Small Lp Research Articles

Regional localization of intestinal dendritic cell subsets control Th‐17 responses

Mucosal immunity is influenced in large part by the dynamic interplay between various intestinal antigen‐presenting cell subsets and T lymphocytes. Using 10‐color flow cytometry, we have defined the major DC and macrophage subsets in the small and large intestine LP as distinguishable by the reciprocal expression of CD103 and F4/80, respectively, and not exclusively by CD11b or CD11c. Intestinal F4/80+ macrophages expressed IL‐10, TGF‐β, retinoic acid‐generating enzymes and promoted the differentiation of inducible FoxP3+ regulatory T cells. Alternatively, CD11b+, but not CD11b−, CD103+ LP DCs expressed IL‐6 and TGF‐β as well as retinoic acid‐generating enzymes and efficiently induced the differentiation of TH‐17 cells. These CD103+ LP DC subsets displayed striking region‐specific localization along the intestine with CD11b−CD103+ LP DCs appearing most abundantly in the large intestine while CD11b+CD103+ LP DCs were most prevalent in the upper small intestine. The distribution pattern of CD11b+CD103+ LP DCs in particular correlated with the representation of TH‐17 cells in the intestine and during intestinal inflammation CD11b+CD103+ LP DCs accumulated in the colonic LP as did TH‐17 cells. Our results suggest that CD11b+CD103+ LP DCs may be targets for modulating IL‐17 producing T cell responses during intestinal inflammation.

Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease

An increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood. We used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects. Three chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished. We identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.

Robust ℓp stability and robust ℓ∞ stabilization over a rate-limited digital channel

This paper is concerned with robust stabilization of an uncertain system over a rate-limited digital channel from the viewpoint of input-output stability. Because of the quantization in the communication channel, it is impossible to apply the traditional small gain theorem to establish robust stability of the feedback system. To overcome this difficulty, we introduce a new notion of small ℓp signal ℓp stability, and derive a sufficient robust stability condition against ℓp gain-bounded uncertainty based on this notion. Furthermore, for the case of p = ∞, a sufficient data rate for the existence of a robustly stabilizing encoder-controller pair is explicitly given.

Glacial long period seismic events at Katla volcano, Iceland

Repeating long‐period (lp) earthquakes are commonly observed in volcanic regions worldwide. They are usually explained in terms of a volcanic source effect or anomalous propagation through the volcano. Recently, large lp events have also been associated with the motion of massive ice streams. Our joint analysis of climatic and new seismic data shows that small lp events observed at Katla volcano, Iceland, are in fact related to ice movement in a steep outlet glacier and not, as previously thought, to volcanic intrusive activity. The over 13000 lp events recorded since 2000 are consistent in character and magnitude with seasonal changes of the glacier. As the current global warming trend could cause similar earthquake sequences at other glacier covered volcanoes, identifying them as glacial rather than eruption precursors is vital.

High Rate of Survival in Transformed Lymphoma after Autologous Stem Cell Transplant (ASCT): Pathologic Analysis and Comparison with De Novo DLBCL.

Introduction: Survival gains in follicular lymphoma (FL) have been variably attributed to improved first line and salvage therapies, and a decreasing frequency of histologic transformation (HT). Although ASCT is often used in patients (pts) with transformed lymphoma (TL), optimal pt selection and factors predictive of outcome are unclear. Although immunohistochemistry (IHC) has been applied to prognostication in de novo DLBCL, few studies have investigated IHC as a prognostic factor in TL. The purpose of this analysis was to review outcomes using ASCT for TL at the Cleveland Clinic Taussig Cancer Insitute (CCTCI) in light of modern IHC-based pathologic analysis.Methods: All pts undergoing ASCT for diffuse large B-cell lymphoma from 2003–2008 at CCTCI (n=130) were identified. IHC analysis for markers CD10, BCL2, BCL6, and MUM-1 was available for 56 pts, who were analyzed further. Pts with TL (n=25) were compared as a group to de novo cases (n=31).Baseline characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests. Relapse-free and overall survival (RFS and OS) were estimated with the Kaplan-Meier method and compared via log-rank test. Cox proportional hazards analysis was used to examine features predicting outcome after ASCT.Results: Median age was 57 years. Of 25 TL pts, 16 had prior FL, 1 each had small lymphocytic lymphoma and nodular LP Hodgkin lymphoma, and 7 presented with coexistent DLBCL and FL in the same biopsy specimen. Among 18 TL pts with metachronous presentation, HT occurred at a median of 26 months (range, 8–198 months).Pathologic characteristics (%) are:GroupCD10BCL6MUM-1BCL2GCB phenotype*MedianKI67 indext(14;18)TL8495388492708/10de novo6188436371801/8P value.08.621.0.18.09.63.02*Criteria from Hans et al, Blood2004;103(1):275–82Age and disease status at time of transplant were similar between groups. Three de novo pts and 2 TL patients underwent ASCT during first remission; all others underwent ASCT for relapsed/refractory disease.With a median follow-up of 25 months, 4 year RFS was 64% vs. 59% (p=.82) and OS 63% vs. 59% (p=.68) for TL and de novo pts, respectively (see Figures 1 and 2).No IHC feature predicted RFS or OS. Elevated LDH at time of ASCT predicted poor RFS (HR 4.6, p=.008) and OS (HR 6.3, p=.005) on multivariate analysis, and increasing number of prior regimens predicted poor RFS only (HR 1.4, p=.003).Conclusions: TL resembled de novo DLBCL in terms of IHC characteristics, but a higher proportion of TL cases bore the t(14;18) translocation.ASCT was effective in treating TL, with a 4-year RFS and OS exceeding 60%. This was indistinguishable from outcomes for de novo DLBCL pts treated with ASCT over the same period. Baseline characteristics were similar between TL and de novo pts.Survival in FL may be improving in part due to good outcomes using ASCT for TL. Confirmation of our observed RFS/OS among TL pts requires longer follow-up, given the ongoing risk of relapse of indolent disease. Outcome after ASCT cannot be predicted by IHC, and novel approaches are needed to improve pt selection and elucidate the biology of HT. [Display omitted] [Display omitted]

Static and dynamic scaling of semiflexible polymer chains—a molecular dynamics simulation study of single chains and melts

A molecular dynamics study of the effect of increasing molecular chain stiffness on the dynamic properties of single linear chains and polymer melts is presented. The chain stiffness is controlled by a bending potential. By means of a normal mode analysis the systematic crossover behavior of coarse-grained linear polymer systems from Rouse modes to bending modes with increasing mode number p is presented systematically for the first time via simulation data. The magnitude and the onset of the region where crossover behavior occurs is investigated in dependence of a systematic variation of the chains’ persistence lengths. For long wavelength modes the well-known p−2 behavior is observed which represents the Rouse scaling, whereas for the bending modes one observes a distinct p−4 scaling of the mean square mode amplitudes and the relaxation times. Additionally, the effect of this crossover behavior on the monomer dynamics given by their mean square displacements is investigated. The findings are contrasted with previous simulation studies of semiflexible chain behavior and it is shown that those studies—due to too small persistence lengths Lp—were actually limited to the crossover regime where both, Rouse and bending modes contribute to the chain dynamics, and no distinct p−4 scaling can be observed. Using an expansion of the monomer position vector, a simple theory of the observed scaling behavior is proposed which allows for deriving analytic expressions that describe the presented simulation data very well.

Association of polymorphisms of the apolipoprotein(a) gene with lipoprotein(a) levels and myocardial infarction.

Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (<or=8 PN 66.1 mg/dL versus >8 PN 8.7 mg/dL; P<0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (<or=22 K4 repeats; OR 1.47 for men and 1.69 for women; P<0.002) and in women with <or=8 PN repeats (OR 1.46, P=0.009). Interestingly, in women, the frequent haplotype with <or=8 PN and <or=22 K4 repeats, which is related to high levels of small Lp(a) particles, resulted in an elevated OR for MI (1.79; P=0.01) independently of Lp(a) serum concentration. The K4 and PN repeat polymorphisms largely explain the high variability of serum Lp(a) levels. A haplotype with <or=8 PN and <or=22 K4 repeats is characterized by high concentrations of small Lp(a) particles. Our observation that this haplotype was associated with MI independently of Lp(a) serum levels may suggest that Lp(a) particle size in addition to its concentration may modulate MI risk in women.

Electronic Localization and Bandtail Hopping Charge Transport

Our previous modeling of hopping in localized bandtails has improved the description of electrical transport in amorphous carbon films and elemental amorphous semiconductors. This model is further developed to understand the role of the wavefunction localization radius γ -1 and density of states (DOS) distribution N(E) on the T dependence of the conductivity and the thermopower in disordered solids. Using values of the localization parameter LP = N(E F ) γ -3 in the range from 10 -4 to 1 eV -1 , our simulations show that: (i) The assumption of extremely low LP values made in previous works is often irrelevant for comparison with experiments. (ii) For low temperatures or large LP values, a linear relation holds between the dominant transport energy (E t - E F ) and temperature (with a stronger dependence as LP decreases) while a logarithmic dependence is obtained in the high-T range for small LP values. (iii) In the weak localization condition, a T-independent thermopower S(T) is predicted with an absolute value of eS/k (LP) -1/3 . (iv) The relationship σT 1/2 = σ 00 exp (-(T 0 /T) 1/4 holds, as expected for 3D hopping, over a wide temperature range (50-500 K); using the LP value as a parameter, the positive linear correlation between In (σ 00 ) and T 1/4 0 is a signature of an exponential localized bandtail distribution, clearly incompatible with Mott's hypothesis for 'Variable Range Hopping' in an energy-independent DOS distribution near the Fermi level.

Water permeability of plasma membranes of cultured rice, grape, and CH27 cells measured dielectrically.

The capacitance of suspensions of cultured rice cells (Oryza sativa L. ssp. japonica), grape cells (Vitis sp.), and CH27 cells originated from murine B-cell lymphoma was measured in the frequency range of 0.2 to 10 MHz. The relationship between the increase in capacitance caused by the presence of cells at 0.4 MHz, delta C, and the cell density was linear. Measurement of capacitance was useful in measurement of transitional changes in cell volume under external osmotic stress when sucrose was added. From the course of volume changes with such stress, the water permeabilities of the plasma membrane, Lp, were measured to be 0.015, 0.020, and 0.090 pm/(s.Pa) at 25 degrees C, for rice cells, grape cells, and CH27 cells, respectively. The smaller Lp for plant cells seemed to explain why preservation of plant cells by freezing is more difficult than for animal cells. From the temperature dependence of Lp, the apparent activation energies were calculated to be 12.0 +/- 2.9 and 13.0 +/- 5.2 kcal/mol for rice cells and CH27 cells, respectively.

Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer. Studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy.

The two major subclasses of HDL contain apo A-I only (Lp A-I) or both apo A-I and apo A-II (Lp A-I/A-II). We have carried out experiments to quantify the participation of Lp A-I and Lp A-I/A-II in the neutral lipid transfer reaction in normal and hypertriglyceridemic subjects. Thirteen hypertriglyceridemic subjects were studied before and after fenofibrate therapy. Fenofibrate treatment resulted in decreases in total cholesterol, triglycerides (TG), and VLDL cholesterol of 19%, 48%, and 70%, respectively, and a 28% increase in HDL cholesterol, with no significant change in the proportion of Lp A-I and Lp A-I/A-II particles. The abundance of cholesteryl ester transfer protein (CETP) mRNA in peripheral adipose tissue decreased with treatment in four of five patients studied; however, no change occurred in plasma CETP mass. Using an isotopic transfer assay, we demonstrated that both Lp A-I and Lp A-I/A-II participated in the CE transfer reaction, with no change after fenofibrate therapy. This finding suggests that the marked increase in HDL cholesterol during fenofibrate therapy is due to normalization of plasma TG and hence decreased opportunity for mass transfer of lipid between HDL and TG-rich proteins in vivo. In this population of hypertriglyceridemic subjects, CETP was distributed in both the Lp A-I and Lp A-I/A-II subfractions of HDL, with preferential association with the smaller Lp A-I poor. In contrast, in nine normal subjects studied, negligible amounts of CETP were associated with Lp A-I/A-II. Nonetheless, the Lp A-I/A-II fraction of HDL contributed significantly to total CE mass transfer in normolipidemic plasma. Lp A-I/A-II is an efficient donor for CE transfer to TG-rich lipoproteins, and its low affinity for CETP may in fact facilitate neutral lipid transfer either by a shuttle mechanism or by formation of a ternary complex.

PAF-acetylhydrolase activity on Lp(a) before and during Cu 2+-induced oxidative modification in vitro

In human plasma with no detectable lipoprotein (a) (Lp(a)) levels, platelet-activating factor acetylhydrolase (PAF-AH) is associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) with a distribution of 70 and 30%, respectively. We used a density gradient ultracentrifugation procedure to study the distribution of PAF-AH among lipoproteins in plasma containing Lp(a). Lp(a) was migrated as a broad band in the density region of d = 1.050 – 1.100 g/ml, independently of its isoform size. In plasma with Lp(a) levels 30–40 mg/dl or 80–100 mg/dl the PAF-AH activity migrated in this density region was 4 or 9% higher as compared to plasma having Lp(a) levels < 8 mg/dl ( P < 0.05 or P < 0.02, respectively). Enrichment of plasma with the dense LDL 5 subfraction, significantly increased the enzyme activity distributed in this density region. The physicochemical properties of the Lp(a)-associated PAF-AH activity were similar to those reported for the LDL-associated enzyme. However, the kinetic constants in small Lp(a) isoforms were significantly higher compared to large ones. Isoform F had apparent Km = 117 ± 9 μmol/l and V max = 94 ± 5 nmol/mg protein per min, and isoform S2 S3 had apparent K m = 36 ± 9 μmol/l and V max = 25 ± 5 nmol/mg protein per min. Removal of apolipoprotein (a) (apo(a)) from Lp(a) by reductive cleavage with dithiothreitol, slightly affected the amount of PAF-AH existing on Lp(a) since, only 15 ± 5% of the total enzyme activity dissociated from its particle after density gradient ultracentrifugation. During Cu 2+-induced Lp(a) oxidation, the PAF-AH activity decreased from 10.90 ± 2.30 nmol/mg per min to 2.57 ± 0.56 nmol/mg per min 4 h after the initiation of the oxidation ( P < 0.001). The apparent K m of the enzyme remained essentially unchanged during oxidation, whereas V max was significantly decreased from 58.6 ± 7.8 nmol/mg protein per min to 38.2 ± 8.7 nmol/mg protein per min ( P < 0.03). An extensive hydrolysis of the endogenous phosphatidylcholine (PC) to lysophosphatidylcholine (Lyso-PC) was observed during Lp(a) oxidation, since the Lyso-PC/sphingomyelin molar ratio at the end of oxidation (0.55 ± 0.09) was significantly higher than that before oxidation (0.19 ± 0.01, P < 0.001). Our results show that the existence of Lp(a) in plasma alters the distribution of PAF-AH among the other lipoproteins. Apo(a) seems to affect the association of the enzyme with Lp(a) but does not bind itself to PAF-AH. During Lp(a) oxidation, the PAF-AH activity decreases whereas an extensive hydrolysis of the endogenous PC to Lyso-PC is observed which is possibly due to the PAF-AH activity.

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T 4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T 4 therapy. The mean concentration of LDL decreased significantly ( P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly ( P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged ( P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T 4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).

Effect of parasitic capacitance and inductance on the dynamics and noise of dc superconducting quantum interference devices

Practical thin-film dc superconducting quantum interference devices (SQUIDs) are often built with an integrated input coil which leads to the formation of various parasitic elements. We have designed and fabricated several square washer-shaped dc SQUID test devices with various amounts of parasitic capacitance formed by covering the washer slits with superconducting coverplates of various widths. In the simplest approximation, the parasitic capacitance Cp appears entirely across the Josephson junctions; in a better approximation, Cp divides the total inductance into two parts, an effective SQUID loop inductance L and a small parasitic inductance Lp. For both models, noise-free and noise-rounded current-voltage and voltage-flux characteristics are calculated for various values of the ratios L/Lp and Cp/C, where C is the Josephson junction capacitance. The SQUID dynamics are significantly affected by Cp and Lp. The energy resolution ε at first deteriorates with increasing Cp for Cp/C ≲ 2, but as Cp/C becomes large, ε improves to less than twice the value for Cp/C ≊ 0. The optimal points of operation for large Cp, however, are found at voltages above the low-frequency resonance determined by L and Cp where the flux-to-voltage transfer function is low. Furthermore, for devices with Cp/C ≫ 1 and Lp≠0, the double-loop geometry leads to an additional resonance determined by Lp and C that appears at high frequencies. The energy resolution inside this high-frequency resonance is nearly independent of Cp and comparable to the energy resolution of a device having the same total inductance but with Cp/C ≪ 1. Extensive noise mappings on several different test devices have been carried out using a computer-controlled measurement system. The measured characteristics and noise performance are shown to be in good agreement with the simulations.

On the continuity of the Wiener-Hopf factorization operation

AbstractThe problem of passing from an L∞ function to a Wiener-Hopf factorization is considered. It is shown that a small L∞ perturbation which does not change the factorization indices will lead to small Lp (1 &lt; p &lt; ∞) perturbations in the Wiener-Hopf factors, but can lead to large L∞ perturbations, unless the derivatives are controlled during the perturbation.

Mucosal mast cells: III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells

Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin, apigenin, chrysin, and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Unbounded operators and random Fourier series

0·0. Let G be an infinite compact abelian group with dual X. Parseval's identity shows that if f ∈ C(G) and ω ∈ l∞(X) then . Edwards has shown in (2) that L2(G) here cannot, in general, be replaced by any smaller Lp(G) space. Precisely: there exist f ∈ C(G) and ω: X → {± 1} such that . We strengthen this result by showing much more can be said about the summability of the Fourier series of f than . For example, when G is the circle group, f can be chosen to also satisfyThe functions introduced here and called darts, generalize this type of series condition.

SHONA LITURGICAL SERIES: 29 small LP records. Mambo Press, P.O. Box 779, Gwelo, Rhodesia, 70c each

SHONA LITURGICAL SERIES: 29 small LP records. Mambo Press, P.O. Box 779, Gwelo, Rhodesia, 70c each

A Study of Holders Inequality in New Spaces

The central attraction of this paper is to prove holders inequality in some new spaces such as Grand Lebesgue Space LP). Small Lebesgue space LP)' and Banach Lattice space XP.Key words: Holders InequalityDOI: http://dx.doi.org/10.3126/jie.v8i1-2.5119Journal of the Institute of Engineering Vol. 8, No. 1&amp;2, 2010/2011Page: 259-262Uploaded Date: 20 July, 2011

Letters to the editor: An interpretive input routine for linear programming

In this descriptive article an input code is presented which greatly simplifies data input to any linear programming solution routine, for subsequent use either as a predagogical device or for solving rather small LP problems. This latter (limited) use derives not at all from inherent limitations in the code itself, but from an efficiency evaluation: large LP problems would doubtless benefit from an input system more suited for bulk data handling than the input code described. From a user's standpoint, input appears almost exactly as a textbook presentation of the LP problem (limited only by a keypunch's inability to write subscripts, etc.). The input interpreter scans columnwise, thus no fixed format data preparation is required. The user may also, under very general requirements only, liberally use editorial comments throughout the input deck as an aid in identification, e.g., of row constraints. The article includes examples of input, output from a solution routine presently in use, and a skeleton flowchart of the input interpreter.