Subpt. BBBB, Table 3 Table... Municipal Waste Combustion Units a b c Municipal waste combustion technology Limits for class I municipal...

The multiscale expansions of difference equations in the small lattice spacing regime, and a vicinity and integrability test: I

NASA Astrophysics Data System (ADS)

Santini, Paolo Maria

2010-01-01

We propose an algorithmic procedure (i) to study the 'distance' between an integrable PDE and any discretization of it, in the small lattice spacing epsilon regime, and, at the same time, (ii) to test the (asymptotic) integrability properties of such discretization. This method should provide, in particular, useful and concrete information on how good is any numerical scheme used to integrate a given integrable PDE. The procedure, illustrated on a fairly general ten-parameter family of discretizations of the nonlinear Schrödinger equation, consists of the following three steps: (i) the construction of the continuous multiscale expansion of a generic solution of the discrete system at all orders in epsilon, following Degasperis et al (1997 Physica D 100 187-211) (ii) the application, to such an expansion, of the Degasperis-Procesi (DP) integrability test (Degasperis A and Procesi M 1999 Asymptotic integrability Symmetry and Perturbation Theory, SPT98, ed A Degasperis and G Gaeta (Singapore: World Scientific) pp 23-37 Degasperis A 2001 Multiscale expansion and integrability of dispersive wave equations Lectures given at the Euro Summer School: 'What is integrability?' (Isaac Newton Institute, Cambridge, UK, 13-24 August); Integrability (Lecture Notes in Physics vol 767) ed A Mikhailov (Berlin: Springer)), to test the asymptotic integrability properties of the discrete system and its 'distance' from its continuous limit; (iii) the use of the main output of the DP test to construct infinitely many approximate symmetries and constants of motion of the discrete system, through novel and simple formulas.

Optimization of bicelle lipid composition and temperature for EPR spectroscopy of aligned membranes.

PubMed

McCaffrey, Jesse E; James, Zachary M; Thomas, David D

2015-01-01

We have optimized the magnetic alignment of phospholipid bilayered micelles (bicelles) for EPR spectroscopy, by varying lipid composition and temperature. Bicelles have been extensively used in NMR spectroscopy for several decades, in order to obtain aligned samples in a near-native membrane environment and take advantage of the intrinsic sensitivity of magnetic resonance to molecular orientation. Recently, bicelles have also seen increasing use in EPR, which offers superior sensitivity and orientational resolution. However, the low magnetic field strength (less than 1 T) of most conventional EPR spectrometers results in homogeneously oriented bicelles only at a temperature well above physiological. To optimize bicelle composition for magnetic alignment at reduced temperature, we prepared bicelles containing varying ratios of saturated (DMPC) and unsaturated (POPC) phospholipids, using EPR spectra of a spin-labeled fatty acid to assess alignment as a function of lipid composition and temperature. Spectral analysis showed that bicelles containing an equimolar mixture of DMPC and POPC homogeneously align at 298 K, 20 K lower than conventional DMPC-only bicelles. It is now possible to perform EPR studies of membrane protein structure and dynamics in well-aligned bicelles at physiological temperatures and below. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of small subunit in mediating assembly of red-type form I Rubisco.

PubMed

Joshi, Jidnyasa; Mueller-Cajar, Oliver; Tsai, Yi-Chin C; Hartl, F Ulrich; Hayer-Hartl, Manajit

2015-01-09

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme involved in photosynthetic carbon fixation, converting atmospheric CO2 to organic compounds. Form I Rubisco is a cylindrical complex composed of eight large (RbcL) subunits that are capped by four small subunits (RbcS) at the top and four at the bottom. Form I Rubiscos are phylogenetically divided into green- and red-type. Some red-type enzymes have catalytically superior properties. Thus, understanding their folding and assembly is of considerable biotechnological interest. Folding of the green-type RbcL subunits in cyanobacteria is mediated by the GroEL/ES chaperonin system, and assembly to holoenzyme requires specialized chaperones such as RbcX and RAF1. Here, we show that the red-type RbcL subunits in the proteobacterium Rhodobacter sphaeroides also fold with GroEL/ES. However, assembly proceeds in a chaperone-independent manner. We find that the C-terminal β-hairpin extension of red-type RbcS, which is absent in green-type RbcS, is critical for efficient assembly. The β-hairpins of four RbcS subunits form an eight-stranded β-barrel that protrudes into the central solvent channel of the RbcL core complex. The two β-barrels stabilize the complex through multiple interactions with the RbcL subunits. A chimeric green-type RbcS carrying the C-terminal β-hairpin renders the assembly of a cyanobacterial Rubisco independent of RbcX. Our results may facilitate the engineering of crop plants with improved growth properties expressing red-type Rubisco. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

High p-Smad2 expression in stromal fibroblasts predicts poor survival in patients with clinical stage I to IIIA non-small cell lung cancer.

PubMed

Chen, Yongbing; Xing, Pengfei; Chen, Yuanyuan; Zou, Li; Zhang, Yongsheng; Li, Feng; Lu, Xueguan

2014-11-05

Increasing evidence indicates that the TGFβ/Smad signaling pathway plays a prominent role in tumor initiation, progression, and metastasis. Therefore, we investigate the expression of p-Smad2 in surgical resection specimens from non-small cell lung cancer, and evaluate the prognostic significance of p-Smad2 expression in stromal fibroblasts and cancer cells for patients with clinical stage I to IIIA non-small cell lung cancer. The immunohistochemical expression of p-Smad2 was evaluated in 78 formalin-fixed paraffin-embedded surgical resection specimens from clinical stage I to IIIA non-small cell lung cancer. Correlations between p-Smad2 expression and clinicopathologic characteristics were determined by Chi-square test. The prognostic significance of p-Smad2 expression in stromal fibroblasts and cancer cells with regard to overall survival was determined by Kaplan-Meier. There were 38.5% (30/78) and 92.3% (72/78) patients with high p-Smad2 expression in stromal fibroblasts and cancer cells, respectively. There was a positive correlation between the p-Smad2 expression level in stromal fibroblasts and the p-Smad2 expression level in cancer cells (χ2=4.176, P=0.045). No significant correlation of p-Smad2 expression in stromal fibroblasts or cancer cells with any of clinicopathologic characteristics was found. The 3-year overall survival rates with low and high p-Smad2 expression in stromal fibroblasts were 53.7% and 37.7%, respectively (χ2=3.86, P=0.049). No significant association was found between low and high p-Smad2 expression in cancer cells with respect to overall survival, respectively (χ2=0.34, P=0.562). The results suggested that high p-Smad2 expression in stromal fibroblasts predicted poor survival in patients with clinical stage I to IIIA non-small cell lung cancer.

A Flight Control Approach for Small Reentry Vehicles

NASA Technical Reports Server (NTRS)

Bevacqoa, Tim; Adams, Tony; Zhu. J. Jim; Rao, P. Prabhakara

2004-01-01

Flight control of small crew return vehicles during atmospheric reentry will be an important technology in any human space flight mission undertaken in the future. The control system presented in this paper is applicable to small crew return vehicles in which reaction control system (RCS) thrusters are the only actuators available for attitude control. The control system consists of two modules: (i) the attitude controller using the trajectory linearization control (TLC) technique, and (ii) the reaction control system (RCS) control allocation module using a dynamic table-lookup technique. This paper describes the design and implementation of the TLC attitude control and the dynamic table-lookup RCS control allocation for nonimal flight along with design verification test results.

Advanced I&C for Fault-Tolerant Supervisory Control of Small Modular Reactors

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

Cole, Daniel G.

In this research, we have developed a supervisory control approach to enable automated control of SMRs. By design the supervisory control system has an hierarchical, interconnected, adaptive control architecture. A considerable advantage to this architecture is that it allows subsystems to communicate at different/finer granularity, facilitates monitoring of process at the modular and plant levels, and enables supervisory control. We have investigated the deployment of automation, monitoring, and data collection technologies to enable operation of multiple SMRs. Each unit's controller collects and transfers information from local loops and optimize that unit’s parameters. Information is passed from the each SMR unitmore » controller to the supervisory controller, which supervises the actions of SMR units and manage plant processes. The information processed at the supervisory level will provide operators the necessary information needed for reactor, unit, and plant operation. In conjunction with the supervisory effort, we have investigated techniques for fault-tolerant networks, over which information is transmitted between local loops and the supervisory controller to maintain a safe level of operational normalcy in the presence of anomalies. The fault-tolerance of the supervisory control architecture, the network that supports it, and the impact of fault-tolerance on multi-unit SMR plant control has been a second focus of this research. To this end, we have investigated the deployment of advanced automation, monitoring, and data collection and communications technologies to enable operation of multiple SMRs. We have created a fault-tolerant multi-unit SMR supervisory controller that collects and transfers information from local loops, supervise their actions, and adaptively optimize the controller parameters. The goal of this research has been to develop the methodologies and procedures for fault-tolerant supervisory control of small modular reactors. To

Small Business Management Training Tools Directory.

ERIC Educational Resources Information Center

American Association of Community and Junior Colleges, Washington, DC. National Small Business Training Network.

This directory is designed to assist in the identification of supplementary materials to support program development for small businesses. Following introductory comments and an overview of small business management training, section I lists training tools available from the Small Business Administration (SBA). Section II provides descriptions and…

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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

Zheng, Xiangpeng; Schipper, Matthew; Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgerymore » studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.« less

A small-scale anatomical dosimetry model of the liver

NASA Astrophysics Data System (ADS)

Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

2014-07-01

Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and 125I, 90Y, 211At, 99mTc, 111In, 177Lu, 131I and 18F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons (125I) or high-LET alpha particles (211At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

RNAP-II transcribes two small RNAs at the promoter and terminator regions of the RNAP-I gene in Saccharomyces cerevisiae.

PubMed

Mayán, Maria D

2013-01-01

Three RNA polymerases coexist in the ribosomal DNA of Saccharomyces cerevisiae. RNAP-I transcribes the 35S rRNA, RNAP-III transcribes the 5S rRNA and RNAP-II is found in both intergenic non-coding regions. Previously, we demonstrated that RNAP-II molecules bound to the intergenic non-coding regions (IGS) of the ribosomal locus are mainly found in a stalled conformation, and the stalled polymerase mediates chromatin interactions, which isolate RNAP-I from the RNAP-III transcriptional domain. Besides, RNAP-II transcribes both IGS regions at low levels, using different cryptic promoters. This report demonstrates that RNAP-II also transcribes two sequences located in the 5'- and 3'-ends of the 35S rRNA gene that overlap with the sequences of the 35S rRNA precursor transcribed by RNAP-I. The sequence located at the promoter region of RNAP-I, called the p-RNA transcript, binds to the transcription termination-related protein, Reb1p, while the T-RNA sequence, located in the termination sites of RNAP-I gene, contains the stem-loop recognized by Rtn1p, which is necessary for proper termination of RNAP-I. Because of their location, these small RNAs may play a key role in the initiation and termination of RNAP-I transcription. To correctly synthesize proteins, eukaryotic cells may retain a mechanism that connects the three main polymerases. This report suggests that cryptic transcription by RNAP-II may be required for normal transcription by RNAP-I in the ribosomal locus of S. cerevisiae. Copyright © 2012 John Wiley & Sons, Ltd.

A novel approach to oral apoA-I mimetic therapy[S

PubMed Central

Chattopadhyay, Arnab; Navab, Mohamad; Hough, Greg; Gao, Feng; Meriwether, David; Grijalva, Victor; Springstead, James R.; Palgnachari, Mayakonda N.; Namiri-Kalantari, Ryan; Su, Feng; Van Lenten, Brian J.; Wagner, Alan C.; Anantharamaiah, G. M.; Farias-Eisner, Robin; Reddy, Srinivasa T.; Fogelman, Alan M.

2013-01-01

Transgenic tomato plants were constructed with an empty vector (EV) or a vector expressing an apoA-I mimetic peptide, 6F. EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR−/−) mice at 45 mg/kg/day 6F. After 13 weeks, the percent of the aorta with lesions was 4.1 ± 4%, 3.3 ± 2.4%, and 1.9 ± 1.4% for WD, WD + EV, and WD + 6F, respectively (WD + 6F vs. WD, P = 0.0134; WD + 6F vs. WD + EV, P = 0.0386; WD + EV vs. WD, not significant). While body weight did not differ, plasma serum amyloid A (SAA), total cholesterol, triglycerides, and lysophosphatidic acid (LPA) levels were less in WD + 6F mice; P < 0.0295. HDL cholesterol and paroxonase-1 activity (PON) were higher in WD + 6F mice (P = 0.0055 and P = 0.0254, respectively), but not in WD + EV mice. Plasma SAA, total cholesterol, triglycerides, LPA, and 15-hydroxyeicosatetraenoic acid (HETE) levels positively correlated with lesions (P < 0.0001); HDL cholesterol and PON were inversely correlated (P < 0.0001). After feeding WD + 6F: i) intact 6F was detected in small intestine (but not in plasma); ii) small intestine LPA was decreased compared with WD + EV (P < 0.0469); and iii) small intestine LPA 18:2 positively correlated with the percent of the aorta with lesions (P < 0.0179). These data suggest that 6F acts in the small intestine and provides a novel approach to oral apoA-I mimetic therapy. PMID:23378594

psRNATarget: a plant small RNA target analysis server

PubMed Central

Dai, Xinbin; Zhao, Patrick Xuechun

2011-01-01

Plant endogenous non-coding short small RNAs (20–24 nt), including microRNAs (miRNAs) and a subset of small interfering RNAs (ta-siRNAs), play important role in gene expression regulatory networks (GRNs). For example, many transcription factors and development-related genes have been reported as targets of these regulatory small RNAs. Although a number of miRNA target prediction algorithms and programs have been developed, most of them were designed for animal miRNAs which are significantly different from plant miRNAs in the target recognition process. These differences demand the development of separate plant miRNA (and ta-siRNA) target analysis tool(s). We present psRNATarget, a plant small RNA target analysis server, which features two important analysis functions: (i) reverse complementary matching between small RNA and target transcript using a proven scoring schema, and (ii) target-site accessibility evaluation by calculating unpaired energy (UPE) required to ‘open’ secondary structure around small RNA’s target site on mRNA. The psRNATarget incorporates recent discoveries in plant miRNA target recognition, e.g. it distinguishes translational and post-transcriptional inhibition, and it reports the number of small RNA/target site pairs that may affect small RNA binding activity to target transcript. The psRNATarget server is designed for high-throughput analysis of next-generation data with an efficient distributed computing back-end pipeline that runs on a Linux cluster. The server front-end integrates three simplified user-friendly interfaces to accept user-submitted or preloaded small RNAs and transcript sequences; and outputs a comprehensive list of small RNA/target pairs along with the online tools for batch downloading, key word searching and results sorting. The psRNATarget server is freely available at http://plantgrn.noble.org/psRNATarget/. PMID:21622958

48 CFR 8.405-5 - Small business.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Small business. 8.405-5... REQUIRED SOURCES OF SUPPLIES AND SERVICES Federal Supply Schedules 8.405-5 Small business. (a) Although the...— (i) Set aside orders for any of the small business concerns identified in 19.000(a)(3); and (ii) Set...

48 CFR 8.405-5 - Small business.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Small business. 8.405-5... REQUIRED SOURCES OF SUPPLIES AND SERVICES Federal Supply Schedules 8.405-5 Small business. (a) Although the...— (i) Set aside orders for any of the small business concerns identified in 19.000(a)(3); and (ii) Set...

48 CFR 8.405-5 - Small business.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Small business. 8.405-5... REQUIRED SOURCES OF SUPPLIES AND SERVICES Federal Supply Schedules 8.405-5 Small business. (a) Although the...— (i) Set aside orders for any of the small business concerns identified in 19.000(a)(3); and (ii) Set...

Structural evolution of photocrosslinked silk fibroin and silk fibroin-based hybrid hydrogels: A small angle and ultra-small angle scattering investigation.

PubMed

Whittaker, Jasmin L; Balu, Rajkamal; Knott, Robert; de Campo, Liliana; Mata, Jitendra P; Rehm, Christine; Hill, Anita J; Dutta, Naba K; Roy Choudhury, Namita

2018-07-15

Regenerated Bombyx mori silk fibroin (RSF) is a widely recognized protein for biomedical applications; however, its hierarchical gel structure is poorly understood. In this paper, the hierarchical structure of photocrosslinked RSF and RSF-based hybrid hydrogel systems: (i) RSF/Rec1-resilin and (ii) RSF/poly(N-vinylcaprolactam (PVCL) is reported for the first time using small-angle scattering (SAS) techniques. The structure of RSF in dilute to concentrated solution to fabricated hydrogels were characterized using small angle X-ray scattering (SAXS), small angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) techniques. The RSF hydrogel exhibited three distinctive structural characteristics: (i) a Porod region in the length scale of 2 to 3nm due to hydrophobic domains (containing β-sheets) which exhibits sharp interfaces with the amorphous matrix of the hydrogel and the solvent, (ii) a Guinier region in the length scale of 4 to 20nm due to hydrophilic domains (containing turns and random coil), and (iii) a Porod-like region in the length scale of few micrometers due to water pores/channels exhibiting fractal-like characteristics. Addition of Rec1-resilin or PVCL to RSF and subsequent crosslinking systematically increased the nanoscale size of hydrophobic and hydrophilic domains, whereas decreased the homogeneity of pore size distribution in the microscale. The presented results have implications on the fundamental understanding of the structure-property relationship of RSF-based hydrogels. Copyright © 2018. Published by Elsevier B.V.

Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

PubMed

Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

2000-12-01

The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

Experience of the Small Grower

Treesearch

Emmett Jordon

2002-01-01

The small grower cannot afford costly facilities, equipment, or containers. The grower usually does about everything by hand and gets help from family members and friends to get started. I describe the approach I use to produce longleaf pine container stock.

The Evolution of iSchool Movement (1988-2013): A Bibliometric View

ERIC Educational Resources Information Center

Shu, Fei; Mongeon, Phillippe

2016-01-01

The iSchool movement is a controversial topic within the library and information science (LIS) community. While some argue that the movement isolates small size schools and splits the LIS community others insist it will broaden the field of LIS and form an open and boundaryless iField. This study investigates the evolution of the iSchool movement…

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904

PubMed Central

Bogart, Jeffrey A.; Hodgson, Lydia; Seagren, Stephen L.; Blackstock, A. William; Wang, Xiaofei; Lenox, Robert; Turrisi, Andrew T.; Reilly, John; Gajra, Ajeet; Vokes, Everett E.; Green, Mark R.

2010-01-01

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted. PMID:19933904

Improving ungulate habitat in a region undergoing rapid energy development: Consequences for songbirds and small mammals

NASA Astrophysics Data System (ADS)

Bombaci, Sara Petrita

Habitat manipulation intended to mitigate the impact of energy development on game animals is well underway in the western U.S. Yet, the consequences of these actions for other species are not well understood. A habitat manipulation experiment was established in the Piceance Basin, a region of Colorado undergoing rapid energy development, to evaluate alternative methods (i.e. chaining, hydro-axe, and roller-chop treatments) for reducing pinyon-juniper woodlands to promote mule deer habitat. I use this experimental design to additionally test the initial effects of these treatments on birds and small mammals, and to evaluate selection of habitat components in treatments by birds and small mammals. I found lower bird species occupancy in all treatment plots compared to control plots; however the strength of this response varied by bird guild. I found a positive relationship between bird species occupancy and percent tree cover and a negative relationship between bird species occupancy and percent grass and forb cover. I found no evidence of differences in small mammal species occupancy or density between controls and treatments. I found a positive relationship between small mammal species occupancy and percent grass and forb cover. Species richness did not significantly differ between control and treatment plots for birds or small mammals. My approach and research findings can be used to inform habitat management and multiple-species conservation objectives in pinyon-juniper and sage-steppe ecosystems undergoing energy development. Specifically, I have identified that recently developed roller-chop and hydro-axe treatments have similar impacts to woodland bird guilds as traditional chaining treatments. I have also identified species that are sensitive to habitat mitigation treatments, and thus should be monitored if woodland reduction continues to be used as a habitat mitigation strategy. Since all bird guilds were positively associated with tree cover, woodland

Effects of small impoundments on downstream crayfish assemblages

Treesearch

Susan B. Adams

2013-01-01

Dams and impoundments, both large and small, affect downstream physicochemical characteristics and up- and downstream biotic communities. I tested whether small dams and their impoundments altered downstream crayfish assemblages in northern Mississippi. I sampled crayfish and measured physicochemical variables at 4 sites downstream of impoundments (outlet sites) and 4...

Another Perspective: The iPad Is a REAL Musical Instrument

ERIC Educational Resources Information Center

Williams, David A.

2014-01-01

This article looks at the iPad's role as a musical instrument through the lens of a live performance ensemble that performs primarily on iPads. It also offers an overview of a pedagogical model used by this ensemble, which emphasizes musician autonomy in small groups, where music is learned primarily through aural means and concerts are…

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

PubMed

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

Prognostic signature of protocadherin 10 methylation in curatively resected pathological stage I non-small-cell lung cancer.

PubMed

Harada, Hiroaki; Miyamoto, Kazuaki; Yamashita, Yoshinori; Taniyama, Kiyomi; Mihara, Kazuko; Nishimura, Mitsuki; Okada, Morihito

2015-10-01

Although curative resection is the current treatment of choice for localized non-small-cell lung cancer (NSCLC), patients show a wide spectrum of survival even after complete resection of pathological stage I NSCLC. Thus, identifying molecular biomarkers that help to accurately select patients at high risk of relapse is an important key to improving the treatment strategy. The purpose of this study was to evaluate the prognostic signature of protocadherin 10 (PCDH10) promoter methylation in curatively resected pathological stage I NSCLC. Using methylation-specific polymerase chain reaction assays, methylation of PCDH10 promoter was assessed in cancer tissues of 109 patients who underwent curative resection of pathological stage I NSCLC. Associations between PCDH10 methylation status and disease outcome was analyzed. PCDH10 promoter methylation was detected in 46/109 patients (42.2%). Patients with methylated PCDH10 showed significantly worse recurrence-free, overall, and disease-specific survival compared with those without methylation (P < 0.0001, P = 0.0004, P = 0.0002, respectively). Multivariate Cox proportional hazard regression analysis revealed that adjusted hazard ratios of methylated PCDH10 were 5.159 for recurrence-free, 1.817 for overall, and 5.478 for disease-specific survival (P = 0.0005, P = 0.1475, P = 0.0109, respectively). The pattern of recurrence was not significantly different between patients with and without PCDH10 methylation (P = 0.5074). PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I NSCLC. Assessment of PCDH10 methylation status might assist in patient stratification for determining an appropriate adjuvant treatment and follow-up strategy. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

40 CFR 80.551 - How does a refiner obtain approval as a small refiner under this subpart?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Applications for motor vehicle diesel fuel small refiner status must be submitted to EPA by December 31, 2001. (ii) Applications for NRLM diesel fuel small refiner status must be submitted to EPA by December 31, 2004. (2)(i) In the case of a refiner who acquires or reactivates a refinery that was shutdown or non...

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

PubMed

Guerrera, Francesco; Errico, Luca; Evangelista, Andrea; Filosso, Pier Luigi; Ruffini, Enrico; Lisi, Elena; Bora, Giulia; Asteggiano, Elena; Olivetti, Stefania; Lausi, Paolo; Ardissone, Francesco; Oliaro, Alberto

2015-06-01

Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P < 0.20, after a backward selection. Missing data in evaluated predictors were multiple-imputed and combined estimates were obtained from 10 imputed data sets. Analysis was performed on 848 consecutive patients. The median follow-up was 48 months. Two hundred and nine patients died (25%), with a 5-year overall survival (OS) rate of 74%. The final Cox model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. We designed an effective prognostic model based on clinical, pathological and surgical

Development of a high-sensitivity BGO well counter for small animal PET studies.

PubMed

Yamamoto, Seiichi; Watabe, Hiroshi; Kanai, Yasukazu; Watabe, Tadashi; Imaizumi, Masao; Shimosegawa, Eku; Hatazawa, Jun

2012-01-01

In quantitative measurements of small animal PET studies, blood sampling is limited due to the small amounts of blood such animals can provide. In addition, injection doses are quite limited. In this situation, a high-sensitivity well counter would be useful for reducing the amount of the blood sample needed from small animals. Bismuth germinate (BGO) has a high stopping power for high-energy gamma rays compared to NaI(Tl), which is commonly used for conventional well counters. We have developed a BGO well counter and have tested it for blood-sampling measurements in small animals. The BGO well counter uses a square BGO block (59 × 59 × 50 mm) with a square open space (27 × 27 × 34 mm) in the center of the block. The BGO block was optically coupled to a 59-mm square-shaped photomultiplier tube (PMT). Signals from the PMT were digitally processed for the integration and energy window setting. The results showed that the energy spectrum of the BGO well counter measured with a Na-22 point source provided counts that were about 6 times higher for a 1022-keV (511 keV × 2) gamma peak than the spectrum of a 2-in. NaI(Tl) well counter. The relative sensitivity of the developed BGO well counter was 3.4 times higher than that of a NaI(Tl) well counter. The time activity curve of arterial blood was obtained successfully with the BGO well counter for a F-18-FDG study on rat. The BGO well counter will contribute to reducing the amount of sampled blood and to improving the throughput of quantitative measurements in small animal PET studies.

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

Standardized Curriculum for Small Engine Repair.

ERIC Educational Resources Information Center

Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

This curriculum guide for small engine repair was developed by the state of Mississippi to standardize vocational education course titles and core contents. The objectives contained in this document are common to all small engine repair programs in the state. The guide contains objectives for small engine repair I and II courses. Units in course I…

Melittin-induced cholesterol reorganization in lipid bilayer membranes

DOE PAGES

Qian, Shuo; Heller, William T.

2015-06-12

The peptide melittin, a 26 amino acid, cationic peptide from honey bee ( Apis mellifera) venom, disrupts lipid bilayer membranes in a concentration-dependent manner. Rather than interacting with a specific receptor, the peptide interacts directly with the lipid matrix of the membrane in a manner dependent on the lipid composition. Here, a small-angle neutron scattering study of the interaction of melittin with lipid bilayers made of mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) is presented. Through the use of deuterium-labeled DMPC, changes in the distribution of the lipid and cholesterol in unilamellar vesicles were observed for peptide concentrations below thosemore » that cause pores to form. In addition to disrupting the in-plane organization of Chol, melittin produces vesicles having inner and outer leaflet compositions that depend on the lipid–Chol molar ratio and on the peptide concentration. The changes seen at high cholesterol and low peptide concentration are similar to those produced by alamethicin (Qian, S. et al., J. Phys. Chem. B 2014, 118, 11200–11208), which points to an underlying physical mechanism driving the redistribution of Chol, but melittin displays an additional effect not seen with alamethicin. Furthermore, a model for how the peptide drives the redistribution of Chol is proposed. The results suggest that redistribution of the lipids in a target cell membrane by membrane active peptides takes places as a prelude to the lysis of the cell.« less

Melittin-induced cholesterol reorganization in lipid bilayer membranes

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

Qian, Shuo; Heller, William T.

The peptide melittin, a 26 amino acid, cationic peptide from honey bee ( Apis mellifera) venom, disrupts lipid bilayer membranes in a concentration-dependent manner. Rather than interacting with a specific receptor, the peptide interacts directly with the lipid matrix of the membrane in a manner dependent on the lipid composition. Here, a small-angle neutron scattering study of the interaction of melittin with lipid bilayers made of mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) is presented. Through the use of deuterium-labeled DMPC, changes in the distribution of the lipid and cholesterol in unilamellar vesicles were observed for peptide concentrations below thosemore » that cause pores to form. In addition to disrupting the in-plane organization of Chol, melittin produces vesicles having inner and outer leaflet compositions that depend on the lipid–Chol molar ratio and on the peptide concentration. The changes seen at high cholesterol and low peptide concentration are similar to those produced by alamethicin (Qian, S. et al., J. Phys. Chem. B 2014, 118, 11200–11208), which points to an underlying physical mechanism driving the redistribution of Chol, but melittin displays an additional effect not seen with alamethicin. Furthermore, a model for how the peptide drives the redistribution of Chol is proposed. The results suggest that redistribution of the lipids in a target cell membrane by membrane active peptides takes places as a prelude to the lysis of the cell.« less

40 CFR Table 3 to Subpart Bbbb of... - Model Rule-Class I Nitrogen Oxides Emission Limits for Existing Small Municipal Waste Combustion...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Emission Limits for Existing Small Municipal Waste Combustion Unitsa,b,c 3 Table 3 to Subpart BBBB of Part... Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Pt. 60, Subpt. BBBB, Table 3 Table... Municipal Waste Combustion Unitsa,b,c Municipal waste combustion technology Limits for class I municipal...

40 CFR Table 3 to Subpart Bbbb of... - Model Rule-Class I Nitrogen Oxides Emission Limits for Existing Small Municipal Waste Combustion...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Emission Limits for Existing Small Municipal Waste Combustion Unitsa,b,c 3 Table 3 to Subpart BBBB of Part... Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Pt. 60, Subpt. BBBB, Table 3 Table... Municipal Waste Combustion Unitsa,b,c Municipal waste combustion technology Limits for class I municipal...

40 CFR Table 3 to Subpart Bbbb of... - Model Rule-Class I Nitrogen Oxides Emission Limits for Existing Small Municipal Waste Combustion...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Emission Limits for Existing Small Municipal Waste Combustion Unitsa,b,c 3 Table 3 to Subpart BBBB of Part... Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Pt. 60, Subpt. BBBB, Table 3 Table... Municipal Waste Combustion Unitsa,b,c Municipal waste combustion technology Limits for class I municipal...

40 CFR Table 3 to Subpart Bbbb of... - Model Rule-Class I Nitrogen Oxides Emission Limits for Existing Small Municipal Waste Combustion...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Emission Limits for Existing Small Municipal Waste Combustion Unitsa,b,c 3 Table 3 to Subpart BBBB of Part... Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Pt. 60, Subpt. BBBB, Table 3 Table... Municipal Waste Combustion Unitsa,b,c Municipal waste combustion technology Limits for class I municipal...

A history of intraspinal analgesia, a small and personal journey.

PubMed

Krames, Elliot S

2012-01-01

There is a large and robust literature on the spinal use of opioids and non-opioids alike, but unless one is my age and older, very few persons know how we got here. This small history offering tells us how we got to where we are today regarding the science, clinical uses, and management of intraspinal analgesia. I have reviewed the literature bases of Google Scholar and the National Library of Medicine using the key words: history, opium, spinal analgesia, spinal morphine, intrathecal (IT), opioid receptors, endogenous opioids, IT delivery of opioids, and IT side-effects/complications. In this personal review of the history of intraspinal analgesia, I relate my own early and later experiences of the science and clinical uses of intraspinal morphine, other opioids, and non-opioids alike to a historical context. This review outlines a rather small history of opium, the historical use of opium and its various compounds, and the search for and answer to the question, "why was the poppy created for wondrous medicinal uses for mankind?" This search led to the discovery of endogenous opioid like chemicals, the discovery of opiate receptors for these endogenous opioids, the first uses of intraspinal opioids in animal models and man, and, finally, our understanding of the appropriate and inappropriate clinical uses of intraspinal analgesia. Within this paper, I acknowledge the works of my colleagues and the "heroes" who have laid the foundation for our understanding of intraspinal analgesia. The history of the use of intraspinal analgesia is rich and guides us to advance the science and clinical use of intraspinal analgesia without reinventing the wheel. © 2012 International Neuromodulation Society.

Localization and Ordering of Lipids Around Aquaporin-0: Protein and Lipid Mobility Effects.

PubMed

Briones, Rodolfo; Aponte-Santamaría, Camilo; de Groot, Bert L

2017-01-01

Hydrophobic matching, lipid sorting, and protein oligomerization are key principles by which lipids and proteins organize in biological membranes. The Aquaporin-0 channel (AQP0), solved by electron crystallography (EC) at cryogenic temperatures, is one of the few protein-lipid complexes of which the structure is available in atomic detail. EC and room-temperature molecular dynamics (MD) of dimyristoylglycerophosphocholine (DMPC) annular lipids around AQP0 show similarities, however, crystal-packing and temperature might affect the protein surface or the lipids distribution. To understand the role of temperature, lipid phase, and protein mobility in the localization and ordering of AQP0-lipids, we used MD simulations of an AQP0-DMPC bilayer system. Simulations were performed at physiological and at DMPC gel-phase temperatures. To decouple the protein and lipid mobility effects, we induced gel-phase in the lipids or restrained the protein. We monitored the lipid ordering effects around the protein. Reducing the system temperature or inducing lipid gel-phase had a marginal effect on the annular lipid localization. However, restraining the protein mobility increased the annular lipid localization around the whole AQP0 surface, resembling EC. The distribution of the inter-phosphate and hydrophobic thicknesses showed that stretching of the DMPC annular layer around AQP0 surface is the mechanism that compensates the hydrophobic mismatch in this system. The distribution of the local area-per-lipid and the acyl-chain order parameters showed particular fluid- and gel-like areas that involved several lipid layers. These areas were in contact with the surfaces of higher and lower protein mobility, respectively. We conclude that the AQP0 surfaces induce specific fluid- and gel-phase prone areas. The presence of these areas might guide the AQP0 lipid sorting interactions with other membrane components, and is compatible with the squared array oligomerization of AQP0 tetramers

Influence of the active compounds of Perilla frutescens leaves on lipid membranes.

PubMed

Duelund, Lars; Amiot, Arnaud; Fillon, Alexandra; Mouritsen, Ole G

2012-02-24

The leaves of the annual plant Perilla frutescens are used widely as a spice and a preservative in Asian food as well as in traditional medicine. The active compounds in the leaves are the cyclic monoterpene limonene (1) and its bio-oxidation products, perillaldehyde (2), perillyl alcohol (3), and perillic acid (4). These compounds are known to be biologically active and exhibit antimicrobial, anticancer, and anti-inflammatory effects that could all be membrane mediated. In order to assess the possible biophysical effects of these compounds on membranes quantitatively, the influence of limonene and its bio-oxidation products has been investigated on a membrane model composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), and electron paramagnetic resonance spectroscopy (EPR). It was found that limonene (1), perillyl alcohol (2), and perillaldehyde (3) partitioned into the DMPC membrane, whereas perillic acid (4) did not. The DSC results demonstrated that all the partitioning compounds strongly perturbed the phase transition of DMPC, whereas no perturbation of the local membrane order was detected by EPR spectroscopy. The results of the study showed that limonene (1) and its bio-oxidation products affect membranes in rather subtle ways.

Draft Reformulation. Phase I. General Design Memorandum and Draft Environmental Impact Statement: Geneva-on-the-Lake, Ohio Small Boat Harbor. Revision.

DTIC Science & Technology

1981-04-01

east of Arcola Creek. The Interim Report gave a favorable recommendation for the harbor project and the results were published in House Document No. 91...Draft Reformulation Phase I GDM Re]port (Draft Stage 3 Report) The purpi se of this )rf t Stag. 3 Report Is to present the results of the Stage 3...Iirements for a small-boat harbor at Geneva State Park. Results of the bathymetric survey and sediment sampling program are presented in Appendix A. (3

Transient regulation of three clustered tomato class-I small heat-shock chaperone genes by ethylene is mediated by SIMADS-RIN transcription factor

USDA-ARS?s Scientific Manuscript database

An intronless cluster of three class I small heat shock protein (sHSP) chaperone genes, Sl17.6, Sl20.0 and Sl20.1, resident on the short arm of chromosome 6 in tomato, was previously characterized (Goyal et al., 2012). This shsp chaperone gene cluster was found decorated with cis sequences known to ...

Small Tharsis Volcano

NASA Technical Reports Server (NTRS)

2004-01-01

30 August 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a small volcano located southwest of the giant volcano, Pavonis Mons, near 2.5oS, 109.4oW. Lava flows can be seen to have emanated from the summit region, which today is an irregularly-shaped collapse pit, or <i>caldera>. A blanket of dust mantles this volcano. Dust covers most martian volcanoes, none of which are young or active today. This picture covers an area about 3 km (1.9 mi) across; sunlight illuminates the scene from the left.

Magnetically Alignable Bicelles with Unprecedented Stability Using Tunable Surfactants Derived from Cholic Acid.

PubMed

Matsui, Ryoichi; Uchida, Noriyuki; Ohtani, Masataka; Yamada, Kuniyo; Shigeta, Arisu; Kawamura, Izuru; Aida, Takuzo; Ishida, Yasuhiro

2016-12-05

Five novel surfactants were prepared by modifying the three hydroxy groups of sodium cholate with triethylene glycol chains endcapped with an amide (SC-C 1 , SC- n C 4 , and SC- n C 5 ) or a carbamoyl group (SC-O n C 4 and SC-O t C 4 ). The phase behavior of aqueous mixtures of these surfactants with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) was systematically studied by 31 P NMR spectroscopy. The surfactants endcapped with carbamate groups (SC-O n C 4 and SC-O t C 4 ) formed magnetically alignable bicelles over unprecedentedly wide ranges of conditions, in terms of temperature (from 21-23 to >90 °C), lipid/surfactant ratio (from 5 to 8), total lipid content (5-20 wt %), and lipid type [DMPC, 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC), or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)]. In conjunction with appropriate phospholipids, the carbamate-endcapped surfactants afforded unique bicelles, characterized by exceptional thermal stabilities (from 0 to >90 °C), biomimetic lipid compositions (DMPC/POPC=25:75 to 50:50), and extremely large 2 H quadrupole splittings (up to 71 Hz). © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolic costs of capital energy storage in a small-bodied ectotherm.

PubMed

Griffen, Blaine D

2017-04-01

Reproduction is energetically financed using strategies that fall along a continuum from animals that rely on stored energy acquired prior to reproduction (i.e., capital breeders) to those that rely on energy acquired during reproduction (i.e., income breeders). Energy storage incurs a metabolic cost. However, previous studies suggest that this cost may be minimal for small-bodied ectotherms. Here I test this assumption. I use a laboratory feeding experiment with the European green crab Carcinus maenas to establish individuals with different amounts of energy storage. I then demonstrate that differences in energy storage account for 26% of the variation in basal metabolic costs. The magnitudes of these costs for any individual crab vary through time depending on the amount of energy it has stored, as well as on temperature-dependent metabolism. I use previously established relationships between temperature- and mass-dependent metabolic rates, combined with a feasible annual pattern of energy storage in the Gulf of Maine and annual sea surface temperature patterns in this region, to estimate potential annual metabolic costs expected for mature female green crabs. Results indicate that energy storage should incur an ~8% increase in metabolic costs for female crabs, relative to a hypothetical crab that did not store any energy. Translated into feeding, for a medium-sized mature female (45 mm carapace width), this requires the consumption of an additional ~156 mussels annually to support the metabolic cost of energy storage. These results indicate, contrary to previous assumptions, that the cost of energy storage for small-bodied ectotherms may represent a considerable portion of their basic operating energy budget. An inability to meet these additional costs of energy storage may help explain the recent decline of green crabs in the Gulf of Maine where reduced prey availability and increased consumer competition have combined to hamper green crab foraging success in

Surficial redistribution of fallout 131iodine in a small temperate catchment

NASA Astrophysics Data System (ADS)

Landis, Joshua D.; Hamm, Nathan T.; Renshaw, Carl E.; Dade, W. Brian; Magilligan, Francis J.; Gartner, John D.

2012-03-01

Isotopes of iodine play significant environmental roles, including a limiting micronutrient (127I), an acute radiotoxin (131I), and a geochemical tracer (129I). But the cycling of iodine through terrestrial ecosystems is poorly understood, due to its complex environmental chemistry and low natural abundance. To better understand iodine transport and fate in a terrestrial ecosystem, we traced fallout 131iodine throughout a small temperate catchment following contamination by the 11 March 2011 failure of the Fukushima Daiichi nuclear power facility. We find that radioiodine fallout is actively and efficiently scavenged by the soil system, where it is continuously focused to surface soils over a period of weeks following deposition. Mobilization of historic (pre-Fukushima) 137cesium observed concurrently in these soils suggests that the focusing of iodine to surface soils may be biologically mediated. Atmospherically deposited iodine is subsequently redistributed from the soil system via fluvial processes in a manner analogous to that of the particle-reactive tracer 7beryllium, a consequence of the radionuclides' shared sorption affinity for fine, particulate organic matter. These processes of surficial redistribution create iodine hotspots in the terrestrial environment where fine, particulate organic matter accumulates, and in this manner regulate the delivery of iodine nutrients and toxins alike from small catchments to larger river systems, lakes and estuaries.

Small-town migration to metropolitan centres: a case in Peninsular Malaysia.

PubMed

Lee Boon Thong

1979-12-01

In Malaysia small towns are an important source of population gowth in metropolitan areas. To provide empirical evidence of the magnitude and roles of small urban centers as complementary sources of population growth in metropolitan areas, a small survey was conducted in 10 small towns in the State of Selangor. Criteria for the selection of these towns include a fair geographical spread over the State, and each area must characteristically possess a dominant urban center. The questionnaires were directed to the heads of 300 households with the intention of investigating the socioeconomic background of the households and the magnitude and characteristics of those members of the households who have migrated elsewhere. The total number of outmigrants from each area varied from 27-57, giving an overall average figure of 1.53 outmigrants/household. About 77% of the outmigrants had moved to the metropolitan centers. As the majority of the metropolitan migrants were more attracted to Kuala Lumpur, Klang, and Petaling Jaya, it may be assumed that the total outmigrants from small towns as derived would have consitituted about 39% of the population in the Klang Valley region. Based on this estimate, the role of small towns in metropolitan population growth is important. In the survey conducted, 2 broad categories of movements were involved: "economic movers," i.e., those who migrated to work or to establish businesses in the metropolitan areas; and "noneconomic movers," i.e., those who moved to continue their studies or to follow their spouses, and so forth. The economic mover stream made up 71% of the total metropolitan migrants. 2 variables--marital status and sex--were significantly related to the economic or noneconomic nature of the metropolitan migrants. The movement of males tended to be associated with economic motives whereas noneconomic reasons for movement tended to be the case among females migrants. The most important occupational group of the economically

Phase I Study of SU5416, a Small Molecule Inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGFR) in Refractory Pediatric Central Nervous System Tumors

PubMed Central

Kieran, Mark W.; Supko, Jeffrey G.; Wallace, Dana; Fruscio, Robert; Poussaint, Tina Young; Phillips, Peter; Pollack, Ian; Packer, Roger; Boyett, James M.; Blaney, Susan; Prados, Michael; Geyer, Russ; Friedman, Henry; Goldman, Stewart; Kun, Larry E.; MacDonald, Tobey

2009-01-01

SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation study stratified by concurrent use (stratum II) or absence (Stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110mg/m2 while stratum II started at 48mg/m2. Thirty-three eligible patients were treated on stratum I (n=23) and stratum II (n=10). Tumor types included 23 glial tumors, 4 neural tumors, 4 ependymomas and 2 choroid plexus carcinomas. The MTD in Stratum I was initially estimated to be 110mg/m2. The protocol was amended to determine the MTD after excluding transient AST elevation. Re-estimation of the MTD began at the 145mg/m2 dose level but due to development of SU5416 being stopped by the sponsor, the trial was closed before completion. The most serious drug-related toxicities were grade 3 liver enzyme abnormalities, arthralgia and hallucinations. The plasma pharmacokinetics of SU5416 was not significantly affected by the concurrent administration of enzyme-inducing anticonvulsant drugs. Mean values of the total body clearance, apparent volume of distribution, and terminal phase half-life of SU5416 for the 19 patients in Stratum I were 26.1 ± 12.5 liter/h/m2, 41.9 ± 21.4 liter/m2, and 1.11 ± 0.41 h, respectively. The plasma pharmacokinetics of SU5416 in children was similar to previously reported findings in adult cancer patients. Prolonged disease stabilization was observed in 4 of 16 stratum 1 patients. PMID:19065567

The Astronaut Glove Challenge: Big Innovation from a (Very) Small Team

NASA Technical Reports Server (NTRS)

Homer, Peter

2008-01-01

Many measurements were taken by test engineers from Hamilton Sundstrand, the prime contractor for the current EVA suit. Because the raw measurements needed to be converted to torques and combined into a final score, it was impossible to keep track of who was ahead in this phase. The final comfort and dexterity test was performed in a depressurized glove box to simulate real on-orbit conditions. Each competitor was required to exercise the glove through a defined set of finger, thumb, and wrist motions without any sign of abrasion or bruising of the competitor's hand. I learned a lot about arm fatigue! This was a pass-fail event, and both of the remaining competitors came through intact. After taking what seemed like an eternity to tally the final scores, the judges announced that I had won the competition. My glove was the only one to have achieved lower finger-bending torques than the Phase VI glove. Looking back, I see three sources of the success of this project that I believe also operate in other programs where small teams have broken new ground in aerospace technologies. These are awareness, failure, and trust. By remaining aware of the big picture, continuously asking myself, "Am I converging on a solution?" and "Am I converging fast enough?" I was able to see that my original design was not going to succeed, leading to the decision to start over. I was also aware that, had I lingered over this choice or taken time to analyze it, I would not have been ready on the first day of competition. Failure forced me to look outside conventional thinking and opened the door to innovation. Choosing to make incremental failures enabled me to rapidly climb the learning curve. Trusting my "gut" feelings-which are really an internalized accumulation of experiences-and my newly acquired skills allowed me to devise new technologies rapidly and complete both gloves just in time. Awareness, failure, and trust are intertwined: failure provides experiences that inform awareness

Origins of extreme boundary lubrication by phosphatidylcholine liposomes.

PubMed

Sorkin, Raya; Kampf, Nir; Dror, Yael; Shimoni, Eyal; Klein, Jacob

2013-07-01

Phosphatidylcholine (PC) vesicles have been shown to have remarkable boundary lubricating properties under physiologically-high pressures. Here we carry out a systematic study, using a surface force balance, of the normal and shear (frictional) forces between two opposing surfaces bearing different PC vesicles across water, to elucidate the origin of these properties. Small unilamellar vesicles (SUVs, diameters < 100 nm) of the symmetric saturated diacyl PCs DMPC (C(14)), DPPC (C(16)) and DSPC (C(18)) attached to mica surfaces were studied in their solid-ordered (SO) phase on the surface. Overall liposome lubrication ability improves markedly with increasing acyl chain length, and correlates strongly with the liposomes' structural integrity on the substrate surface: DSPC-SUVs were stable on the surface, and provided extremely efficient lubrication (friction coefficient μ ≈ 10(-4)) at room temperature at pressures up to at least 18 MPa. DMPC-SUVs ruptured following adsorption, providing poor high-pressure lubrication, while DPPC-SUVs behavior was intermediate between the two. These results can be well understood in terms of the hydration-lubrication paradigm, but suggest that an earlier conjecture, that highly-efficient lubrication by PC-SUVs depended simply on their being in the SO rather than in the liquid-disordered phase, should be more nuanced. Our results indicate that the resistance of the SUVs to mechanical deformation and rupture is the dominant factor in determining their overall boundary lubrication efficiency in our system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dissolution of fludrocortisone from phospholipid coprecipitates.

PubMed

Vudathala, G K; Rogers, J A

1992-03-01

The physical properties and dissolution behavior of phospholipid coprecipitates of fludrocortisone acetate (FA) prepared from ethyl acetate, as well as the effect of added polymer, have been determined. The fraction dissolved after 90 min and the initial dissolution rate (IDR) of coprecipitates containing dimyristoyl phosphatidylcholine (DMPC) (4:1, w/w; FA:DMPC) were 77% and 3.5-fold greater than for FA at pH 2.0 and 37 degrees C. The mechanisms of dissolution were similar to those previously established for griseofulvin, but no aging occurred over 4 months at room temperature in a desiccator. The addition of 0.01 mol% of dextran (MW = 2 million) or 0.1 mol% of poly(lactic acid) reduced the fraction of FA dissolved in 90 min by 15% and reduced the IDR by 35%. The addition of poly(vinylpyrrolidone) (PVP) resulted in a minimum of dissolution efficiency at 1 mol% of PVP 10 (MW = 10,000) or PVP 24 (MW = 24,000) and at 0.1 mol% PVP 40 (MW = 40,000). Only PVP 24 influenced the melting point and heat of fusion of the coprecipitates (determined by differential thermal analysis). Coprecipitate dissolution was reasonably described by either second-order or Weibull distribution kinetic models. These results support the application of high drug-containing solid dispersions using phospholipids to increase the dissolution behavior of poorly water-soluble drug solvates and the possibility of modifying drug release by the incorporation of small amounts of polymers.

Three-Dimensional Coculture of Meniscal Cells and Mesenchymal Stem Cells in Collagen Type I Hydrogel on a Small Intestinal Matrix-A Pilot Study Toward Equine Meniscus Tissue Engineering.

PubMed

Kremer, Antje; Ribitsch, Iris; Reboredo, Jenny; Dürr, Julia; Egerbacher, Monika; Jenner, Florien; Walles, Heike

2017-05-01

Meniscal injuries are the most frequently encountered soft tissue injuries in the equine stifle joint. Due to the inherent limited repair potential of meniscal tissue, meniscal injuries do not only affect the meniscus itself but also lead to impaired joint homeostasis and secondary osteoarthritis. The presented study compares 3D coculture constructs of primary equine mesenchymal stem cells (MSC) and meniscus cells (MC) seeded on three different scaffolds-a cell-laden collagen type I hydrogel (Col I gel), a tissue-derived small intestinal matrix scaffold (SIS-muc) and a combination thereof-for their qualification to be applied for meniscus tissue engineering. To investigate cell attachment of primary MC and MSC on SIS-muc matrix SEM pictures were performed. For molecular analysis, lyophilized samples of coculture constructs with different cell ratios (100% MC, 100% MSC, and 50% MC and 50% MSC, 20% MC, and 80% MSC) were digested and analyzed for DNA and GAG content. Active matrix remodeling of 3D coculture models was indicated by matrix metalloproteinases detection. For comparison of tissue-engineered constructs with the histologic architecture of natural equine menisci, paired lateral and medial menisci of 15 horses representing different age groups were examined. A meniscus phenotype with promising similarity to native meniscus tissue in its GAG/DNA expression in addition to Col I, Col II, and Aggrecan production was achieved using a scaffold composed of Col I gel on SIS-muc combined with a coculture of MC and MSC. The results encourage further development of this scaffold-cell combination for meniscus tissue engineering.

Small Business Management. Part II. A Suggested Adult Course Outline.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Continuing Education Curriculum Development.

This teacher's guide is a companion to "Small Business Management Part I" published by the New York State Education Department in 1968. The course outlined by the guide is primarily for those who aspire to own and operate their own business, and those in business who wish to improve their operations. The course consists of six lessons covering…

Confocal mapping of myelin figures with micro-Raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Jung-Ren; Cheng, Yu-Che; Huang, Hung Ji; Chiang, Hai-Pang

2018-01-01

We employ confocal micro-Raman spectroscopy (CMRS) with submicron spatial resolution to study the myelin structures (cylindrical lamellae) composed of nested surfactant C12E3 or lipid DMPC bilayers. The CMRS mapping indicates that for a straight C12E3 myelin, the surfactant concentration increases with the myelin width and is higher in the center region than in the peripheral region. For a curved C12E3 myelin, the convex side has a higher surfactant concentration than the corresponding concave side. The spectrum of DMPC myelins undergoes a qualitative change as the temperature increases above 60 °C, suggesting that the surfactant molecules may be damaged. Our work demonstrates the utility of CMRS in bio-soft material research.

A small, linear, piezoelectric ultrasonic cryomotor

NASA Astrophysics Data System (ADS)

Dong, Shuxiang; Yan, Li; Wang, Naigang; Viehland, Dwight; Jiang, Xiaoning; Rehrig, Paul; Hackenberger, Wes

2005-01-01

A small, linear-type, piezoelectric ultrasonic cryomotor has been developed for precision positioning at extremely low temperatures (⩾-200°C). This cryomotor consists of a pair of Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystal stacks, which are piezoelectrically excited into the rotating third-bending mode of the cryomotor stator's center, which in turn drives a contacted slider into linear motion via frictional forces. The performance characteristics achieved by the cryomotor are: (i) a maximum linear speed of >50mm /s; (ii) a stroke of >10mm; (iii) a driving force of >0.2N; (iv) a response time of ˜29ms; and (v) a step resolution of ˜20nm.

47 CFR 95.139 - Adding a small base station or a small control station.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Adding a small base station or a small control... base station or a small control station. (a) Except for a GMRS system licensed to a non-individual, one or more small base stations or a small control station may be added to a GMRS system at any point...

Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer.

PubMed

Macke, Ryan A; Schuchert, Matthew J; Odell, David D; Wilson, David O; Luketich, James D; Landreneau, Rodney J

2015-04-01

A suggested benefit of sublobar resection for stage I non-small cell lung cancer (NSCLC) compared to lobectomy is a relative preservation of pulmonary function. Very little objective data exist, however, supporting this supposition. We sought to evaluate the relative impact of both anatomic segmental and lobar resection on pulmonary function in patients with resected clinical stage I NSCLC. The records of 159 disease-free patients who underwent anatomic segmentectomy (n = 89) and lobectomy (n = 70) for the treatment of stage I NSCLC with pre- and postoperative pulmonary function tests performed between 6 to 36 months after resection were retrospectively reviewed. Changes in forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were analyzed based upon the number of anatomic pulmonary segments removed: 1-2 segments (n = 77) or 3-5 segments (n = 82). Preoperative pulmonary function was worse in the lesser resection cohort (1-2 segments) compared to the greater resection group (3-5 segments) (FEV1(%predicted): 79% vs. 85%, p = 0.038; DLCO(%predicted): 63% vs. 73%, p = 0.010). A greater decline in FEV1 was noted in patients undergoing resection of 3-5 segments (FEV1 (observed): 0.1 L vs. 0.3 L, p = 0.003; and FEV1 (% predicted): 4.3% vs. 8.2%, p = 0.055). Changes in DLCO followed this same trend (DLCO(observed): 1.3 vs. 2.4 mL/min/mmHg, p = 0.015; and DLCO(% predicted): 3.6% vs. 5.9%, p = 0.280). Parenchymal-sparing resections resulted in better preservation of pulmonary function at a median of one year, suggesting a long-term functional benefit with small anatomic segmental resections (1-2 segments). Prospective studies to evaluate measurable functional changes, as well as quality of life, between segmentectomy and lobectomy with a larger patient cohort appear justified.

Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent.

PubMed

Zhu, Jianwei; Li, Rui; Tiselius, Eva; Roudi, Raheleh; Teghararian, Olivia; Suo, Chen; Song, Huan

2017-12-16

Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For patients with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. While several new agents have now entered phase III clinical trials, we felt a systematic review was needed to address the question of the effectiveness and safety of immunotherapy in patients with stages I to III NSCLC. To evaluate the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) in patients with localised NSCLC (stages I to III) who received surgery or radiotherapy with curative intent. We searched the following databases (from inception to 20 January 2017): CENTRAL, MEDLINE, Embase, and CINAHL, and five trial registers. We also manually checked abstracts or reports from relevant conference proceedings and the reference lists of included trials. We searched for randomised controlled trials (RCTs) in adults (≥ 18 years) with histologically-confirmed early-stage (stages I to III) NSCLC after surgical resection, and those with unresectable locally advanced stage III NSCLC who had received radiotherapy with curative intent. For patients who had received primary surgical treatment, postoperative radiotherapy or chemoradiotherapy was allowed if it was used for both experimental and control groups. Two review authors independently selected eligible trials, assessed risk of bias, and extracted data. We used survival analysis to pool time-to-event data, expressing the intervention effect as a hazard ratio (HR). We calculated risk ratios (RR) for dichotomous data, and mean differences for continuous data, with 95% confidence intervals (CI). Due to clinical heterogeneity (immunotherapeutic agents with different underlying mechanisms), we used random-effects models for our meta-analyses. We

Investigating structural details of lipid-cholesterol-A β interactions

NASA Astrophysics Data System (ADS)

Rai, Durgesh; Anunciado, Divina; Heller, William; O'Neill, Hugh; Urban, Volker; Qian, Shuo

2015-03-01

Alzheimer's disease (AD) is the most common form of dementia and is predicted to affect 1 in 85 people around the world by 2050. Amyloid beta (A β) -peptide, a peptide composed of 40- 42 amino acids that is the product of cleavage from the amyloid precursor protein (APP), is regarded to play a major role in the development of AD. In addition, accumulating evidence points to a positive association between cholesterol and AD. Here, we present results from our studies about A β-peptide and cholesterol in bilayer by small-angle neutron scattering (SANS) using a combination of dimyristoyl, phosphocholine (DMPC) and partially deuterated cholesterol (cholesterol-d7) with and without A β. We compare the results using grazing incidence and transmission SANS on lipid bilayer films and unilamellar vesicles respectively. The structural details on vesicles and bilayers work in conjunction with the circular dichroism on peptide in solution and oriented circular dichroism in bilayer films. The studies confirm a positive association of A β with the membrane layers. The results from different studies will be compared and contrasted in presentation.

77 FR 46805 - Small Business Innovation Research Program Policy Directive

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... Small Business Innovation Research Program Policy Directive; Small Business Technology Transfer Program Policy Directive; Small Business Innovation Research (SBIR) Program and Small Business Technology... ADMINISTRATION 13 CFR Chapter I RIN 3245-AF84 Small Business Innovation Research Program Policy Directive AGENCY...

Nonresected Non-Small-Cell Lung Cancer in Stages I Through IIIB: Accelerated, Twice-Daily, High-Dose Radiotherapy-A Prospective Phase I/II Trial With Long-Term Follow-Up

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

Wurstbauer, Karl, E-mail: k.wurstbauer@salk.a; radART-Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg; Deutschmann, Heinz

2010-08-01

Purpose: Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials: Thirty consecutive patients with histologically/cytologically proven non-small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6-90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4-72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily,more » with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62-74 months). Results: We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose-positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions: This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.« less

Small 'l' leadership.

PubMed

Parsons, Jenni

2009-05-01

Recently I attended the RACGP Leadership Masterclass in Sydney. When I enrolled, I thought, 'Yes... sounds interesting...good speakers... I need to learn something about leadership...'As the time drew closer I started to get a bit anxious about the whole thing. I realised that the title, 'Masterclass', probably implied that the attendees were expected to already know something about leadership and its theories, if not have considerable expertise and experience in leadership. I also wondered how the workshop sessions were going to go and I started to feel a bit sorry for the facilitators. Imagine trying to facilitate a group of 10 aspiring leaders... a bit like trying to herd cats. A few days later I received a call from the organisers,saying they were a bit short of facilitators and could I help out if necessary. Great... better do a crash course in cat herding! Then there was the first 'predisposing activity'. Step 1: think of leaders you admire. Easy enough. Leaders of social justice and social change on a world stage, people who have shown great courage of their convictions and great orators popped into my head... Ghandi, Martin Luther King, Mandela, JFK. Step 2:describe the ways in which you are like these leaders. Whoa!Never going to measure up here. I wondered if there was going to be sessions on 'leadership for introverts', or 'leadership of small things', or 'leaders without grand vision or fabulous oratory skills', or perhaps 'leadership for people who are deeply suspicious of the corrupting influence of power'.

Arrays of Very Small Voltammetric Electrodes Based on Reticulated Vitreous Carbon.

DTIC Science & Technology

1983-10-14

1H D-fli34 73ifARRAYS OF VERY SMALL YOLTAMMETRIC ELECTRODES BA5ED ON i/i RETICULATED VITREOUS CARBON (U) STATE UNIV OF NEW YORK I AT BUFFALO AMHERST N...PEIOiUD COVI[R9 1^. Arrays of Very Small Voltametric Electrodes 0 Based on Reticulated Vitreous Carbon - S. PRFROG OG. REPORT NUM A 7. AUTNOR) 0...Cofigi nueu eav’e,o *ee i necesaery and Iden lly by block number) L.Uj Reticulated vitreous carbon ; microelectrodes; nonlinear diffusion; vol tammetry

Assumptions, Emotions, and Interpretations as Ethical Moments: Navigating a Small-Scale Cross-Cultural Online Interviewing Study

ERIC Educational Resources Information Center

Frisoli, Paul St. John

2010-01-01

In this paper, I map important "messy" elements that I learned from my five-month small-scale research project, one that was designed around pivotal works on online social research. I used computers and the Internet with Minan, a young man living in Guinea, West Africa, in order to examine his perceptions surrounding the value of these…

Facilities for small-molecule crystallography at synchrotron sources.

PubMed

Barnett, Sarah A; Nowell, Harriott; Warren, Mark R; Wilcox, Andrian; Allan, David R

2016-01-01

Although macromolecular crystallography is a widely supported technique at synchrotron radiation facilities throughout the world, there are, in comparison, only very few beamlines dedicated to small-molecule crystallography. This limited provision is despite the increasing demand for beamtime from the chemical crystallography community and the ever greater overlap between systems that can be classed as either small macromolecules or large small molecules. In this article, a very brief overview of beamlines that support small-molecule single-crystal diffraction techniques will be given along with a more detailed description of beamline I19, a dedicated facility for small-molecule crystallography at Diamond Light Source.

2005 9th Annual Army Small Business Conference

DTIC Science & Technology

2005-11-03

field commanders who conduct acquisitions. All the Army’s major commands located in the United States will be represented. The conference...Engineer Squad Vehicle i r i l Mobile Gun System il yst Medical Evacuation Vehicle i l v ti i l Reconnaissance Vehicle iss i l Mortar Carrier rt r rri r...Manned Systems Unmanned Air Vehicles Class I ARV-A (L) Small (Manpackable) UGV Non-Line of Sight Cannon Non-Line of Sight Mortar Medical Treatment and

Surficial redistribution of fallout 131iodine in a small temperate catchment

PubMed Central

Landis, Joshua D.; Hamm, Nathan T.; Renshaw, Carl E.; Dade, W. Brian; Magilligan, Francis J.; Gartner, John D.

2012-01-01

Isotopes of iodine play significant environmental roles, including a limiting micronutrient (127I), an acute radiotoxin (131I), and a geochemical tracer (129I). But the cycling of iodine through terrestrial ecosystems is poorly understood, due to its complex environmental chemistry and low natural abundance. To better understand iodine transport and fate in a terrestrial ecosystem, we traced fallout 131iodine throughout a small temperate catchment following contamination by the 11 March 2011 failure of the Fukushima Daiichi nuclear power facility. We find that radioiodine fallout is actively and efficiently scavenged by the soil system, where it is continuously focused to surface soils over a period of weeks following deposition. Mobilization of historic (pre-Fukushima) 137cesium observed concurrently in these soils suggests that the focusing of iodine to surface soils may be biologically mediated. Atmospherically deposited iodine is subsequently redistributed from the soil system via fluvial processes in a manner analogous to that of the particle-reactive tracer 7beryllium, a consequence of the radionuclides’ shared sorption affinity for fine, particulate organic matter. These processes of surficial redistribution create iodine hotspots in the terrestrial environment where fine, particulate organic matter accumulates, and in this manner regulate the delivery of iodine nutrients and toxins alike from small catchments to larger river systems, lakes and estuaries. PMID:22378648

77 FR 32167 - Revocation of License of Small Business Investment Company

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... SMALL BUSINESS ADMINISTRATION Revocation of License of Small Business Investment Company Pursuant... Delaware limited partnership, to function as a small business investment company under the Small Business Investment Company License No. 03730213 issued to Women's Growth Capital Fund I, LLLP, on June 17, 1998 and...

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Lam I-joists : a new structural building product from small-diameter, fire-prone timber

Treesearch

John F. Hunt; Jerrold E. Winandy

2003-01-01

The goal of our research is to promote healthy and sustainable forests by developing value-added uses for curved and small-diameter trees. In typical North American logging or thinning operations, much of this low- value timber is felled and left on the ground, chipped, or burned because most mills are not equipped to handle it. By understanding the fundamental...

Permeability of lipid bilayers to amino acids and phosphate

NASA Technical Reports Server (NTRS)

Chakrabarti, A. C.; Deamer, D. W.

1992-01-01

Permeability coefficients for amino acid classes, including neutral, polar, hydrophobic, and charged species, were measured and compared with values for other ionic solutes such as phosphate. The rates of efflux of glycine, lysine, phenylalanine, serine and tryptophan were determined after they were passively entrapped in large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine (EPC) or dimyristoylphosphatidylcholine (DMPC). The following permeability coefficients were obtained for: glycine, 5.7 x 10(-12) cm s-1 (EPC), 2.0 x 10(-11) cm s-1 (DMPC); serine, 5.5 x 10(-12) cm s-1 (EPC), 1.6 x 10(-11) cm s-1 (DMPC); lysine, 5.1 x 10(-12) cm s-1 (EPC), 1.9 x 10(-11) cm s-1 (DMPC); tryptophan, 4.1 x 10(-10) cm s-1 (EPC); and phenylalanine, 2.5 x 10(-10) cm s-1 (EPC). Decreasing lipid chain length increased permeability slightly, while variations in pH had only minor effects on the permeability coefficients of the amino acids tested. Phosphate permeability was in the range of 10(-12)-10(-13) cm s-1 depending on the pH of the medium. The values for the polar and charged amino acids were surprisingly similar to those previously measured for monovalent cations such as sodium and potassium, which are in the range of 10(-12)-10(-13) cm s-1, depending on conditions and the lipid species used. This observation suggests that the permeation rates for the neutral, polar and charged amino acids are controlled by bilayer fluctuations and transient defects, rather than partition coefficients and Born energy barriers. The results are relevant to the permeation of certain peptides into lipid bilayers during protein translocation and membrane biogenesis.

A survey of small RNAs in human sperm

PubMed Central

Krawetz, Stephen A.; Kruger, Adele; Lalancette, Claudia; Tagett, Rebecca; Anton, Ester; Draghici, Sorin; Diamond, Michael P.

2011-01-01

BACKGROUND There has been substantial interest in assessing whether RNAs (mRNAs and sncRNAs, i.e. small non-coding) delivered from mammalian spermatozoa play a functional role in early embryo development. While the cadre of spermatozoal mRNAs has been characterized, comparatively little is known about the distribution or function of the estimated 24 000 sncRNAs within each normal human spermatozoon. METHODS RNAs of <200 bases in length were isolated from the ejaculates from three donors of proved fertility. RNAs of 18–30 nucleotides in length were then used to construct small RNA Digital Gene Expression libraries for Next Generation Sequencing. Known sncRNAs that uniquely mapped to a single location in the human genome were identified. RESULTS Bioinformatic analysis revealed the presence of multiple classes of small RNAs in human spermatozoa. The primary classes resolved included microRNA (miRNAs) (≈7%), Piwi-interacting piRNAs (≈17%), repeat-associated small RNAs (≈65%). A minor subset of short RNAs within the transcription start site/promoter fraction (≈11%) frames the histone promoter-associated regions enriched in genes of early embryonic development. These have been termed quiescent RNAs. CONCLUSIONS A complex population of male derived sncRNAs that are available for delivery upon fertilization was revealed. Sperm miRNA-targeted enrichment in the human oocyte is consistent with their role as modifiers of early post-fertilization. The relative abundance of piRNAs and repeat-associated RNAs suggests that they may assume a role in confrontation and consolidation. This may ensure the compatibility of the genomes at fertilization. PMID:21989093

Small Business and Minority Contracting with the U.S. Government.

DTIC Science & Technology

1982-09-01

business tends to be marginally capitalized, generally with expensive short term financing (Hol lander, 1968). 3. Small business management is characterized...Forces of Small Business ." Journal of Small Business Management , January 1977, p. 30. Chism, David Meredith. A Critical Analysis of the Small Business ...Steinmetz, Lawrence L.; Kline, John B.; and Stegall, Donald P. Managing the Small Business . Homewood, lI].: Irwin, Inc.,

A unique cell-surface protein phenotype distinguishes human small-cell from non-small-cell lung cancer

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

Baylin, S.B.; Gazdar, A.F.; Minna, J.D.

1982-08-01

Radioiodination (/sup 125/I) and two-dimensional polyacrylamide gel electrophoresis was used to determine that small-(oat) cell lung carcinoma (SCC)-a tumor with neuroedocrine features-possesses a surface protein pattern distinct from the other types of lung cancer cells (squamous, adeno-, and large-cell undifferentiated carcinoma). Twelve distinguishing proteins, 40 to 70 kilodaltons (kDal), characterized four separate lines of SCC; three of these, designated E (60 kDal; pI = 7.3), S (30 kDal; pI = 6.0), and U 57 kDal; pI = 5.6), may be unique SCC gene products and were identified only in (/sup 35/S)methionine labeling of SCC and not in non-SCC or humanmore » fibroblasts. Two lines of adeno-, one of squamous, and one of undifferentiated large-cell lung carcinoma exhibited similar surface protein patterns to one another. Nine distinguishing proteins (40 to 100 kDal) and at least five large proteins (>100 kDal) were unique to these lines. The surface protein phenotypes for SCC and non-SCC were distinct from those for human lymphoblastoid cells and fibroblasts. However, the neuroendocrine features of SCC were further substantiated because 6 of the 12 distinguishing SCC surface proteins, including E and U, were identified on human neuroblastoma cells. The proteins identified should (i) help define differentiation steps for normal and neoplastic bronchial epithelial cells, (ii) prove useful in better classifying lung cancers, and (iii) be instrumental in tracing formation of neuroendocrine cells.« less

Chairing a Small Department.

ERIC Educational Resources Information Center

Bowker, Lee H.; Lynch, David M.

Ten management problems for chairs of small departments in small colleges are discussed, along with problem-solving strategies for these administrators. Serious disagreements within a small and intimate department may create a country club culture in which differences are smoothed over and the personal idiosyncrasies of individual members are…

SmallSat Database

NASA Technical Reports Server (NTRS)

Petropulos, Dolores; Bittner, David; Murawski, Robert; Golden, Bert

2015-01-01

required. When completed it will interface with the SCENIC environment to allow modeling of smallSats. The SmallSat Relational Database can also be integrated with the SCENIC Simulation modeling system that is currently in development. The SmallSat Relational Database simulation will be of great significance in assisting the NASA SCaN group to understand the impact the smallSats have made which have populated the lower orbit around our mother earth. What I have created and worked on this summer session 2015, is the basis for a tool that will be of value to the NASA SCaN SCENIC Simulation Environment for years to come.

Small employers and the challenge of sponsoring a retirement plan: results of the 1998 Small Employer Retirement Survey.

PubMed

Yakoboski, P; Ostuw, P

1998-10-01

Forty-two million individuals work for small employers; 9 million are participating in an employment-based retirement plan, while 33 million are not participating in a plan. This Issue Brief examines the barriers that prevent small employers from sponsoring a retirement plan, their level of knowledge about plans, and changes that might lead to plan sponsorship. It also examines the motivations of small employers that sponsor retirement plans. Small employers identify three main reasons for not offering a plan: employees' preferences for wages and/or other benefits, administrative costs, and uncertain revenue that makes it difficult to commit to a plan. Small employers without plans report being familiar with 401(k) and profit-sharing plans, but little else. Forty-seven percent report never having heard of the savings incentive match plan for employees (SIMPLE), and 55 percent report never having heard of simplified employee pensions (SEPs). There is apparent misunderstanding about retirement plans among small employers that do not sponsor one, especially with regard to costs. For example, 35 percent do not know that a plan can be set up for less than $2,000. What changes would lead to serious consideration of retirement plan sponsorship? In order of reported importance: increased company profits (66 percent), a business tax credit (64 percent), reduced administrative requirements (50 percent), demand from employees (49 percent), allowing key executives to save more in the plan (49 percent), and easing, i.e., lengthening, of vesting requirements (40 percent). Many small employers that sponsor a retirement plan cite business reasons among their motivations. Sixty-eight percent cite a "positive effect on employee attitude and performance" as a major reason for offering a plan. Fifty-six percent cite a "competitive advantage in employee recruitment and retention" as a major reason. Small employers with a retirement plan report direct benefits from sponsorship, but many

Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib.

PubMed

Ou, Sai-Hong Ignatius; Klempner, Samuel J; Greenbowe, Joel R; Azada, Michele; Schrock, Alexa B; Ali, Siraj M; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A

2014-12-01

Huntingtin-interacting protein 1 (HIP1) has recently been identified as a new fusion partner fused to anaplastic lymphoma kinase (ALK) in non-small-cell lung cancer (NSCLC). To date, two variants of HIP1-ALK (H21; A20) and (H28; A20) have been identified in NSCLC. However, the response of patients with NSCLC harboring HIP1-ALK to ALK inhibitors and potential resistance mechanisms to such remain unknown. Here, we report a patient with NSCLC harboring a novel HIP1-ALK fusion variant (H30; A20). This patient and another patient with EML4-ALK variant 3a/b initially responded sequentially to crizotinib and then alectinib, a next-generation ALK inhibitor, but developed acquired resistance to alectinib with the presence of a mutation in amino acid residue 1171 (I1171N and I1171S respectively) located in the hydrophobic regulatory spine (R-spine) of the ALK kinase in both the cases as identified by a comprehensive next-generation sequencing-based assay performed on biopsies of new liver metastases that developed during alectinib treatment.

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2013-07-01

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

INEXPENSIVE DRINKING WATER CHLORINATION UNIT FOR SMALL COMMUNITIES - PHASE I

EPA Science Inventory

More than 250 drinking water systems exist for small communities in Puerto Rico that serve between 25 and 500 individuals. These water systems fall outside of the Puerto Rico Aqueduct and Sewer Authority and, thus, have insufficient water treatment systems or no water treatmen...

Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

PubMed

Kim, Hyun Jin; Kim, Jin Hyun; Moon, Won; Park, Jongha; Park, Seun Ja; Song, Geun Am; Han, Seung Hee; Lee, Jong Hun

2015-01-01

5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-β1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-β1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

Effects of phenylpropanolamine (PPA) on in vitro human erythrocyte membranes and molecular models

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

Suwalsky, Mario, E-mail: msuwalsk@udec.cl; Zambrano, Pablo; Mennickent, Sigrid

Research highlights: {yields} PPA is a common ingredient in cough-cold medication and appetite suppressants. {yields} Reports on its effects on human erythrocytes are very scarce. {yields} We found that PPA induced in vitro morphological changes to human erythrocytes. {yields} PPA interacted with isolated unsealed human erythrocyte membranes. {yields} PPA interacted with class of lipid present in the erythrocyte membrane outer monolayer. -- Abstract: Norephedrine, also called phenylpropanolamine (PPA), is a synthetic form of the ephedrine alkaloid. After reports of the occurrence of intracranial hemorrhage and other adverse effects, including several deaths, PPA is no longer sold in USA and Canada.more » Despite the extensive information about PPA toxicity, reports on its effects on cell membranes are scarce. With the aim to better understand the molecular mechanisms of the interaction of PPA with cell membranes, ranges of concentrations were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of cell membranes. The latter consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, respectively. The capacity of PPA to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). This study presents evidence that PPA affects human red cell membranes as follows: (a) in SEM studies on human erythrocytes it was observed that 0.5 mM PPA induced shape changes; (b) in IUM PPA induced a sharp decrease in the fluorescence anisotropy in the lipid bilayer acyl chains in a concentration range lower than 100 {mu}M; (c) X-ray diffraction studies showed that PPA in the 0

A new small-angle X-ray scattering set-up on the crystallography beamline I711 at MAX-lab.

PubMed

Knaapila, M; Svensson, C; Barauskas, J; Zackrisson, M; Nielsen, S S; Toft, K N; Vestergaard, B; Arleth, L; Olsson, U; Pedersen, J S; Cerenius, Y

2009-07-01

A small-angle X-ray scattering (SAXS) set-up has recently been developed at beamline I711 at the MAX II storage ring in Lund (Sweden). An overview of the required modifications is presented here together with a number of application examples. The accessible q range in a SAXS experiment is 0.009-0.3 A(-1) for the standard set-up but depends on the sample-to-detector distance, detector offset, beamstop size and wavelength. The SAXS camera has been designed to have a low background and has three collinear slit sets for collimating the incident beam. The standard beam size is about 0.37 mm x 0.37 mm (full width at half-maximum) at the sample position, with a flux of 4 x 10(10) photons s(-1) and lambda = 1.1 A. The vacuum is of the order of 0.05 mbar in the unbroken beam path from the first slits until the exit window in front of the detector. A large sample chamber with a number of lead-throughs allows different sample environments to be mounted. This station is used for measurements on weakly scattering proteins in solutions and also for colloids, polymers and other nanoscale structures. A special application supported by the beamline is the effort to establish a micro-fluidic sample environment for structural analysis of samples that are only available in limited quantities. Overall, this work demonstrates how a cost-effective SAXS station can be constructed on a multipurpose beamline.

3c/4e [small sigma, Greek, circumflex]-type long-bonding competes with ω-bonding in noble-gas hydrides HNgY (Ng = He, Ne, Ar, Kr, Xe, Rn; Y = F, Cl, Br, I): a NBO/NRT perspective.

PubMed

Zhang, Guiqiu; Li, Hong; Weinhold, Frank; Chen, Dezhan

2016-03-21

Noble-gas hydrides HNgY are frequently described as a single ionic form (H-Ng)(+)Y(-). We apply natural bond orbital (NBO) and natural resonance theory (NRT) analyses to a series of noble-gas hydrides HNgY (Ng = He, Ne, Ar, Kr, Xe, Rn; Y = F, Cl, Br, I) to gain quantitative insight into the resonance bonding of these hypervalent molecules. We find that each of the studied species should be better represented as a resonance hybrid of three leading resonance structures, namely, H-Ng(+ -):Y (I), H:(- +)Ng-Y (II), and H^Y (III), in which the "ω-bonded" structures I and II arise from the complementary donor-acceptor interactions nY → σ*HNg and nH → σ*NgY, while the "long-bond" ([small sigma, Greek, circumflex]-type) structure III arises from the nNg → [small sigma, Greek, circumflex]*HY/[small sigma, Greek, circumflex]HY interaction. The bonding for all of the studied molecules can be well described in terms of the continuously variable resonance weightings of 3c/4e ω-bonding and [small sigma, Greek, circumflex]-type long-bonding motifs. Furthermore, we find that the calculated bond orders satisfy a generalized form of "conservation of bond order" that incorporates both ω-bonding and long-bonding contributions [viz., (bHNg + bNgY) + bHY = bω-bonding + blong-bonding = 1]. Such "conservation" throughout the title series implies a competitive relationship between ω-bonding and [small sigma, Greek, circumflex]-type long-bonding, whose variations are found to depend in a chemically reasonable manner on the electronegativity of Y and the outer valence-shell character of the central Ng atom. The calculated bond orders are also found to exhibit chemically reasonable correlations with bond lengths, vibrational frequencies, and bond dissociation energies, in accord with Badger's rule and related empirical relationships. Overall, the results provide electronic principles and chemical insight that may prove useful in the rational design of noble-gas hydrides of

Electrostatic 2D assembly of bionanoparticles on a cationic lipid monolayer.

NASA Astrophysics Data System (ADS)

Kewalramani, Sumit; Wang, Suntao; Fukuto, Masafumi; Yang, Lin; Niu, Zhongwei; Nguyen, Giang; Wang, Qian

2010-03-01

We present a grazing-incidence small-angle X-ray scattering (GISAXS) study on 2D assembly of cowpea mosaic virus (CPMV) under a mixed cationic-zwitterionic (DMTAP^+-DMPC) lipid monolayer at the air-water interface. The inter-particle and particle-lipid electrostatic interactions were varied by controlling the subphase pH and the membrane charge density. GISAXS data show that 2D crystals of CPMV are formed above a threshold membrane charge density and only in a narrow pH range just above CPMV's isoelectric point, where the charge on CPMV is expected to be weakly negative. The particle density for the 2D crystals is similar to that for the densest lattice plane in the 3D crystals of CPMV. The results show that the 2D crystallization is achieved in the part of the phase space where the electrostatic interactions are expected to maximize the adsorption of CPMV onto the lipid membrane. This electrostatics-based strategy for controlling interfacial nanoscale assembly should be generally applicable to other nanoparticles.

Top 10 Reasons Students Dislike Working in Small Groups... and Why I Do It Anyway

ERIC Educational Resources Information Center

Taylor, Ann

2011-01-01

Last semester, the author had a particularly vocal class that made it clear that they disliked small group exercises. In an attempt to understand their discomfort, she had this class generate a list of the top 10 reasons they disliked small group exercises. Some of the reasons listed by the students are exactly why the author uses small group work…

The effect of furazolidone on the physico-chemical properties of dimyristoylphosphatidylcholine bilayers: Relevance to anti-leishmanial therapy

NASA Astrophysics Data System (ADS)

Martins, Victor Hugo Giendruczak; Rodrigues, Marisa Raquel; Mascarenhas, Layoan Dantas; de Azambuja, Carla Roberta Lopes; Londoño, Julian Londoño; de Lima, Vânia Rodrigues

2014-02-01

In this study, the influence of furazolidone, an anti-leishmanial drug, on dimyristoylphosphatidylcholine (DMPC) liposome hydration degree, mobility and thermodynamics was investigated by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). FTIR results showed that furazolidone was responsible for an increase in the hydrogen bound number and mobility of the lipid phosphate group. Furazolidone also affected the lipid choline group by increasing its motional freedom, as shown by FTIR and 1H NMR spin-lattice relaxation time measurements. At the DMPC interfacial region, FTIR results showed a drug-induced reduction of the carbonyl hydration and order degrees. Very weak interaction among furazolidone and the hydrophobic lipid chains was also observed. However, no furazolidone-induced changes on thermodynamical parameters, such as phase transition temperature (Tm) and enthalpy variation (ΔH), were detected by the DSC technique. Thus, furazolidone seems to interact preferentially with lipid polar and interfacial regions, enhancing the freedom for gauche-trans isomerization of the first methylene groups of DMPC acyl chains. Responses described in this paper may explain the improved activity of furazolidone-encapsulated liposomes by comparison with the effect of the free drug, described in literature. The findings can also improve further strategies for the potential therapeutic application of liposomal furazolidone as a drug delivery system and minimize the risk of drug resistance and collateral effects related to high toxicity.

Theoretical modeling of multiprotein complexes by iSPOT: Integration of small-angle X-ray scattering, hydroxyl radical footprinting, and computational docking.

PubMed

Huang, Wei; Ravikumar, Krishnakumar M; Parisien, Marc; Yang, Sichun

2016-12-01

Structural determination of protein-protein complexes such as multidomain nuclear receptors has been challenging for high-resolution structural techniques. Here, we present a combined use of multiple biophysical methods, termed iSPOT, an integration of shape information from small-angle X-ray scattering (SAXS), protection factors probed by hydroxyl radical footprinting, and a large series of computationally docked conformations from rigid-body or molecular dynamics (MD) simulations. Specifically tested on two model systems, the power of iSPOT is demonstrated to accurately predict the structures of a large protein-protein complex (TGFβ-FKBP12) and a multidomain nuclear receptor homodimer (HNF-4α), based on the structures of individual components of the complexes. Although neither SAXS nor footprinting alone can yield an unambiguous picture for each complex, the combination of both, seamlessly integrated in iSPOT, narrows down the best-fit structures that are about 3.2Å and 4.2Å in RMSD from their corresponding crystal structures, respectively. Furthermore, this proof-of-principle study based on the data synthetically derived from available crystal structures shows that the iSPOT-using either rigid-body or MD-based flexible docking-is capable of overcoming the shortcomings of standalone computational methods, especially for HNF-4α. By taking advantage of the integration of SAXS-based shape information and footprinting-based protection/accessibility as well as computational docking, this iSPOT platform is set to be a powerful approach towards accurate integrated modeling of many challenging multiprotein complexes. Copyright © 2016 Elsevier Inc. All rights reserved.

Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

PubMed Central

Rinaldi, F; Lin, M; Shapiro, M J; Petersheim, M

1997-01-01

D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores. Images FIGURE 1 FIGURE 8 PMID:9414244

Maybe Small Is Too Small a Term: Introduction to Advancing Small Sample Prevention Science.

PubMed

Fok, Carlotta Ching Ting; Henry, David; Allen, James

2015-10-01

Prevention research addressing health disparities often involves work with small population groups experiencing such disparities. The goals of this special section are to (1) address the question of what constitutes a small sample; (2) identify some of the key research design and analytic issues that arise in prevention research with small samples; (3) develop applied, problem-oriented, and methodologically innovative solutions to these design and analytic issues; and (4) evaluate the potential role of these innovative solutions in describing phenomena, testing theory, and evaluating interventions in prevention research. Through these efforts, we hope to promote broader application of these methodological innovations. We also seek whenever possible, to explore their implications in more general problems that appear in research with small samples but concern all areas of prevention research. This special section includes two sections. The first section aims to provide input for researchers at the design phase, while the second focuses on analysis. Each article describes an innovative solution to one or more challenges posed by the analysis of small samples, with special emphasis on testing for intervention effects in prevention research. A concluding article summarizes some of their broader implications, along with conclusions regarding future directions in research with small samples in prevention science. Finally, a commentary provides the perspective of the federal agencies that sponsored the conference that gave rise to this special section.

How To Set Up Your Own Small Business. Volumes I-II and Overhead Transparencies.

ERIC Educational Resources Information Center

Fallek, Max

This two-volume textbook and collection of overhead transparency masters is intended for use in a course in setting up a small business. The following topics are covered in the first volume: getting off to a good start, doing market research, forecasting sales, financing a small business, understanding the different legal needs of different types…

Polymer-cushioned bilayers. II. An investigation of interaction forces and fusion using the surface forces apparatus.

PubMed Central

Wong, J Y; Park, C K; Seitz, M; Israelachvili, J

1999-01-01

We have created phospholipid bilayers supported on soft polymer "cushions" which act as deformable substrates (see accompanying paper, Wong, J. Y., J. Majewski, M. Seitz, C. K. Park, J. N. Israelachvili, and G. S. Smith. 1999. Biophys. J. 77:1445-1457). In contrast to "solid-supported" membranes, such "soft-supported" membranes can exhibit more natural (higher) fluidity. Our bilayer system was constructed by adsorption of small unilamellar dimyristoylphosphatidylcholine (DMPC) vesicles onto polyethylenimine (PEI)-supported Langmuir-Blodgett lipid monolayers on mica. We used the surface forces apparatus (SFA) to investigate the long-range forces, adhesion, and fusion of two DMPC bilayers both above and below their main transition temperature (T(m) approximately 24 degrees C). Above T(m), hemi-fusion activation pressures of apposing bilayers were considerably smaller than for solid-supported bilayers, e.g., directly supported on mica. After separation, the bilayers naturally re-formed after short healing times. Also, for the first time, complete fusion of two fluid (liquid crystalline) phospholipid bilayers was observed in the SFA. Below T(m) (gel state), very high pressures were needed for hemi-fusion and the healing process became very slow. The presence of the polymer cushion significantly alters the interaction potential, e.g., long-range forces as well as fusion pressures, when compared to solid-supported systems. These fluid model membranes should allow the future study of integral membrane proteins under more physiological conditions. PMID:10465756

Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

ClinicalTrials.gov

2017-06-29

Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

Membrane-Dependent Effects of a Cytoplasmic Helix on the Structure and Drug Binding of the Influenza Virus M2 Protein

PubMed Central

Cady, Sarah; Wang, Tuo; Hong, Mei

2011-01-01

The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22 to 46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45 to 62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21–61). 13C-2H distance measurements of 13C-labeled protein and 2H-labeled amantadine showed that in DMPC bilayers, the first equivalent of drug bound S31 inside the M2(21–61) pore, similar to the behavior of M2TM in DMPC bilayers. The non-specific surface site of D44 observed in M2TM is disfavored in the longer peptide. Thus, the pharmacologically relevant drug-binding site in the fully functional M2(21–61) is S31 in the TM pore. Interestingly, when M2(21–61) was reconstituted into a virus-mimetic membrane containing 30% cholesterol, no chemical shift perturbation was observed for pore-lining residues, while M2TM in the same membrane exhibited drug-induced chemical shift changes. Reduction of the cholesterol level and the use of unsaturated phospholipids shifted the conformational equilibrium of M2TM fully to the bound state, but did not rescue drug binding to M2(21–61). These results suggest that the amphipathic helix, together with cholesterol, modulates the ability of the TM helices to bind amantadine. Thus, the M2 protein interacts with the lipid membrane and small-molecule inhibitors in a complex fashion, and a careful examination of the environmental dependence of the protein conformation is required to fully understand the structure-function relation of this protein. PMID:21661724

Minerva-Red: Small Planets Orbiting Small Stars

NASA Astrophysics Data System (ADS)

Blake, Cullen

2018-06-01

Recent results from Kepler and ground-based exoplanet surveys suggest that low-mass stars are host to numerous small planets. Since low-mass stars are intrinsically faint at optical wavelengths, obtaining the Doppler precision necessary to detect these companions remains a challenge for existing instruments. I will describe MINERVA-Red, a project to use a robotic, near-infrared optimized 0.7-meter telescope and a specialized Doppler spectrometer to carry out an intensive, multi-year campaign designed to reveal the planetary systems orbiting some of the closest stars to the Sun. The MINERVA-Red cross-dispersed echelle spectrograph is optimized for the “deep red”, between 800 nm and 900 nm, where the stars that will be targeted are relatively bright. The instrument is very compact and designed for the ultimate in Doppler precision – it uses a single-mode fiber input. I will describe the spectrometer and the status of the MINERVA-Red project, which is expected to begin routine operations at Whipple Observatory on Mt Hopkins, Arizona, in 2018.

Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes.

PubMed

Suwalsky, Mario; Belmar, Jessica; Villena, Fernando; Gallardo, María José; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

2013-11-01

Despite the well-documented information, there are insufficient reports concerning the effects of salicylate compounds on the structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of acetylsalicylic acid (ASA) and salicylic acid (SA) with cell membranes, human erythrocyte membranes and molecular models were utilized. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of ASA and SA to perturb the multibilayer structures of DMPC and DMPE was evaluated by X-ray diffraction while DMPC unilamellar vesicles (LUV) were studied by fluorescence spectroscopy. Moreover, we took advantage of the capability of differential scanning calorimetry (DSC) to detect the changes in the thermotropic phase behavior of lipid bilayers resulting from ASA and SA interaction with PC and PE molecules. In an attempt to further elucidate their effects on cell membranes, the present work also examined their influence on the morphology of intact human erythrocytes by means of defocusing and scanning electron microscopy, while isolated unsealed human erythrocyte membranes (IUM) were studied by fluorescence spectroscopy. Results indicated that both salicylates interact with human erythrocytes and their molecular models in a concentration-dependent manner perturbing their bilayer structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Aspirin locally disrupts the liquid-ordered phase

NASA Astrophysics Data System (ADS)

Alsop, Richard J.; Himbert, Sebastian; Dhaliwal, Alexander; Schmalzl, Karin; Rheinstädter, Maikel C.

2018-02-01

Local structure and dynamics of lipid membranes play an important role in membrane function. The diffusion of small molecules, the curvature of lipids around a protein and the existence of cholesterol-rich lipid domains (rafts) are examples for the membrane to serve as a functional interface. The collective fluctuations of lipid tails, in particular, are relevant for diffusion of membrane constituents and small molecules in and across membranes, and for structure and formation of membrane domains. We studied the effect of aspirin (acetylsalicylic acid, ASA) on local structure and dynamics of membranes composed of dimyristoylphosphocholine (DMPC) and cholesterol. Aspirin is a common analgesic, but is also used in the treatment of cholesterol. Using coherent inelastic neutron scattering experiments and molecular dynamics (MD) simulations, we present evidence that ASA binds to liquid-ordered, raft-like domains and disturbs domain organization and dampens collective fluctuations. By hydrogen-bonding to lipid molecules, ASA forms `superfluid' complexes with lipid molecules that can organize laterally in superlattices and suppress cholesterol's ordering effect.

Small-size biofuel cell on paper.

PubMed

Zhang, Lingling; Zhou, Ming; Wen, Dan; Bai, Lu; Lou, Baohua; Dong, Shaojun

2012-05-15

In this work, we demonstrated a novel paper-based mediator-less and compartment-less biofuel cell (BFC) with small size (1.5 cm × 1.5 cm). Ionic liquid functionalized carbon nanotubes (CNTs-IL) nanocomposite was used as support for both stably confining the anodic biocatalyst (i.e., NAD(+)-dependent glucose dehydrogenase, GDH) for glucose electrooxidation and for facilitating direct electrochemistry of the cathodic biocatalyst (i.e., bilirubin oxidase, BOD) for O(2) electroreduction. Such BFC provided a simple approach to fabricate low-cost and portable power devices on small-size paper, which can harvest energy from a wide range of commercial beverages containing glucose (e.g., Nescafe instant coffee, Maidong vitamin water, Watermelon fresh juice, and Minute Maid grape juice). These made the low-cost paper-based biodevice potential for broad energy applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Using spin-label W-band EPR to study membrane fluidity profiles in samples of small volume

NASA Astrophysics Data System (ADS)

Mainali, Laxman; Hyde, James S.; Subczynski, Witold K.

2013-01-01

Conventional and saturation-recovery (SR) EPR at W-band (94 GHz) using phosphatidylcholine spin labels (labeled at the alkyl chain [n-PC] and headgroup [T-PC]) to obtain profiles of membrane fluidity has been demonstrated. Dimyristoylphosphatidylcholine (DMPC) membranes with and without 50 mol% cholesterol have been studied, and the results have been compared with similar studies at X-band (9.4 GHz) (L. Mainali, J.B. Feix, J.S. Hyde, W.K. Subczynski, J. Magn. Reson. 212 (2011) 418-425). Profiles of the spin-lattice relaxation rate (T1-1) obtained from SR EPR measurements for n-PCs and T-PC were used as a convenient quantitative measure of membrane fluidity. Additionally, spectral analysis using Freed's MOMD (microscopic-order macroscopic-disorder) model (E. Meirovitch, J.H. Freed J. Phys. Chem. 88 (1984) 4995-5004) provided rotational diffusion coefficients (R⊥ and R||) and order parameters (S0). Spectral analysis at X-band provided one rotational diffusion coefficient, R⊥. T1-1, R⊥, and R|| profiles reflect local membrane dynamics of the lipid alkyl chain, while the order parameter shows only the amplitude of the wobbling motion of the lipid alkyl chain. Using these dynamic parameters, namely T1-1, R⊥, and R||, one can discriminate the different effects of cholesterol at different depths, showing that cholesterol has a rigidifying effect on alkyl chains to the depth occupied by the rigid steroid ring structure and a fluidizing effect at deeper locations. The nondynamic parameter, S0, shows that cholesterol has an ordering effect on alkyl chains at all depths. Conventional and SR EPR measurements with T-PC indicate that cholesterol has a fluidizing effect on phospholipid headgroups. EPR at W-band provides more detailed information about the depth-dependent dynamic organization of the membrane compared with information obtained at X-band. EPR at W-band has the potential to be a powerful tool for studying membrane fluidity in samples of small volume, ˜30 n

GC13I-0857: Designing a Frost Forecasting Service for Small Scale Tea Farmers in East Africa

NASA Technical Reports Server (NTRS)

Adams, Emily C.; Wanjohi, James Nyaga; Ellenburg, Walter Lee; Limaye, Ashutosh S.; Mugo, Robinson M.; Flores Cordova, Africa Ixmucane; Irwin, Daniel; Case, Jonathan; Malaso, Susan; Sedah, Absae

2017-01-01

Kenya is the third largest tea exporter in the world, producing 10% of the world's black tea. Sixty percent of this production occurs largely by small scale tea holders, with an average farm size of 1.04 acres, and an annual net income of $1,075. According to a recent evaluation, a typical frost event in the tea growing region causes about $200 dollars in losses which can be catastrophic for a small holder farm. A 72-hour frost forecast would provide these small-scale tea farmers with enough notice to reduce losses by approximately 80 USD annually. With this knowledge, SERVIR, a joint NASA-USAID initiative that brings Earth observations for improved decision making in developing countries, sought to design a frost monitoring and forecasting service that would provide farmers with enough lead time to react to and protect against a forecasted frost occurrence on their farm. SERVIR Eastern and Southern Africa, through its implementing partner, the Regional Centre for Mapping of Resources for Development (RCMRD), designed a service that included multiple stakeholder engagement events whereby stakeholders from the tea industry value chain were invited to share their experiences so that the exact needs and flow of information could be identified. This unique event allowed enabled the design of a service that fit the specifications of the stakeholders. The monitoring service component uses the MODIS Land Surface Temperature product to identify frost occurrences in near-real time. The prediction component, currently under testing, uses the 2-m air temperature, relative humidity, and 10-m wind speed from a series of high-resolution Weather Research and Forecasting (WRF) numerical weather prediction model runs over eastern Kenya as inputs into a frost prediction algorithm. Accuracy and sensitivity of the algorithm is being assessed with observations collected from the farmers using a smart phone app developed specifically to report frost occurrences, and from data shared

Development and application of a quantitative multiplexed small GTPase activity assay using targeted proteomics.

PubMed

Zhang, Cheng-Cheng; Li, Ru; Jiang, Honghui; Lin, Shujun; Rogalski, Jason C; Liu, Kate; Kast, Juergen

2015-02-06

Small GTPases are a family of key signaling molecules that are ubiquitously expressed in various types of cells. Their activity is often analyzed by western blot, which is limited by its multiplexing capability, the quality of isoform-specific antibodies, and the accuracy of quantification. To overcome these issues, a quantitative multiplexed small GTPase activity assay has been developed. Using four different binding domains, this assay allows the binding of up to 12 active small GTPase isoforms simultaneously in a single experiment. To accurately quantify the closely related small GTPase isoforms, a targeted proteomic approach, i.e., selected/multiple reaction monitoring, was developed, and its functionality and reproducibility were validated. This assay was successfully applied to human platelets and revealed time-resolved coactivation of multiple small GTPase isoforms in response to agonists and differential activation of these isoforms in response to inhibitor treatment. This widely applicable approach can be used for signaling pathway studies and inhibitor screening in many cellular systems.

PySCIs: a user friendly Python tool to quickly applying Small Circle methods

NASA Astrophysics Data System (ADS)

Calvín, Pablo; José Villalaín, Juan; Casas, Antonio; Torres, Sara

2017-04-01

Small Circle (SC) methods are common tools in paleomagnetic working on synfolding paleomagnetic components. These methods have a twofold applicability. On one hand, the Small Circle Intersection (SCI) method allows obtaining the local remagnetization direction and on the other the SCs can be used to restitute the attitude of the sedimentary beds at the moment of the remagnetization acquisition. The bases of the SCI method are as follows. (i) The paleomagnetic direction for each site follows a path which draws a SC under progressive untinting of the beds; this SC links the paleomagnetic direction before and after the tectonic correction. (ii) Considering that the beds have been deformed only by tilting around the bedding strike, the remagnetization direction is placed upon the small circle of each site. (iii) The acquisition of the remagnetization was simultaneous for the analyzed rocks. Therefore, the remagnetization direction must to be placed upon the small circle for all sites and hence the all small circle must to intersect in one direction which corresponds with the remagnetization direction. Actually the method looks for the direction in the space closest to the set of SCs by means of A/n parameter (this is the sum of the angular distances between one direction and each SC normalized by the number of sites). Once the remagnetization direction is known, it is possible to calculate the paleomagnetic direction upon each SC closest to the calculated remagnetization direction, called as Best Fit Direction (BFD). After that the paleodip of the bed (i.e. the dip of the bed at the moment of the remagnetization event) can be calculated for each site (the paleodip is the angle measured over the SC between the BFD and the paleomagnetic direction after the complete bedding correction) and perform a palinspastic reconstruction of a region. We present pySCIs, a new python tool which allows applying this methodology in an easy way. The program has two different modules, py

Use of small stand-alone Internet nodes as a distributed control system

NASA Astrophysics Data System (ADS)

Goodwin, Robert W.; Kucera, Michael J.; Shea, Michael F.

1994-12-01

For several years, the standard model for accelerator control systems has been workstation consoles connected to VME local stations by a Local Area Network with analog and digital data being accessed via a field bus to custom I/O interface electronics. Commercially available hardware has now made it possible to implement a small stand-alone data acquisition station that combines the LAN connection, the computer, and the analog and digital I/O interface on a single board. This eliminates the complexity of a field bus and the associated proprietary I/O hardware. A minimum control system is one data acquisition station and a Macintosh or workstation console, both connected to the network; larger systems have more consoles and nodes. An implementation of this architecture is described along with performance and operational experience.

Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer.

PubMed

Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kunizaki, Masaki; Taniguchi, Daisuke; Nagayasu, Takeshi

2015-04-01

The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Disease-specific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year

Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

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

Louie, Alexander V.; Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Department of Epidemiology/Biostatistics, University of Western Ontario, London, ON

Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely withmore » those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.« less

A simple extension of the SM that can explain the ( g-2 ) μ anomaly, small neutrino mass and a dark matter

NASA Astrophysics Data System (ADS)

Dhargyal, Lobsang

2018-07-01

In this work we propose a simple extension of the Standard Model (SM) by adding to it eleven new particles. Three heavy lepton (f e , f μ , f τ ), singlets under {SU}{(3)}c× {SU}{(2)}L carrying respective lepton numbers, charged under U{(1)}Y with Y = ‑2 and transforming under a discrete symmetry as {f}i\\to -{f}i. One scalar (ϕ 2), a singlet under all the SM gauge groups and transforms under the discrete symmetry as {φ }2\\to -{φ }2 which does not develop a non zero vacuum-expectation-value (VEV). One more scalar (ϕ 3), a singlet under all the SM gauge groups and invariant under discrete symmetry which develops a non zero VEV (v 3) and gives masses to f i s, ϕ 2 and neutrinos. Three right handed neutrinos ({ν }{iR}) and three left handed Majorana neutrinos (s iL ). With these new additional particles added to the SM we have been able to give explanations to the long standing muon (g-2) anomaly as well as the smallness of neutrino masses by the inverse seesaw mechanism. Also in this model we have a very suitable scalar dark matter (DM) candidate in ϕ 2 with allows a mass as high as 53 GeV, although due to a large Yukawa coupling required to explain the muon (g-2), its contribution to the DM relic density turn out to be too small and so it can account only for a small fraction of the DM relic density of the Universe.

A small-signal generator based on a multi-layer graphene/molybdenum disulfide heterojunction

NASA Astrophysics Data System (ADS)

Tan, Zhen; Tian, He; Feng, Tingting; Zhao, Lianfeng; Xie, Dan; Yang, Yi; Xiao, Lei; Wang, Jing; Ren, Tian-Ling; Xu, Jun

2013-12-01

In this work, we fabricate a heterojunction small-signal generator (HSSG) based on a graphene-molybdenum disulfide (MoS2) heterojunction. The HSSG is fundamentally different from any analog device developed previously. The HSSG is composed of two quasi-2D heterojunctions and has three terminals named injector (I), recombinator (R), and generator (G). MoS2 serves as I and G, and graphene works as R in the HSSG. The scale coefficient (β = IG/IR) of the HSSG is 1.14 × 10-4 (VIG, IR = 0.2 V) to 1.95 × 10-4 (VIG, IR = 1 V). The current generated from G could be as low as pA scale, which reveals the good performance of the HSSG.

The Small-Scale Structure of High-Velocity Na I Absorption Toward M81

NASA Astrophysics Data System (ADS)

Roth, K. C.; Meyer, D. M.; Lauroesch, J. T.

2000-12-01

We present high-resolution (R=20,000) integral field spectra of the Na I absorption toward the nucleus of the nearby spiral galaxy M81 (NGC 3031) obtained in April 2000 with the WIYN 3.5-m telescope and the DensePak fiber optic bundle. Our DensePak map covers the central 27 x 43 arcsec of M81 at a spatial resolution of 4 arcsec which corresponds to a projected length scale of 63 pc at the distance of the galaxy (3.25 Mpc). These data were intended to explore the spatial extent of high-velocity (v = 110-130 km/s) gas seen in Na I, Mg I and Mg II absorption toward SN 1993J by Bowen et al. (1994), which they proposed is due to tidal material associated with interactions between M81 and nearby M82 (Yun, Ho & Lo 1993). No H I gas at these velocities has been detected in 21 cm interferometry maps near the position of SN 1993J (2.6 arcmin SW of the M81 nucleus). Our Na I map of the M81 core shows no evidence of the strong absorption seen at v = 110-130 km/s toward SN 1993J. However, our map does reveal a strong Na I component at v = 220 km/s in several fibers that appears to trace a filamentary structure running from the SW to the NE across the M81 nuclear region. The origin and distance of this filament are unknown. No H I gas at v = 220 km/s has previously been detected in 21 cm studies of the core. At the location of SN 1993J, Bowen et al. measured weak Mg II absorption at this velocity but found no evidence of corresponding Na I absorption. The only known H I gas that corresponds to this velocity in the M81 group are the H I streamers found around M82 by Yun, Ho, & Lo that they interpreted as tidally disrupted M82 disk material.

Spectropolarimetric Observations of a Small Active Region with IBIS

NASA Astrophysics Data System (ADS)

Tarr, Lucas; Judge, Philip G.

2014-06-01

We have used the Interferometric BI--dimensional Spectrograph (IBIS) instrument at the Dunn Solar Telescope to measure the polarimetric Stokes IQUV signals for the small active region, NOAA 11304. We used three lines generally corresponding to three atmospheric heights ranging from the photosphere to low corona: Fe I 6302Å, NaI 5896Å, and CaII 8542Å. Each set of profiles has been inverted using the NICOLE code to determine the vector magnetic field at the three heights throughout the field of view, or the line--of--sight field, as allowed by the level of polarization signal. Comparisons are made between the magnetic and thermal structures with the goal of constraining chromospheric models with the information obtained at multiple heights.

Investigation of phase transitions of saturated phosphocholine lipid bilayers via molecular dynamics simulations.

PubMed

Khakbaz, Pouyan; Klauda, Jeffery B

2018-08-01

Lipid bilayers play an important role in biological systems as they protect cells against unwanted chemicals and provide a barrier for material inside a cell from leaking out. In this paper, nearly 30 μs of molecular dynamics (MD) simulations were performed to investigate phase transitions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-phosphocholine (DPPC) lipid bilayers from the liquid crystalline (L α ) to the ripple (P β ) and to the gel phase (L β ). Our MD simulations accurately predict the main transition temperature for the single-component bilayers. A key focus of this work is to quantify the structure of the P β phase for DMPC and compare with measures from x-ray experiments. The P β major arm has similar structure to that of the L β , while the thinner minor arm has interdigitated chains and the transition region between these two regions has large chain splay and disorder. At lower temperatures, our MD simulations predict the formation of the L β phase with tilted fatty acid chains. The P β and L β phases are studied for mixtures of DMPC and DPPC and compare favorably with experiment. Overall, our MD simulations provide evidence for the relevancy of the CHARMM36 lipid force field for structures and add to our understanding of the less-defined P β phase. Copyright © 2018 Elsevier B.V. All rights reserved.

Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-12-16

Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Small area estimation for semicontinuous data.

PubMed

Chandra, Hukum; Chambers, Ray

2016-03-01

Survey data often contain measurements for variables that are semicontinuous in nature, i.e. they either take a single fixed value (we assume this is zero) or they have a continuous, often skewed, distribution on the positive real line. Standard methods for small area estimation (SAE) based on the use of linear mixed models can be inefficient for such variables. We discuss SAE techniques for semicontinuous variables under a two part random effects model that allows for the presence of excess zeros as well as the skewed nature of the nonzero values of the response variable. In particular, we first model the excess zeros via a generalized linear mixed model fitted to the probability of a nonzero, i.e. strictly positive, value being observed, and then model the response, given that it is strictly positive, using a linear mixed model fitted on the logarithmic scale. Empirical results suggest that the proposed method leads to efficient small area estimates for semicontinuous data of this type. We also propose a parametric bootstrap method to estimate the MSE of the proposed small area estimator. These bootstrap estimates of the MSE are compared to the true MSE in a simulation study. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Small Business Management. Getting a Small Business Management Education Program Started.

ERIC Educational Resources Information Center

Minnesota Univ., St. Paul. Dept. of Agricultural Education.

This set of materials was developed to assist with the dissemination of the Minnesota model for small business management education, five sections of information are presented. The first of five sections is on small business management needs assessment and describes a method of determining the number of small businesses that would constitute a…

A two-photon view of an enzyme at work: Crotalus atrox venom PLA2 interaction with single-lipid and mixed-lipid giant unilamellar vesicles.

PubMed Central

Sanchez, Susana A; Bagatolli, Luis A; Gratton, Enrico; Hazlett, Theodore L

2002-01-01

We describe the interaction of Crotalus atrox-secreted phospholipase A2 (sPLA2) with giant unilamellar vesicles (GUVs) composed of single and binary phospholipid mixtures visualized through two-photon excitation fluorescent microscopy. The GUV lipid compositions that we examined included 1-palmitoyl-2-oleoyl-phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) (above their gel-liquid crystal transition temperatures) and two well characterized lipid mixtures, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE):DMPC (7:3) and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC)/1,2-diarachidoyl-sn-glycero-3-phosphocholine (DAPC) (1:1) equilibrated at their phase-coexistence temperature regime. The membrane fluorescence probes, 6-lauroyl-2-(dimethylamino) napthalene, 6-propionyl-2-(dimethylamino) naphthalene, and rhodamine-phosphatidylethanolamine, were used to assess the state of the membrane and specifically mark the phospholipid domains. Independent of their lipid composition, all GUVs were reduced in size as sPLA2-dependent lipid hydrolysis proceeded. The binding of sPLA2 was monitored using a fluorescein-sPLA2 conjugate. The sPLA2 was observed to associate with the entire surface of the liquid phase in the single phospholipid GUVs. In the mixed-lipid GUV's, at temperatures promoting domain coexistence, a preferential binding of the enzyme to the liquid regions was also found. The lipid phase of the GUV protein binding region was verified by the introduction of 6-propionyl-2-(dimethylamino) naphthalene, which partitions quickly into the lipid fluid phase. Preferential hydrolysis of the liquid domains supported the conclusions based on the binding studies. sPLA2 hydrolyzes the liquid domains in the binary lipid mixtures DLPC:DAPC and DMPC:DMPE, indicating that the solid-phase packing of DAPC and DMPE interferes with sPLA2 binding, irrespective of the phospholipid headgroup. These studies

A stellar overdensity associated with the Small Magellanic Cloud

NASA Astrophysics Data System (ADS)

Pieres, A.; Santiago, B. X.; Drlica-Wagner, A.; Bechtol, K.; Marel, R. P. van der; Besla, G.; Martin, N. F.; Belokurov, V.; Gallart, C.; Martinez-Delgado, D.; Marshall, J.; Nöel, N. E. D.; Majewski, S. R.; Cioni, M.-R. L.; Li, T. S.; Hartley, W.; Luque, E.; Conn, B. C.; Walker, A. R.; Balbinot, E.; Stringfellow, G. S.; Olsen, K. A. G.; Nidever, D.; da Costa, L. N.; Ogando, R.; Maia, M.; Neto, A. Fausti; Abbott, T. M. C.; Abdalla, F. B.; Allam, S.; Annis, J.; Benoit-Lévy, A.; Rosell, A. Carnero; Kind, M. Carrasco; Carretero, J.; Cunha, C. E.; D'Andrea, C. B.; Desai, S.; Diehl, H. T.; Doel, P.; Flaugher, B.; Fosalba, P.; García-Bellido, J.; Gruen, D.; Gruendl, R. A.; Gschwend, J.; Gutierrez, G.; Honscheid, K.; James, D.; Kuehn, K.; Kuropatkin, N.; Menanteau, F.; Miquel, R.; Plazas, A. A.; Romer, A. K.; Sako, M.; Sanchez, E.; Scarpine, V.; Schubnell, M.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Suchyta, E.; Swanson, M. E. C.; Tarle, G.; Tucker, D. L.; Wester, W.

2017-06-01

We report the discovery of a stellar overdensity 8° north of the centre of the Small Magellanic Cloud (SMC; Small Magellanic Cloud Northern Over-Density; SMCNOD), using data from the first 2 yr of the Dark Energy Survey (DES) and the first year of the MAGellanic SatelLITEs Survey (MagLiteS). The SMCNOD is indistinguishable in age, metallicity and distance from the nearby SMC stars, being primarily composed of intermediate-age stars (6 Gyr, Z=0.001), with a small fraction of young stars (1 Gyr, Z=0.01). The SMCNOD has an elongated shape with an ellipticity of 0.6 and a size of ˜ 6° × 2°. It has an absolute magnitude of MV ≅ -7.7, rh = 2.1 kpc, and μV(r < rh) = 31.2 mag arcsec-2. We estimate a stellar mass of ˜105 M⊙, following a Kroupa mass function. The SMCNOD was probably removed from the SMC disc by tidal stripping, since it is located near the head of the Magellanic Stream, and the literature indicates likely recent Large Magellanic Cloud-SMC encounters. This scenario is supported by the lack of significant H I gas. Other potential scenarios for the SMCNOD origin are a transient overdensity within the SMC tidal radius or a primordial SMC satellite in advanced stage of disruption.

A stellar overdensity associated with the Small Magellanic Cloud

DOE PAGES

Pieres, Adriano; Santiago, Basilio X.; Drlica-Wagner, A.; ...

2017-02-28

Here, we report the discovery of a stellar overdensity 8° north of the centre of the Small Magellanic Cloud (SMC; Small Magellanic Cloud Northern Over-Density; SMCNOD), using data from the first 2 yr of the Dark Energy Survey (DES) and the first year of the MAGellanic SatelLITEs Survey (MagLiteS). The SMCNOD is indistinguishable in age, metallicity and distance from the nearby SMC stars, being primarily composed of intermediate-age stars (6 Gyr, Z = 0.001), with a small fraction of young stars (1 Gyr, Z = 0.01). The SMCNOD has an elongated shape with an ellipticity of 0.6 and a sizemore » of ~6° × 2°. It has an absolute magnitude of MV ≅ –7.7, rh = 2.1 kpc, and μV(r < rh) = 31.2 mag arcsec –2. We estimate a stellar mass of ~10 5 M⊙, following a Kroupa mass function. The SMCNOD was probably removed from the SMC disc by tidal stripping, since it is located near the head of the Magellanic Stream, and the literature indicates likely recent Large Magellanic Cloud-SMC encounters. This scenario is supported by the lack of significant H i gas. Other potential scenarios for the SMCNOD origin are a transient overdensity within the SMC tidal radius or a primordial SMC satellite in advanced stage of disruption.« less

Making Small Schools Work: A Handbook for Teachers in Small Rural Schools.

ERIC Educational Resources Information Center

Sigsworth, Alan; Solstad, Karl Jan

This handbook addresses the provision of an equitable basic education in rural areas, particularly in developing countries, by means of small schools located close to the pupils' homes. It is based on beliefs that small schools can be good schools; the appropriate place for a small school and its teachers is within the community; and small schools…

In vitro effects of the anti-Alzheimer drug memantine on the human erythrocyte membrane and molecular models.

PubMed

Zambrano, Pablo; Suwalsky, Mario; Villena, Fernando; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

2017-01-29

Memantine is a NMDA antagonist receptor clinically used for treating Alzheimer's disease. NMDA receptors are present in the human neurons and erythrocyte membranes. The aim of the present study was to investigate the effects of memantine on human erythrocytes. With this purpose, the drug was developed to in vitro interact with human red cells and bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). The latter represent lipids respectively present in both outer and inner monolayers of the red cell membrane. Results obtained by scanning electron microscopy (SEM) showed that memantine changed the normal biconcave shape of red cells to cup-shaped stomatocytes. According to the bilayer-couple hypothesis the drug intercalated into the inner monolayer of the erythrocyte membrane. Experimental results obtained by X-ray diffraction on multibilayers of DMPC and DMPE, and by differential scanning calorimetry on multilamellar vesicles indicated that memantine preferentially interacted with DMPC in a concentration-dependent manner. Thus, it can be concluded that in the low therapeutic plasma concentration of circa 1 μM memantine is located in NMDA receptor channel without affecting the erythrocyte shape. However, at higher concentrations, once the receptors became saturated excess of memantine molecules (20 μM) would interact with phosphoinositide lipids present in the inner monolayer of the erythrocyte membrane inducing the formation of stomatocytes. However, 40-50 μM memantine was required to interact with isolated phosphatidylcholine bilayers. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluorescence studies on the interaction of choline-binding domain B of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.

PubMed

Damai, Rajani S; Anbazhagan, V; Rao, K Babu; Swamy, Musti J

2009-12-01

The microenvironment and accessibility of the tryptophan residues in domain B of PDC-109 (PDC-109/B) in the native state and upon ligand binding have been investigated by fluorescence quenching, time-resolved fluorescence and red-edge excitation shift (REES) studies. The increase in the intrinsic fluorescence emission intensity of PDC-109/B upon binding to lysophosphatidylcholine (Lyso-PC) micelles and dimyristoylphosphatidylcholine (DMPC) membranes was considerably less as compared to that observed with the whole PDC-109 protein. The degree of quenching achieved by different quenchers with PDC-109/B bound to Lyso-PC and DMPC membranes was significantly higher as compared to the full PDC-109 protein, indicating that membrane binding afforded considerably lesser protection to the tryptophan residues of domain B as compared to those in the full PDC-109 protein. Finally, changes in red-edge excitation shift (REES) seen with PDC-109/B upon binding to DMPC membranes and Lyso-PC micelles were smaller that the corresponding changes in the REES values observed for the full PDC-109. These results, taken together suggest that intact PDC-109 penetrates deeper into the hydrophobic parts of the membrane as compared to domain B alone, which could be the reason for the inability of PDC-109/B to induce cholesterol efflux, despite its ability to recognize choline phospholipids at the membrane surface.

Small collision systems: Theory overview on cold nuclear matter effects

NASA Astrophysics Data System (ADS)

Armesto, Néstor

2018-02-01

Many observables measured at the Relativistic Heavy Ion Collider and the Large Hadron Collider show a smooth transition between proton-proton and protonnucleus collisions (small systems), and nucleus-nucleus collisions (large systems), when represented versus some variable like the multiplicity in the event. In this contribution I review some of the physics mechanisms, named cold nuclear matter effects, that may lead to a collective-like behaviour in small systems beyond the macroscopic description provided by relativistic hydrodynamics. I focus on the nuclear modification of parton densities, single inclusive particle production and correlations.

A coupled model of transport-reaction-mechanics with trapping. Part I - Small strain analysis

NASA Astrophysics Data System (ADS)

Salvadori, A.; McMeeking, R.; Grazioli, D.; Magri, M.

2018-05-01

A fully coupled model for mass and heat transport, mechanics, and chemical reactions with trapping is proposed. It is rooted in non-equilibrium rational thermodynamics and assumes that displacements and strains are small. Balance laws for mass, linear and angular momentum, energy, and entropy are stated. Thermodynamic restrictions are identified, based on an additive strain decomposition and on the definition of the Helmholtz free energy. Constitutive theory and chemical kinetics are studied in order to finally write the governing equations for the multi-physics problem. The field equations are solved numerically with the finite element method, stemming from a three-fields variational formulation. Three case-studies on vacancies redistribution in metals, hydrogen embrittlement, and the charge-discharge of active particles in Li-ion batteries demonstrate the features and the potential of the proposed model.

EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

ClinicalTrials.gov

2015-04-10

Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

Osteogenesis imperfecta type I: Molecular heterogeneity for COL1A1 null alleles of type I collagen

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

Willing, M.C.; Deschenes, S.P.; Pitts, S.H.

Osteogenesis imperfecta (OI) type I is the mildest form of inherited brittle-bone disease. Dermal fibroblasts from most affected individuals produce about half the usual amount of type I procollagen, as a result of a COL1A1 {open_quotes}null{close_quotes} allele. Using PCR amplification of genomic DNA from affected individuals, followed by denaturing gradient gel electrophoresis (DGGE) and SSCP, we identified seven different COL1A1 gene mutations in eight unrelated families with OI type I. Three families have single nucleotide substitutions that alter 5{prime} donor splice sites; two of these unrelated families have the same mutation. One family has a point mutation, in an exon,more » that creates a premature termination codon, and four have small deletions or insertions, within exons, that create translational frameshifts and new termination codons downstream of the mutation sites. Each mutation leads to both marked reduction in steady-state levels of mRNA from the mutant allele and a quantitative decrease in type I procollagen production. Our data demonstrate that different molecular mechanisms that have the same effect on type I collagen production result in the same clinical phenotype. 58 refs., 4 figs., 1 tab.« less

25 CFR 39.145 - Can a school receive both a small school adjustment and a small high school adjustment?

Code of Federal Regulations, 2012 CFR

2012-04-01

... small high school adjustment? 39.145 Section 39.145 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Adjustment § 39.145 Can a school receive both a small school adjustment and a small high school adjustment? A school that meets the criteria in § 39.140 can receive both a small school adjustment and a small high...

25 CFR 39.145 - Can a school receive both a small school adjustment and a small high school adjustment?

Code of Federal Regulations, 2014 CFR

2014-04-01

... small high school adjustment? 39.145 Section 39.145 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Adjustment § 39.145 Can a school receive both a small school adjustment and a small high school adjustment? A school that meets the criteria in § 39.140 can receive both a small school adjustment and a small high...

25 CFR 39.145 - Can a school receive both a small school adjustment and a small high school adjustment?

Code of Federal Regulations, 2013 CFR

2013-04-01

... small high school adjustment? 39.145 Section 39.145 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Adjustment § 39.145 Can a school receive both a small school adjustment and a small high school adjustment? A school that meets the criteria in § 39.140 can receive both a small school adjustment and a small high...

';EXPERIMENTING with a Small Planet' as AN Experiment

NASA Astrophysics Data System (ADS)

Hay, W. W.

2013-12-01

Communicating science to the American public is difficult. The book ';Experimenting with a Small Planet' is a radical but sucessful departure from tradition. My background has been in study of the warm climate of the Cretaceous using numerical climate models -- not directly with modern climate change. The Arctic sea-ice meltback of 2007 was a startling event; it wasn't expected before the end of this century. Earth had gone past a tipping point toward an ice-free pole condition. I decided to try to write a book for the general public explaining the basics of climate and the significance of what is happening to our planet. Over 50 years I had written more than 200 technical papers in the peer-reviewed literature. I had also written 27 annual reviews on Geology for the high-school level World Book Encyclopedia. I had experience in communicating with the general public as Director of the University of Colorado Museum. Using my retirement community neighbors (businessmen, hedge fund manager, rancher, doctors, engineer, grade school teacher) as initial reviewers, I learned that: 1) the metric system is totally foreign and unintelligible - metric measurements must also be given in US feet, pounds, Fahrenheit temperatures, etc.; 2) readers stop if they encounter references to papers scattered in the text; 3) mathematics beyond arithmetic is feared; 4) scientific terminology is unknown; as is 5) the history of how we have come to understand physics, chemistry, biology, and geology. The average level of scientific knowledge of a successful retired American today is at best that of about 40 years ago; of our pubic school teachers, about 20 years old. Members of the US Congress have mostly law degrees, and at best took a few freshman-level courses in science when they were in college 30 years or more ago. Most Americans believe in the dogma of some religion, not in science. I discovered that most geologists know nothing about climatology, and most climatologists know next

10 CFR 905.15 - What are the requirements for the small customer plan alternative?

Code of Federal Regulations, 2010 CFR

2010-01-01

... summary form the following information: (i) Customer name, address, phone number, email and Website if... approves the request for small customer status. Small customers must submit, in writing, a small customer...

Why the United States Has the Small Business Program

DTIC Science & Technology

1987-04-01

Essential Emergency Communications Program. Mr. Pickles has also negotiated and managed large small business ($3M) and minority small business ($60M...I .4 AIR COMMAND AMDSTAFF COLLEGE TUENT RPORT DTIC- : WHY THE UNITED STATES HAS EClEFTHE SMALL BUSINESS PROGRAMIf .. N 88-13 JOHN J. PICKLES 87...included with any reproduced or adapted portions of this document. -P. - 7 ]REPORT NUMBER 87-2010 TITIJ WHY THE UNITED STATES HAS THE SMALL BUSINESS PROGRAM

Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

ClinicalTrials.gov

2014-10-30

Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Nucleic acids encoding phloem small RNA-binding proteins and transgenic plants comprising them

DOEpatents

Lucas, William J.; Yoo, Byung-Chun; Lough, Tony J.; Varkonyi-Gasic, Erika

2007-03-13

The present invention provides a polynucleotide sequence encoding a component of the protein machinery involved in small RNA trafficking, <i>Cucurbita maxima i>phloem small RNA-binding protein (CmPSRB 1), and the corresponding polypeptide sequence. The invention also provides genetic constructs and transgenic plants comprising the polynucleotide sequence encoding a phloem small RNA-binding protein to alter (e.g., prevent, reduce or elevate) non-cell autonomous signaling events in the plants involving small RNA metabolism. These signaling events are involved in a broad spectrum of plant physiological and biochemical processes, including, for example, systemic resistance to pathogens, responses to environmental stresses, e.g., heat, drought, salinity, and systemic gene silencing (e.g., viral infections).

A semantic web ontology for small molecules and their biological targets.

PubMed

Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

2010-05-24

A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

Short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy with a very small remnant stomach for cStage I proximal gastric carcinoma.

PubMed

Furukawa, Haruna; Kurokawa, Yukinori; Takiguchi, Shuji; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Yamasaki, Makoto; Nakajima, Kiyokazu; Mori, Masaki; Doki, Yuichiro

2018-05-01

Total or proximal gastrectomy is usually performed for early proximal gastric carcinoma, but the optimal type of gastrectomy is still unknown. We evaluated short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy (LsTG) in comparison with laparoscopic total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG). We analyzed 113 patients who underwent LsTG (n = 38), LTG (n = 48), or LPG (n = 27) for cStage I gastric cancer located in the upper third of the stomach. Postoperative morbidities, nutritional status including body weight, serum albumin, hemoglobin, the prognostic nutritional index (PNI), and endoscopic findings at 1 year after surgery were compared between LsTG and both LTG and LPG. Operation time and intraoperative blood loss were similar among the three groups. The incidence of postoperative morbidities was lower in LsTG than in LTG. The degree of body weight loss was significantly smaller in LsTG than in LTG at 6 and 12 months. At 12 months, LsTG resulted in better serum albumin and PNI than LPG, and better hemoglobin than LTG. Endoscopic examination demonstrated that one LsTG patient and two LPG patients had reflux esophagitis. Remnant gastritis was observed more frequently in LPG than in LsTG. No LsTG patient had bile reflux, although it was observed in four LPG patients. LsTG with a very small remnant stomach had favorable short-term outcomes and nutritional status compared with LTG and LPG, so it may be a better treatment option for cStage I proximal gastric carcinoma.

Lipid and Lipid-Polymer Mixtures at an Interface

NASA Astrophysics Data System (ADS)

Kim, Joon Heon; Kim, Mahn Won

2000-03-01

The surface pressure (Π) and surface area/molecule (A) isotherms of a mixture of DMPC (DL-α-phosphatidylcholine,Dimyristoyl) and PEG-DMPE (1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly(ethylene glycol)5000]) system were measured at various compositions by the Langmuir surface balance technique at an air/water interface. In the range where the surface pressure is less than about 8 dynes/cm, a PEG polymer chain of PEG-DMPE molecules remains on the surface and the isotherm can be explained by the 2-D power law behavior of chains in a good solvent. In the range above 8 dynes/cm, a part of the PEG polymer segment is dissolved into the water phase, and the surface pressure can be explained as the sum of the 2-D component and 3-D component. Furthermore, the mixing energy is negative, which indicates an attractive interaction between DMPC and PEG-DMPE.

Lipid and lipid-polymer mixtures at an interface

NASA Astrophysics Data System (ADS)

Kim, Joon Heon; Kim, Mahn Won

2000-06-01

The surface pressure (Π) and surface area/molecule (A) isotherms of a mixture of DMPC (DL-α-phosphatidylcholine, Dimyristoyl) and PEG-DMPE (1,2-Diacyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly(ethylene glycol)5000]) system were measured at various compositions by the Langmuir surface balance technique at an air/water interface. In the range where the surface pressure is less than about 8 dynes/cm, a PEG polymer chain of PEG-DMPE molecules remains on the surface and the isotherm can be explained by the 2-D power law behavior of chains in a good solvent. In the range above 8 dynes/cm, a part of the PEG polymer segment is dissolved into the water phase, and the surface pressure can be explained as the sum of the 2-D component and 3-D component. Furthermore, the mixing energy is negative, which indicates an attractive interaction between DMPC and PEG-DMPE. .

A comprehensive study of small non-frameshift insertions/deletions in proteins and prediction of their phenotypic effects by a machine learning method (KD4i)

PubMed Central

2014-01-01

Background Small insertion and deletion polymorphisms (Indels) are the second most common mutations in the human genome, after Single Nucleotide Polymorphisms (SNPs). Recent studies have shown that they have significant influence on genetic variation by altering human traits and can cause multiple human diseases. In particular, many Indels that occur in protein coding regions are known to impact the structure or function of the protein. A major challenge is to predict the effects of these Indels and to distinguish between deleterious and neutral variants. When an Indel occurs within a coding region, it can be either frameshifting (FS) or non-frameshifting (NFS). FS-Indels either modify the complete C-terminal region of the protein or result in premature termination of translation. NFS-Indels insert/delete multiples of three nucleotides leading to the insertion/deletion of one or more amino acids. Results In order to study the relationships between NFS-Indels and Mendelian diseases, we characterized NFS-Indels according to numerous structural, functional and evolutionary parameters. We then used these parameters to identify specific characteristics of disease-causing and neutral NFS-Indels. Finally, we developed a new machine learning approach, KD4i, that can be used to predict the phenotypic effects of NFS-Indels. Conclusions We demonstrate in a large-scale evaluation that the accuracy of KD4i is comparable to existing state-of-the-art methods. However, a major advantage of our approach is that we also provide the reasons for the predictions, in the form of a set of rules. The rules are interpretable by non-expert humans and they thus represent new knowledge about the relationships between the genotype and phenotypes of NFS-Indels and the causative molecular perturbations that result in the disease. PMID:24742296

"No One Really Knows What It Is That I Need": Learning a New Job at a Small Private College

ERIC Educational Resources Information Center

Olson, Joann S.

2015-01-01

Colleges and universities are sites of learning, not only for tuition-paying students, but also for those employed by the institution. This qualitative study explored the workplace learning experiences of non-faculty staff at a small, faith-based private college in the upper Midwest who had recently changed jobs within the institution. Learning to…

Changes in Small Town Social Capital and Civic Engagement

ERIC Educational Resources Information Center

Besser, Terry L.

2009-01-01

Small towns are often depicted as places with many interpersonal relationships and generalized trust, or high social capital. Social capital is a resource which towns can use to solve problems and improve the local quality of life. In this paper, I determined if social capital and civic engagements have declined in small towns in the U.S. Midwest…

A Study of Sociolinguistic Variation in a Small Community: Puerto Rican Spanish in Amsterdam, New York

ERIC Educational Resources Information Center

Mumin, Zahir

2017-01-01

The objective of the current study is to contribute to the larger body of sociophonetic variation research by describing and analyzing Spanish as spoken in a small Puerto Rican community in the US. First, I describe phonological and morphosyntactic features of Spanish as used by four different groups of Puerto Rican informants in Amsterdam, New…

FEDERAL RESEARCH: Small Business Involvement in Federal Research and Development.

DTIC Science & Technology

1988-02-01

Subcommittee on Innovation, Technology and Productivity, Committee on Small Business , U.S. Senate SFebruary 1988 FEDERAL RESEARCH Small Business ...Subcommittee on Innovation, Technology, and Productivity Committee on Small Business ~u United States Senate Dear 1r. Chairman: I In your September 30...1987, letter and in surbsequent discussions with your office, you asked us to&Lobtainj. information on the role of small business in the federal

Remedial Investigation Addendum Report Data Item A009. Volume 4: Appendices I-Z

DTIC Science & Technology

1993-12-01

Impatien~s capensis FACW Yellow Iris Iris pseudoacorus OBL Blueflag Iris Iris versicolor OBL 1 21 I NEW ENGLAND ENVIRONMENTAL, INC. Duckweed Lemna spp...small mammal community in the food web model. American woodcock (Scolopax minor ). This small bird is often j found in forested wetlands and forages...34Drinking Water and Health" Safe Drinking Water Committee, Washington, D.C. Thallium Thallium is a naturally occurring soft metal that is a minor

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing.

PubMed

Morozov, Giora I; Zhao, Huaying; Mage, Michael G; Boyd, Lisa F; Jiang, Jiansheng; Dolan, Michael A; Venna, Ramesh; Norcross, Michael A; McMurtrey, Curtis P; Hildebrand, William; Schuck, Peter; Natarajan, Kannan; Margulies, David H

2016-02-23

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.

Occupational health and safety in small animal veterinary practice: Part I--nonparasitic zoonotic diseases.

PubMed

Weese, J S; Peregrine, A S; Armstrong, J

2002-08-01

Zoonotic diseases are an ever-present concern in small animal veterinary practice and are often overlooked. A variety of nonparasitic zoonotic diseases may be encountered in small animal practice, including cat scratch disease (bartonellosis), cat bite abscesses, rabies, leptospirosis, methicillin-resistant Staphylococcus aureus, Clostridium difficile-associated diarrhea, salmonellosis, avian chlamydiosis, campylobacteriosis, dermatophytosis, and blastomycosis. These may cause human disease ranging from mild and self-limiting to fatal. The risk of development of a zoonotic disease can be lessened by early recognition of infected animals, proper animal handling, basic biosecurity precautions, and, most importantly, personal hygiene.

Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy.

PubMed

Akthar, Adil S; Ferguson, Mark K; Koshy, Matthew; Vigneswaran, Wickii T; Malik, Renuka

2017-02-01

Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography-computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography-computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography-computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography-computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography-computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography-computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively ( P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively ( P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64%, respectively. Occult lymph node involvement was not associated with

Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy

PubMed Central

Akthar, Adil S.; Ferguson, Mark K.; Koshy, Matthew; Vigneswaran, Wickii T.

2016-01-01

Purpose/Objectives: Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography–computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography–computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. Materials/Methods: A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography–computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography–computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography–computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. Results: A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography–computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively (P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively (P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64

Collaborative Manufacturing for Small-Medium Enterprises

NASA Astrophysics Data System (ADS)

Irianto, D.

2016-02-01

Manufacturing systems involve decisions concerning production processes, capacity, planning, and control. In a MTO manufacturing systems, strategic decisions concerning fulfilment of customer requirement, manufacturing cost, and due date of delivery are the most important. In order to accelerate the decision making process, research on decision making structure when receiving order and sequencing activities under limited capacity is required. An effective decision making process is typically required by small-medium components and tools maker as supporting industries to large industries. On one side, metal small-medium enterprises are expected to produce parts, components or tools (i.e. jigs, fixture, mold, and dies) with high precision, low cost, and exact delivery time. On the other side, a metal small- medium enterprise may have weak bargaining position due to aspects such as low production capacity, limited budget for material procurement, and limited high precision machine and equipment. Instead of receiving order exclusively, a small-medium enterprise can collaborate with other small-medium enterprise in order to fulfill requirements high quality, low manufacturing cost, and just in time delivery. Small-medium enterprises can share their best capabilities to form effective supporting industries. Independent body such as community service at university can take a role as a collaboration manager. The Laboratory of Production Systems at Bandung Institute of Technology has implemented shared manufacturing systems for small-medium enterprise collaboration.

Treatment recommendations by clinicians in stage I non-small cell lung cancer: A study of factors that influence the likelihood of accounting for the patient's preference.

PubMed

Hopmans, Wendy; Damman, Olga C; Porsius, Jarry T; Zwaan, Laura; Senan, Suresh; Timmermans, Danielle R M

2016-11-01

Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with stage I non-small cell lung cancer (NSCLC). Shared decision making (SDM) has been advocated in this patient group. This study explored clinician decision making in relation to the stated treatment preferences of patients. In a previous study, we conducted a binary choice experiment with hypothetical cases among 126 clinicians. Secondary data analysis was performed using multilevel logistic regression models, in which random differences between clinicians' decisions were taken into account. We analyzed the influence of patient- and clinician-related characteristics, and uncertainty as experienced by clinicians about their recommendation on the clinician's decision (either in line with the patient's preference or not). Significant interactions were observed between patient- and clinician-related characteristics, indicating that patient preferences were selectively taken into account, depending on clinicians' specialty, their views about the comparability of cancer-related outcomes following surgery and SABR, and the degree of uncertainty about the treatment recommendation. Our findings suggest that SDM for stage I NSCLC care is largely influenced by how clinicians weigh available scientific evidence. Clinicians should involve lung cancer patients more and ask for their preferences in making treatment recommendations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Harmony in the small-world

NASA Astrophysics Data System (ADS)

Marchiori, Massimo; Latora, Vito

2000-10-01

The small-world phenomenon, popularly known as six degrees of separation, has been mathematically formalized by Watts and Strogatz in a study of the topological properties of a network. Small-world networks are defined in terms of two quantities: they have a high clustering coefficient C like regular lattices and a short characteristic path length L typical of random networks. Physical distances are of fundamental importance in applications to real cases; nevertheless, this basic ingredient is missing in the original formulation. Here, we introduce a new concept, the connectivity length D, that gives harmony to the whole theory. D can be evaluated on a global and on a local scale and plays in turn the role of L and 1/ C. Moreover, it can be computed for any metrical network and not only for the topological cases. D has a precise meaning in terms of information propagation and describes in a unified way, both the structural and the dynamical aspects of a network: small-worlds are defined by a small global and local D, i.e., by a high efficiency in propagating information both on a local and global scale. The neural system of the nematode C. elegans, the collaboration graph of film actors, and the oldest US subway system, can now be studied also as metrical networks and are shown to be small-worlds.

"Non-cold" dark matter at small scales: a general approach

NASA Astrophysics Data System (ADS)

Murgia, R.; Merle, A.; Viel, M.; Totzauer, M.; Schneider, A.

2017-11-01

Structure formation at small cosmological scales provides an important frontier for dark matter (DM) research. Scenarios with small DM particle masses, large momenta or hidden interactions tend to suppress the gravitational clustering at small scales. The details of this suppression depend on the DM particle nature, allowing for a direct link between DM models and astrophysical observations. However, most of the astrophysical constraints obtained so far refer to a very specific shape of the power suppression, corresponding to thermal warm dark matter (WDM), i.e., candidates with a Fermi-Dirac or Bose-Einstein momentum distribution. In this work we introduce a new analytical fitting formula for the power spectrum, which is simple yet flexible enough to reproduce the clustering signal of large classes of non-thermal DM models, which are not at all adequately described by the oversimplified notion of WDM . We show that the formula is able to fully cover the parameter space of sterile neutrinos (whether resonantly produced or from particle decay), mixed cold and warm models, fuzzy dark matter, as well as other models suggested by effective theory of structure formation (ETHOS). Based on this fitting formula, we perform a large suite of N-body simulations and we extract important nonlinear statistics, such as the matter power spectrum and the halo mass function. Finally, we present first preliminary astrophysical constraints, based on linear theory, from both the number of Milky Way satellites and the Lyman-α forest. This paper is a first step towards a general and comprehensive modeling of small-scale departures from the standard cold DM model.

Healthy food availability in small urban food stores: a comparison of four US cities.

PubMed

Laska, Melissa Nelson; Borradaile, Kelley E; Tester, June; Foster, Gary D; Gittelsohn, Joel

2010-07-01

Given that small food stores may be important retail food sources in low-income urban communities, our objective was to examine cross-city comparative data documenting healthy food availability within such facilities, particularly those located in low-income areas and nearby schools. Food stores in Baltimore, Maryland; Minneapolis/St. Paul, Minnesota; Oakland, California; and Philadelphia, Pennsylvania were selected for assessment based on proximity to low-income schools. Stores were defined as: (i) single-aisle (n 45); (ii) small (2-5 aisles; n 52); and (iii) large (> or = 6 aisles; n 8). Staff conducted in-store audits to assess the presence/absence of twenty-eight healthy items, organized within five categories: (i) fresh fruits/vegetables, (ii) processed fruits/vegetables, (iii) healthy beverages/low-fat dairy, (iv) healthy snacks and (v) other healthy staple foods. The availability of healthy food items was low, particularly in single-aisle and small stores, and there was significant cross-site variability in the availability of healthy snacks (P < 0.0001) and other healthy staple foods (P < 0.0001). No cross-site differences existed for fruits/vegetables or healthy beverages/low-fat dairy availability. Healthy food availability scores increased significantly with store size for nearly all food/beverage categories (P < 0.01). Overall, healthy food availability in these venues was limited. Region-specific factors may be important to consider in understanding factors influencing healthy food availability in small urban markets. Data suggest that efforts to promote healthy diets in low-income communities may be compromised by a lack of available healthy foods. Interventions targeting small stores need to be developed and tailored for use in urban areas across the USA.

Collapse of a pollination web in small conservation areas.

PubMed

Pauw, Anton

2007-07-01

A suspected global decline in pollinators has heightened interest in their ecological significance. In a worst-case scenario, the decline of generalist pollinators is predicted to trigger cascades of linked declines among the multiple specialist plant species to which they are linked, but this has not been documented. I studied a portion of a pollination web involving a generalist pollinator, the oil-collecting bee Rediviva peringueyi, and a community of oil-secreting plants. Across 27 established conservation areas located in the Cape Floral Region, I found substantial variation in the bees' occurrence in relation to soil type and the successional stage of the vegetation. Anthropogenic declines were detectable against this background of naturally occurring variation: R. peringueyi was absent from small conservation areas (< 385 ha) in an urban matrix. In the absence of the bee, seed set failed in six specialist plant species that are pollinated only by R. peringueyi but remained high in a pollination generalist, which had replacement pollinators. The findings are consistent with theoretical predictions of the importance of generalist pollinators in maintaining the structure of pollination webs.

The Phenomenology of Small-Scale Turbulence

NASA Astrophysics Data System (ADS)

Sreenivasan, K. R.; Antonia, R. A.

I have sometimes thought that what makes a man's work classic is often just this multiplicity [of interpretations], which invites and at the same time resists our craving for a clear understanding. Wright (1982, p. 34), on Wittgenstein's philosophy Small-scale turbulence has been an area of especially active research in the recent past, and several useful research directions have been pursued. Here, we selectively review this work. The emphasis is on scaling phenomenology and kinematics of small-scale structure. After providing a brief introduction to the classical notions of universality due to Kolmogorov and others, we survey the existing work on intermittency, refined similarity hypotheses, anomalous scaling exponents, derivative statistics, intermittency models, and the structure and kinematics of small-scale structure - the latter aspect coming largely from the direct numerical simulation of homogeneous turbulence in a periodic box.

A PCR-aided transcript titration assay (PATTY) to measure topoisomerase I gene expression in human tumor specimens.

PubMed

Meersma, G J; Bakker, M; Groen, H J; Van der Zee, A G; Jensen, P B; Giaccone, G; De Vries, E G; Smit, E F

1999-01-01

Topoisomerase I (topo I) inhibitors are promising anticancer agents with demonstrated activity against a wide range of solid tumors. Quantitative information on topol mRNA levels in tumor biopsies may predict response to topo I inhibitors. A polymerase chain reaction aided transcript titration assay (PATTY) was developed to allow quantitation of topol mRNA in small samples. Concentrations of topol mRNA in total RNA samples were estimated by RT-PCR analysis in a human small cell lung cancer (SCLC) cell line (GLC,) and its topotecan (GL2C/SK and F) and camptothecin (GL2C/Campt) resistant sublines, human non-small cell lung cancer (NSCLC) and ovarian carcinoma samples. Topol PATTY showed a decreased topo I mRNA level in GLC2/SK and F (4.5 pg/100 ng total RNA) and GLC,/Campt (2.2 pg/100 ng total RNA), respectively, compared to the parent cell line GLC2 (5.4 pg/100 ng total RNA). Topol protein levels as measured by Western blotting were compatible with topol mRNA levels. Median (range) topol mRNA levels were 3.23 (2.33-5.10) pg/100 ng total RNA in resected NSCLC specimen (n = 6), and 2.03 (0.54-0.95) pg/100 ng total RNA in resected ovarian cancer specimen (n = 6). We conclude that topol PATTY is a new assay that quantitates topol mRNA levels in cell lines and small tumor samples.

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

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

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

DOE PAGES

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.; ...

2016-02-11

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting.

PubMed

Hsu, Ching-Yun; Yang, Shih-Chun; Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5-125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions.

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting

PubMed Central

Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5–125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions. PMID:29184410

Doublecortin and CaM kinase-like-1 expression in pathological stage I non-small cell lung cancer.

PubMed

Tao, Hiroyuki; Tanaka, Toshiki; Okabe, Kazunori

2017-08-01

Doublecortin and CaM kinase-like-1 (DCLK1) regulates microtubule polymerization in migrating neurons. Recently, DCLK1 has been reported to act as an intestinal tumor stem cell marker and has been shown to be expressed in cancer cells and in the stroma of breast, colon, pancreatic, and prostate cancers. Here, we studied DCLK1 expression in non-small cell lung cancer (NSCLC) by immunohistochemistry in association with clinicopathological factors and patient prognosis. DCLK1 expression was analyzed by immunohistochemical staining of surgical specimens from 232 patients with pathological stage I NSCLC, including 187 adenocarcinomas. Relationships between the expression status of DCLK1 and clinicopathological factors were examined. The impact of DCLK1 expression status and other clinicopathological factors on survival was evaluated by univariate and multivariate analyses. Thirty-three (14.2%) of 232 patients had DCLK1-positive cancer cells. DCLK1 was also expressed in the tumor stroma in most of the specimens and was significantly associated with DCLK1 expression in cancer cells. DCLK1-positive cancer cells were more common in non-adenocarcinoma tissues (44.4%) than in adenocarcinoma tissues (7.0%). Moreover, positive DCLK1 expression in cancer cells and stromal cells was correlated with a worse prognosis. Histological analyses revealed that the presence of DCLK1-positive cancer cells was an independent risk factor for poor prognosis in adenocarcinoma, but was not significantly associated with prognosis in non-adenocarcinoma. DCLK1 expression was observed in tumor cells in patients with pathological stage I NSCLC and was correlated with adverse prognosis, especially in patients with adenocarcinoma. DCLK1 may be a potential new therapeutic target.

Paramagnetic alignment of small grains: A novel method for measuring interstellar magnetic fields

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

Hoang, Thiem; Martin, P. G.; Lazarian, A.

2014-07-20

We present a novel method to measure the strength of interstellar magnetic fields using ultraviolet (UV) polarization of starlight that is in part produced by weakly aligned, small dust grains. We begin with calculating the degrees of the paramagnetic alignment of small (size a ∼ 0.01 μm) and very small (a ∼ 0.001 μm) grains in the interstellar magnetic field due to the Davis-Greenstein relaxation and resonance relaxation. To calculate the degrees of paramagnetic alignment, we use Langevin equations and take into account various interaction processes essential for the rotational dynamics of small grains. We find that the alignment ofmore » small grains is necessary to reproduce the observed polarization in the UV, although the polarization arising from these small grains is negligible at the optical and infrared (IR) wavelengths. Based on fitting theoretical models to observed extinction and polarization curves, we find that the best-fit model for the case with the peak wavelength of polarization λ{sub max} < 0.55 μm requires a higher degree of alignment of small grains than for the typical case with λ{sub max} = 0.55 μm. We interpret the correlation between the systematic increase of the UV polarization relative to maximum polarization (i.e., of p(6 μm{sup –1})/p{sub max}) with λ{sub max}{sup −1} for cases of low λ{sub max} by appealing to the higher degree of alignment of small grains. We utilize the correlation of the paramagnetic alignment of small grains with the magnetic field strength B to suggest a new way to measure B using the observable parameters λ{sub max} and p(6 μm{sup –1})/p{sub max}.« less

Helix Fraying and Lipid-Dependent Structure of a Short Amphipathic Membrane-Bound Peptide Revealed by Solid-State NMR.

PubMed

Strandberg, Erik; Grau-Campistany, Ariadna; Wadhwani, Parvesh; Bürck, Jochen; Rabanal, Francesc; Ulrich, Anne S

2018-06-14

The amphipathic α-helical peptide KIA14 [(KIAGKIA) 2 -NH 2 ] was studied in membranes using circular dichroism and solid-state NMR spectroscopy to obtain global as well as local structural information. By analyzing 2 H NMR data from 10 analogues of KIA14 that were selectively labeled with Ala- d 3 , those positions that are properly folded into a helix could be determined within the membrane-bound peptide. The N-terminus was found to be unraveled, whereas positions 4-14 formed an ideal helix all the way to the C-terminus. The helicity did not change when Gly residues were replaced by Ala- d 3 but was reduced when Ile was replaced, indicating that large hydrophobic residues are required for membrane binding and helix formation. The reduced helicity was strongly correlated with a decrease in peptide-induced leakage from lipid vesicles. The orientation of the short KIA14 peptide was assessed in several lipid systems and compared with that of the longer KIA21 sequence [(KIAGKIA) 3 -NH 2 ]. In 1,2-dioleoyl- sn-glycero-3-phosphatidylcholine, both peptides are aligned flat on the membrane surface, whereas in 1,2-dimyristoyl- sn-glycero-3-phosphatidylcholine (DMPC)/1-myristoyl-2-hydroxy- sn-glycero-3-phosphatidylcholine (lyso-MPC) both are inserted into the membrane in an upright orientation. These two types of lipid systems had been selected for their strongly negative and positive spontaneous curvature, respectively. We propose that in these cases, the peptide orientation is largely determined by the lipid properties. On the other hand, in plain DMPC and 1,2-dilauroyl- sn-glycero-3-phosphatidylcholine, which have only a slight positive curvature, a marked difference in orientation is evident: the short KIA14 lies almost flat on the membrane surface, whereas the longer KIA21 is more tilted. We thus propose that out of the lipid systems tested here, DMPC (with hardly any curvature) is the least biased lipid system in which peptide orientation and realignment can be

Safety and efficacy of phacoemulsification and intraocular lens implantation through a small pupil using minimal iris manipulation.

PubMed

Papaconstantinou, Dimitris; Kalantzis, George; Brouzas, Dimitris; Kontaxakis, Anastasios; Koutsandrea, Chryssanthi; Diagourtas, Andreas; Georgalas, Ilias

2016-01-01

The aim of this study was to compare the results of phacoemulsification through a small pupil using minimal iris manipulation versus phacoemulsification through a well-dilated pupil. This prospective randomized control (comparative) study comprised 78 patients (group I) with a maximally dilated pupil size of ≤4.00 mm and 45 patients (group II) with dilated pupil size of ≥7.00 mm. In group I patients, only viscodilation and minimal push-and-pull iris stretching with two collar-button iris-retractor hooks were utilized without iris manipulation. Phacoemulsification was performed by two senior surgeons and the technique used consisted of either stop and chop or quick chop, infusion/aspiration of lens cortex, capsular bag refill with ocular viscoelastic devices, and implantation of an acrylic foldable intraocular lens. Patients were examined on the first day and 1 month postoperatively. Forty-six eyes of group I patients had pseudoexfoliation syndrome, eleven eyes had previous glaucoma surgery, 14 eyes had angle-closure or open-angle glaucoma, and seven eyes had posterior synechiae with iritis. In group I patients, the mean pupil size measured under an operating microscope was 3.2 mm preoperatively, 4.3 mm after viscoelastic and mechanical pupil dilation, and 4.1 mm at the end of a surgical procedure. Rupture of the zonular fibers occurred in six patients of group I and the intraocular lens was implanted in the sulcus. Small iris-sphincter rupture and small hemorrhages occurred in four eyes during pupillary manipulation, but they were not evident at the end of the surgery. In group II patients, no intraoperative complications occurred. Signs of significant corneal edema and iritis were observed more frequently in group I eyes (26 eyes and 20 eyes, respectively) on the first postoperative day in comparison with group II eyes (ten eyes and six eyes, respectively). Intraocular pressure was <20 mmHg in all eyes of both groups. One month postoperatively, the pupil was

Bumping into the Butterfly, When I Was But a Bud

NASA Astrophysics Data System (ADS)

Hofstadter, Douglas

I will recount the main events that led me to discover the so-called ''Hofstadter butterfly'' when I was a physics student, over 40 years ago. A key moment in the tale was when, after years of futile struggle, I finally abandoned particle physics, and chose, with much trepidation, to try solid-state physics instead, a field of which I knew nothing at all. I was instinctively drawn to a long-standing classic unsolved problem in the field - What is the nature of the energy spectrum of Bloch electrons in a magnetic field? - when Professor Gregory Wannier told me that it involved a weird distinction between ''rational'' and ''irrational'' magnetic fields, which neither he nor anyone else understood. This mystery allured me, as I was sure that the rational/irrational distinction cannot possibly play a role in physical phenomena. I tried manipulating equations for a long time but was unable to make any headway, and so, as a last resort, I wound up using brute-force calculation instead. I programmed a small desktop computer to give me numbers that I then plotted by hand on paper, and one fine day, to my shock, my eyes suddenly recognized a remarkable type of pattern that I had discovered twelve years earlier, when I was an undergraduate math major exploring number theory. All at once, I realized that the theoretical energy spectrum I'd plotted by hand consisted of infinitely many copies of itself, nested infinitely deeply, and it looked a little like a butterfly, whence its name. This unanticipated discovery eventually led to many new insights into the behavior of quantum systems featuring two competing periodicities. I will briefly describe some of the consequences I found back then of the infinitely nested spectrum, and in particular how the baffling rational/irrational distinction melted away, once the butterfly's nature had been deeply understood.