Artykuły w czasopismach: „Restricted Loops”

1

Chen, Yuanlong, i Xiaoying Wu. "Chaos on Discrete Neural Network Loops with Self-Feedback". Discrete Dynamics in Nature and Society 2020 (30.11.2020): 1–9. http://dx.doi.org/10.1155/2020/3528684.

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In this paper, the complex dynamical behaviors in a discrete neural network loop with self-feedback are studied. Specifically, an invariant closed set of the system of neural network loops is built and the subsystem restricted on this invariant closed set is topologically conjugate to a two-sided symbolic dynamical system which has two symbols. In the end, some illustrative numerical examples are given to demonstrate our theoretical results.

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2

Sempere, José M. "On Compensation Loops in Genomic Duplications". International Journal of Foundations of Computer Science 31, nr 01 (styczeń 2020): 133–42. http://dx.doi.org/10.1142/s0129054120400092.

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In this paper, we investigate the compensation loops, a DNA rearrangement in chromosomes due to unequal crossing over. We study the effect of compensation loops over the gene duplication, and we formalize it as a restricted case of gene duplication in general. We study this biological process under the point of view of formal languages, and we provide some results about the languages defined in this way.

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Dolenc, Jožica, Beat H. Meier, Victor H. Rusu i Wilfred F. van Gunsteren. "Investigation of the structural preference and flexibility of the loop residues in amyloid fibrils of the HET-s prion". Physical Chemistry Chemical Physics 18, nr 8 (2016): 5860–66. http://dx.doi.org/10.1039/c6cp00057f.

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Hoang, Tuan, i Eliot Fried. "Influence of a spanning liquid film on the stability and buckling of a circular loop with intrinsic curvature or intrinsic twist density". Mathematics and Mechanics of Solids 23, nr 1 (3.10.2016): 43–66. http://dx.doi.org/10.1177/1081286516666135.

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A variational model is used to study the behavior of a flexible but inextensible loop spanned by a liquid film, with the objective of explaining the stability and buckling of flat circular configurations. Loops made from filaments with intrinsic curvature and/or intrinsic twist density are considered, but attention is restricted to filaments with circular cross sections and uniform mechanical properties. Loops made with intrinsic curvature but no intrinsic twist density exhibit in-plane and out-of-plane buckling modes corresponding to stable solution branches that bifurcate from the branch of flat circular solutions and out-of-plane buckling occurs at a lower value of the dimensionless surface tension of the liquid film than does in-plane buckling. Additionally, however, the destabilizing influence of the intrinsic curvature can be countered by increasing the torsional rigidity relative to the flexural rigidity. For a loop with both intrinsic curvature and intrinsic twist density, only one branch of stable solutions bifurcates from the flat circular solution branch, the in-plane and out-of-plane buckling modes are intertwined, and bifurcation occurs at a value of the dimensionless surface tension less than that governing the behavior of loops made from filaments that are intrinsically rectilinear. Moreover, increasing the torsional rigidity relative to the flexural rigidity has no or little stabilizing effect if the loop is either too short or too long and, in contrast to what occurs for loops with only intrinsic curvature, if the intrinsic twist density is sufficiently large then the destabilizing influence of the intrinsic curvature cannot be countered by increasing the torsional rigidity relative to the flexural rigidity, regardless of the length of the loop.

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Růžičková, M., P. Hájek, R. Všolák, J. Berka i J. Šmejkalová. "New Experimental Loops for Research Reactor LVR-15". Materials Science Forum 595-598 (wrzesień 2008): 559–70. http://dx.doi.org/10.4028/www.scientific.net/msf.595-598.559.

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Two experimental loops for operation in research reactor LVR-15 in ÚJV Řež are recently under preparation: High Temperature Helium Loop (HTHL) and SuperCritical Water Loop (SCWL). Pure helium will be used as working medium in HTHL and its main physical parameters are: operating pressure 7MPa, max. temperature in the test section 900°C and flow rate 36kg/h. HTHL will include helium purification system, system for dosage of impurities (e.g. CO2, H2, H2O, O2, N2 etc.) and helium sampling. Helium purification experiments and testing of materials in simulated HTR conditions will take place in HTHL in the future. Main parameters of the SCWL are 25MPa, max. temperature in the test section 600°C, flow rate max. 200kg/h. SCWL will be used for corrosion tests of candidate materials, studies of water radiolysis at supercritical conditions and for testing of water chemistry suitable for operation. Both loops possess an irradiation channel with quite complicated internals design, whose complexity is imposed by current constraints on constructional materials of nuclear experimental devices, which limit the choice and maximum surface temperature of material of construction to 500°C for austenitic stainless steel. The working temperature will thus be attained only in a restricted volume of the test section. The channel internals will be briefly described. The mentioned loops will represent novel experimental devices, whose objective is to gain and extend knowledge on materials and environment performance under the influence of radiation.

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Cox, Nicholas J. "Speaking Stata: Loops, again and again". Stata Journal: Promoting communications on statistics and Stata 20, nr 4 (grudzień 2020): 999–1015. http://dx.doi.org/10.1177/1536867x20976340.

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Two commands in official Stata, foreach and forvalues, provide structures for looping through lists of values (variable names, numbers, arbitrary text) and repeating commands using members of those lists in turn. These commands may be used interactively, and none is restricted to use in Stata programs. They are explained and compared in some detail with a variety of examples. In addition, a self-contained exposition is given on local macros, understanding of which is needed for use of foreach and forvalues. This column is a revision of the column “How to face lists with fortitude”, which appeared in Stata Journal 2: 202–222 (2002). (The bizarre bibliographical details are too, too extraordinary not to be flagged but were pure happenstance.) The presentation here has been trimmed of now historic content and corrected, improved, and updated in several minor details.

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Reugels, Alexander M., Roman Kurek, Ulrich Lammermann i Hans Bünemann. "Mega-introns in the Dynein Gene DhDhc7(Y) on the Heterochromatic Y Chromosome Give Rise to the Giant Threads Loops in Primary Spermatocytes of Drosophila hydei". Genetics 154, nr 2 (1.02.2000): 759–69. http://dx.doi.org/10.1093/genetics/154.2.759.

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Abstract The heterochromatic Y chromosomes of several Drosophila species harbor a small number of male fertility genes (fertility factors) with several unusual features. Expression of their megabase-sized loci is restricted to primary spermatocytes and correlates with the unfolding of species-specific lampbrush loop-like structures resulting from huge transcripts mainly derived from clusters of loop-specific Y chromosomal satellites. Otherwise, there is evidence from genetic mapping and biochemical experiments that at least two of these loops, Threads in Drosophila hydei and kl-5 in D. melanogaster, colocalize with the genes for the axonemal dynein β heavy chain proteins DhDhc7(Y) and Dhc-Yh3, respectively. Here, we make use of particular Threads mutants with megabase-sized deletions for direct mapping of DhDhc7(Y)-specific exons among the large clusters of satellite DNA within the 5.1-Mb Threads transcription unit. PCR experiments with exon-specific primer pairs, in combination with hybridization experiments with exon- and satellite-specific probes on filters with large PFGE-generated DNA fragments, offer a simple solution for the long-lasting paradox between megabase-sized loops and protein-encoding transcription units; the lampbrush loops Threads and the DhDhc7(Y) gene are one and the same transcription unit, and the giant size of the DhDhc7(Y) gene as well as its appearance as a giant lampbrush loop are merely the result of transcription of huge clusters of satellite DNA within some of its 20 introns.

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De Genst, Erwin, Karen Silence, Mehdi Arbabi Ghahroudi, Klaas Decanniere, Remy Loris, Jörg Kinne, Lode Wyns i Serge Muyldermans. "Strong in Vivo Maturation Compensates for Structurally Restricted H3 Loops in Antibody Repertoires". Journal of Biological Chemistry 280, nr 14 (19.01.2005): 14114–21. http://dx.doi.org/10.1074/jbc.m413011200.

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Kruth, Karina A., Mimi Fang, Dawne N. Shelton, Ossama Abu-Halawa, Ryan Mahling, Hongxing Yang, Jonathan S. Weissman i in. "Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia". Blood 129, nr 22 (1.06.2017): 3000–3008. http://dx.doi.org/10.1182/blood-2017-02-766204.

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Key PointsNext-generation functional genomics identifies B-cell development genes, pathways, and feedback loops that affect dex activity in B-ALL. Suppression of lymphoid-restricted PI3Kδ synergizes with dex in B-ALL by enhancing or restoring regulation of cell-death genes.

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10

Smith, G. P., i D. J. Ellar. "Mutagenesis of two surface-exposed loops of the Bacillus thuringiensis CryIC δ-endotoxin affects insecticidal specificity". Biochemical Journal 302, nr 2 (1.09.1994): 611–16. http://dx.doi.org/10.1042/bj3020611.

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Site-directed mutagenesis was used to determine the role of two surface-exposed loops (Gly-317-Phe-320 and Gln-374-Pro-377) in the insecticidal specificity of the Bacillus thuringiensis CryIC delta-endotoxin. Mutant toxins were generated by PCR using degenerate oligonucleotide primers, and expressed in Escherichia coli. More than 50 mutant toxins were screened for toxicity to the lepidopteran Spodoptera frugiperda Sf9 cell line using an in vitro lawn assay. A panel of these mutant toxins, which included toxic and non-toxic variants from both loops, was further screened for activity towards Aedes aegypti larvae. The activity of these mutants to Sf9 cells was quantified more precisely using a cell lysis assay. Three categories of mutants were identified: (1) those non-toxic to either Sf9 cells or Aedes aegypti larvae; (2) those fully toxic to both genera; and (3) those which were only toxic to Sf9 cells. For the first loop, the differential specificity was not restricted to any single residue. In the second loop, two mutant toxins with a Pro-377-->Ala substitution displayed this phenotype. The time dependence of toxicity towards Sf9 cells was examined using the same panel of mutants. All toxic mutants displayed an identical time course to the wild-type toxin, with the exception of the two Pro-377-->Ala mutants of the second loop. These toxins displayed a lower time dependence, no cell death occurring within the first hour of incubation. These results show that the two loops are important determinants of both the activity and specificity of the CryIC delta-endotoxin.

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Chintapalli, Sree V., Christopher J. R. Illingworth, Graham J. G. Upton, Sophie Sacquin-Mora, Philip J. Reeves, Hani S. Mohammedali i Christopher A. Reynolds. "Assessing the effect of dynamics on the closed-loop protein-folding hypothesis". Journal of The Royal Society Interface 11, nr 91 (6.02.2014): 20130935. http://dx.doi.org/10.1098/rsif.2013.0935.

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The closed-loop (loop-n-lock) hypothesis of protein folding suggests that loops of about 25 residues, closed through interactions between the loop ends (locks), play an important role in protein structure. Coarse-grain elastic network simulations, and examination of loop lengths in a diverse set of proteins, each supports a bias towards loops of close to 25 residues in length between residues of high stability. Previous studies have established a correlation between total contact distance (TCD), a metric of sequence distances between contacting residues (cf. contact order), and the log-folding rate of a protein. In a set of 43 proteins, we identify an improved correlation ( r 2 = 0.76), when the metric is restricted to residues contacting the locks, compared to the equivalent result when all residues are considered ( r 2 = 0.65). This provides qualified support for the hypothesis, albeit with an increased emphasis upon the importance of a much larger set of residues surrounding the locks. Evidence of a similar-sized protein core/extended nucleus (with significant overlap) was obtained from TCD calculations in which residues were successively eliminated according to their hydrophobicity and connectivity, and from molecular dynamics simulations. Our results suggest that while folding is determined by a subset of residues that can be predicted by application of the closed-loop hypothesis, the original hypothesis is too simplistic; efficient protein folding is dependent on a considerably larger subset of residues than those involved in lock formation.

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Shayakul, C., M. A. Knepper, C. P. Smith, S. R. DiGiovanni i M. A. Hediger. "Segmental localization of urea transporter mRNAs in rat kidney". American Journal of Physiology-Renal Physiology 272, nr 5 (1.05.1997): F654—F660. http://dx.doi.org/10.1152/ajprenal.1997.272.5.f654.

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Renal epithelia express at least two distinct urea transporter mRNAs, termed UT1 and UT2, that are derived from a single UT gene by alternative splicing. Previous immunolocalization studies using a polyclonal antibody that does not distinguish between the protein products of these two transcripts revealed that expression of urea transporter protein is restricted to inner medullary collecting ducts and descending thin limbs of Henle's loop. To identify which transcripts account for protein expression in these two structures, we carried out reverse transcription-polymerase chain reaction studies in microdissected structures using UT1- and UT2-specific primers. UT1 mRNA was detected only in the inner medullary collecting duct, consistent with its identification as the vasopressin-regulated urea transporter. In contrast, UT2-mRNA was detected in the late part of descending thin limbs of short loops of Henle and in the inner medullary part of descending thin limbs of long loops of Henle. This localization is consistent with the predicted role of UT2 in medullary urea recycling. Thus, in conjunction with foregoing physiological studies, our data indicate that these transporters play central roles in the urinary concentrating mechanism.

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13

Lin, Hai. "Relation between large dimension operators and oscillator algebra of Young diagrams". International Journal of Geometric Methods in Modern Physics 12, nr 04 (kwiecień 2015): 1550047. http://dx.doi.org/10.1142/s0219887815500474.

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The operators with large scaling dimensions can be labeled by Young diagrams. Among other bases, the operators using restricted Schur polynomials have been known to have a large N but nonplanar limit under which they map to states of a system of harmonic oscillators. We analyze the oscillator algebra acting on pairs of long rows or long columns in the Young diagrams of the operators. The oscillator algebra can be reached by a Inonu–Wigner contraction of the u(2) algebra inside of the u(p) algebra of p giant gravitons. We present evidences that integrability in this case can persist at higher loops due to the presence of the oscillator algebra which is expected to be robust under loop corrections in the nonplanar large N limit.

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Санина, В. А., Б. Х. Ханнанов, Е. И. Головенчиц i М. П. Щеглов. "Электрическая поляризация в ErCrO-=SUB=-3-=/SUB=-, индуцированная локальными полярными областями". Физика твердого тела 61, nr 3 (2019): 501. http://dx.doi.org/10.21883/ftt.2019.03.47242.286.

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AbstractElectric polarization in ErCrO_3 single crystals has been investigated in the temperature range of 5‒370 K. Ferroelectric ordering has not been found in any of the directions. However, electric polarization induced by restricted polar domains of structural origin has been observed. These domains are formed in the crystal matrix near impurity Bi^3+ ions partially substituting Er^3+ ions during the growth of single crystals by the method of spontaneous crystallization using solvent Bi_2O_3. The restricted polar domains form the superparaelectric state. Hysteresis loops with remanent polarization, both along the c axis and in the [110] directions, have been observed below some temperatures T _fr (in the frozen superparaelectric state). The polarization exists up to certain temperatures, which depend on the applied electric field orientation with respect to the crystal axes and exceed significantly temperature T _N of magnetic ordering. These temperatures correspond to the condition kT _fr ≈ E _A for activation barriers at the boundaries of the restricted polar domains.

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Zwick, Michael B., Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Paul W. H. I. Parren i Dennis R. Burton. "A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12". Journal of Virology 77, nr 12 (15.06.2003): 6965–78. http://dx.doi.org/10.1128/jvi.77.12.6965-6978.2003.

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ABSTRACT The V1/V2 and V3 loops are proximal to the CD4 binding site (CD4bs) of human immunodeficiency virus type 1 (HIV-1) gp120 and undergo conformational change upon CD4 receptor engagement by the HIV-1 envelope spike. Nearly all of the reported monoclonal antibodies (MAbs) against the CD4bs exhibit a very limited capacity to neutralize HIV-1. However, one such human MAb, immunoglobulin G1 (IgG1) b12, is uniquely able to neutralize primary isolates across subtypes with considerable potency. The molecular basis for the anti-HIV-1 activity of b12 is not fully understood but is relevant to vaccine design. Here we describe a novel human MAb, 4KG5, whose binding to monomeric gp120 is moderately enhanced by IgG1 b12. In sharp contrast, 4KG5 binding to gp120 is inhibited by soluble CD4 (sCD4) and by all other (n = 14) anti-CD4bs MAbs tested. 4KG5 is unable to recognize gp120 in which either V1, V2, or V3 has been deleted, and MAbs against the V2 or V3 loops inhibit the binding of 4KG5 to gp120. Moreover, 4KG5 is able to inhibit the binding of the CD4-induced MAbs 17b and X5 in the absence of sCD4, whereas 17b and X5 only weakly inhibit the binding of 4KG5 to gp120. Mutagenesis of gp120 provides further evidence of a discontinuous epitope of 4KG5 that is formed by the V1/V2 loop, the V3 loop, and a portion of the bridging sheet (C4). 4KG5 was isolated as a single-chain Fv from a phage display library constructed from the bone marrow of an HIV-1-seropositive subject (FDA2) whose serum neutralizes HIV-1 across subtypes. Despite its source, we observed no significant neutralization with 4KG5 against the autologous (R2) virus and several other strains of HIV-1. The results suggest a model in which antibody access to the CD4bs on the envelope spike of HIV-1 is restricted by the orientation and/or dynamics of the V1/V2 and V3 loops, and b12 avoids these restrictions.

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Cheng, Lingling, Wenjie Wang, Yao Yao i Qianwen Sun. "Mitochondrial RNase H1 activity regulates R-loop homeostasis to maintain genome integrity and enable early embryogenesis in Arabidopsis". PLOS Biology 19, nr 8 (3.08.2021): e3001357. http://dx.doi.org/10.1371/journal.pbio.3001357.

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Plant mitochondrial genomes undergo frequent homologous recombination (HR). Ectopic HR activity is inhibited by the HR surveillance pathway, but the underlying regulatory mechanism is unclear. Here, we show that the mitochondrial RNase H1 AtRNH1B impairs the formation of RNA:DNA hybrids (R-loops) and participates in the HR surveillance pathway in Arabidopsis thaliana. AtRNH1B suppresses ectopic HR at intermediate-sized repeats (IRs) and thus maintains mitochondrial DNA (mtDNA) replication. The RNase H1 AtRNH1C is restricted to the chloroplast; however, when cells lack AtRNH1B, transport of chloroplast AtRNH1C into the mitochondria secures HR surveillance, thus ensuring the integrity of the mitochondrial genome and allowing embryogenesis to proceed. HR surveillance is further regulated by the single-stranded DNA-binding protein ORGANELLAR SINGLE-STRANDED DNA BINDING PROTEIN1 (OSB1), which decreases the formation of R-loops. This study uncovers a facultative dual targeting mechanism between organelles and sheds light on the roles of RNase H1 in organellar genome maintenance and embryogenesis.

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Mata, A. M., I. Matthews, R. E. A. Tunwell, R. P. Sharma, A. G. Lee i J. M. East. "Definition of surface-exposed and trans-membranous regions of the (Ca2+-Mg2+)-ATPase of sarcoplasmic reticulum using anti-peptide antibodies". Biochemical Journal 286, nr 2 (1.09.1992): 567–80. http://dx.doi.org/10.1042/bj2860567.

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Peptides have been synthesized representing parts of the transduction, phosphorylation, nucleotide-binding and hinge domains of the (Ca(2+)-Mg2+)-ATPase of skeletal muscle sarcoplasmic reticulum (SR), and corresponding to segments of all of the postulated short inter-membranous loops of the (Ca(2+)-Mg2+)-ATPase (residues 77-88, 277-287, 780-791, 808-818, 915-924 and 949-958). A number of antibodies raised to these peptides have been shown to bind to the ATPase, defining surface-exposed regions. Many of these are concentrated in the phosphorylation and nucleotide-binding domains, suggesting that these domains could be exposed on the top surface of the ATPase. The cytoplasmic location of the loop containing residues 808-818 was confirmed by the finding that proteinase K treatment of intact SR vesicles enhanced the binding of antibodies against this segment. These findings support the 10-alpha-helix model of the ATPase. These results also suggest that only inter-membranous loops larger than about 20 residues are likely to be detected by immunological methods in transmembranous proteins. Binding of anti-peptide antibodies to proteolytic fragments of the ATPase has been used to define the domain structure of the enzyme. Some of the anti-peptide antibodies have been characterized by studying their binding to sets of hexameric peptides synthesized on plastic pegs. A wide pattern of responses is observed, with a restricted range of epitopes being recognized by each anti-peptide antibody.

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Pancera, Marie, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski i Richard Wyatt. "Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with aHeterologous Trimerization Motif: Characterization and Ligand Binding Analysis". Journal of Virology 79, nr 15 (1.08.2005): 9954–69. http://dx.doi.org/10.1128/jvi.79.15.9954-9969.2005.

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ABSTRACT The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, mediates binding to the viral receptors and, along with the transmembrane glycoprotein gp41, is a major target for neutralizing antibodies. We asked whether replacing the gp41 fusion/trimerization domain with a stable trimerization motif might lead to a more stable gp120 trimer that would be amenable to structural and immunologic analysis. To obtain stable gp120 trimers, a heterologous trimerization motif, GCN4, was appended to the C terminus of YU2gp120. Biochemical analysis indicated that the gp120-GCN4 trimers were superior to gp140 molecules in their initial homogeneity, and trilobed structures were observable by electron microscopy. Biophysical analysis of gp120-GCN4 trimers by isothermal titration calorimetry (ITC) and ultracentrifugation analyses indicated that most likely two molecules of soluble CD4 could bind to one gp120-GCN4 trimer. To further examine restricted CD4 stoichiometric binding to the gp120-GCN4 trimers, we generated a low-affinity CD4 binding trimer by introducing a D457V change in the CD4 binding site of each gp120 monomeric subunit. The mutant trimers could definitively bind only one soluble CD4 molecule, as determined by ITC and sedimentation equilibrium centrifugation. These data indicate that there are weak interactions between the gp120 monomeric subunits of the GCN4-stabilized trimers that can be detected by low-affinity ligand sensing. By similar analysis, we also determined that removal of the variable loops V1, V2, and V3 in the context of the gp120-GCN4 proteins allowed the binding of three CD4 molecules per trimer. Interestingly, both the gp120-GCN4 variants displayed a restricted stoichiometry for the CD4-induced antibody 17b of one antibody molecule binding per trimer. This restriction was not evident upon removal of the variable loops V1 and V2 loops, consistent with conformational constraints in the wild-type gp120 trimers and similar to those inherent in the functional Env spike. Thus, the gp120-GCN4 trimers demonstrate several properties that are consistent with some of those anticipated for gp120 in the context of the viral spike.

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Yang, Zhi-yong, Bimal K. Chakrabarti, Ling Xu, Brent Welcher, Wing-pui Kong, Kwanyee Leung, Amos Panet, John R. Mascola i Gary J. Nabel. "Selective Modification of Variable Loops Alters Tropism and Enhances Immunogenicity of Human Immunodeficiency Virus Type 1 Envelope". Journal of Virology 78, nr 8 (15.04.2004): 4029–36. http://dx.doi.org/10.1128/jvi.78.8.4029-4036.2004.

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ABSTRACT Although the B clade of human immunodeficiency virus type 1 (HIV-1) envelopes (Env) includes five highly variable regions, each of these domains contains a subset of sequences that remain conserved. The V3 loop has been much studied for its ability to elicit neutralizing antibodies, which are often restricted to a limited number of closely related strains, likely because a large number of antigenic structures are generated from the diverse amino acid sequences in this region. Despite these strain-specific determinants, subregions of V3 are highly conserved, and the effects of different portions of the V3 loop on Env tropism and immunogenicity have not been well delineated. For this report, selective deletions in V3 were introduced by shortening of the stem of the V3 loop. These mutations were explored in combination with deletions of selected V regions. Progressive shortening of the stem of V3 abolished the immunogenicity as well as the functional activity of HIV Env; however, two small deletions on both arms of the V3 stem altered the tropism of the dualtropic 89.6P viral strain so that it infected only CXCR4+ cells. When this smaller deletion was combined with removal of the V1 and V2 loops and used as an immunogen in guinea pigs, the antisera were able to neutralize multiple independent clade B isolates with a higher potency. These findings suggest that highly conserved subregions within V3 may be relevant targets for eliciting neutralizing antibody responses, affecting HIV tropism, and increasing the immunogenicity of AIDS vaccines.

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Shan, Lu, Yufeng Tong, Tao Xie, Min Wang i Jinfeng Wang. "Restricted Backbone Conformational and Motional Flexibilities of Loops Containing Peptidyl−Proline Bonds Dominate the Enzyme Activity of Staphylococcal Nuclease†,‡". Biochemistry 46, nr 41 (październik 2007): 11504–13. http://dx.doi.org/10.1021/bi7009794.

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Et. al., Siva Sankara Phani T. ,. "CGRA MODULO SCHEDULING FOR ACHIEVING BETTER PERFORMANCE AND INCREASED EFFICIENCY". Turkish Journal of Computer and Mathematics Education (TURCOMAT) 12, nr 4 (10.04.2021): 1400–1413. http://dx.doi.org/10.17762/turcomat.v12i4.1225.

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Coarse-Grained Reconfigurable Architectures (CGRA) is an effective solution for speeding up computer-intensive activities due to its high energy efficiency and flexibility sacrifices. The timely implementation of CGRA loops was one of the hardest problems in the analysis. Modulo scheduling (MS) was productive in order to implement loops on CGRAs. The problem remains with current MS algorithms, namely to map large and irregular circuits to CGRAs over a fair period of compilation with restricted computational and high-performance routing tools. This is mainly due to an absence of awareness of major mapping limits and a time consuming approach to solving temporary and space-related mapping using CGRA buffer tools. It aims to boost the performance and robust compilation of the CGRA modulo planning algorithm. The problem with the CGRA MS is divided into time and space and the mechanisms between the two problems have to be reorganized. We have a detailed, systematic mapping fluid that addresses the algorithms of the time mapping problem with a powerful buffer algorithm and efficient connection and calculation limitations. We create a fast-stable algorithm for spatial mapping with a retransmission and rearrangement mechanism. With higher performance and quicker build-up time, our MS algorithm can map loops to CBGRA. The results show that, given the same compilation budget, our mapping algorithm results in a better rate for compilation. The performance of this method will be increased from 5% to 14%, better than the standard CGRA mapping algorithms available.

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Vandenbark, Arthur A., Nicole Culbertson, Tom Finn, David Barnes, Abigail Buenafe, Gregory G. Burrows, Sandra Law, Yuan K. Chou i Halina Offner. "Human TCR as Antigen: Homologies and Potentially Cross-Reactive HLA-DR2-Restricted Epitopes Within the AV and BV CDR2 Loops". Critical Reviews™ in Immunology 20, nr 1 (2000): 28. http://dx.doi.org/10.1615/critrevimmunol.v20.i1.30.

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Silva Cascales, Helena, Kamila Burdova, Anna Middleton, Vladislav Kuzin, Erik Müllers, Henriette Stoy, Laura Baranello, Libor Macurek i Arne Lindqvist. "Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate PLK1". Life Science Alliance 4, nr 3 (5.01.2021): e202000980. http://dx.doi.org/10.26508/lsa.202000980.

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Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2 phase, but why active Cyclin A2-CDK2 during the S phase does not trigger mitotic kinase activation remains unclear. Here, we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. Expression of predominately cytoplasmic Cyclin A2 or phospho-mimicking PLK1 T210D can partially rescue a G2 arrest caused by Cyclin A2 depletion. Cytoplasmic presence of Cyclin A2 is restricted by p21, in particular after DNA damage. Cyclin A2 chromatin association during DNA replication and additional mechanisms contribute to Cyclin A2 localisation change in the G2 phase. We find no evidence that such mechanisms involve G2 feedback loops and suggest that cytoplasmic appearance of Cyclin A2 at the S/G2 transition functions as a trigger for mitotic kinase activation.

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Blevins, Sydney J., Brian G. Pierce, Nishant K. Singh, Timothy P. Riley, Yuan Wang, Timothy T. Spear, Michael I. Nishimura, Zhiping Weng i Brian M. Baker. "How structural adaptability exists alongside HLA-A2 bias in the human αβ TCR repertoire". Proceedings of the National Academy of Sciences 113, nr 9 (16.02.2016): E1276—E1285. http://dx.doi.org/10.1073/pnas.1522069113.

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How T-cell receptors (TCRs) can be intrinsically biased toward MHC proteins while simultaneously display the structural adaptability required to engage diverse ligands remains a controversial puzzle. We addressed this by examining αβ TCR sequences and structures for evidence of physicochemical compatibility with MHC proteins. We found that human TCRs are enriched in the capacity to engage a polymorphic, positively charged “hot-spot” region that is almost exclusive to the α1-helix of the common human class I MHC protein, HLA-A*0201 (HLA-A2). TCR binding necessitates hot-spot burial, yielding high energetic penalties that must be offset via complementary electrostatic interactions. Enrichment of negative charges in TCR binding loops, particularly the germ-line loops encoded by the TCR Vα and Vβ genes, provides this capacity and is correlated with restricted positioning of TCRs over HLA-A2. Notably, this enrichment is absent from antibody genes. The data suggest a built-in TCR compatibility with HLA-A2 that biases receptors toward, but does not compel, particular binding modes. Our findings provide an instructional example for how structurally pliant MHC biases can be encoded within TCRs.

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Nicoletti, Rodrigo, i Robert Liebich. "Analysis of long wind turbine blades with shape memory alloy wires in super-elastic phase". Journal of Intelligent Material Systems and Structures 29, nr 15 (5.07.2018): 3108–23. http://dx.doi.org/10.1177/1045389x18783078.

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In this work, shape memory alloy wires are modeled and included in the model of a wind turbine blade, in order to numerically study their effect on blade vibrations under operating conditions. The blade is modeled using finite elements considering flapwise, edgewise, and torsional motion subjected to the effects of rotation and to a normal wind profile. The shape memory alloy wires are modeled in the super-elastic phase, thus presenting a hysteresis loop as a function of strain and ambient temperature. Such a hysteretic behavior of the shape memory alloy material adds damping to the structure that it is attached to. The numerical results show that inserting shape memory alloy wires in the wind turbine blade presents drawbacks, because the excitation level of the normal wind profile is not big enough for the blade to present significant strain. Hence, the hysteresis loops in the shape memory alloy material mounted on the blade have small areas which, consequently, reduce the amount of damping added to the blade. Besides, the added damping is restricted to the upper 30% of the blade (area of higher strain in the blade).

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Klimpel, G. R., A. K. Chopra, K. E. Langley, J. Wypych, C. A. Annable, D. Kaiserlian, P. B. Ernst i J. W. Peterson. "A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin." Journal of Experimental Medicine 182, nr 6 (1.12.1995): 1931–42. http://dx.doi.org/10.1084/jem.182.6.1931.

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The role of stem cell factor (SCF) and its receptor (c-kit) in the intestinal secretory response to cholera toxin (CT) was investigated using a ligated intestinal loop model in mice having mutations in the dominant white spotting (W) locus and the steel (Sl) locus. W/Wv mice, which express an aberrant form of the c-kit protein, failed to give an intestinal secretory response after luminal CT challenge. In contrast, W/Wv mice and their control littermates had equivalent intestinal secretory responses to Escherichia coli heat-stable enterotoxin (STa). Sl/Sld mice, which express only a soluble truncated form of SCF, also gave a significantly reduced intestinal secretory response to CT when compared to the secretory response of their littermate controls. The unresponsiveness of W/Wv mice to CT was restricted to the intestinal tract since these mice had foot pad swelling responses to CT challenge that were equivalent to their littermate controls. Restoration of mast cells in W/Wv mice by bone marrow transplantation of control littermate bone marrow did not reverse the CT-unresponsiveness of the intestinal tract. Histological evaluation of the gastrointestinal tract from W/Wv mice showed a normal distribution of enterochromaffin cells (ECC). CT challenge of either ligated intestinal loops from C57B1/6 mice or a mouse intestinal epithelial cell line (MODE-K) resulted in elevated levels of mRNA for SCF. MODE-K cells exposed to CT also had enhanced expression of c-kit. Finally, fluid obtained from CT-challenged ligated intestinal loops from C57B1/6 mice contained significant levels of SCF. Taken together, the above results suggest that CT-induced intestinal secretory responses are dependent upon SCF-c-kit interactions. These interactions appear to be induced as a consequence of CT stimulation of the intestinal tract and may also play a role in the development or functionality of the enteric nervous system.

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Iordanov, Iordan, Marie Renault, Valérie Réat, Patrick D. Bosshart, Andreas Engel, Olivier Saurel i Alain Milon. "Dynamics of Klebsiella pneumoniae OmpA transmembrane domain: The four extracellular loops display restricted motion behavior in micelles and in lipid bilayers". Biochimica et Biophysica Acta (BBA) - Biomembranes 1818, nr 9 (wrzesień 2012): 2344–53. http://dx.doi.org/10.1016/j.bbamem.2012.05.004.

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Grant, Ethan P., Massimo Degano, Jean-Pierre Rosat, Steffen Stenger, Robert L. Modlin, Ian A. Wilson, Steven A. Porcelli i Michael B. Brenner. "Molecular Recognition of Lipid Antigens by T Cell Receptors". Journal of Experimental Medicine 189, nr 1 (4.01.1999): 195–205. http://dx.doi.org/10.1084/jem.189.1.195.

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The T cell antigen receptor (TCR) mediates recognition of peptide antigens bound in the groove of major histocompatibility complex (MHC) molecules. This dual recognition is mediated by the complementarity-determining residue (CDR) loops of the α and β chains of a single TCR which contact exposed residues of the peptide antigen and amino acids along the MHC α helices. The recent description of T cells that recognize hydrophobic microbial lipid antigens has challenged immunologists to explain, in molecular terms, the nature of this interaction. Structural studies on the murine CD1d1 molecule revealed an electrostatically neutral putative antigen-binding groove beneath the CD1 α helices. Here, we demonstrate that α/β TCRs, when transferred into TCR-deficient recipient cells, confer specificity for both the foreign lipid antigen and CD1 isoform. Sequence analysis of a panel of CD1-restricted, lipid-specific TCRs reveals the incorporation of template-independent N nucleotides that encode diverse sequences and frequent charged basic residues at the V(D)J junctions. These sequences permit a model for recognition in which the TCR CDR3 loops containing charged residues project between the CD1 α helices, contacting the lipid antigen hydrophilic head moieties as well as adjacent CD1 residues in a manner that explains antigen specificity and CD1 restriction.

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Lunde, E., V. Lauvrak, I. B. Rasmussen, K. W. Schjetne, K. M. Thompson, T. E. Michaelsen, O. H. Brekke, L. M. Sollid, B. Bogen i I. Sandlie. "Troybodies and Pepbodies". Biochemical Society Transactions 30, nr 4 (1.08.2002): 500–506. http://dx.doi.org/10.1042/bst0300500.

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All antibodies (Abs) with effector function are produced in mammalian cells, whereas bacterial production is restricted to smaller targeting fragments (scFv and Fab) without effector functions. In this project, we isolated different peptides that bind one of several Ab effector molecules. We have developed bacterial expression vectors for direct cloning of these peptides as fusions to scFv and Fab, and have obtained targeting fragments that also have the ability to bind Ab effector molecules. Some of these fusions (pepbodies) may also initiate Ab effector functions. We have also genetically inserted T-cell epitopes into Abs with specificity for antigen-presenting cell (APC) surface molecules to target the Ab-T-cell epitope fusions (Troybodies) to APCs. The approach is to exchange loops in Ig constant domains with single copies of well-defined T-cell epitopes. We have shown that a number of such T-cell epitopes are loaded on to MHC class II on APCs and are presented to specific T-cells. An increase in T-cell activation of up to four orders of magnitude is achieved compared with synthetic peptide. Our current goal is to identify all the loops in all Ig constant domains that may be loaded with T-cell epitopes to produce a multi-vaccine.

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Tarahi Tabrizi, Shabnam, David B. Langley, Stephen J. Harrop, Anthony P. Duff i Robert D. Willows. "Structure of GUN4 fromChlamydomonas reinhardtii". Acta Crystallographica Section F Structural Biology Communications 71, nr 8 (29.07.2015): 1094–99. http://dx.doi.org/10.1107/s2053230x15012248.

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The genomes uncoupled 4 (GUN4) protein stimulates chlorophyll biosynthesis by increasing the activity of Mg-chelatase, the enzyme that inserts magnesium into protoporphyrin IX (PPIX) in the chlorophyll biosynthesis pathway. One of the roles of GUN4 is in binding PPIX and Mg-PPIX. In eukaryotes, GUN4 also participates in plastid-to-nucleus signalling, although the mechanism for this is unclear. Here, the first crystal structure of a eukaryotic GUN4, fromChlamydomonas reinhardtii, is presented. The structure is in broad agreement with those of previously solved cyanobacterial structures. Most interestingly, conformational divergence is restricted to several loops which cover the porphyrin-binding cleft. The conformational dynamics suggested by this ensemble of structures lend support to the understanding of how GUN4 binds PPIX or Mg-PPIX.

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Groma, István, Ildikó Szenthe, Éva Ódor, Bertalan Jóni, Gyula Zilahi, Zoltán Dankházi, Gábor Ribárik i Zoltán Hózer. "Evolution of dislocation microstructure in irradiated Zr alloys determined by X-ray peak profile analysis". Journal of Applied Crystallography 54, nr 1 (1.02.2021): 280–86. http://dx.doi.org/10.1107/s1600576720015885.

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During neutron irradiation of metals, owing to the enhanced number of vacancies and interstitial atoms, the climb motion of dislocations becomes significant at room temperature, leading to a recrystallization of the material. Moreover, the vacancies and interstitial atoms tend to form prismatic dislocation loops that play a crucial role in the plastic properties of the materials. X-ray peak profile analysis is an efficient nondestructive method to determine the properties of dislocation microstructure. In the first half of this article, the foundation of the asymptotic peak broadening theory and the related restricted-moments peak-evaluation method is summarized. After this, the microstructural parameters obtained by X-ray peak profile analysis are reported for irradiated E110 and E110G Zr alloys used as cladding material in the nuclear industry.

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Leddin, Mathias, Chiara Perrod, Maarten Hoogenkamp, Saeed Ghani, Salam Assi, Sven Heinz, Nicola K. Wilson i in. "Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells". Blood 117, nr 10 (10.03.2011): 2827–38. http://dx.doi.org/10.1182/blood-2010-08-302976.

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Abstract The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type–specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements.

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Andrews-Polymenis, Helene L., Wolfgang Rabsch, Steffen Porwollik, Michael McClelland, Carlos Rosetti, L. Garry Adams i Andreas J. Bäumler. "Host Restriction of Salmonella enterica Serotype Typhimurium Pigeon Isolates Does Not Correlate with Loss of Discrete Genes". Journal of Bacteriology 186, nr 9 (1.05.2004): 2619–28. http://dx.doi.org/10.1128/jb.186.9.2619-2628.2004.

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ABSTRACT The definitive phage types (DT) 2 and 99 of Salmonella enterica serotype Typhimurium are epidemiologically correlated with a host range restricted to pigeons, in contrast to phage types with broader host ranges such as epidemic cattle isolates (DT104 and DT204). To determine whether phage types with broad host range possess genetic islands absent from host-restricted phage types, we compared the genomes of four pigeon isolates to serotype Typhimurium strain LT2 using a DNA microarray. Three of the four isolates tested caused fluid accumulation in bovine ligated ileal loops, but they had reduced colonization of liver and spleen in susceptible BALB/c mice and were defective for intestinal persistence in Salmonella-resistant CBA mice. The genomes of the DT99 and DT2 isolates were extremely similar to the LT2 genome, with few notable differences on the level of complete individual genes. Two large groups of genes representing the Fels-1 and Fels-2 prophages were missing from the DT2 and DT99 phage types we analyzed. One of the DT99 isolates examined was lacking a third cluster of five chromosomal genes (STM1555 to -1559). Results of the microarray analysis were extended using Southern analysis to a collection of 75 serotype Typhimurium clinical isolates of 24 different phage types. This analysis revealed no correlation between the presence of Fels-1, Fels-2, or STM1555 to -1559 and the association of phage types with different host reservoirs. We conclude that serotype Typhimurium phage types with broad host range do not possess genetic islands influencing host restriction, which are absent from the host-restricted pigeon isolates.

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DiSpirito, Joanna R., David Zemmour, Deepshika Ramanan, Jun Cho, Rapolas Zilionis, Allon M. Klein, Christophe Benoist i Diane Mathis. "Molecular diversification of regulatory T cells in nonlymphoid tissues". Science Immunology 3, nr 27 (14.09.2018): eaat5861. http://dx.doi.org/10.1126/sciimmunol.aat5861.

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Foxp3+CD4+regulatory T cells (Tregs) accumulate in certain nonlymphoid tissues, where they control diverse aspects of organ homeostasis. Populations of tissue Tregs, as they have been termed, have transcriptomes distinct from those of their counterparts in lymphoid organs and other nonlymphoid tissues. We examined the diversification of Tregsin visceral adipose tissue, skeletal muscle, and the colon vis-à-vis lymphoid organs from the same individuals. The unique transcriptomes of the various tissue Tregpopulations resulted from layering of tissue-restricted open chromatin regions over regions already open in the spleen, the latter tagged by super-enhancers and particular histone marks. The binding motifs for a small number of transcription factor (TF) families were repeatedly enriched within the accessible chromatin stretches of Tregsin the three nonlymphoid tissues. However, a bioinformatically and experimentally validated transcriptional network, constructed by integrating chromatin accessibility and single-cell transcriptomic data, predicted reliance on different TF families in the different tissues. The network analysis also revealed that tissue-restricted and broadly acting TFs were integrated into feed-forward loops to enforce tissue-specific gene expression in nonlymphoid-tissue Tregs. Overall, this study provides a framework for understanding the epigenetic dynamics of T cells operating in nonlymphoid tissues, which should inform strategies for specifically targeting them.

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35

Rodriguez Barrera, Mario A., i Walter Pereira Carpes Jr. "Particle swarm optimization for the design of square loop frequency selective surfaces considering a model of dielectric effective permittivity". COMPEL - The international journal for computation and mathematics in electrical and electronic engineering 35, nr 5 (5.09.2016): 1643–55. http://dx.doi.org/10.1108/compel-10-2015-0362.

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Purpose The purpose of this paper is to present the results of a particle swarm optimization (PSO) method applied in the design of a square-loop frequency selective surface (FSS) via the equivalent circuit model (ECM), considering the dielectric effective permittivity as a variable in the optimization problem. Design/methodology/approach In the optimization process considered, besides the FSS square loop geometric parameters, the thickness and relative permittivity of dielectric material used as support are included as variables in the search space, using for this a model of dielectric effective permittivity introduced by the authors in a previous work. Findings Square loops were designed and the obtained results were compared with designs reported in literature for applications in wireless local area network and long-term evolution 4G systems. The low computational cost is remarkable as well as the acceptable accuracy obtained with the proposed approach. The PSO method results were implemented with the ECM and compared with those obtained via Ansys – high frequency structure simulator commercial software simulations. Originality/value The lack of a model of dielectric effective permittivity for the ECM causes a restricted search space in the stochastic FSS design process limited to only geometric parameters, as it is reported in the available literature. The proposed approach simplifies and makes more flexible the design process, and allows guiding the FSS design to unit cell surface and/or dielectric thickness of small dimensions.

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Hein, Sibyll, Vladimir Prassolov, Yuanming Zhang, Dmitry Ivanov, Jürgen Löhler, Susan R. Ross i Carol Stocking. "Sodium-Dependent myo-Inositol Transporter 1 Is a Cellular Receptor for Mus cervicolor M813 Murine Leukemia Virus". Journal of Virology 77, nr 10 (15.05.2003): 5926–32. http://dx.doi.org/10.1128/jvi.77.10.5926-5932.2003.

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ABSTRACT Retrovirus infection is initiated by binding of the surface (SU) portion of the viral envelope glycoprotein (Env) to specific receptors on cells. This binding triggers conformational changes in the transmembrane portion of Env, leading to membrane fusion and cell entry, and is thus a major determinant of retrovirus tissue and species tropism. The M813 murine leukemia virus (MuLV) is a highly fusogenic gammaretrovirus, isolated from Mus cervicolor, whose host range is limited to mouse cells. To delineate the molecular mechanisms of its restricted host range and its high fusogenic potential, we initiated studies to characterize the cell surface protein that mediates M813 infection. Screening of the T31 mouse-hamster radiation hybrid panel for M813 infectivity localized the receptor gene to the distal end of mouse chromosome 16. Expression of one of the likely candidate genes (slc5a3) within this region in human cells conferred susceptibility to both M813 infection and M813-induced fusogenicity. slc5a3 encodes sodium myo-inositol transporter 1 (SMIT1), thus adding another sodium-dependent transporter to the growing list of proteins used by MuLVs for cell entry. Characterization of SMIT1 orthologues in different species identified several amino acid variations within two extracellular loops that may restrict susceptibility to M813 infection.

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Elfituri, Osama, Nathan Aardsma, Suman Setty, Frederick Behm i Kimberly Czech. "Atypical Plasmacytic Proliferation in a Case of C3 Glomerulopathy". Journal of Investigative Medicine High Impact Case Reports 5, nr 1 (styczeń 2017): 232470961769074. http://dx.doi.org/10.1177/2324709617690746.

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An 11-year-old Hispanic female underwent evaluation of asymptomatic proteinuria and hematuria. The patient denied fever, edema, and gross hematuria. Urinalysis showed mild proteinuria, and a urine microscopic examination revealed red blood cells. Screening tests for glomerulonephritis revealed a low C3 and negative ANA, ASO, DNAse-B, and ANCA. Histological examination of a renal biopsy specimen showed glomeruli with endocapillary proliferation, a predominant C3 deposition in the capillary loops by immunofluorescence, and electron dense deposits in the mesangium, paramesangium, and capillary walls by electron microscopy consistent with a diagnosis of C3 glomerulopathy. An interstitial plasmacytosis was also present with focal clustering of plasma cells, which were found to be kappa light chain restricted by in situ hybridization suggestive of a clonal proliferation. One can speculate that these plasma cells may be directly responsible for the renal pathology that was seen.

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38

Brooks, Michael J., Cassie A. Laurence, Eric J. Hansen i Scott D. Gray-Owen. "Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins". Journal of Bacteriology 189, nr 1 (13.10.2006): 76–82. http://dx.doi.org/10.1128/jb.00788-06.

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ABSTRACT Moraxella catarrhalis is a human-restricted pathogen that can cause respiratory tract infections. In this study, we identified a previously uncharacterized 24-kDa outer membrane protein with a high degree of similarity to Neisseria Opa protein adhesins, with a predicted β-barrel structure consisting of eight antiparallel β-sheets with four surface-exposed loops. In striking contrast to the antigenically variable Opa proteins, the M. catarrhalis Opa-like protein (OlpA) is highly conserved and constitutively expressed, with 25 of 27 strains corresponding to a single variant. Protease treatment of intact bacteria and isolation of outer membrane vesicles confirm that the protein is surface exposed yet does not bind host cellular receptors recognized by neisserial Opa proteins. Genome-based analyses indicate that OlpA and Opa derive from a conserved family of proteins shared by a broad array of gram-negative bacteria.

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39

Nishimura, H., E. Yaoita, M. Nameta, K. Yamaguchi, M. Sato, C. Ihoriya, L. Zhao i in. "Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail". Journal of Developmental Origins of Health and Disease 8, nr 3 (6.02.2017): 287–300. http://dx.doi.org/10.1017/s2040174416000787.

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Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail,Coturnix japonica, in which partial (8–10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins,N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for ‘fetal programming,’ which appears to have evolved phylogenetically early.

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Casanova, J. L., J. C. Cerottini, M. Matthes, A. Necker, H. Gournier, C. Barra, C. Widmann, H. R. MacDonald, F. Lemonnier i B. Malissen. "H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity." Journal of Experimental Medicine 176, nr 2 (1.08.1992): 439–47. http://dx.doi.org/10.1084/jem.176.2.439.

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We previously showed that H-2Kd-restricted cytotoxic T lymphocyte (CTL) clones specific for a single nonapeptide derived from the Plasmodium berghei circumsporozoite (PbCS) protein displayed T cell receptors (TCRs) of highly diverse primary structure. We have now analyzed the TCR repertoire of CTLs that recognize a peptide derived from the human class I major histocompatibility complex (MHC) molecule HLA-Cw3 in association with the same murine class I MHC molecule H-2Kd. We first sequenced the TCR alpha and beta genes of the CTL clone Cw3/1.1 and, based on this genomic analysis, the TCR alpha and beta cDNA junctional regions of 23 independent H-2Kd-restricted CTL clones specific for HLA-Cw3. The results show that the TCR chains display very limited heterogeneity, both in terms of V alpha, J alpha, V beta, and J beta segments, and in terms of length and sequence of the CDR3 alpha and beta loops. The TCR repertoire used in vivo was then analyzed by harvesting CTL populations from the peritoneal cavity of immune mice. The peritoneal exudate lymphocytes (PELs) displayed HLA-Cw3-specific cytolytic activity in the absence of any stimulation in vitro. Remarkably, most of these freshly isolated PELs expressed TCRs that shared the same structural features as those from HLA-Cw3-reactive CTL clones. Thus, our results show that a peptide from HLA-Cw3 presented by H-2Kd selects CTLs that bear TCRs of very limited diversity in vivo. When taken together with the high diversity of the TCRs specific for the PbCS peptide, these findings suggest that natural tolerance to self peptides presented by class I MHC molecules may substantially reduce the size of the TCR repertoire of CTLs specific for antigenic peptides homologous to self.

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El-Achkar, Tarek M., Zoya Plotkin, Branislav Marcic i Pierre C. Dagher. "Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent". American Journal of Physiology-Renal Physiology 293, nr 4 (październik 2007): F1187—F1196. http://dx.doi.org/10.1152/ajprenal.00217.2007.

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Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis upregulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion ( TLR4−/−). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4−/− mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4−/− mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein.

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Taraszka, Karen S., Jonathan M. G. Higgins, Kemin Tan, Didier A. Mandelbrot, Jia-huai Wang i Michael B. Brenner. "Molecular Basis for Leukocyte Integrin αEβ7 Adhesion to Epithelial (E)-Cadherin". Journal of Experimental Medicine 191, nr 9 (1.05.2000): 1555–67. http://dx.doi.org/10.1084/jem.191.9.1555.

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Cadherins are expressed in tissue-restricted patterns and typically mediate homophilic adhesion. Cadherins also mediate lymphocyte adhesion, providing the opportunity for lymphocyte attachment to parenchymal cells. The best characterized example of lymphocyte adhesion to a tissue-specific cell adhesion molecule, as opposed to a vascular endothelial adhesion molecule, is the interaction between integrin αEβ7 on intraepithelial lymphocytes and E-cadherin on epithelial cells. However, the molecular basis for an integrin–cadherin interaction is not well defined. Realization that the cadherin domain adopts a topology similar to the immunoglobulin (Ig) fold suggested that integrin recognition of E-cadherin might be similar to recognition of Ig superfamily ligands. Thus, we modeled domain 1 of human E-cadherin and studied the role of solvent-exposed loops that connect Ig-like core-forming β strands. Mutational analyses localized the integrin αEβ7 recognition site to the top of domain 1 at the face formed by the BC and FG loops, a site distinct from the region recognized in intercellular adhesion molecule (ICAM)-1, -2, and -3, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), vascular cell adhesion molecule 1 (VCAM-1), and fibronectin by their integrin ligands. Moreover, the integrin αEβ7 binding site is distinct from the homophilic binding site on E-cadherin. These studies provide a conceptual basis for integrin–cadherin binding and extend the model that an Ig-like fold can serve as a scaffold for recognition.

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43

Trapp, B. D., S. B. Andrews, C. Cootauco i R. Quarles. "The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes." Journal of Cell Biology 109, nr 5 (1.11.1989): 2417–26. http://dx.doi.org/10.1083/jcb.109.5.2417.

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The myelin-associated glycoprotein (MAG) is a member of the immunoglobulin gene superfamily that is selectively expressed by myelin-forming cells. A developmentally regulated, alternative splicing of a single MAG transcript produces two MAG polypeptides (72 and 67 kD) in the central nervous system (CNS). MAG occurs predominantly as the 67-kD polypeptide in the peripheral nervous system (PNS). This study determined the subcellular localization of CNS MAG at different postnatal times when the 72-kD form (7-d) and 67-kD form (adult) are quantitatively abundant. These distributions were also compared to those of MAG in the PNS. In adult rat, MAG is selectively enriched in periaxonal membranes of CNS myelin internodes. This restricted distribution differs from that in PNS myelin internodes where MAG is also enriched in paranodal loops, Schmidt-Lanterman incisures, and mesaxon membranes. In 7-d-old rat CNS, MAG was associated with periaxonal membranes during axonal ensheathment and enriched in Golgi membranes and cytoplasmic organelles having the appearance of multivesicular bodies (MVBs). MAG-enriched MVBs were found in oligodendrocyte perinuclear regions, in processes extending to myelin internodes, and along the myelin internode in outer tongue processes and paranodal loops. MAG-enriched MVBs were not found in oligodendrocytes from adult animals or in myelinating Schwann cells. These findings raise the possibility that the 72-kD MAG polypeptide is associated with receptor-mediated endocytosis of components from the periaxonal space or axolemma during active stages of myelination.

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Kiyomizu, Kazunobu, Hirokazu Kashiwagi, Tsuyoshi Nakazawa, Seiji Tadokoro, Shigenori Honda, Yuzuru Kanakura i Yoshiaki Tomiyama. "Recognition of highly restricted regions in the β-propeller domain of αIIb by platelet-associated anti-αIIbβ3 autoantibodies in primary immune thrombocytopenia". Blood 120, nr 7 (16.08.2012): 1499–509. http://dx.doi.org/10.1182/blood-2012-02-409995.

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AbstractPlatelet-associated (PA) IgG autoantibodies play an essential role in primary immune thrombocytopenia (ITP). However, little is known about the epitopes of these Abs. This study aimed to identify critical binding regions for PA anti-αIIbβ3 Abs. Because PA anti-αIIbβ3 Abs bound poorly to mouse αIIbβ3, we created human-mouse chimera constructs. We first examined 76 platelet eluates obtained from patients with primary ITP. Of these, 26 harbored PA anti-αIIbβ3 Abs (34%). Further analysis of 15 patients who provided sufficient materials showed that the epitopes of these Abs were mainly localized in the N-terminal half of the β-propeller domain in αIIb (L1-W235). We could identify 3 main recognition sites in the region; 2 eluates recognized a conformation formed by the W1:1-2 and W2:3-4 loops, 5 recognized W1:2-3, and 4 recognized W3:4-1. The remaining 4 eluates could not be defined by the binding sites. Within these regions, we identified residues critical for binding, including S29 and R32 in W1:1-2; G44 and P45 in W1:2-3; and P135, E136, and R139 in W2:3-4. Of 11 eluates whose recognition sites were identified, 5 clearly showed restricted κ/λ-chain usage. These results suggested that PA anti-αIIbβ3 Abs in primary ITP tended to recognize highly restricted regions of αIIb with clonality.

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Qa'dan, Maen, Kenneth A. Christensen, Lei Zhang, Thomas M. Roberts i R. John Collier. "Membrane Insertion by Anthrax Protective Antigen in Cultured Cells". Molecular and Cellular Biology 25, nr 13 (1.07.2005): 5492–98. http://dx.doi.org/10.1128/mcb.25.13.5492-5498.2005.

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ABSTRACT The enzymatic moieties of anthrax toxin enter the cytosol of mammalian cells via a pore in the endosomal membrane formed by the protective antigen (PA) moiety. Pore formation involves an acidic pH-induced conformational rearrangement of a heptameric precursor (the prepore), in which the seven 2β2-2β3 loops interact to generate a 14-strand transmembrane β-barrel. To investigate this model in vivo, we labeled PA with the fluorophore 7-nitrobenz-2-oxa-1,3-diazole (NBD) at cysteine residues introduced into the 2β2-2β3 loop. Each labeled PA was bound to CHO cells, and NBD fluorescence was monitored over time in stirred cell suspensions or by confocal microscopy. A strong increase was observed with NBD at positions 305, 307, 309, and 311, sites where side chains are predicted to face the bilayer, and little change was seen at residues 304, 306, 308, 310, and 312, sites where side chains are predicted to face the pore lumen. The increase at position 305 was inhibited by membrane-restricted quenchers, low temperature, or various reagents known to affect toxin action. Of the 24 NBD attachment sites examined, all but three gave results qualitatively consistent with the β-barrel model. Besides supporting the β-barrel model of membrane insertion, our results describe the time course of insertion and identify PA residues where NBD gives a strong signal upon membrane insertion in vivo.

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Chaturvedi, P. "Utilization of intestinal clamps for precise cutting of the pectoralis major muscle while raising a myocutaneous flap". Journal of Laryngology & Otology 118, nr 3 (marzec 2004): 221–22. http://dx.doi.org/10.1258/002221504322928017.

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A variety of approaches have been employed for the reconstruction of head and neck defects and most of the techniques involve the use of arterialized vascular flaps alone, or in conjunction with other regional or local tissues. We frequently use a pectoralis major myocutaneous (PMMC) flap in our hospital in addition to other pedicled or free tissue transfers. A PMMC flap is a reliable flap with acceptable complications, needs a small learning curve, takes less time, and does not require additional investment (i.e. microscopes, loops etc). The disadvantages of the PMMC flap is that it has a restricted arc of rotation, gives a cosmetically unacceptable bulk in the neck, it is difficult in females and causes significant shoulder dysfunction. We have made a small improvization in the flap-raising technique which is helpful for the surgeon. This involves utilization of intestinal clamps to hold and cut the pectoralis major muscle.

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Zeller, Marc, i Christian Prehofer. "A Multi-Layered Control Approach for Self-Adaptation in Automotive Embedded Systems". Advances in Software Engineering 2012 (4.10.2012): 1–15. http://dx.doi.org/10.1155/2012/971430.

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We present an approach for self-adaptation in automotive embedded systems using a hierarchical, multi-layered control approach. We model automotive systems as a set of constraints and define a hierarchy of control loops based on different criteria. Adaptations are performed at first locally on a lower layer of the architecture. If this fails due to the restricted scope of the control cycle, the next higher layer is in charge of finding a suitable adaptation. We compare different options regarding responsibility split in multi-layered control in a self-healing scenario with a setup adopted from automotive in-vehicle networks. We show that a multi-layer control approach has clear performance benefits over a central control, even though all layers work on the same set of constraints. Furthermore, we show that a responsibility split with respect to network topology is preferable over a functional split.

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Fukui, Yoshinori, Osamu Hashimoto, Ayumi Inayoshi, Takahiro Gyotoku, Tetsuro Sano, Takahiro Koga, Toshifumi Gushima i Takehiko Sasazuki. "Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex–Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor β Chain". Journal of Experimental Medicine 188, nr 5 (7.09.1998): 897–907. http://dx.doi.org/10.1084/jem.188.5.897.

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The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of α/β-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-β chains with a single rearranged TCR-β irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC–peptide complex express highly restricted TCR-α chains in terms of Vα usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.

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Dowland, Samson N., Romanthi J. Madawala, Connie E. Poon, Laura A. Lindsay i Christopher R. Murphy. "Prominin-1 glycosylation changes throughout early pregnancy in uterine epithelial cells under the influence of maternal ovarian hormones". Reproduction, Fertility and Development 29, nr 6 (2017): 1194. http://dx.doi.org/10.1071/rd15432.

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In preparation for uterine receptivity, the uterine epithelial cells (UECs) exhibit a loss of microvilli and glycocalyx and a restructuring of the actin cytoskeleton. The prominin-1 protein contains large, heavily glycosylated extracellular loops and is usually restricted to apical plasma membrane (APM) protrusions. The present study examined rat UECs during early pregnancy using immunofluorescence, western blotting and deglycosylation analyses. Ovariectomised rats were injected with oestrogen and progesterone to examine how these hormones affect prominin-1. At the time of fertilisation, prominin-1 was located diffusely in the apical domain of UECs and 147- and 120-kDa glycoforms of prominin-1 were identified, along with the 97-kDa core protein. At the time of implantation, prominin-1 concentrates towards the APM and densitometry revealed that the 120-kDa glycoform decreased (P < 0.05), but there was an increase in the 97-kDa core protein (P < 0.05). Progesterone treatment of ovariectomised rats resulted in prominin-1 becoming concentrated towards the APM. The 120-kDa glycoform was increased after oestrogen treatment (P < 0.0001), whereas the 97-kDa core protein was increased after progesterone treatment (P < 0.05). Endoglycosidase H analysis demonstrated that the 120-kDa glycoform is in the endoplasmic reticulum, undergoing protein synthesis. These results indicate that oestrogen stimulates prominin-1 production, whereas progesterone stimulates the deglycosylation and concentration of prominin-1 to the apical region of the UECs. This likely presents the deglycosylated extracellular loops of prominin-1 to the extracellular space, where they may interact with the implanting blastocyst.

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HAUCOURT, EMMANUEL. "The geometry of conservative programs". Mathematical Structures in Computer Science 28, nr 10 (17.10.2017): 1723–69. http://dx.doi.org/10.1017/s0960129517000226.

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The programs, we consider are written in a restricted form of the language introduced by Dijkstra (1968). A program is said to beconservativewhen each of its loops restores all the resources it consumes. We define the geometric model of such a program and prove that the collection of directed paths on it is a reasonable over-approximation of its set of execution traces. In particular, two directed paths that are close enough with respect to theuniform distanceresult in the same action on the memory states of the system. The same holds forweakly dihomotopicdirected paths. As a by-product, we obtain a notion of independence, which is favourably compared to more common ones. The geometric models actually belong to a handy class oflocal pospaceswhose elements are calledisothetic regions. The local pospaces we use differ from the original ones, we carefully explain why the alternative notion should be preferred. The title intentionally echoes the article by Carson and Reynolds (1987).

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