gebhart/patrepeval huggingface dataset:
Signaling Events Induced by Lipopolysaccharide-Activated Toll-Like Receptor 2 (1999)

Human Toll-like receptor 2 (TLR2) is a signaling receptor that responds to LPS and activates NF-kappaB. Here, we investigate further the events triggered by TLR2 in response to LPS. We show that TLR2 associates with the high-affinity LPS binding protein membrane CD14 to serve as an LPS receptor complex, and that LPS treatment enhances the oligomerization of TLR2. Concomitant with receptor oligomerization, the IL-1R-associated kinase (IRAK) is recruited to the TLR2 complex. Intracellular deletion variants of TLR2 lacking C-terminal 13 or 141 aa fail to recruit IRAK, which is consistent with the inability of these mutants to transmit LPS cellular signaling. Moreover, both deletion mutants could still form complexes with wild-type TLR2 and act in a dominant-negative (DN) fashion to block TLR2-mediated signal transduction. DN constructs of myeloid differentiation protein, IRAK, TNF receptor-associated factor 6, and NF-kappaB-inducing kinase, when coexpressed with TLR2, abrogate TLR2-mediated NF-kappaB activation. These results reveal a conserved signaling pathway for TLR2 and IL-1Rs and suggest a molecular mechanism for the inhibition of TLR2 by DN variants.
Encoding of Direction of Fingertip Forces by Human Tactile Afferents (2001)

In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode the direction of fingertip forces at magnitudes, rates, and directions comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to a standard site on the fingertip while recording impulse activity in 196 tactile afferents with receptive fields distributed over the entire terminal phalanx. Forces were applied in one of five directions: normal force and forces at a 20 degrees angle from the normal in the radial, distal, ulnar, or proximal directions. Nearly all afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and fast adapting (FA)-I afferents were broadly tuned to a preferred direction of force. Among afferents of each type, the preferred directions were distributed in all angular directions with reference to the stimulation site, but not uniformly. The SA-I population was biased for tangential force components in the distal direction, the SA-II population was biased in the proximal direction, and the FA-I population was biased in the proximal and radial directions. Anisotropic mechanical properties of the fingertip and the spatial relationship between the receptive field center of the afferent and the stimulus site appeared to influence the preferred direction in a manner dependent on afferent type. We conclude that tactile afferents from the whole terminal phalanx potentially contribute to the encoding of direction of fingertip forces similar to those that occur when subjects manipulate objects under natural conditions.
Nonthermal Irreversible Electroporation for Tissue Decellularization (2010)

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature's ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body's host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.
Validation of a Clostridium Endospore Viability Assay and Analysis of Greenland Ices and Atacama Desert Soils (2011)

A microscopy-based endospore viability assay (micro-EVA) capable of enumerating germinable Clostridium endospores (GCEs) in less than 30 min has been validated and employed to determine GCE concentrations in Greenland ices and Atacama Desert soils. Inoculation onto agarose doped with Tb(3+) and d-alanine triggers Clostridium spore germination and the concomitant release of ∼10(8) molecules of dipicolinic acid (DPA) per endospore, which, under pulsed UV excitation, enables enumeration of resultant green Tb(3+)-DPA luminescent spots as GCEs with time-gated luminescence microscopy. The intensity time courses of the luminescent spots were characteristic of stage I Clostridium spore germination dynamics. Micro-EVA was validated against traditional CFU cultivation from 0 to 1,000 total endospores/ml (i.e., phase-bright bodies/ml), yielding 56.4% ± 1.5% GCEs and 43.0% ± 1.0% CFU. We also show that d-alanine serves as a Clostridium-specific germinant (three species tested) that inhibits Bacillus germination of spores (five species tested) in that endospore concentration regime. Finally, GCE concentrations in Greenland ice cores and Atacama Desert soils were determined with micro-EVA, yielding 1 to 2 GCEs/ml of Greenland ice (versus <1 CFU/ml after 6 months of incubation) and 66 to 157 GCEs/g of Atacama Desert soil (versus 40 CFU/g soil).
Enzymatic esterification of glycerol I. Lipase‐catalyzed synthesis of regioisomerically pure 1,3‐sn‐diacylglycerols (1992)

Regioisomerically pure 1,3‐ sn ‐diacylglycerols are conveniently prepared in high yields (&gt;80%) and in large quantities by enzymatic esterification of glycerol in the presence of various 1,3‐selective lipases (Chromobacterium viscosum, Rhizopus delemar, Rhizomucor miehei) and a variety of different acyl donors like free fatty acids, fatty acid alkyl esters and vinyl esters. All reactions are carried out in aprotic organic solvents of low water content, namely n ‐hexane, diethyl ether or tBuOMe. The creation of an artificial interphase between the solvent‐immiscible hydrophilic glycerol and the hydrophobic reaction media by the adsorption of glycerol onto a solid support prior to use was essential for the success of these transformations. The effects of reaction conditions and the regioselectivities of the lipases on the product yields are described in detail.
ShapeSynth: Parameterizing model collections for coupled shape exploration and synthesis (2014)

Abstract Recent advances in modeling tools enable non‐expert users to synthesize novel shapes by assembling parts extracted from model databases. A major challenge for these tools is to provide users with relevant parts, which is especially difficult for large repositories with significant geometric variations. In this paper we analyze unorganized collections of 3D models to facilitate explorative shape synthesis by providing high‐level feedback of possible synthesizable shapes. By jointly analyzing arrangements and shapes of parts across models, we hierarchically embed the models into low‐dimensional spaces. The user can then use the parameterization to explore the existing models by clicking in different areas or by selecting groups to zoom on specific shape clusters. More importantly, any point in the embedded space can be lifted to an arrangement of parts to provide an abstracted view of possible shape variations. The abstraction can further be realized by appropriately deforming parts from neighboring models to produce synthesized geometry. Our experiments show that users can rapidly generate plausible and diverse shapes using our system, which also performs favorably with respect to previous modeling tools.
Conformational Adaption May Explain the Slow Dissociation Kinetics of Roniciclib (BAY 1000394), a Type I CDK Inhibitor with Kinetic Selectivity for CDK2 and CDK9 (2016)

Roniciclib (BAY 1000394) is a type I pan-CDK (cyclin-dependent kinase) inhibitor which has revealed potent efficacy in xenograft cancer models. Here, we show that roniciclib displays prolonged residence times on CDK2 and CDK9, whereas residence times on other CDKs are transient, thus giving rise to a kinetic selectivity of roniciclib. Surprisingly, variation of the substituent at the 5-position of the pyrimidine scaffold results in changes of up to 3 orders of magnitude of the drug-target residence time. CDK2 X-ray cocrystal structures have revealed a DFG-loop adaption for the 5-(trifluoromethyl) substituent, while for hydrogen and bromo substituents the DFG loop remains in its characteristic type I inhibitor position. In tumor cells, the prolonged residence times of roniciclib on CDK2 and CDK9 are reflected in a sustained inhibitory effect on retinoblastoma protein (RB) phosphorylation, indicating that the target residence time on CDK2 may contribute to sustained target engagement and antitumor efficacy.
Deinococcus geothermalis sp. nov. and Deinococcus murrayi sp. nov., Two Extremely Radiation-Resistant and Slightly Thermophilic Species from Hot Springs (1997)

Strains of Deinococcus geothermalis sp. nov. were isolated from the hot spring and runoff at Agnano, Naples, Italy, and from the hot spring at São Pedro do Sul in central Portugal, while strains of Deinococcus murrayi sp. nov. were isolated from the hot springs at São Pedro do Sul, São Gemil, and Alcafache in central Portugal. The strains of D. geothermalis and D. murrayi produce orange-pigmented colonies and have an optimum growth temperature of about 45 to 50 degrees C. The type strains of the two new species are extremely gamma radiation resistant. The fatty acids of these new species are primarily branched-chain fatty acids. The two new species can be distinguished from each other by the lower pH range of D. geothermalis than of D. murrayi, by their fatty acid compositions, and by several biochemical parameters, including the ability of D. geothermalis to grow in minimal medium without yeast extract. 16S rRNA gene sequencing also showed that the isolates constitute two species and that these species are distinct from the other species of the genus Deinococcus. The type strain of D. geothermalis is AG-3a (= DSM 11300), and the type strain of D. murrayi is ALT-1b (= DSM 11303).
The Bw-Tree: A B-tree for new hardware platforms (2013)

The emergence of new hardware and platforms has led to reconsideration of how data management systems are designed. However, certain basic functions such as key indexed access to records remain essential. While we exploit the common architectural layering of prior systems, we make radically new design decisions about each layer. Our new form of B-tree, called the Bw-tree achieves its very high performance via a latch-free approach that effectively exploits the processor caches of modern multi-core chips. Our storage manager uses a unique form of log structuring that blurs the distinction between a page and a record store and works well with flash storage. This paper describes the architecture and algorithms for the Bw-tree, focusing on the main memory aspects. The paper includes results of our experiments that demonstrate that this fresh approach produces outstanding performance.
Hydrogels for buccal drug delivery: Properties relevant for muco‐adhesion (1988)

In order to develop a muco-adhesive hydrogel for buccal drug delivery it is necessary to understand fully the properties determining adhesiveness as well as mechanisms involved. In this study we measured glass transition temperatures, water contact angles and the peel- and shear detachment forces from porcine oral mucosa, of acrylic acid and butyl acrylate copolymers. The contact angle maximizes at 50% butyl acrylate content. The glass transition temperature decreases from 0% to 100% butyl acrylate. There seems to exist a certain combination of contact angle and glass transition temperature which is related to adhesiveness. This strongly suggests that, in order to obtain a muco-adhesive hydrogel, at least two properties have to be optimized: (1) the polarity of the polymer surface and (2) the molecular mobility of the polymer groups.
Surface termination and subsurface restructuring of perovskite-based solid oxide electrode materials (2014)

The surface and near-surface composition in perovskite-based electroceramics is analysed at the atomic scale using highly surface sensitive low-energy ion scattering (LEIS).
Tumor-targeted delivery of siRNA by non-viral vector: safe and effective cancer therapy (2020)

RNA interference technology has been developed as a potential therapeutic agent for many indications, including cancer. Silencing a specific oncogene in tumor cells brings about cell death both in vitro and in vivo. However, there is a great need for powerful delivery strategies to enhance the therapeutic effect of small interfering RNA (siRNA). This review summarizes different signaling pathways inhibited by siRNA and the advantages of targeted siRNA as a delivery system.
Causes and effects of foaming in anaerobic sludge digesters (1997)

Full scale anaerobic digesters treating mixed sludge containing primary sludge and thickened waste activated sludge were investigated for causes and effects of foaming. Sludge samples were collected from different depths of two full scale digesters, one gas-mixed, and the other mechanically-mixed, to determine the extent of foaming and its effects on anaerobic digestion; both digesters were fed the same feed sludge (3.4% TS) and at the same feed rate (about 2.2 kg TS/m3.day). The average depth of the surface foam layer in the gas-mixed and mechanically-mixed digester were 2.4 and 1.3 m respectively. Higher total solids concentrations were found at the surface (about 5% TS) than those found at the bottom (about 2% TS) in both gas-mixed and mechanically-mixed digesters, indicating an inverse total solids profile. Presence of excessive levels of Nocardia filaments (&amp;gt;106 number/g VSS) in the activated sludge caused thicker foam layer at the surface, and this effect was more pronounced in the gas-mixed digester than in the mechanically-mixed digester. Gas-mixed digester (0.74 m3/kg VS destroyed) produced less sludge gas than the mechanically-mixed digester (0.93 m3/kg VS destroyed), however, gas-mixed digester (62% VS reduction) destroyed more volatile solids than the mechanically-mixed digester (54% VS reduction). These results indicate that gas-mixed digesters are more prone to foaming than mechanically-mixed digesters, and that the foaming can increase when excessive levels of Nocardia filaments are present in the feed sludge causing decreased digester performance.
Improved prediction of prostate cancer recurrence based on an automated tissue image analysis system (2005)

Prostate tissue characteristics play an important role in predicting the recurrence of prostate cancer. Currently, experienced pathologists manually grade these prostate tissues using the GIeason scoring system, a subjective approach which summarizes the overall progression and aggressiveness of the cancer. Using advanced image processing techniques, Aureon Biosciences Corporation has developed a proprietary image analysis system (MAGIC/spl trade/), which here is specifically applied to prostate tissue analysis and designed to be capable of processing a single prostate tissue hematoxylin-and-eosin (H&E) stained image and automatically extracting a variety of raw measurements (spectral, shape, etc.) of histopathological objects along with spatial relationships amongst them. In the context of predicting prostate cancer recurrence, the performance of the image features is comparable to that achieved using the GIeason scoring system. Moreover, an improved prediction rate is observed by combining the GIeason scores with the image features obtained using MAGIC/spl trade/, suggesting that the image data itself may possess information complementary to that of GIeason scores.
Abstract 4135: Plasma miRNAs as potential predictive/prognostic biomarker for ovarian cancer (2012)

Abstract Background: Ovarian cancer is the fifth leading cause of cancer death in women worldwide. While the survival rates of women with early stage ovarian cancer are high, most cases are diagnosed late. Due to asymptomatic development and few screening options, almost 70% of women present at late stages of carcinogenesis. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for ovarian cancer. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in ovarian cancer. Methods/ Principle findings: We scan the circulating plasma miRNAs by Taqman Low Density Array, then identify and validated 30 markers in plasma samples among 70 cases and 70 controls by real-time PCR assay. Promising associations were evaluated in a second stage, comprising 150 cases and 150 controls. We found that compared with normal, there are 9 miRNAs (miR-205, miR-200a, miR-184, miR-34a*, miR-141, miR-483-5p, miR-193b*, let-7e*, miR-363*) expressed higher in ovarian cancer group, while the miR-98 and let-7f have the lower levels in ovarian cancer. Compared with early stage cases (stage I), there is only miR-483-5p expressed higher in advanced stages (stage II-IV). Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of these identified miRNAs and CA-125, a widely used marker for ovarian cancer, further improved the accuracy of detection. Furthermore, our analysis showed that high levels of plasma miR-483-5p or low levels of let-7f predicted poor prognosis of ovarian cancer patients, consistent with the expression of miRNAs in ovarian cancer tissues. Conclusions/Significance: We propose that plasma miRNAs (miR-205, miR-200a, miR-184, miR-34a*, miR-141, miR-483-5p, miR-193b*, let-7e*, miR-363*) are potential biomarkers that complements CA-125 in detecting ovarian cancer; miR-483-5p and let-7f may predict the prognosis of ovarian cancer. It may provide new avenues for the detection, diagnosis, and therapy of this deadly disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4135. doi:1538-7445.AM2012-4135
Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation (2000)

Increasing evidence has shown that some neurotransmitters act as growth-regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell-derived progenitor cells during neural cell lineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU+) cells, both of which were abolished by atropine. Exposure of bFGF-deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth-stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2-bis-(O-aminophenoxy)-ethane-N,N,N', N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G-proteins, the protein kinase C inhibitor H7 and the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MAPK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth-regulatory signal during neurogenesis via pathways involving pertussis toxin-sensitive G-proteins, Ca2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis.
Observation of a calcium-binding site in the γ-class carbonic anhydrase fromPyrococcus horikoshii (2008)

Carbonic anhydrases are zinc-containing metalloenzymes that catalyze the interconversion of carbon dioxide and bicarbonate. Three crystal structures of gamma-class carbonic anhydrase (one of which is bound to a bicarbonate molecule) from the aerobic OT3 strain of the hyperthermophilic archeon Pyrococcus horikoshii have been solved by molecular replacement in space group F4(1)32. The asymmetric unit contains a monomer of 173 amino acids and a catalytic Zn2+ ion. The protein fold is a regular prism formed by a left-handed beta-helix, similar to previously reported structures. The active-site Zn2+ ion located at the interface between the two monomers is bound to three histidyl residues and a water molecule in a tetrahedral fashion. In addition to the 20 beta-strands comprising the beta-helix, there is also a long C-terminal alpha-helix. For the first time, Ca2+ ions have been observed in addition to the catalytic Zn2+ ion. It is hypothesized that Tyr159 (which corresponds to the catalytically important Asn202 in previously reported structures) utilizes C-H...pi interactions to fulfill its functions. This study may shed light on the catalytic mechanism of the enzyme and throw open new questions on the mechanism of product removal in carbonic anhydrases.
Exciton interaction in molecular beacons: a sensitive sensor for short range modifications of the nucleic acid structure (2001)

Molecular beacons are hairpin-shaped, single-stranded oligonucleotides constituting sensitive fluorescent DNA probes widely used to report the presence of specific nucleic acids. In its closed form the stem of the hairpin holds the fluorophore covalently attached to one end, close to the quencher, which is covalently attached to the other end. Here we report that in the closed form the fluorophore and the quencher form a ground state intramolecular heterodimer whose spectral properties can be described by exciton theory. Formation of the heterodimers was found to be poorly sensitive to the stem sequence, the respective positions of the dyes and the nature of the nucleic acid (DNA or RNA). The heterodimer allows strong coupling between the transition dipoles of the two chromophores, leading to dramatic changes in the absorption spectrum that are not compatible with a Förster-type fluorescence resonance energy transfer (FRET) mechanism. The excitonic heterodimer and its associated absorption spectrum are extremely sensitive to the orientation of and distance between the dyes. Accordingly, the application of molecular beacons can be extended to monitoring short range modifications of the stem structure. Moreover, the excitonic interaction was also found to operate for doubly end-labeled duplexes.