gebhart/patrepeval huggingface dataset:
Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries (2005)

Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast). The clr mutants derepressed similar subsets of genes, many of which also became transcriptionally activated in cells that were exposed to environmental stresses such as nitrogen starvation. Many genes that were repressed by the Clr proteins clustered in extended regions close to the telomeres. Surprisingly few genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing.
XML gets down to business (1999)

article XML gets down to business Share on Author: Aaron Weiss View Profile Authors Info & Claims netWorkerVolume 3Issue 3Sept. 1999 pp 36–43https://doi.org/10.1145/315129.315142Online:01 September 1999Publication History 6citation810DownloadsMetricsTotal Citations6Total Downloads810Last 12 Months2Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Immunization with Staphylococcus aureus Clumping Factor B, a Major Determinant in Nasal Carriage, Reduces Nasal Colonization in a Murine Model (2006)

Staphylococcus aureus is responsible for a wide range of infections, including soft tissue infections and potentially fatal bacteremias. The primary niche for S. aureus in humans is the nares, and nasal carriage is a documented risk factor for staphylococcal infection. Previous studies with rodent models of nasal colonization have implicated capsule and teichoic acid as staphylococcal surface factors that promote colonization. In this study, a mouse model of nasal colonization was utilized to demonstrate that S. aureus mutants that lack clumping factor A, collagen binding protein, fibronectin binding proteins A and B, polysaccharide intercellular adhesin, or the accessory gene regulator colonized as well as wild-type strains colonized. In contrast, mutants deficient in sortase A or clumping factor B (ClfB) showed reduced nasal colonization. Mice immunized intranasally with killed S. aureus cells showed reduced nasal colonization compared with control animals. Likewise, mice that were immunized systemically or intranasally with a recombinant vaccine composed of domain A of ClfB exhibited lower levels of colonization than control animals exhibited. A ClfB monoclonal antibody (MAb) inhibited S. aureus binding to mouse cytokeratin 10. Passive immunization of mice with this MAb resulted in reduced nasal colonization compared with the colonization observed after immunization with an isotype-matched control antibody. The mouse immunization studies demonstrate that ClfB is an attractive component for inclusion in a vaccine to reduce S. aureus nasal colonization in humans, which in turn may diminish the risk of staphylococcal infection. As targets for vaccine development and antimicrobial intervention are assessed, rodent nasal colonization models may be invaluable.
Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model (2010)

Harnessing the immune system to clear protein aggregates is emerging as a promising approach to treat various neurodegenerative diseases. In Alzheimer's disease (AD), several clinical trials are ongoing using active and passive immunotherapy targeting the amyloid-β (Aβ) peptide. Limited emphasis has been put into clearing tau/tangle pathology, another major hallmark of the disease. Recent findings from the first Aβ vaccination trial suggest that this approach has limited effect on tau pathology and that Aβ plaque clearance may not halt or slow the progression of dementia in individuals with mild-to-moderate AD. To assess within a reasonable timeframe whether targeting tau pathology with immunotherapy could prevent cognitive decline, we developed a new model with accelerated tangle development. It was generated by crossing available strains that express all six human tau isoforms and the M146L presenilin mutation. Here, we show that this unique approach completely prevents severe cognitive impairment in three different tests. This remarkable effect correlated well with extensive clearance of abnormal tau within the brain. Overall, our findings indicate that immunotherapy targeting pathological tau is very feasible for tauopathies, and should be assessed in clinical trials in the near future.
Rechargeable LiNiO2 / Carbon Cells (1991)

Rechargeable cells can be made using two different intercalation compounds, in which the chemical potential of the intercalant differs by several eV, for the electrodes. We discuss the factors that play a role in the selection of appropriate lithium intercalation compounds for such cells. For ease of cell assembly the cathode should be stable in air when it is fully intercalated, like . For the anode, the chemical potential of the intercalated Li should be close to that of Li metal, like it is in . We discuss the intercalation of Li in and then in petroleum coke. Then, we show that cells have high energy density, long cycle life, excellent high‐temperature performance, low self‐discharge rates, can be repeatedly discharged to zero volts without damage, and are easily fabricated. In our opinion this type of cell shows far more promise for widespread applications than traditional secondary Li cells using metallic Li anodes.
Molecular mechanisms of blood vessel growth (2001)

The basic molecular mechanisms governing how endothelial cells, periendothelial cells and matrix molecules interact with each other and with numerous growth factors and receptors, to form blood vessels have been presented. The many insights gained from this basic knowledge are being extended to further understand pathological angiogenesis associated with disorders such as arterial stenosis, myocardial ischemia, atherosclerosis, allograft transplant stenosis. wound healing and tissue repair. As a result, novel angiogenic and anti-angiogenic molecules are rapid-ly entering the clinic, with the promise of relief from a host of medical disorders.
Both insulin and epidermal growth factor stimulate lipogenesis and acetyl-CoA carboxylase activity in isolated adipocytes. Importance of homogenization procedure in avoiding artefacts in acetyl-CoA carboxylase assay (1986)

Epidermal growth factor (EGF) stimulates lipogenesis by 3-4-fold in isolated adipocytes, with a half-maximal effect at 10 nM-EGF. In the same batches of cells insulin stimulated lipogenesis by 15-fold. Freezing and prolonged homogenization of adipocytes results in release of large quantities of pyruvate carboxylase from broken mitochondria, and sufficient pyruvate can be carried through into assays for this enzyme to cause significant interference with assays of acetyl-CoA carboxylase in crude adipocyte extracts. This may account for the high amount of citrate-independent acetyl-CoA carboxylase activity reported to be present in adipocyte extracts in some previous publications. This problem may be eliminated by homogenizing very briefly without freezing. By using the modified homogenization procedure, EGF treatment of adipocytes was shown to produce an effect on acetyl-CoA carboxylase activity almost identical with that of insulin. Both messengers increase Vmax. without significant effect on the Ka for the allosteric activator, citrate.
β-Casein Adsorption at the Silicon Oxide-Aqueous Solution Interface:  Calcium Ion Effects (2004)

Neutron reflectometry was used to investigate effects of calcium ions on the interfacial behavior of beta-casein at the silicon oxide-aqueous solution interface. The structural characteristics of the adsorbed layer were determined from reflectivity curves fitted to three- and two-layer optical models. The results showed that the presence of divalent calcium ions decreased the specific electrostatic adsorption affinity of the protein to silica compared with the calcium-free buffer system studied in an earlier work. In addition, it speeded up the adsorption suggesting that the slow kinetics seen in the calcium-free system are related to conformational adjustments of the beta-casein structure driven by the maximization of the number of positive charges on the polypeptide interacting with negative surface charges. In the calcium-free system, a dense inner layer resulted from this process, with cationic segments firmly bound to the negative surface, whereas in the presence of calcium, a less dense inner layer was formed. The difference in binding is also mirrored by the effects on the interfacial layer of a specific proteolytic enzyme, i.e., endoproteinase Asp-N. In the calcium-free case, an inner dense layer remained at the surface after the proteolytic cleavage of the polypeptide, whereas virtually nothing was left after enzymatic action in the presence of calcium ions.
The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination (2000)

Analysis of several mutations in the mouse is providing useful insights into the nature of the genes required for the establishment of the left-right axis during early development. Here we describe a new targeted allele of the mouse Tg737 gene, Tg737(Delta)2-3(beta)Gal), which causes defects in left-right asymmetry and other abnormalities during embryogenesis. The Tg737 gene was originally identified based on its association with the mouse Oak Ridge Polycystic Kidney (orpk) insertional mutation, which causes polycystic kidney disease and other defects. Complementation tests between the original orpk mutation and the new targeted knock-out mutation demonstrate that Tg737(Delta)2-3(beta)Gal) behaves as an allele of Tg737. The differences in the phenotype between the two mutations suggest that the orpk mutation is a hypomorphic allele of the Tg737 gene. Unlike the orpk allele, where all homozygotes survive to birth, embryos homozygous for the Tg737(Delta)2-3(beta)Gal) mutation arrest in development at mid-gestation and exhibit neural tube defects, enlargement of the pericardial sac and, most notably, left-right asymmetry defects. At mid-gestation the direction of heart looping is randomized, and at earlier stages in development lefty-2 and nodal, which are normally expressed asymmetrically, exhibit symmetrical expression in the mutant embryos. Additionally, we determined that the ventral node cells in mutant embryos fail to express the central cilium, which is a characteristic and potentially functional feature of these cells. The expression of both Shh and Hnf3(beta) is downregulated in the midline at E8.0, indicating that there are significant alterations in midline development in the Tg737(Delta)2-3(beta)Gal) homozygous embryos. We propose that the failure of ventral node cells to fully mature alters their ability to undergo differentiation as they migrate out of the node to contribute to the developing midline structures. Analysis of this new knockout allele allows us to define a critical role for the Tg737 gene during early embryogenesis. We have named the product of the Tg737 gene Polaris, which is based on the various polarity related defects associated with the different alleles of the Tg737 gene.
Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis (2011)

Cellular microvesicles and nanovesicles (exosomes) are involved in many disease processes and have major potential as biomarkers. However, developments in this area are constrained by limitations in the technology available for their measurement. Here we report on the use of fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles. In this system vesicles are visualized by light scattering using a light microscope. A video is taken, and the NTA software tracks the brownian motion of individual vesicles and calculates their size and total concentration. Using human placental vesicles and plasma, we have demonstrated that NTA can measure cellular vesicles as small as ∼50 nm and is far more sensitive than conventional flow cytometry (lower limit ∼300 nm). By combining NTA with fluorescence measurement we have demonstrated that vesicles can be labeled with specific antibody-conjugated quantum dots, allowing their phenotype to be determined. The authors of this study utilized fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles, demonstrating that NTA is far more sensitive than conventional flow cytometry.
RAPID AND EFFICIENT PHOSPHONATION OF ARYL HALIDES CATALYSED BY PALLADIUM UNDER MICROWAVES IRRADIATION (1997)

Abstract Diethyl arylphosphonates are efficiently and rapidly prepared from aryl halides, by a palladium catalysis, performed in a Teflon autoclave under microwave radiation generated by a commercial microwave oven.
Learning Individual Styles of Conversational Gesture (2019)

Human speech is often accompanied by hand and arm gestures. We present a method for cross-modal translation from "in-the-wild" monologue speech of a single speaker to their conversational gesture motion. We train on unlabeled videos for which we only have noisy pseudo ground truth from an automatic pose detection system. Our proposed model significantly outperforms baseline methods in a quantitative comparison. To support research toward obtaining a computational understanding of the relationship between gesture and speech, we release a large video dataset of person-specific gestures.
Learning text analysis rules for domain-specific natural language processing (1996)

An enormous amount of knowledge is needed to infer the meaning of unrestricted natural language. The problem can be reduced to a manageable size by restricting attention to a specific domain, which is a corpus of texts together with a predefined set of concepts that are of interest to that domain. Two widely different domains are used to illustrate this domain-specific approach. One domain is a collection of Wall Street Journal articles in which the target concept is management succession events: identifying persons moving into corporate management positions or moving out. A second domain is a collection of hospital discharge summaries in which the target concepts are various classes of diagnosis or symptom. The goal of an information extraction system is to identify references to the concept of interest for a particular domain. A key knowledge source for this purpose is a set of text analysis rules based on the vocabulary, semantic classes, and writing style peculiar to the domain. This thesis presents CRYSTAL, an implemented system that automatically induces domain-specific text analysis rules from training examples. CRYSTAL learns rules that approach the performance of hand-coded rules, are robust in the face of noise and inadequate features, and require only a modest amount of training data. CRYSTAL belongs to a class of machine learning algorithms called covering algorithms, and presents a novel control strategy with time and space complexities that are independent of the number of features. CRYSTAL navigates efficiently through an extremely large space of possible rules. CRYSTAL also demonstrates that expressive rule representation is essential for high performance, robust text analysis rules. While simple rules are adequate to capture the most salient regularities in the training data, high performance can only be achieved when rules are expressive enough to reflect the subtlety and variability of unrestricted natural language.
Prototyping of Masks, Masters, and Stamps/Molds for Soft Lithography Using an Office Printer and Photographic Reduction (2000)

This paper describes a practical method for the fabrication of photomasks, masters, and stamps/molds used in soft lithography that minimizes the need for specialized equipment. In this method, CAD files are first printed onto paper using an office printer with resolution of 600 dots/in. Photographic reduction of these printed patterns transfers the images onto 35-mm film or microfiche. These photographic films can be used, after development, as photomasks in 1:1 contact photolithography. With the resulting photoresist masters, it is straightforward to fabricate poly(dimethylsiloxane) (PDMS) stamps/molds for soft lithography. This process can generate microstructures as small as 15 microm; the overall time to go from CAD file to PDMS stamp is 4-24 h. Although access to equipment-spin coater and ultraviolet exposure tool-normally found in the clean room is still required, the cost of the photomask itself is small, and the time required to go from concept to device is short. A comparison between this method and all other methods that generate film-type photomasks has been performed using test patterns of lines, squares, and circles. Three microstructures have also been fabricated to demonstrate the utility of this method in practical applications.
Olefin cross-metathesis, a mild, modular approach to functionalized cellulose esters (2014)

Olefin cross-metathesis has been demonstrated to be a modular pathway for synthesis of a series of functionalized cellulose esters. As a proof of concept, cellulose acetate was acylated with two terminally olefinic acid chlorides, pent-4-enoyl chloride and undec-10-enoyl chloride, providing olefin-terminated cellulose esters with different side-chain lengths. These ω-unsaturated cellulose esters were then reacted with a variety of cross-metathesis partners, including acrylic acid, methyl acrylate, 2-hydroxyethyl acrylate, poly(ethylene glycol) methyl ether acrylate, and allyl alcohols, using Hoveyda–Grubbs’ 2nd generation catalyst. Complete conversion to cross-metathesis products was achieved in reactions with acrylic acid or acrylates using 3–5 mol% catalyst at 40 °C within 1 h. We further demonstrate successful hydrogenation of these α,β-unsaturated esters and acids, thereby eliminating the potential for radical-induced crosslinking during storage.
Purification and Properties of Two Thermostable Alkaline Xylanases from an Alkaliphilic Bacillus sp (1998)

Two xylanases, designated XylA and XylB, were purified from the culture supernatant of the alkaliphilic Bacillus sp. strain AR-009. The molecular masses of the two enzymes were estimated to be 23 kDa (XylA) and 48 kDa (XylB) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The optimum pHs for activity were 9 for XylA and 9 to 10 for XylB. The temperature optima for the activity of XylA were 60 degreesC at pH 9 and 70 degreesC at pH 8. XylB was optimally active at 75 degreesC at pH 9 and 70 degreesC at pH 8. Both enzymes were stable in a broad pH range and showed good stability when incubated at 60 and 65 degreesC in pH 8 and 9 buffers.
Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype (1999)

Hereditary peripheral neuropathies represent a spectrum of disorders due to underlying defects in myelin structure or formation.
A Comparative Study on Excess-Loop-Delay Compensation Techniques for Continuous-Time Sigma–Delta Modulators (2008)

Excess loop delay (ELD) is well known for its detrimental effect on the performance and stability of continuous-time sigma-delta modulators. A detailed analysis on the most recently published compensation techniques for single-stage modulators is performed in this paper, thus enabling their application to an arbitrary modulator. Based on different characteristics such as circuit complexity, achievable dynamic range, or requirements on the operational amplifiers, their advantages and disadvantages are investigated. Subsequently, the analysis is extended to cascaded modulators. Contrary to intuition, the results indicate that a compensation of ELD in every stage of the cascade is insufficient for optimal performance. Although not configured in a feedback configuration and as such not suffering from stability problems, each coupling network between two stages must additionally be compensated for ELD.
An ErbB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation (2010)

ErbB3 is a critical activator of phosphoinositide 3-kinase (PI3K) signaling in epidermal growth factor receptor (EGFR; ErbB1), ErbB2 [human epidermal growth factor receptor 2 (HER2)], and [hepatocyte growth factor receptor (MET)] addicted cancers, and reactivation of ErbB3 is a prominent method for cancers to become resistant to ErbB inhibitors. In this study, we evaluated the in vivo efficacy of a therapeutic anti-ErbB3 antibody, MM-121. We found that MM-121 effectively blocked ligand-dependent activation of ErbB3 induced by either EGFR, HER2, or MET. Assessment of several cancer cell lines revealed that MM-121 reduced basal ErbB3 phosphorylation most effectively in cancers possessing ligand-dependent activation of ErbB3. In those cancers, MM-121 treatment led to decreased ErbB3 phosphorylation and, in some instances, decreased ErbB3 expression. The efficacy of single-agent MM-121 was also examined in xenograft models. A machine learning algorithm found that MM-121 was most effective against xenografts with evidence of ligand-dependent activation of ErbB3. We subsequently investigated whether MM-121 treatment could abrogate resistance to anti-EGFR therapies by preventing reactivation of ErbB3. We observed that an EGFR mutant lung cancer cell line (HCC827), made resistant to gefitinib by exogenous heregulin, was resensitized by MM-121. In addition, we found that a de novo lung cancer mouse model induced by EGFR T790M-L858R rapidly became resistant to cetuximab. Resistance was associated with an increase in heregulin expression and ErbB3 activation. However, concomitant cetuximab treatment with MM-121 blocked reactivation of ErbB3 and resulted in a sustained and durable response. Thus, these results suggest that targeting ErbB3 with MM-121 can be an effective therapeutic strategy for cancers with ligand-dependent activation of ErbB3.
Unmet needs: Research helps regulators do their jobs (2015)

A plethora of innovative new medical products along with the need to apply modern technologies to medical-product evaluation has spurred seminal opportunities in regulatory sciences. Here, we provide eight examples of regulatory science research for diverse products. Opportunities abound, particularly in data science and precision health.
Sialic acid is an essential moiety of mucin as a hydroxyl radical scavenger (2007)

In this work, we examined the antioxidant role of mucin, a typical sialic acid containing high-molecular weight glycoprotein. The function of mucin as a hydroxyl radical (.OH) scavenger was characterized using bovine submaxillary gland mucin (BSM). Non-treated BSM effectively protected DNA from the attack of .OH; however, desialylated BSM lost this potential. Moreover, we estimated the scavenging effects of BSM against .OH generated by UV irradiation of hydrogen peroxide using ESR analysis. Our results indicate that BSM has .OH scavenging ability the and sialic acid in mucin is an essential moiety to scavenge .OH.