gebhart/patrepeval huggingface dataset:
Earthquake source scaling relationships from −1 to 5 ML using seismograms recorded at 2.5‐km depth (1995)

The scaling relationships of earthquake sources less than about magnitude 3 have been the subject of considerable controversy over the last two decades. Studies of such events have shown a tendency for the constant stress drop, self similarity of larger earthquakes to breakdown at small magnitudes, and an apparent minimum source dimension of about 100 m has been observed. Other studies showed that this apparent breakdown in scaling could be an artifact of severe near‐surface attenuation, limiting the spatial resolution of surface data. In this study, source parameters are determined for over 100 nearby, tectonic earthquakes, from recordings at a depth of 2.5 km (in granite) in the Cajon Pass scientific drill hole, southern California. Comparison of the seismograms recorded at this depth with those at the wellhead clearly demonstrates the effect of the severe attenuation in the upper kilometers of the Earth's crust. Source parameters are calculated by spectral modeling of three‐component P and S waves, assuming four source models based on the Brune ω −2 ( n = 2) model. In model l, n = 2 is fixed, and Q of P and S waves is determined to be 912 (581–1433) and 1078 (879–1323), respectively (the numbers in parentheses are ±1 standard deviation). In model 2, Q P = Q S = 1000 is assumed and n is allowed to vary. The ω −2 model is a good average for the data set, but there is some real scatter supported by the data. In model 3, Q P = Q S = 1000 is also assumed and ω −2 is constrained, and in model 4, attenuation is ignored and n is allowed to vary. Source dimensions of less than 10m are observed for all four models, 10 times smaller than the proposed “minimum”. No breakdown in constant stress drop scaling is seen in the downhole data (approximately M L ‐1 to 5.5, M 0 = 10 9 ‐ 10 16 Nm). The ratio between radiated seismic energy (estimated by integrating the velocity squared spectra with adequate signal bandwidth) and seismic moment appears to decrease gradually with decreasing moment in the magnitude range −1 to 7. This is not incompatible with a constant stress drop but could result from errors in calculating energy. The ratio of the S wave energy to that radiated by the P waves is about 14, after correction for attenuation. This low value is consistent with the corner frequency shift of about 1.3. This corner frequency shift is observed for all four source models and therefore is interpreted as being source controlled.
Proteins in Ionic Liquids: Current Status of Experiments and Simulations (2017)

In the last two decades, while searching for interesting applications of ionic liquids as potent solvents, their solvation properties and their general impact on biomolecules, and in particular on proteins, gained interest. It turned out that ionic liquids are excellent solvents for protein refolding and crystallization. Biomolecules showed increased solubilities and stabilities, both operational and thermal, in ionic liquids, which also seem to prevent self-aggregation during solubilization. Biomolecules can be immobilized, e.g. in highly viscous ionic liquids, for particular biochemical processes and can be designed to some extent by the proper choice of the ionic liquid cations and anions, which can be characterized by the Hofmeister series.
Synthetic histatin analogues with broad-spectrum antimicrobial activity (1997)

Histatins are salivary histidine-rich cationic peptides, ranging from 7 to 38 amino acid residues in length, that exert a potent killing effect in vitro on Candida albicans. Starting from the C-terminal fungicidal domain of histatin 5 (residues 11-24, called dh-5) a number of substitution analogues were chemically synthesized to study the effect of amphipathicity of the peptide in helix conformation on candidacidal activity. Single substitutions in dh-5 at several positions did not have any effect on fungicidal activity. However, multi-site substituted analogues (dhvar1 and dhvar2) exhibited a 6-fold increased activity over dh-5. In addition, dhvar1 and dhvar2 inhibited the growth of the second most common yeast found in clinical isolates, Torulopsis glabrata, of oral- and non-oral pathogens such as Prevotella intermedia and Streptococcus mutans, and of a methicillin-resistant Staphylococcus aureus. In their broad-spectrum activity, dhvar1 and dhvar2 were comparable to magainins (PGLa and magainin 2), antimicrobial peptides of amphibian origin. Both the fungicidal and the haemolytic activities of dhvar1, dhvar2 and magainins increased at decreasing ionic strength.
Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events (1992)

The Leukocytic cell-adhesion molecule (beta 2 integrin) family of adhesion molecules play a key role in the intercellular adhesive interactions necessary for normal immune cell function. In this study, we report an antibody that recognizes an epitope on the Leukocytic cell-adhesion molecule common beta-chain (CD18) and promotes both lymphocyte function-associated Ag-1- and CR3-dependent adhesion events. The antibody recognizes a temperature-sensitive epitope that is not dependent on the presence of divalent cations. It is proposed that antibody binding promotes a conformational change in both lymphocyte function-associated Ag-1 and CR3, which may mimic a natural activation mechanism, resulting in increased cellular adhesion.
CDMA/HDR: a bandwidth efficient high speed wireless data service for nomadic users (2000)

This article presents an approach to providing very high-data-rate downstream Internet access by nomadic users within the current CDMA physical layer architecture. A means for considerably increasing the throughput by optimizing packet data protocols and by other network and coding techniques are presented and supported by simulations and laboratory measurements. The network architecture, based on Internet protocols adapted to the mobile environment, is described, followed by a discussion of economic considerations in comparison to cable and DSL services.
Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies? (2005)

Adhesive BM-derived CD45- CD73+ CD90+ MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.
A multi-marker assay to distinguish malignant melanomas from benign nevi (2009)

The histopathological diagnosis of melanoma can be challenging. No currently used molecular markers accurately distinguish between nevus and melanoma. Recent transcriptome analyses have shown the differential expression of several genes in melanoma progression. Here, we describe a multi-marker diagnostic assay using 5 markers (ARPC2, FN1, RGS1, SPP1, and WNT2) overexpressed in melanomas. Immunohistochemical marker expression was analyzed in 693 melanocytic neoplasms comprising a training set (tissue microarray of 534 melanomas and nevi), and 4 independent validation sets: tissue sections of melanoma arising in a nevus; dysplastic nevi; Spitz nevi; and misdiagnosed melanocytic neoplasms. Both intensity and pattern of expression were scored for each marker. Based on the differential expression of these 5 markers between nevi and melanomas in the training set, a diagnostic algorithm was obtained. Using this algorithm, the lesions in the validation sets were diagnosed as nevus or melanoma, and the results were compared with the known histological diagnoses. Both the intensity and pattern of expression of each marker were significantly different in melanomas compared to nevi. The diagnostic algorithm exploiting these differences achieved a specificity of 95% and a sensitivity of 91% in the training set. In the validation sets, the multi-marker assay correctly diagnosed a high percentage of melanomas arising in a nevus, Spitz nevi, dysplastic nevi, and misdiagnosed lesions. The multi-marker assay described here can aid in the diagnosis of melanoma.
The Transcription Factor CCAAT/Enhancer-binding Protein β Regulates Gluconeogenesis and Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription during Diabetes (1999)

CCAAT/enhancer-binding protein (C/EBP) beta and C/EBPalpha are members of the c/ebp gene family and are highly expressed in mammalian liver and adipose tissue. C/EBPalpha is essential for adipogenesis and neonatal gluconeogenesis, as shown by the C/EBPalpha knockout mouse. C/EBPbeta binds to several sequences of the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter with high affinity, and C/EBPbeta protein is increased 200% in the livers of streptozotocin-diabetic mice, concurrent with increased PEPCK mRNA. To elucidate the role of C/EBPbeta in the control of gluconeogenesis during diabetes, we studied the levels of plasma metabolites and hormones related to energy metabolism during diabetes in adult mice heterozygous and homozygous for a null mutation of the gene for C/EBPbeta. We also examined the expression of PEPCK and glucose 6-phosphatase mRNAs and regulation of blood glucose, including the contribution of gluconeogenesis to blood glucose in c/ebpbeta-/- mice. C/EBPbeta was not essential to basal PEPCK mRNA levels. However, C/EBPbeta deletion affected streptozotocin-diabetic response by: (a) delaying hyperglycemia, (b) preventing the increase of plasma free fatty acids, (c) limiting the full induction of PEPCK and glucose 6-phosphatase genes, and (d) preventing the increase in gluconeogenesis rate. Gel supershifts of transcription factor C/EBPalpha, bound to CRE, P3I, and AF-2 sites of the PEPCK promoter, was not increased in diabetic c/ebpbeta-/- mouse liver nuclei, suggesting that C/EBPalpha does not substitute for C/EBPbeta in the diabetic response of liver gene transcription. These results link C/EBPbeta to the metabolic and gene regulatory responses to diabetes and implicate C/EBPbeta as an essential factor underlying glucocorticoid-dependent activation of PEPCK gene transcription in the intact animal.
Abstract 3751: Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models (2018)

Abstract Adenosine signaling through the high affinity adenosine 2A receptor (A2AR) on immune cells elicits a range of immunosuppressive effects which can promote tumor growth and limit the efficacy of immune checkpoint inhibitors. AZD4635 (HTL-1071) is a potent and selective oral A2AR antagonist, currently in a Phase 1 clinical trial as a single agent and in combination with durvalumab (anti-PD-L1 Ab) in patients with solid malignancies. In functional in vitro assays, the IC50 of AZD4635 for inhibition of A2AR signaling is dependent on adenosine concentrations and ranges from 1, 10.0, 143 nM in the presence of 0.1, 1, 10 μM adenosine, respectively. However, full understanding of the impact of adenosine on AZD4635 mediated anti-tumor responses requires characterization of intratumoral adenosine concentration and spatial heterogeneity. Using a novel LC/MS based method, measurement of intratumoral adenosine concentrations in a panel of syngeneic tumor models demonstrated a wide range of adenosine levels (5-122 μM). Additionally, measurement of intratumoral adenosine by desorption electrospray ionisation - mass spectroscopy (DESI-MS) demonstrated that adenosine levels are spatially heterogeneous, with levels varying up to 50-fold among regions of a single tumor. High intratumoral adenosine concentrations were correlated with decreased intratumoral CD8 infiltration in vivo. The therapeutic benefit of A2AR blockade alone and in combination with anti-PD-L1 was evaluated in a panel of syngeneic mouse tumor models with varying adenosine concentrations. In sensitive models, inhibition of A2AR signaling with AZD4635 led to a dose dependent reduction in tumor growth alone and in combination with checkpoint inhibitors. Tumors harvested from the treated mice exhibited increases in the functional activity of T cell and myeloid subsets. These results demonstrate that AZD4635 is a potent and selective A2AR inhibitor, that blockade of A2AR signaling with an inhibitor such as AZD4635 can reduce tumor burden and enhance antitumor immunity. Citation Format: Alexandra Borodovsky, Yanjun Wang, Minwei Ye, Joseph C. Shaw, Kris Sachsenmeier, Nanhua Deng, Kelly Goodwin, James D. Clarke, Richard Goodwin, Nicole Strittmatter, Carl Hay, Vasu Sah, Lawson Deborah, Corinne Reimer, Miles Congreve, Jonathan Mason, Fiona Marshall, Paul Lyne, Richard Woessner. Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3751.
Removal of poly‐histidine fusion tags from recombinant proteins purified by expanded bed adsorption (2005)

Enzymatic methods have been used to cleave the C- or N-terminus polyhistidine tags from histidine tagged proteins following expanded bed purification using immobilized metal affinity chromatography (IMAC). This study assesses the use of Factor Xa and a genetically engineered exopeptidase dipeptidyl aminopeptidase-1 (DAPase-1) for the removal of C-terminus and N-terminus polyhistidine tags, respectively. Model proteins consisting of maltose binding protein (MBP) having a C- or N-terminal polyhistidine tag were used. Digestion of the hexahistidine tag of MBP-His(6) by Factor Xa and HT15-MBP by DAPase-1 was successful. The time taken to complete the conversion of MBP-His(6) to MBP was 16 h, as judged by SDS-PAGE and Western blots against anti-His antibody. When the detagged protein was purified using subtractive IMAC, the yield was moderate at 71% although the overall recovery was high at 95%. Likewise, a yield of 79% and a recovery of 97% was obtained when digestion was performed with using "on-column" tag digestion. On-column tag digestion involves cleavage of histidine tag from polyhistidine tagged proteins that are still bound to the IMAC column. Digestion of an N-terminal polyhistidine tag from HT15-MBP (1 mg/mL) by the DAPase-I system was superior to the results obtained with Factor Xa with a higher yield and recovery of 99% and 95%, respectively. The digestion by DAPase-I system was faster and was complete at 5 h as opposed to 16 h for Factor Xa. The detagged MBP proteins were isolated from the digestion mixtures using a simple subtractive IMAC column procedure with the detagged protein appearing in the flowthrough and washing fractions while residual dipeptides and DAPase-I (which was engineered to exhibit a poly-His tail) were adsorbed to the column. FPLC analysis using a MonoS cation exchanger was performed to understand and monitor the progress and time course of DAPase-I digestion of HT15-MBP to MBP. Optimization of process variables such as temperature, protein concentration, and enzyme activity was developed for the DAPase-I digesting system on HT15-MBP to MBP. In short, this study proved that the use of either Factor Xa or DAPase-I for the digestion of polyhistidine tags is simple and efficient and can be carried out under mild reaction conditions.
Toll-Like Receptors Confer Responsiveness to Lipopolysaccharide fromPorphyromonas gingivalisin Human Gingival Fibroblasts (2000)

ABSTRACT Gingival fibroblasts produce proinflammatory cytokines in response to lipopolysaccharide (LPS) from periodontopathic bacteria. Recently it has become evident that the human homologue of Drosophila Toll can transduce intracellular signaling by LPS stimulation. Toll-like receptors (TLRs) have been identified in myeloid cells; however, their role in nonmyeloid cells such as gingival fibroblasts has not been fully elucidated. Here, we report that human gingival fibroblasts constitutively express TLR2 and TLR4 and that their levels of expression are increased by stimulation with LPS from Porphyromonas gingivalis . Upregulated expression of interleukin-6 gene and protein in fibroblasts stimulated with LPS is inhibited by anti-TLR4 antibody. These findings suggest that TLRs may confer responsiveness to LPS in gingival fibroblasts.
Contribution of sensory feedback to ongoing ankle extensor activity during the stance phase of walking (2004)

Numerous investigations over the past 15 years have demonstrated that sensory feedback plays a critical role in establishing the timing and magnitude of muscle activity during walking. Here we review recent studies reporting that sensory feedback makes a substantial contribution to the activation of extensor motoneurons during the stance phase. Quantitative analysis of the effects of loading and unloading ankle extensor muscles during walking on a horizontal surface has shown that sensory feedback can increase the activity of ankle extensor muscles by up to 60%. There is currently some uncertainty about which sensory receptors are responsible for this enhancement of extensor activity, but likely candidates are the secondary spindle endings in the ankle extensors of humans and the Golgi tendon organs in the ankle extensors of humans and cats. Two important issues arise from the finding that sensory feedback from the leg regulates the magnitude of extensor activity. The first is the extent to which differences in the magnitude of activity in extensor muscles during different locomotor tasks can be directly attributed to changes in the magnitude of sensory signals, and the second is whether the enhancement of extensor activity is determined primarily by feedback from a specific group of receptors or from numerous groups of receptors distributed throughout the leg. Limitations of current experimental strategies prevent a straightforward empirical resolution of these issues. A potentially fruitful approach in the immediate future is to develop models of the known and hypothesized neuronal networks controlling motoneuronal activity, and use these simulations to control forward dynamic models of the musculo-skeletal system. These simulations would help understand how sensory signals are modified with a change in locomotor task and, in conjunction with physiological experiments, establish the extent to which these modifications can account for changes in the magnitude of motoneuronal activity.
Multicenter Evaluation of Use of Dried Blood and Plasma Spot Specimens in Quantitative Assays for Human Immunodeficiency Virus RNA: Measurement, Precision, and RNA Stability (2003)

Eleven laboratories evaluated the use of dried blood and plasma spots for quantitation of human immunodeficiency virus (HIV) RNA by two commercially available RNA assays, the Roche Amplicor HIV-1 Monitor and the bioMerieux NucliSens HIV-1 QT assays. The recovery of HIV RNA was linear over a dynamic range extending from 4,000 to 500,000 HIV type 1 RNA copies/ml. The Monitor assay appeared to have a broader dynamic range and seemed more sensitive at lower concentrations. However, the NucliSens assay gave more consistent results and could be performed without modification of the kit. HIV RNA was stable in dried whole blood or plasma stored at room temperature or at -70 degrees C for up to 1 year. Dried blood and dried plasma spots can be used as an easy and inexpensive means for the collection and storage of specimens under field conditions for the diagnosis of HIV infection and the monitoring of antiretroviral therapy.
[Effectiveness of total hip arthroplasty in the treatment of involved hips in patients with ankylosing spondylitis]. (2017)

THA is an effective method to treat involved hips in patients with AS; especially for patients having shorter duration of the disease, THA shows better effectiveness when the bigger diameter of prosthetic femoral head and ceramic-on-ceramic bearing are used.
Glucocorticoids Increase Osteopontin Expression in Cardiac Myocytes and Microvascular Endothelial Cells (1995)

In heart muscle, the cytokine-inducible isoform of nitric oxide synthase (NOS2) is expressed in both cardiac myocytes and microvascular endothelial cells (CMEC). mRNA levels for both NOS2 and for osteopontin, a multifunctional extracellular matrix phosphoprotein containing and RGD integrin binding domain, are increased in cardiac muscle following intraperitoneal injection of adult rats with lipopolysaccharide. In vitro, interleukin-1 beta and interferon-gamma increased osteopontin mRNA levels in CMEC as well as NOS2 expression in both CMEC and cardiac myocytes. However, osteopontin mRNA levels in heart muscle in vivo, and in cardiac myocytes and CMEC in vitro, also are increased 10-30-fold by the synthetic glucocorticoid dexamethasone, an agent that suppresses cytokine induction of NOS2 in both cell types. The hexapeptide GRGDSP, which interrupts binding of RGD-containing proteins to cell surface integrins, increased NOS2 mRNA, while a synthetic osteopontin peptide analogue decreased NOS2 mRNA and protein levels in both cytokine-pretreated cardiac myocytes and CMEC cultures. Also, transfection with a full-length antisense-osteopontin cDNA in cytokine-pretreated CMEC decreased endogenous osteopontin mRNA and increased NOS2 mRNA levels. These results suggest that osteopontin could regulate the location and extent of NOS2 induction in the heart. Increased expression of osteopontin also may be one mechanism by which glucocorticoids suppress NOS2 activity in cardiac myocytes and microvascular endothelial cells.
Induction of immunodeficiency virus‐specific immune responses in rhesus monkeys following gene gun‐mediated DNA vaccination (1996)

The Accell gene delivery system (gene gun) was used to deliver gold particles coated with HIV-1LAI and SIVmac239 expression constructs into the epidermis of rhesus macaques, resulting in the elicitation of env- and gag-specific humoral responses. One microgram of vector DNA per dose was sufficient to induce immune responses in monkeys using SIVmac239 gp160 and gp120 vectors driven by the CMV-intron A promoter. Several parameters, including the identity of the vector, the length of the rest period between immunizations, the number of immunizations, and the amount of DNA per immunization, are all important in designing an optimal DNA immunization regimen. In addition, gene gun-based DNA immunization using low efficiency expression vectors is an effective means of priming for the induction of vigorous antibody responses in macaques following boosting with recombinant subunits.
Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning (2020)

This study shows that a prediction of RNA expression classifiers can be made from H&E images, opening the door to simple, cheap and reliable biological stratification within routine workflows.
Salmonella typhi Vaccine Strain CVD 908 Expressing the Circumsporozoite Protein of Plasmodium falciparum: Strain Construction and Safety and Immunogenicity in Humans (1994)

rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite protein (CSP), under control of tacP was integrated into the chromosomal delta aroC locus of attenuated delta aroC, delta aroD Salmonella typhi CVD 908. By immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than from the single chromosomal gene. CVD 908 omega (delta aroC1019::tacP-rcsp) was well tolerated by 10 volunteers who were fed two doses of 5 x 10(7) organisms 8 days apart. Seven subjects excreted the vaccine strain for 1-3 days. All subjects developed serologic responses to O and H antigens of the live vector, whereas 3 vaccinees responded to the foreign antigen: 1 developed an 80-fold rise in serum anti-sporozoite antibody, another had a 4-fold rise in antibody to a recombinant portion of CSP (residues 309-345), while a third vaccinee developed CSP-specific CD8+ cytotoxic T lymphocyte activity. This is the first report of attenuated S. typhi eliciting a human serologic or a cytotoxic T lymphocyte response to a foreign protein. Improved foreign gene expression should enhance immunogenicity.