cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
RNA Polymerase II Carboxyl-terminal Domain Phosphorylation Regulates Protein Stability of the Set2 Methyltransferase and Histone H3 Di- and Trimethylation at Lysine 36
Creators: name: Strahl, Brian D.
name: Fuchs, Stephen M.
name: Braberg, Hannes
name: Krogan, Nevan J.
name: Kizer, Kelby O.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Methylation of lysine 36 on histone H3 (H3K36) is catalyzed by the Set2 methyltransferase and is linked to transcriptional regulation. Previous studies have shown that trimethylation of H3K36 by Set2 is directed through its association with the phosphorylated repeats of the RNA polymerase C-terminal domain (RNAPII CTD). Here, we show that disruption of this interaction through the use of yeast mutants defective in CTD phosphorylation at serine 2 results in a destabilization of Set2 protein levels and H3K36 methylation. Consistent with this, we find that Set2 has a short half-life and is co-regulated, with RNAPII CTD phosphorylation levels, during logarithmic growth in yeast. To probe the functional consequence of uncoupling Set2-RNAPII regulation, we expressed a truncated and more stable form of Set2 that is capable of dimethylation but not trimethylation in vivo. Results of high throughput synthetic genetic analyses show that this Set2 variant has distinct genetics from either SET2 or set2Δ and is synthetically sick or lethal with a number of transcription elongation mutants. Collectively, these results provide molecular insight into the regulation of Set2 protein levels that influence H3K36 methylation states.
Optical discovery and multiwavelength investigation of supernova remnant MCSNR J0512-6707 in the Large Magellanic Cloud
Creators: name: Reid, Warren A.
name: Stupar, Milorad
name: Bozzetto, Luke M.
name: Parker, Quentin A.
name: Filipovic, Miroslav D.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: We present optical, radio and X-ray data that confirm a new supernova remnant (SNR) in the Large Magellanic Cloud (LMC) discovered using our deep H-alpha imagery. Optically, the new SNR has a somewhat filamentary morphology and a diameter of 56 x 64 arcsec (13.5 x 15.5 pc at the 49.9 kpc distance of the LMC). Spectroscopic follow-up of multiple regions show high [SII]/H-alpha emission-line ratios ranging from 0.66+/-0.02 to 0.93+/-0.01, all of which are typical of an SNR. We found radio counterparts for this object using our new Australia Telescope Compact Array (ATCA) 6cm pointed observations as well as a number of available radio surveys at 8 640 MHz, 4 850 MHz, 1 377 MHz and 843 MHz. With these combined data we provide a spectral index (alpha) = -0.5 between 843 and 8640 MHz. Both spectral line analysis and the magnetic field strength, ranging from 124 - 184 mG, suggest a dynamical age between 2,200 and 4,700 yrs. The SNR has a previously catalogued X-ray counterpart listed as HP 483 in the ROSAT Position Sensitive Proportional Counter (PSPC) catalogue.
description: 10 pages, 11 figures. Published MNRAS. New version in order to update acknowledgements
Sequence Variation in Promoter of Ica1 Gene, Which Encodes Protein Implicated in Type 1 Diabetes, Causes Transcription Factor Autoimmune Regulator (AIRE) to Increase Its Binding and Down-regulate Expression
Creators: name: Morran, Michael P.
name: Trucco, Giuliana
name: Beems, Megan
name: Polychronakos, Constantin
name: Trucco, Massimo
name: Chang, Yigang
name: Solimena, Michele
name: Bonner, Samantha M.
name: Pugliese, Alberto
name: Pietropaolo, Massimo
name: Palumbo, Michael O.
name: Giannoukakis, Nick
name: Sethupathy, Praveen
name: Fan, Yong
name: Pietropaolo, Susan L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: ICA69 (islet cell autoantigen 69 kDa) is a protein implicated in type 1 diabetes mellitus in both the non-obese diabetic (NOD) mouse model and humans. ICA69 is encoded by the Ica1 gene on mouse chromosome 6 A1-A2. We previously reported reduced ICA69 expression in the thymus of NOD mice compared with thymus of several non-diabetic mouse strains. We propose that reduced thymic ICA69 expression could result from variations in transcriptional regulation of the gene and that polymorphisms within the Ica1 core promoter may partially determine this transcriptional variability. We characterized the functional promoter of Ica1 in NOD mice and compared it with the corresponding portions of Ica1 in non-diabetic C57BL/6 mice. Luciferase reporter constructs demonstrated that the NOD Ica1 promoter region exhibited markedly reduced luciferase expression in transiently transfected medullary thymus epithelial (mTEC+) and B-cell (M12)-derived cell lines. However, in a non-diabetic strain, C57BL/6, the Ica1 promoter region was transcriptionally active when transiently transfected into the same cell lines. We concomitantly identified five single nucleotide polymorphisms within the NOD Ica1 promoter. One of these single nucleotide polymorphisms increases the binding affinity for the transcription factor AIRE (autoimmune regulator), which is highly expressed in thymic epithelial cells, where it is known to play a key role regulating self-antigen expression. We conclude that polymorphisms within the NOD Ica1 core promoter may determine AIRE-mediated down-regulation of ICA69 expression in medullary thymic epithelial cells, thus providing a novel mechanistic explanation for the loss of immunologic tolerance to this self-antigen in autoimmunity.
How development and survival combine to determine the thermal sensitivity of insects
Creators: name: Larsen, Elise A.
name: Parker, Anna L.
name: Kingsolver, Joel
name: Umbanhowar, James
name: Ries, Leslie
name: Earl, Chandra
name: Abarca, Mariana
name: Guralnick, Robert
Publisher: name: Public Library of Science
Year: 2024

description: Thermal performance curves (TPCs) depict variation in vital rates in response to temperature and have been an important tool to understand ecological and evolutionary constraints on the thermal sensitivity of ectotherms. TPCs allow for the calculation of indicators of thermal tolerance, such as minimum, optimum, and maximum temperatures that allow for a given metabolic function. However, these indicators are computed using only responses from surviving individuals, which can lead to underestimation of deleterious effects of thermal stress, particularly at high temperatures. Here, we advocate for an integrative framework for assessing thermal sensitivity, which combines both vital rates and survival probabilities, and focuses on the temperature interval that allows for population persistence. Using a collated data set of Lepidopteran development rate and survival measured on the same individuals, we show that development rate is generally limiting at low temperatures, while survival is limiting at high temperatures. We also uncover differences between life stages and across latitudes, with extended survival at lower temperatures in temperate regions. Our combined performance metric demonstrates similar thermal breadth in temperate and tropical individuals, an effect that only emerges from integration of both development and survival trends. We discuss the benefits of using this framework in future predictive and management contexts.
Forecasting errors from history matched reservoir models
Creators: name: Tabassum Tinni, Afifa
Publisher: name: Imperial College London
Year: 2020

description: The aim of this project is to find out the correlation between the quality of the history match to that of a forecast. It is generally assumed that the better a model fits the past performance of a reservoir the better it will predict the future performance. In this thesis we challenge this assumption and aim to demonstrate the circumstances under which an apparently good history match leads to a poor prediction. An initial investigation of the relationship between the quality of a forecast and that of the history match was made using the IC fault model. This was then extended to a systematic study of a 2D reservoir model with log normally distributed permeability fields to demonstrate the fact that this correlation between the qualities of the history match and the forecast depends on various factors like water breakthrough times, extent of heterogeneity and the duration of history match and forecast period. Generally, it can be said that if both the base and compared case have their water breakthroughs within history match period, the quality of the forecast is good. It is also very interesting to find out that not always good history match leads to a good forecast and bad match leads to a bad forecast but sometimes depending on the forecast duration a moderately bad history match can lead to a good forecast. The quality of the match can be correlated with the ratio of the breakthrough times of the base and the compared cases. We have fitted curves describing the relation between these two as a function of heterogeneity level. Heterogeneity has been controlled by changing the standard deviation of the log normally distributed permeabilities around a mean value. During the third phase we have developed a 3D reservoir model with 5 vertical layers and log normally distributed permeability fields. We repeated the methods applied for the 2D model but only at two different heterogeneity levels to save the computational time. We found that Quantitative results might be case specific but qualitative results are similar for both 2D and 3D models. The main result is to find a quantitative prediction of how the quality of the forecast deteriorates and how rapidly one can go from the situation where the quality of the forecast is good to where it is very poor.
Evidence for a binary origin of a central compact object
Creators: name: Doroshenko, Victor
name: Puehlhofer, Gerd
name: Kavanagh, Patrick
name: Santangelo, Andrea
name: Suleimanov, Valery
name: Klochkov, Dmitry
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: Central compact objects (CCOs) are thought to be young thermally emitting isolated neutron stars that were born during the preceding core-collapse supernova explosion. Here we present evidence that at least in one case the CCO could have been formed within a binary system. We show that the highly reddened optical source IRAS~17287$-$3443, located $25^{\prime \prime}$ away from the CCO candidate XMMUJ173203.3$-$344518 and classified previously as a post asymptotic giant branch star, is indeed surrounded by a dust shell. This shell is heated by the central star to temperatures of $\sim90$\,K and observed as extended infrared emission in 8-160\,$μ$m band. The dust temperature also increases in the vicinity of the CCO which implies that it likely resides within the shell. We estimate the total dust mass to be $\sim0.4-1.5\,M_\odot$ which significantly exceeds expected dust yields by normal stars and thus likely condensed from supernova ejecta. Taking into account that both the age of the supernova remnant and the duration of active mass loss phase by the optical star are much shorter than the total lifetime of either object, the supernova and the onset of the active mass loss phase of the companion have likely occurred approximately simultaneously. This is most easily explained if the evolution of both objects is interconnected. We conclude, therefore, that both stars were likely members of the same binary system disrupted by a supernova.
description: 7 pages, 5 figures, accepted in MNRAS
Specificity of the dRP/AP Lyase of Ku Promotes Nonhomologous End Joining (NHEJ) Fidelity at Damaged Ends
Creators: name: Strande, Natasha
name: Roberts, Steven A.
name: Hendrickson, Eric A.
name: Oh, Sehyun
name: Ramsden, Dale A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Nonhomologous end joining (NHEJ) is essential for efficient repair of chromosome breaks. However, the NHEJ ligation step is often obstructed by break-associated nucleotide damage, including base loss (abasic site or 5′-dRP/AP sites). Ku, a 5′-dRP/AP lyase, can excise such damage at ends in preparation for the ligation step. We show here that this activity is greatest if the abasic site is within a short 5′ overhang, when this activity is necessary and sufficient to prepare such termini for ligation. In contrast, Ku is less active near 3′ strand termini, where excision would leave a ligation-blocking α,β-unsaturated aldehyde. The Ku AP lyase activity is also strongly suppressed by as little as two paired bases 5′ of the abasic site. Importantly, in vitro end joining experiments show that abasic sites significantly embedded in double-stranded DNA do not block the NHEJ ligation step. Suppression of the excision activity of Ku in this context therefore is not essential for ligation and further helps NHEJ retain terminal sequence in junctions. We show that the DNA between the 5′ terminus and the abasic site can also be retained in junctions formed by cellular NHEJ, indicating that these sites are at least partly resistant to other abasic site-cleaving activities as well. High levels of the 5′-dRP/AP lyase activity of Ku are thus restricted to substrates where excision of an abasic site is required for ligation, a degree of specificity that promotes more accurate joining.
Some bootstrap approaches to conditional inference
Creators: name: Salazar Serrudo, Lucas
Publisher: name: Imperial College London
Year: 2019

description: To respect the conditionality principle, it may be necessary to consider conditioning on an approximate ancillary, as finding an exact ancillary is not always straightforward. Since several approximate ancillaries exist, a comparison of the properties of two commonly used approximate ancillaries, the affine ancillary (Efron and Hinkley, 1978) and the likelihood ancillary (Barndorff-Nielsen, 1980), is carefully carried out for Butler’s (2004) and Pedersen’s (1981) examples where the parameter of interest is scalar. The inference drawn in both examples show similar outcomes. For inference conditional on the likelihood ancillary, the (unconditional) parametric simulation of the signed root likelihood ratio statistic works well even for small sample sizes, giving highly accurate approximation to exact conditional inference, as good as those obtained by more complicated analytic procedures. For inference conditional on the affine ancillary, we argue that to obtain good approximations it is necessary to consider some form of stratification of the bootstrap simulation (Hinkley and Schechtman, 1987) as the range of the estimator of the parameter of interest depends on the value of the affine ancillary. Our results are different to Butler’s (2004), as on that paper it was not realized that the range of the estimator of the parameter of interest depended on the value of the affine ancillary, as it was suggested for Pedersen’s example in Barndorff-Nielsen (1980). Focus will also be given to models that present multidimensional ancillary statistics. Of particular interest is the location-scale family, where the ancillary statistic can be of a very high dimension, as its dimension is often very close to the sample size n. But also, examples where there are nuisance parameters will be treated. Solutions to conditional inference are offered, whether they are SPA or based on bootstrap methods for the extreme value model and the Weibull regression. Cox and Reid’s (1987) solution is introduced and applied to these models. Given the Cox and Reid’s solution, a quantity relating it to r∗ is derived (DiCiccio and Young, Properties of parametric bootstrap procedures based on signed roots of likelihood ratio statistics, unpublished paper) which could facilitate the computations required to respect Fisher’s conditional principle. An exact solution to conditional inference is given using MCMC techniques, namely Metroplis within Gibbs that could be applied to the joint conditional density of the pivots.
Structure of a Yeast Dyn2-Nup159 Complex and Molecular Basis for Dynein Light Chain-Nuclear Pore Interaction
Creators: name: Romes, Erin M.
name: Slep, Kevin C.
name: Tripathy, Ashutosh
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: The nuclear pore complex gates nucleocytoplasmic transport through a massive, eight-fold symmetric channel capped by a nucleoplasmic basket and structurally unique, cytoplasmic fibrils whose tentacles bind and regulate asymmetric traffic. The conserved Nup82 complex, composed of Nsp1, Nup82, and Nup159, forms the unique cytoplasmic fibrils that regulate mRNA nuclear export. Although the nuclear pore complex plays a fundamental, conserved role in nuclear trafficking, structural information about the cytoplasmic fibrils is limited. Here, we investigate the structural and biochemical interactions between Saccharomyces cerevisiae Nup159 and the nucleoporin, Dyn2. We find that Dyn2 is predominantly a homodimer and binds arrayed sites on Nup159, promoting the Nup159 parallel homodimerization. We present the first structure of Dyn2, determined at 1.85 Å resolution, complexed with a Nup159 target peptide. Dyn2 resembles homologous metazoan dynein light chains, forming homodimeric composite substrate binding sites that engage two independent 10-residue target motifs, imparting a β-strand structure to each peptide via antiparallel extension of the Dyn2 core β-sandwich. Dyn2 recognizes a highly conserved QT motif while allowing sequence plasticity in the flanking residues of the peptide. Isothermal titration calorimetric analysis of the comparative binding of Dyn2 to two Nup159 target sites shows similar affinities (18 and 13 μm), but divergent thermal binding modes. Dyn2 homodimers are arrayed in the crystal lattice, likely mimicking the arrayed architecture of Dyn2 on the Nup159 multivalent binding sites. Crystallographic interdimer interactions potentially reflect a cooperative basis for Dyn2-Nup159 complex formation. Our data highlight the determinants that mediate oligomerization of the Nup82 complex and promote a directed, elongated cytoplasmic fibril architecture.
ON THE PREFERRED FOODS OF SOME AUTOLYTOIDS (POLYCHAETA, SYLLIDAE)
Creators: name: HAMOND, Richard
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 1969

description: Of the eleven Norfolk species of autolytoid, three were successfully used for feeding trials; all were found to feed exclusively on hydroid polyps under laboratory conditions, using the method of feeding described by Okada (1928) and others. Field observations confirm that, in summer, hydroid colonies are the normal habitat of these worms, but that they seek other (as yet unknown) sources of food in winter when the hydroid have died down. Further aspects of food selection by autolytoids arc discussed.
(3941) William Bauchop
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Accurate Prediction of the Ammonia Probes of a Variable Proton-to-Electron Mass Ratio
Creators: name: Owens, Alec
name: Yurchenko, Sergei N.
name: Thiel, Walter
name: Špirko, Vladimir
Publisher: name: arXiv
Year: 2015
Subjects: subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: Atomic Physics (physics.atom-ph)
subject: Chemical Physics (physics.chem-ph)
subject: FOS: Physical sciences

description: A comprehensive study of the mass sensitivity of the vibration-rotation-inversion transitions of $^{14}$NH$_3$, $^{15}$NH$_3$, $^{14}$ND$_3$, and $^{15}$ND$_3$ is carried out variationally using the TROVE approach. Variational calculations are robust and accurate, offering a new way to compute sensitivity coefficients. Particular attention is paid to the $Δk=\pm 3$ transitions between the accidentally coinciding rotation-inversion energy levels of the $ν_2=0^+,0^-,1^+$ and $1^-$ states, and the inversion transitions in the $ν_4=1$ state affected by the "giant" $l$-type doubling effect. These transitions exhibit highly anomalous sensitivities, thus appearing as promising probes of a possible cosmological variation of the proton-to-electron mass ratio $μ$. Moreover, a simultaneous comparison of the calculated sensitivities reveals a sizeable isotopic dependence which could aid an exclusive ammonia detection.
description: 18 pages, 2 figures, 10 tables
Rapid adiabatic preparation of injective PEPS and Gibbs states
Creators: name: Ge, Yimin
name: Molnár, András
name: Cirac, J. Ignacio
Publisher: name: arXiv
Year: 2015
Subjects: subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: We propose a quantum algorithm for many-body state preparation. It is especially suited for injective PEPS and thermal states of local commuting Hamiltonians on a lattice. We show that for a uniform gap and sufficiently smooth paths, an adiabatic runtime and circuit depth of $O(\operatorname{polylog}N)$ can be achieved for $O(N)$ spins. This is an almost exponential improvement over previous bounds. The total number of elementary gates scales as $O(N\operatorname{polylog}N)$. This is also faster than the best known upper bound of $O(N^2)$ on the mixing times of Monte Carlo Markov chain algorithms for sampling classical systems in thermal equilibrium.
description: 5 (+12) pages, 2 figures
(3942) Ann Massone
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
UNE NOUVELLE ESPÈCE DE ZEPPELINA VAILLANT 1890. (ANNÉLIDE POLYCHÈTE : CTENODRILIDAE)
Creators: name: HARRIS, Tegwyn
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 1969

description: Taxonomic description of Zeppelina maculosa sp. nov. A table of comparison between the four known species of Zeppelina is given.
(3937) George Peterkin
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Synergism of the Two Myb Domains of Tay1 Protein Results in High Affinity Binding to Telomeres
Creators: name: Pavlouskova, Jana
name: Willcox, Smaranda
name: Griffith, Jack D.
name: Fajkus, Jiri
name: Tomaska, Lubomir
name: Necasova, Ivona
name: Hofr, Ctirad
name: Visacka, Katarina
name: Nosek, Jozef
name: Wimmerova, Michaela
name: Sepsiova, Regina
name: Simonicova, Lucia
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Double-stranded regions of the telomeres are recognized by proteins containing Myb-like domains conferring specificity toward telomeric repeats. Although biochemical and structural studies revealed basic molecular principles involved in DNA binding, relatively little is known about evolutionary pathways leading to various types of Myb domain-containing proteins in divergent species of eukaryotes. Recently we identified a novel type of telomere-binding protein YlTay1p from the yeast Yarrowia lipolytica containing two Myb domains (Myb1, Myb2) very similar to the Myb domain of mammalian TRF1 and TRF2. In this study we prepared mutant versions of YlTay1p lacking Myb1, Myb2, or both Myb domains and found that YlTay1p carrying either Myb domain exhibits preferential affinity to both Y. lipolytica (GGGTTAGTCA)n and human (TTAGGG)n telomeric sequences. Quantitative measurements of the protein binding to telomeric DNA revealed that the presence of both Myb domains is required for a high affinity of YlTay1p to either telomeric repeat. Additionally, we performed detailed thermodynamic analysis of the YlTay1p interaction with its cognate telomeric DNA, which is to our knowledge the first energetic description of a full-length telomeric-protein binding to DNA. Interestingly, when compared with human TRF1 and TRF2 proteins, YlTay1p exhibited higher affinity not only for Y. lipolytica telomeres but also for human telomeric sequences. The duplication of the Myb domain region in YlTay1p thus produces a synergistic effect on its affinity toward the cognate telomeric sequence, alleviating the need for homodimerization observed in TRF-like proteins possessing a single Myb domain.
Modulation of chemoattractant receptor function by C-terminus interactions
Creators: name: Patel, Pallavi
Publisher: name: Imperial College London
Year: 2020

description: The chemokine receptors CCR3 and CCR4 play key roles in leukocyte recruitment in allergy. Consequently, both receptors are the focus of efforts to block receptor function with potential for the treatment of diseases such as asthma. Responses to chemokines are tightly regulated by the processes of receptor endocytosis and recycling. This thesis set out to examine the mechanisms by which the expression of both receptors are regulated. CCR3 is a key mediator of eosinophil migration and binds the eotaxin family of chemokines. Using a variety of assays with CCR3 transfectants and eosinophils, I observed that CCL11 and CCL24 were more potent ligands than CCL26, pointing to a role for ligand bias in CCR3 activation. Mutation of the C-terminus was found to negatively affect CCR3 expression. This could be rescued by the use of a small molecule antagonist, UCB 35625 as a pharmacoperone, presumed to help the refolding of misfolded CCR3. Given the importance of the CCR3 C-terminus, the identification of novel binding partners for the CCR3 C-terminus was investigated using a yeast-two hybrid (Y2H) approach. This was inconclusive. CCR4 is expressed by Th2 cells and binds the chemokines CCL17 and CCL22. Using a transfectant system, I observed that both ligands induced rapid CCR4 endocytosis, resulting in proteasomal degradation. This was sensitive to C-terminal truncation. Constitutive internalisation of CCR4 and degradation was also observed with cell surface replenishment wholly dependent upon de novo synthesis of CCR4. A Y2H screen identified a novel binding partner, FBXL5, that interacted with the CCR4 C-terminus. This interaction was verified by confocal microscopy, with colocalisation of CCR4 and FBXL5 observed following CCL22 treatment. I conclude that the C-termini of both chemokine receptors plays an important role in modulating receptor trafficking and function. This domain may prove to be a molecular “hot-spot” for receptor blockade by antagonists.
Targeting Serous Epithelial Ovarian Cancer with Designer Zinc Finger Transcription Factors
Creators: name: Fredes, Mauricio Cuello
name: Wang, Yuhua
name: Kato, Sumie
name: Leisewitz, Andrea V.
name: Juárez-Moreno, Karla
name: Yuan, Xinni
name: Beltran, Adriana S.
name: Lara, Haydee
name: Huang, Leaf
name: Connolly, Denise C.
name: Licea, Alexei F.
name: Blancafort, Pilar
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers.
First record of the Oman Blenny Oman ypsilon Springer, 1985 (Teleostei: Blenniidae) from Kuwait and the Persian/Arabian Gulf
Creators: name: ZOGARIS, Stamatis
name: VIDALIS, Aris
name: FRICKE, Ronald
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 2015

description: During a SCUBA diving expedition on thirteen Kuwaiti coral reefs, a single adult Oman Blenny Oman ypsilon Springer, 1985 was observed at Qaru reef. Photographic documentation showing diagnostic characteristics of this distinctive fish confirms identification. The record is approximately 1500 km away from the species' type locality in Oman where it was previously thought to be endemic.
Additional file 1 of Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission
Creators: name: Pooley, Christopher
name: Marion, Glenn
name: Bishop, Stephen
name: Doeschl-Wilson, Andrea
Publisher: name: figshare
Year: 2022
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Biotechnology
subject: 69999 Biological Sciences not elsewhere classified
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Science Policy
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: 60506 Virology
subject: Computational Biology

description: Additional file 1: Provides details on how inference was performed on simulated datasets to generate results against which the analytical expressions could be compared.
(3939) Thomas Stark
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Scale and lateral variability of mass-transport deposits within submarine slope and basinfloor systems
Creators: name: Steventon, Michael J.
Publisher: name: Imperial College London
Year: 2020

description: Mass-transport deposits (MTDs), and their larger-scale occurrence as mass-transport complexes (MTCs), are common in many deep-water sedimentary basins, forming a substantial component of the stratigraphic record in slope and basinfloor environments. They are the result of emplacement by gravitationally driven mass-transport processes that are influenced by allogenic and autogenic controls, which deposit beds at a range of thickness scales (m-dm to 100s m) with marked spatial and stratigraphic variability. 3D seismic reflection data has allowed the occurrence, structure, and morphometry of MTCs to be documented in a diverse range of basin settings. However, uncertainties remain regarding: (i) the quantification and distribution of strain within MTCs, (ii) the lateral variability and stratigraphic occurrence of MTCs along degradational basin margins, and (iii) the distribution and rock properties of sub-seismic MTDs, genetically related transitional flow deposits, and their effect on deep-water turbidite reservoir quality. These questions are considered in the context of three contrasting MTD/MTC settings: (i) the Neogene continental slope, offshore Uruguay; (ii) the Eocene shelf edge system, in the central Santos Basin, offshore Brazil; and (iii) the Upper Jurassic Magnus Sandstone Reservoir, in the Northern North Sea, UK continental shelf. This investigation utilises a variety of subsurface datasets, including 3D seismic-reflection surveys, petrophysical well logs, and core samples, which enables the deposits to be studied in 3D at passive margin-, system-, and bed-scale. The results establish that: (i) on a seismic-scale, the studied MTC did not balance the magnitude of updip extension with downdip contraction, and strain within the contractional domain was depth dependant, with deeper horizons accommodating more strain; (ii) degradational margins may follow a predictable stacking pattern of oversteepening and pre conditioning of the shelf-edge, followed by degradation and emplacement of the collapsed shelf-edge as MTCs, and demonstrates lateral (1-10 km-scale) variability in shelf-edge accretionary styles, and (iii) clay-rich, sub-seismic MTDs can act as competent seals to subsurface fluid flow, and transitional flow deposits may form baffles or barriers impacting sweep efficiency, compartmentalisation and hydrocarbon recovery from turbidite reservoirs. The range of scale of analysis presented here is essential to understand the scale, geometry, and internal characteristics of MTDs/MTCs, to reconstruct basin margin behaviour and to predict MTD rock property distribution.
URODASYS ELONGATUS N. SP. GASTROTRICHE MACRODASYOIDE NOUVEAU DU MÉIOBENTHOS DES TUAMOTU
Creators: name: RENAUD-MORNANT, J.
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 1969

description: This new species of Urodasys is characterized by its being obviously hermaphroditic, its numerous adhesive tubules (over five pairs) distributed along the pharyngeal area as well as the abdominal area; these formations being twice as long on the distal part of the caudal appendage.
title: Engineering site investigations
Creators: name: Crawford, C. B.
Publisher: name: National Research Council of Canada. Division of Building Research
Year: 1962
Subjects: subject: Basements and foundations
valueUri: urn:ircsubjects:IRC0320
subject: Sous-sol et fondations
valueUri: urn:ircsubjects:IRC0320
subject: site analysis
subject: analyse du site
subject: foundations
subject: fondation (ouvrage)
subject: soil investigation
subject: reconnaissance du sol
subject: geology
subject: géologie
subject: soil tests
subject: essai de sol
subject: plate bearing tests
subject: essai à la plaque

description: This Digest suggests the type of information that should be obtained by a proper investigation
Genetic drift promotes and recombination hinders speciation on holey fitness landscapes
Creators: name: Azevedo, Ricardo B. R.
name: Kalirad, Ata
name: Burch, Christina L.
Publisher: name: Public Library of Science
Year: 2024

description: Dobzhansky and Muller proposed a general mechanism through which microevolution, the substitution of alleles within populations, can cause the evolution of reproductive isolation between populations and, therefore, macroevolution. As allopatric populations diverge, many combinations of alleles differing between them have not been tested by natural selection and may thus be incompatible. Such genetic incompatibilities often cause low fitness in hybrids between species. Furthermore, the number of incompatibilities grows with the genetic distance between diverging populations. However, what determines the rate and pattern of accumulation of incompatibilities remains unclear. We investigate this question by simulating evolution on holey fitness landscapes on which genetic incompatibilities can be identified unambiguously. We find that genetic incompatibilities accumulate more slowly among genetically robust populations and identify two determinants of the accumulation rate: recombination rate and population size. In large populations with abundant genetic variation, recombination selects for increased genetic robustness and, consequently, incompatibilities accumulate more slowly. In small populations, genetic drift interferes with this process and promotes the accumulation of genetic incompatibilities. Our results suggest a novel mechanism by which genetic drift promotes and recombination hinders speciation.
Synchronization centrality and explosive synchronization in complex networks
Creators: name: Navas, A.
name: Villacorta-Atienza, J. A.
name: Leyva, I.
name: Almendral, J. A.
name: Sendiña-Nadal, I.
name: Boccaletti, S.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Adaptation and Self-Organizing Systems (nlin.AO)
subject: FOS: Physical sciences

description: Synchronization of networked oscillators is known to depend fundamentally on the interplay between the dynamics of the graph's units and the microscopic arrangement of the network's structure. For non identical elements, the lack of quantitative tools has hampered so far a systematic study of the mechanisms behind such a collective behavior. We here propose an effective network whose topological properties reflect the interplay between the topology and dynamics of the original network. On that basis, we are able to introduce the "synchronization centrality", a measure which quantifies the role and importance of each network's node in the synchronization process. In particular, we use such a measure to assess the propensity of a graph to synchronize explosively, thus indicating a unified framework for most of the different models proposed so far for such an irreversible transition. Taking advantage of the predicting power of this measure, we furthermore discuss a strategy to induce the explosive behavior in a generic network, by acting only upon a small fraction of its nodes.
The Assembly of Nonadhesive Fibrinogen Matrices Depends on the αC Regions of the Fibrinogen Molecule
Creators: name: Oshkadyerov, Stanislav P.
name: Podolnikova, Nataly P.
name: Yermolenko, Ivan S.
name: Ugarova, Tatiana P.
name: Lord, Susan T.
name: Fuhrmann, Alexander
name: Ros, Robert
name: Gorkun, Oleg V.
name: Lishko, Valeryi K.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Adsorption of fibrinogen on fibrin clots and other surfaces strongly reduces integrin-mediated adhesion of platelets and leukocytes with implications for the surface-mediated control of thrombus growth and blood compatibility of biomaterials. The underlying mechanism of this process is surface-induced aggregation of fibrinogen, resulting in the assembly of a nanoscale multilayered matrix. The matrix is extensible, which makes it incapable of transducing strong mechanical forces via cellular integrins, resulting in insufficient intracellular signaling and weak cell adhesion. To determine the mechanism of the multilayer formation, the physical and adhesive properties of fibrinogen matrices prepared from human plasma fibrinogen (hFg), recombinant normal (rFg), and fibrinogen with the truncated αC regions (FgAα251) were compared. Using atomic force microscopy and force spectroscopy, we show that whereas hFg and rFg generated the matrices with a thickness of ∼8 nm consisting of 7–8 molecular layers, the deposition of FgAα251 was terminated at two layers, indicating that the αC regions are essential for the multilayer formation. The extensibility of the matrix prepared from FgAα251 was 2-fold lower than that formed from hFg and rFg. In agreement with previous findings that cell adhesion inversely correlates with the extensibility of the fibrinogen matrix, the less extensible FgAα251 matrix and matrices generated from human fibrinogen variants lacking the αC regions supported sustained adhesion of leukocytes and platelets. The persistent adhesiveness of matrices formed from fibrinogen derivatives without the αC regions may have implications for conditions in which elevated levels of these molecules are found, including vascular pathologies, diabetes, thrombolytic therapy, and dysfibrinogenemia.
The Choreography of HIV-1 Proteolytic Processing and Virion Assembly
Creators: name: Lee, Sook Kyung
name: Swanstrom, Ronald
name: Potempa, Marc
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: HIV-1 has been the target of intensive research at the molecular and biochemical levels for >25 years. Collectively, this work has led to a detailed understanding of viral replication and the development of 24 approved drugs that have five different targets on various viral proteins and one cellular target (CCR5). Although most drugs target viral enzymatic activities, our detailed knowledge of so much of the viral life cycle is leading us into other types of inhibitors that can block or disrupt protein-protein interactions. Viruses have compact genomes and employ a strategy of using a small number of proteins that can form repeating structures to enclose space (i.e. condensing the viral genome inside of a protein shell), thus minimizing the need for a large protein coding capacity. This creates a relatively small number of critical protein-protein interactions that are essential for viral replication. For HIV-1, the Gag protein has the role of a polyprotein precursor that contains all of the structural proteins of the virion: matrix, capsid, spacer peptide 1, nucleocapsid, spacer peptide 2, and p6 (which contains protein-binding domains that interact with host proteins during budding). Similarly, the Gag-Pro-Pol precursor encodes most of the Gag protein but now includes the viral enzymes: protease, reverse transcriptase (with its associated RNase H activity), and integrase. Gag and Gag-Pro-Pol are the substrates of the viral protease, which is responsible for cleaving these precursors into their mature and fully active forms (see Fig. 1A).
Additional file 2 of Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission
Creators: name: Pooley, Christopher
name: Marion, Glenn
name: Bishop, Stephen
name: Doeschl-Wilson, Andrea
Publisher: name: figshare
Year: 2022
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Biotechnology
subject: 69999 Biological Sciences not elsewhere classified
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: Science Policy
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: 60506 Virology
subject: Computational Biology

description: Additional file 2: Derivation of the observed Fisher information matrix [45–47]. Description: This section derives analytical expressions for the matrix in Eq. (4).
(3940) Jean Jarvie
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
The N-terminal Phosphodegron Targets TAZ/WWTR1 Protein for SCF β-TrCP -dependent Degradation in Response to Phosphatidylinositol 3-Kinase Inhibition
Creators: name: Lei, Qun Ying
name: Xiong, Yue
name: Huang, Wei
name: Jiang, Ying
name: Guan, Kun Liang
name: Liu, Chenying
name: Zhang, Heng
name: Lv, Xianbo
name: Zha, Zhengyu
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: The Hippo tumor suppressor pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1) is a transcription co-activator acting downstream of the Hippo pathway, and increased TAZ protein levels have been associated with human cancers, such as breast cancer. Previous studies have shown that TAZ is inhibited by large tumor suppressor (LATS)-dependent phosphorylation, leading to cytoplasmic retention and ubiquitin-dependent degradation. The LATS kinase, a core component of the Hippo pathway, phosphorylates the C-terminal phosphodegron in TAZ to promote its degradation. In this study, we have found that the N-terminal phosphodegron of TAZ also plays a role in TAZ protein level regulation, particularly in response to different status of cellular PI3K signaling. GSK3, which can be inhibited by high PI3K via AKT-dependent inhibitory phosphorylation, phosphorylates the N-terminal phosphodegron in TAZ, and the phosphorylated TAZ binds to β-TrCP subunit of the SCFβ-TrCP E3 ubiquitin ligase, thereby leading to TAZ ubiquitylation and degradation. We observed that the TAZ protein level is elevated in tumor cells with high PI3K signaling, such as in PTEN mutant cancer cells. This study provides a novel mechanism of TAZ regulation and suggests a role of TAZ in modulating tissue growth and tumor development in response to PI3K signaling.