gebhart/patrepeval huggingface dataset:
Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression (2003)

We recently reported the powerful antiapoptotic activity of clusterin against various apoptotic stimuli in prostate cancer model systems; however, the precise mode of clusterin action in target cells remains largely unknown. In the present study, we therefore investigated whether intracellular or extracellular action of clusterin plays a crucial role in cytotoxic chemotherapy-induced apoptosis in androgen-independent human prostate cancer PC3 cells, which express a high level of clusterin. The sensitivity of PC3 cells to paclitaxel was increased by pretreatment with monoclonal antibody (mAb) to clusterin or antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene in a dose-dependent manner at up to 50 microg/ml or 1 microM, respectively. However, clusterin mAb failed to further enhance the sensitivity to paclitaxel of PC3 cells simultaneously treated with 1 microM AS clusterin ODN, whereas AS clusterin ODN further induced the apoptosis of cells treated with 50 microg/ml clusterin mAb. Moreover, the effects of clusterin mAb and AS clusterin ODN on PC3 cells were not reversed by additional treatment with exogenous recombinant clusterin protein. These findings suggest that the sensitivity of PC3 cells to paclitaxel-induced cytotoxicity may be regulated by the intracellular rather than extracellular level of clusterin.
Optimization of Genome Engineering Approaches with the CRISPR/Cas9 System (2014)

Designer nucleases such as TALENS and Cas9 have opened new opportunities to scarlessly edit the mammalian genome. Here we explored several parameters that influence Cas9-mediated scarless genome editing efficiency in murine embryonic stem cells. Optimization of transfection conditions and enriching for transfected cells are critical for efficiently recovering modified clones. Paired gRNAs and wild-type Cas9 efficiently create programmed deletions, which facilitate identification of targeted clones, while paired gRNAs and the Cas9D10A nickase generated smaller targeted indels with lower chance of off-target mutagenesis. Genome editing is also useful for programmed introduction of exogenous DNA sequences at a target locus. Increasing the length of the homology arms of the homology-directed repair template strongly enhanced targeting efficiency, while increasing the length of the DNA insert reduced it. Together our data provide guidance on optimal design of scarless gene knockout, modification, or knock-in experiments using Cas9 nuclease.
Complexes of Casein Phosphopeptide and Calcium Phosphate Prepared from Casein Micelles by Tryptic Digestion (1994)

Casein phosphopeptide (CPPcm), which inhibits the precipitation of calcium phosphate in the intestines, was prepared as a CPPcm-calcium phosphate complex from casein micelles (casein–calcium phosphate conjugates). CPPcm was eluted as seven peaks from a Q-sepharose FF column, the major peaks being identified and agreeing with those of the phosphopeptides (CPPcn) from acid-precipitated casein. The major components of CPPcm were αs1-CN-5P(f59–79) and β-CN-4P(f1–25), CPPcm containing more αs1-CN-5P (f59–79) than CPPcn. The complexes of CPPcm and calcium phosphate contained twice the quantity of calcium phosphate as those of CPPcn.
The mast cell in wound healing (2001)

This review describes the role of the mast cell in the pathobiology of skin healing. After illustrating its main morphofunctional characteristics, with special reference to the dog and cat, we consider the involvement of the mast cell in the various phases of skin repair. With the aid of a wide array of newly formed or preformed mediators released by degranulation, the activated mast cell controls the key events of the healing phases: triggering and modulation of the inflammatory stage, proliferation of connective cellular elements and final remodelling of the newly formed connective tissue matrix. The importance of the mast cell in regulating healing processes is also demonstrated by the fact that a surplus or deficit of degranulated biological mediators causes impaired repair, with the formation of exuberant granulation tissue (e.g. keloids and hypertrophic scars), delayed closure (dehiscence) and chronicity of the inflammatory stage.
Low density lipoprotein receptor–related protein is a calreticulin coreceptor that signals focal adhesion disassembly (2003)

Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinase (ERK) through Galphai2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor-related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP-CRT signaling, as shown by the ability of hep I to stimulate association of Galphai2 with LRP. The isolated proteins LRP and CRT interact, and LRP and CRT are associated with hep I in molecular complexes extracted from cells. These data establish a mechanism of cell surface CRT signaling through its coreceptor, LRP, and suggest a novel function for LRP in regulating cell adhesion.
Selective channel combination of MRI signal phase (2015)

Mapping of signal phase from ultra-high field MRI data undoubtedly provides a wealth of information about the ageing brain and the effects of neurodegenerative disorders. Measurement of signal phase is essential in frequency shift mapping and in quantitative susceptibility mapping. The method used to combine signal phase should be informed by an understanding of the noise distribution in signal phase at the individual channel level. Magn Reson Med 76:1469-1477, 2016. © 2015 International Society for Magnetic Resonance in Medicine.
Polyfunctionalized Aryllead Triacetates in a Cascade Synthesis of Tetracyclic Isochromanocoumarin-Type Compounds (2005)

The three-step one-pot α-arylation-annulation sequence leading to the reaction of 4-hydroxycoumarins with in situ generated 2-(bromomethyl)aryllead triacetates carried out in the presence of a combination of ortho-phenantroline-potassium tert-butoxide afforded tetracyclic benzo[b]pyran compounds in good to high yields.
Free-space grating demultiplexer for densely-spaced, subnanometer wavelength-routed optical networks (2002)

We report on the diffraction-limited performance of a free-space aberration corrected concave grating demultiplexer. The fibre-to-fibre loss was less than 9 dB and channel isolation better than 25 dB for channel spacing of 0.4 nm, in the wavelength range 24 nm around 1.5 /spl mu/m. This device has applications in wavelength routing crossconnects and in optical spectrum analysers.
Electroanatomically Guided Catheter Ablation of Ventricular Tachycardias Causing Multiple Defibrillator Shocks (2001)

With conventional techniques, RF catheter ablation is difficult in patients with unstable VT or with multiple VTs. The feasibility of RF catheter ablation guided by three-dimensional electroanatomic mapping technique in patients whose implanted ICD continued to deliver multiple shocks due to VT despite use of antiarrhythmic medications was assessed in 19 patients (15 men, 4 women; mean age [+/- SD] 70+/-7 years). All had a prior history of MI and subsequently had received an ICD due to VT. During the 12-week preablation period, these patients received 31+/-15 shocks (range 4-62 shocks) due to refractory monomorphic VTs. An electroanatomic mapping technique using the CARTO system was performed to delineate scar tissue. RF catheter ablation was then performed at appropriate sites identified by pace mapping and by substrate mapping. Seventeen patients were on amiodarone at the time of ablation. Twenty-seven VTs were documented clinically, and 45 were induced during electrophysiological evaluation. Of the 45 tachycardias induced, 38 VTs were targeted for ablation. Catheter ablation was performed during sinus rhythm in 31 episodes and during VT in 7 episodes. During a mean follow-up of 26+/-8 weeks (range 18-48 weeks), 13 (66%) patients had no recurrence of VT (P < 0.0001) and antiarrhythmic drugs were discontinued or the number of medications reduced in 17 patients (P < 0.0001). Electroanatomic mapping is helpful in identifying sites for catheter ablation in highly symptomatic patients with refractory VT associated with myocardial scarring.
Predicting species distributions from museum and herbarium records using multiresponse models fitted with multivariate adaptive regression splines (2007)

ABSTRACT Current circumstances — that the majority of species distribution records exist as presence‐only data (e.g. from museums and herbaria), and that there is an established need for predictions of species distributions — mean that scientists and conservation managers seek to develop robust methods for using these data. Such methods must, in particular, accommodate the difficulties caused by lack of reliable information about sites where species are absent. Here we test two approaches for overcoming these difficulties, analysing a range of data sets using the technique of multivariate adaptive regression splines (MARS). MARS is closely related to regression techniques such as generalized additive models (GAMs) that are commonly and successfully used in modelling species distributions, but has particular advantages in its analytical speed and the ease of transfer of analysis results to other computational environments such as a Geographic Information System. MARS also has the advantage that it can model multiple responses, meaning that it can combine information from a set of species to determine the dominant environmental drivers of variation in species composition. We use data from 226 species from six regions of the world, and demonstrate the use of MARS for distribution modelling using presence‐only data. We test whether (1) the type of data used to represent absence or background and (2) the signal from multiple species affect predictive performance, by evaluating predictions at completely independent sites where genuine presence–absence data were recorded. Models developed with absences inferred from the total set of presence‐only sites for a biological group, and using simultaneous analysis of multiple species to inform the choice of predictor variables, performed better than models in which species were analysed singly, or in which pseudo‐absences were drawn randomly from the study area. The methods are fast, relatively simple to understand, and useful for situations where data are limited. A tutorial is included.
Glutathione Deficiency in the Epithelial Lining Fluid of the Lower Respiratory Tract in Idiopathic Pulmonary Fibrosis (1989)

Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH), a sulfhydryl-containing tripeptide produced by most mammalian cells, is an efficient scavenger of toxic oxidants, including hydrogen peroxide, an oxidant that plays a major role in the oxidant burden placed on the epithelial surface of the lower respiratory tract in chronic inflammatory states. GSH is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant protection to the epithelial cells. In this regard, we hypothesized that the lower respiratory tract of patients with IPF may be chronically depleted of this antioxidant, thus leading to an increased susceptibility of lung epithelial cells to oxidant injury. To evaluate this concept, the concentration of glutathione was determined in the epithelial lining fluid of the lower respiratory tract of 15 patients with IPF and compared to that of 19 normal subjects. Strikingly, whereas ELF glutathione concentrations were high in normal subjects (429 +/- 34 microM), a fourfold decrease was found in patients with IPF (97 +/- 18 microM, p less than 0.001). In the context of the known oxidant burden present in the lower respiratory tract of patients with IPF, these observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease.
Rendering from compressed textures (1996)

We present a simple method for rendering directly from compressed textures in hardware and software rendering systems. Textures are compressed using a vector quantization (VQ) method. The advantage of VQ over other compression techniques is that textures can be decompressed quickly during rendering. The drawback of using lossy compression schemes such as VQ for textures is that such methods introduce errors into the textures. We discuss techniques for controlling these losses. We also describe an extension to the basic VQ technique for compressing mipmaps. We have observed compression rates of up to 3 5 : 1 , with minimal loss in visual quality and a small impact on rendering time. The simplicity of our technique lends itself to an efficient hardware implementation.
Intracellular NOD-like receptors in innate immunity, infection and disease (2007)

The innate immune system comprises several classes of pattern-recognition receptors, including Toll-like receptors (TLRs) and nucleotide binding and oligomerization domain-like receptors (NLRs). TLRs recognize microbes on the cell surface and in endosomes, whereas NLRs sense microbial molecules in the cytosol. In this review, we focus on the role of NLRs in host defence against bacterial pathogens. Nod1 and Nod2 sense the cytosolic presence of molecules containing meso-diaminopimelic acid and muramyl dipeptide respectively, and drive the activation of mitogen-activated protein kinase and NF-kappaB. In contrast, Ipaf, Nalp1b and Cryopyrin/Nalp3 promote the assembly of inflammasomes that are required for the activation of caspase-1. Mutation in several NLR members, including NOD2 and Cryopyrin, is associated with the development of inflammatory disorders. Further understanding of NLRs should provide new insights into the mechanisms of host defence and the pathogenesis of inflammatory diseases.
A pneumonia outbreak associated with a new coronavirus of probable bat origin (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats<sup>1-4</sup>. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans<sup>5-7</sup>. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct (1993)

Energy balance and lipid metabolism were investigated in transgenic mice bearing an antisense glucocorticoid receptor (GCR) gene construct that impairs the normal expression of the GCR gene. Food intake was recorded during the 15 days preceding decapitation of adult normal and transgenic mice, and feces were collected to derive the digestible energy intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy was determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lipoprotein lipase (LPL) activity was quantified in epididymal white adipose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measuring the in vitro hydrolysis of labeled triolein in the presence of tissue homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high-performance liquid chromatography (HPLC). Energy intake and expenditure were significantly lower in transgenic mice than in controls. Concurrently, both fat content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. There was no difference between groups in LPL activity in WAT. Finally, heart and BAT NE contents were lower in transgenic animals than in control mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they emphasize the modulatory effects of hypothalamic-pituitary-adrenal axis changes on muscle LPL activity.
Treatment of ischemic optic neuropathy (2002)

Ischemic damage of the optic nerve has no proven effective treatment. While ischemia related to vasculitis (arteritic) is treated with systemic corticosteroids, the primary goal is to prevent further damage, either in the affected or fellow eye. Thrombolytic or anticoagulation supplementive therapy may be considerations for the future. In the more common idiopathic (nonarteritic) form (NAION), multiple attempts at therapy, including systemic corticosteroids, anticoagulants and antiplatelet agents, diphenylhydantoin, hyperbaric oxygen, and optic nerve sheath decompression have been unsuccessful. The use of levodopa has been proposed but is unproven. Megadose intravenous corticosteroid therapy has not been studied in a systematic way. Neuroprotective strategies are under intense investigation for optic neuropathies including NAION, and clinical trials in humans are in progress. Optic nerve regeneration studies are ongoing in animals. Prophylaxis in NAION is unproven.
K-rasOncogene Activation as a Prognostic Marker in Adenocarcinoma of the Lung (1990)

The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load.
Preliminary histopathological study of intra-articular injection of a novel highly cross-linked hyaluronic acid in a rabbit model of knee osteoarthritis (2013)

Osteoarthritis is a degenerative joint disease mostly occurring in the knee and commonly seen in middle-aged and elderly adults. Intra-articular injection of hyaluronic acid has been widely used for treatment of knee osteoarthritis. The aim of this study was to evaluate the efficacy of intra-articular injection of a novel highly cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, on knee articular cartilage in a rabbit model of collagenase-induced knee osteoarthritis. After induction of experimental osteoarthritis by intra-articular injection of collagenase, adult New Zealand white rabbits (n = 12) were divided into 3 groups. Group 1 (control group) received 0.3 ml phosphate buffered saline into the right knee joint. Group 2 received 0.3 ml cross-linked hyaluronic acid (33 mg/ml) into the right knee joint. Group 3 received a mixture of 0.15 ml cross-linked hyaluronic acid (33 mg/ml), 0.05 ml ropivacaine hydrochloride 1 % and 0.1 ml triamcinolone acetonide (10 mg/ml) into the right knee joint. Intra-articular injections were given 4 weeks after first collagenase injection and were administered once a week for 3 weeks. Gross pathology and histological evaluation of rabbits' knee joints were performed after 16 weeks following initial collagenase injection. Histological analysis of sections of right knee joints at lesion sites showed a significant decrease in Mankin's score in groups treated with hyaluronic acid alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide versus control group (p < 0.05 and p < 0.01 respectively). This evidence was consistent with strong articular degenerative changes in control right knee joints (grade III osteoarthritis), while the treated groups revealed less severe articular degenerative changes (grade II osteoarthritis). The present results show that cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, produces a significant improvement in knee articular cartilage degeneration in a rabbit model of collagenase-induced osteoarthritis.
Methods of drug protein binding determinations (1990)

The determination of drug binding to proteins is carried out by several different approaches based mainly on separation methods. The most popular of these is equilibrium dialysis, which requires membranes devoid of non-specific adsorption to drugs. Ultrafiltration techniques have some advantage over dialysis due to shorter measurement times and the possibility of evaluation of the free drug under circumstances corresponding to physiological conditions. Now there is an increasing use of chromatographic techniques for fundamental studies on determination of binding parameters (number of sites, affinity constant). Different procedures can be chosen depending upon the biological materials available. They are based on the presence of the interacting species in the eluent, avoiding any chemical grafting.