gebhart/patrepeval huggingface dataset:
Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans. (1996)

Speed and selectivity of hepatocyte invasion by malaria sporozoites have suggested a receptor-mediated mechanism and the specific interaction of the circumsporozoite (CS) protein with liver-specific heparan sulfate proteoglycans (HSPGs) has been implicated in the targeting to the liver. Here we show that the CS protein interacts not only with cell surface heparan sulfate, but also with the low density lipoprotein receptor-related protein (LRP). Binding of 125I-CS protein to purified LRP occurs with a Kd of 4.9 nM and can be inhibited by the receptor-associated protein (RAP). Blockage of LRP by RAP or anti-LRP antibodies on heparan sulfate-deficient CHO cells results in more than 90% inhibition of binding and endocytosis of recombinant CS protein. Conversely, blockage or enzymatic removal of the cell surface heparan sulfate from LRP-deficient embryonic mouse fibroblasts yields the same degree of inhibition. Heparinase-pretreatment of LRP-deficient fibroblasts or blockage of LRP on heparan sulfate-deficient CHO cells by RAP, lactoferrin, or anti-LRP antibodies reduces Plasmodium berghei invasion by 60-70%. Parasite development in heparinase-pretreated HepG2 cells is inhibited by 65% when RAP is present during sporozoite invasion. These findings suggest that malaria sporozoites utilize the interaction of the CS protein with HSPGs and LRP as the major mechanism for host cell invasion.
Impact of ion-host interactions on the5d-to-4fspectra of lanthanide rare-earth-metal ions. I. A phenomenological crystal-field model (1986)

Dielectric crystals doped with ${\mathrm{Ce}}^{3+}$, ${\mathrm{Eu}}^{2+}$, ${\mathrm{Sm}}^{2+}$, and ${\mathrm{Yb}}^{2+}$ display broadband 5d-to-4f emission, and are candidate solid-state tunable laser materials. The absorption and emission wavelengths, however, are very host sensitive, and a better understanding of 5d crystal-field interactions is needed in order to design lasing materials. This paper focuses on the 5d energy levels of ${\mathrm{Ce}}^{3+}$ in an octahedral complex. A phenomenological model is proposed for the bond-distance dependence of these levels based on first-principles expressions derived by others for contributions to the crystal-field energies. The magnitudes of these contributions are estimated for the ${\mathrm{CeF}}_{6}$ complex.
Inhibition of CD44 Expression by Small Interfering RNA to Suppress the Growth and Metastasis of Ovarian Cancer Cells in Vitro and in Vivo (2008)

Since ovarian cancer cells express CD44, which causes very strong cell adhesion to peritoneal mesothelium and an unfavourable prognosis, we designed small interfering RNA (siRNA) targeting the CD44 gene to analyse the functional consequences of this inhibition in human ovarian cancer. We transfected ovarian cancer cell line SKOV-3 with well-designed CD44 siRNA or control siRNA. Western blot analysis was used to assess the CD44 expression. Following stable transfection, significant inhibition of CD44 expression with 66.13 +/- 4.21 % (P < 0.05) in CD44 siRNA1 cells and 62.01 +/- 3.97 % (P < 0.05) in CD44 siRNA2 cells was detected. We performed in vitro experiments including cellular adhesion to hyaluronan and human peritoneal mesothelial cells, etoposide-induced apoptosis, and Boyden chamber invasion assays. The adhesion percentages of CD44 siRNA1 and CD44 siRNA2 cells were significantly lower than those of the control siRNA cells in adhesion both to hyaluronan and to human peritoneal mesothelium. The CD44 siRNA transfectants showed significant inhibition of in vitro invasion and loss of resistance to apoptosis than the control siRNA cells. In vivo study with BALB/c mice was applied to compare the tumour growth and peritoneal dissemination. Nude mice treated with CD44 siRNA cells revealed significantly lower tumour volume and less peritoneal dissemination compared to mice treated with the control siRNA cells. In conclusion, downregulation of CD44 expression by siRNA inhibits the in vitro adhesion, invasion and resistance to apoptosis of ovarian cancer cells, suppresses tumour growth and peritoneal dissemination of human ovarian cancer xenograft in nude mice.
High-Affinity Inhibitors of Dihydrofolate Reductase:  Antimicrobial and Anticancer Activities of 7,8-Dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with Small Molecular Size (1996)

A series of 7,8-dialkylpyrrolo[3,2-f]quinazolines were prepared as inhibitors of dihydrofolate reductase (DHFR). On the basis of an apparent inverse relationship between compound size and antifungal activity, the compounds were designed to be relatively small and compact. Inhibitor design was aided by GRID analysis of the three-dimensional structure of Candida albicans DHFR, which suggested that relatively small, branched alkyl groups at the 7- and 8-positions of the pyrroloquinazoline ring system would provide optimal interactions with a hydrophobic region of the protein. The compounds were potent inhibitors of fungal and human DHFR, with K(i) values as low as 7.1 and 0.1 pM, respectively, and were highly active against C. albicans and an array of tumor cell lines. In contrast to known lipophilic inhibitors of DHFR such as trimetrexate and piritrexim, members of this series of pyrroloquinazolines were not susceptible to P-glycoprotein-mediated multidrug resistance and also showed significant distribution into lung and brain tissue. The compounds were active in lung and brain tumor models and displayed in vivo activity against Pneumocystis carinii and C. albicans.
Sequential Adeno-Associated Viral Vector Serotype 9–Green Fluorescent Protein Gene Transfer Causes Massive Inflammation and Intense Immune Response in Rat Striatum (2016)

Green fluorescent protein (GFP) is a broadly used live cell reporter for gene transduction although side effects associated with GFP in gene transfer are reported. The present study was designed to systematically examine host responses, including inflammatory and immune responses, induced by persistent overexpression of the GFP gene mediated by adeno-associated viral vector serotype 9 (AAV9), and their effects on GFP gene transduction in rat striatum. Our results show that host responses against AAV9-GFP transduction, and GFP transgene expression in the striatum exhibited a temporal and dose-dependent pattern. Both muscular and striatal delivery of AAV9-GFP increased levels of inflammation and immune reactions against sequential AAV9-GFP transduction in the striatum, leading to reduced levels of GFP expression. We also observed that rat sera from sequential administrations of AAV9-GFP group had significantly higher levels of neutralizing antibody against AAV9 vectors when compared with the age-matched rats. As excessive GFP can trigger vigorous inflammation and intense immune response after GFP gene transduction, the use of GFP as a live cell marker protein should be deliberated, especially in repeated administration studies.
Divergent Therapeutic and Immunologic Effects of Oligodeoxynucleotides with Distinct CpG Motifs (2001)

Immune stimulatory oligodeoxynucleotides (ODN) with unmethylated CpG motifs are potent inducers of both innate and adaptive immunity. It initially appeared that a single type of optimal CpG motif would work in all applications. We now report that specific motifs of CpG ODN can vary dramatically in their ability to induce individual immune effects and that these differences impact on their antitumor activity in different tumor models. In particular, a distinct type of CpG motif, which has a chimeric backbone in combination with poly(G) tails, is a potent inducer of NK lytic activity but has little effect on cytokine secretion or B cell proliferation. One such NK-optimized CpG ODN (1585) can induce regression of established melanomas in mice. Surprisingly, no such therapeutic effects were seen with CpG ODN optimized for activation of B cells and Th1-like cytokine expression (ODN 1826). The therapeutic effects of CpG 1585 in melanoma required the presence of NK but not T or B cells and were not associated with the induction of a tumor-specific memory response. In contrast, CpG 1826, but not CpG 1585, was effective at inducing regression of the EL4 murine lymphoma; this rejection was associated with the induction of a memory response and although NK cells were necessary, they were not sufficient. These results demonstrate that selection of optimal CpG ODN for cancer immunotherapy depends upon a careful analysis of the cellular specificities of various CpG motifs and an understanding of the cellular mechanisms responsible for the antitumor activity in a particular tumor.
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters (2012)

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
Affordances for manipulation of physical versus digital media on interactive surfaces (2007)

This work presents the results of a comparative study in which we investigate the ways manipulation of physical versus digital media are fundamentally different from one another. Participants carried out both a puzzle task and a photo sorting task in two different modes: in a physical 3-dimensional space and on a multi-touch, interactive tabletop in which the digital items resembled their physical counterparts in terms of appearance and behavior. By observing the interaction behaviors of 12 participants, we explore the main differences and discuss what this means for designing interactive surfaces which use aspects of the physical world as a design resource.
Temporal interferometric measurement of femtosecond spectral phase (1996)

Fourier spectral analysis of temporal interference resulting from beats between a reference optical frequency and a number of spectral components of a femtosecond optical pulse yields the spectral phase directly without the need for iterative calculations. A periodic multiple-slit mask placed in the Fourier plane of a femtosecond pulse shaper selects an ensemble of frequency components for measurement by cross correlation. An additional, out-of-period slit selects the reference frequency so that none of the desired beat tones overlaps redundant tones. We measure positive and negative cubic phase distortion introduced when the pulse shaper lens is tilted and the phase discontinuity of a 0-pi pulse (odd pulse) with a 13-slit mask. Finally, we demonstrate measurement of the spectral phase associated with true time delays with 17 slits.
Synergies in Wireless Telephony: Evidence from the Broadband PCS Auctions (1997)

We examine bid data from the first two broadband PCS spectrum auctions for evidence of value synergies.First, we estimate a benchmark regression for the determinants of final auction prices.Then, we include variables reflecting the extent to which bidders ultimately won or already owned the adjacent wireless properties.Consistent with geographic synergies in an ascending-bid auction, prices were higher when the highest-losing bidder had adjacent licenses.The footprints of winning bidders suggest that they were often successful in realizing these synergies.
Mainstream or margin? The current use of family group conferences in child welfare practice in the UK (2003)

ABSTRACT A decade has passed since family group conferences were initially introduced into the UK by Family Rights Group. Ten years on, this paper examines the extent to which family group conferences have developed and become embedded into current social work practice. Despite the initial interest by social work practitioners and the picture often painted of a growing radical movement, the degree to which family group conferencing has become part of mainstream practice has until now remained fairly anecdotal. A number of difficulties have been identified with implementing the model, including fitting it into an existing system and the challenge it poses to professionals to hand over power. Two surveys, the first undertaken in 1999 and the second in 2001, describe the current use of the model in the UK by Councils with Social Services Responsibilities (Councils). The surveys reveal the areas of practice within which family group conferences are being used, the size and capacity of projects and why some Councils have adopted the model whilst others remain hesitant. It concludes by considering why family group conferences remain on the margins of practice.
Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent (2015)

Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- and intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1-10 μM) can result in cell death.
Video-on-Demand Networks: Design Approaches and Future Challenges (2007)

IP network based deployments of interactive video-on-demand (VoD) systems are today very limited in scope, but there is a strong belief among telecommunication companies that this market will expand exponentially in the next few years. In this article, we outline the components of VoD architectures and survey the current approaches to their design. We strive to identify the research challenges that must be addressed in the development of design tools that can determine how to expand upon an existing network infrastructure to support video-on-demand. The long tail of content and extensive growth in usage are expected to have a major impact on the streaming and storage requirements of such systems. Hybrid VoD architectures that incorporate peer-to-peer exchange are an extremely promising paradigm, but there are many challenges in developing operational and economically feasible peer-to-peer systems. VoD networks generate sufficient traffic that their impact should be considered in planning general network infrastructure expansions
Plasma Membrane Lipid Alterations Associated with Cold Acclimation of Winter Rye Seedlings (Secale cereale L. cv Puma) (1987)

Highly enriched plasma membrane fractions were isolated from leaves of nonacclimated (NA) and acclimated (ACC) rye (Secale cereale L. cv Puma) seedlings. Collectively, free sterols, steryl glucosides, and acylated steryl glucosides constituted >50 mole% of the total lipid in both NA and ACC plasma membrane fractions. Glucocerebrosides containing hydroxy fatty acids constituted the major glycolipid class of the plasma membrane, accounting for 16 mole% of the total lipid. Phospholipids, primarily phosphatidylcholine and phosphatidylethanolamine with lesser amounts of phosphatidylglycerol, phosphatidic acid, phosphatidylserine, and phosphatidylinositol, comprised only 32 mole% of the total lipid in NA samples. Following cold acclimation, free sterols increased from 33 to 44 mole%, while steryl glucosides and acylated steryl glucosides decreased from 15 to 6 mole% and 4 to 1 mole%, respectively. Sterol analyses of these lipid classes demonstrated that free beta-sitosterol increased from 21 to 32 mole% (accounting for the increase in free sterols as a class) at the expense of sterol derivatives containing beta-sitosterol. Glucocerebrosides decreased from 16 to 7 mole% of the total lipid following cold acclimation. In addition, the relative proportions of associated hydroxy fatty acids, including 22:0 (h), 24:0 (h), 22:1 (h), and 24:1 (h), were altered. The phospholipid content of the plasma membrane fraction increased to 42 mole% of the total lipid following cold acclimation. Although the relative proportions of the individual phospholipids did not change appreciably after cold acclimation, there were substantial differences in the molecular species. Di-unsaturated molecular species (18:2/18:2, 18:2/18:3, 18:3/18:3) of phosphatidylcholine and phosphatidylethanolamine increased following acclimation. These results demonstrate that cold acclimation results in substantial changes in the lipid composition of the plasma membrane.
Specific Calpain Inhibition by Calpastatin Prevents Tauopathy and Neurodegeneration and Restores Normal Lifespan in Tau P301L Mice (2014)

Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5. Calpain overactivation in brains of these mice is accelerated as a result of the marked depletion of the endogenous calpain inhibitor, calpastatin. When levels of this inhibitor are restored in neurons of JNPL3 mice by overexpressing calpastatin, tauopathy is prevented, including calpain-mediated breakdown of cytoskeletal proteins, cdk5 activation, tau hyperphosphorylation, formation of potentially neurotoxic tau fragments by either calpain or caspase-3, and tau oligomerization. Calpastatin overexpression also prevents loss of motor axons, delays disease onset, and extends survival of JNPL3 mice by 3 months to within the range of normal lifespan. Our findings support the therapeutic promise of highly specific calpain inhibition in the treatment of tauopathies and other neurodegenerative states.
Toshiba’s proactive approach to employee well‐being (2005)

Susan Stevens, head of HR at Toshiba Information Systems UK, describes how the company developed a strategy to measure and improve absence rates and overall employee well‐being.
Simultaneous synthesis of enantiomerically pure (S)‐amino acids and (R)‐amines using coupled transaminase reactions (2003)

For the simultaneous synthesis of enatiomerically pure (S)-amino acids and (R)-amines from corresponding alpha-keto acids and racemic amines, an alpha/omega-transaminase coupled reaction system was designed using favorable reaction equilibrium shift led by omega-transaminase reaction. Cloned tyrB, aspC and avtA, and omegataA were co-expressed in E. coli BL21(DE3) using pET23b(+) and pET24ma, respectively. The coupled reaction produced the (S)-amino acids with 73-90% (> 99% ee(S)) of conversion yield and resolved the racemic amines with 83-99% ee(R) for 5 to 10 hours. In designing the coupled reactions in the cell, alanine and pyruvate were efficiently used in the cell as an amine donor for the alanine transaminase and an amino acceptor for the omega-transaminase, respectively, resulting in an alanine-pyruvate shuttling system. The common problem of the low equilibrium constant of the alpha-transaminase can be efficiently overcome by the coupling with the omega-transaminase. However, overcoming the product inhibition of omega-transaminase by the ketone by-product and increasing the decarboxylation rate of the oxaloacetate produced during the transaminase reaction become barriers to further improving the overall reaction rate and the yield of the coupled reactions.
The Effects of Intercorporate Networks on Corporate Social and Political Behaviour (2006)

ESRC
Targeting glutamine transport to suppress melanoma cell growth (2014)

Amino acids, especially leucine and glutamine, are important for tumor cell growth, survival and metabolism. A range of different transporters deliver each specific amino acid into cells, some of which are increased in cancer. These amino acids consequently activate the mTORC1 pathway and drive cell cycle progression. The leucine transporter LAT1/4F2hc heterodimer assembles as part of a large complex with the glutamine transporter ASCT2 to transport amino acids. In this study, we show that the expression of LAT1 and ASCT2 is significantly increased in human melanoma samples and is present in both BRAF(WT) (C8161 and WM852) and BRAF(V600E) mutant (1205Lu and 451Lu) melanoma cell lines. While inhibition of LAT1 by BCH did not suppress melanoma cell growth, the ASCT2 inhibitor BenSer significantly reduced both leucine and glutamine transport in melanoma cells, leading to inhibition of mTORC1 signaling. Cell proliferation and cell cycle progression were significantly reduced in the presence of BenSer in melanoma cells in 2D and 3D cell culture. This included reduced expression of the cell cycle regulators CDK1 and UBE2C. The importance of ASCT2 expression in melanoma was confirmed by shRNA knockdown, which inhibited glutamine uptake, mTORC1 signaling and cell proliferation. Taken together, our study demonstrates that ASCT2-mediated glutamine transport is a potential therapeutic target for both BRAF(WT) and BRAF(V600E) melanoma.
Comparing the continuous representation of time-series expression profiles to identify differentially expressed genes (2003)

We present a general algorithm to detect genes differentially expressed between two nonhomogeneous time-series data sets. As increasing amounts of high-throughput biological data become available, a major challenge in genomic and computational biology is to develop methods for comparing data from different experimental sources. Time-series whole-genome expression data are a particularly valuable source of information because they can describe an unfolding biological process such as the cell cycle or immune response. However, comparisons of time-series expression data sets are hindered by biological and experimental inconsistencies such as differences in sampling rate, variations in the timing of biological processes, and the lack of repeats. Our algorithm overcomes these difficulties by using a continuous representation for time-series data and combining a noise model for individual samples with a global difference measure. We introduce a corresponding statistical method for computing the significance of this differential expression measure. We used our algorithm to compare cell-cycle-dependent gene expression in wild-type and knockout yeast strains. Our algorithm identified a set of 56 differentially expressed genes, and these results were validated by using independent protein-DNA-binding data. Unlike previous methods, our algorithm was also able to identify 22 non-cell-cycle-regulated genes as differentially expressed. This set of genes is significantly correlated in a set of independent expression experiments, suggesting additional roles for the transcription factors Fkh1 and Fkh2 in controlling cellular activity in yeast.
An update on the genetics of schizophrenia (2006)

The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research. Despite the accumulation of significant genetic data, however, the susceptibility variants have yet to be identified and detailed follow-up studies are now required.