gebhart/patrepeval huggingface dataset:
Degradation of apolipoprotein B-100 by lysosomal cysteine cathepsins (2006)

Although the degradation of cellular or endocytosed proteins comprises the normal function of lysosomal proteinases, these enzymes were also detected extracellularly during diseases such as atherosclerosis. Since lysosomal cysteine cathepsins were demonstrated to transform native LDL particles into a proatherogenic type, the following study was undertaken to characterize the modification of LDL particles and the degradation of apolipoprotein B-100 in more detail. LDL was incubated with cathepsins B, F, K, L, S, and V at pH 5.5 and under physiological conditions (pH 7.4) for 2 h to mimic conditions of limited proteolysis. Gel electrophoretic analysis of the degradation products revealed that cathepsin-mediated proteolysis of apolipoprotein B-100 is a fast process carried out by all enzymes at pH 5.5, and by cathepsin S also at pH 7.4. Electron microscopic analysis showed that cathepsin-mediated degradation of apolipoprotein B-100 rendered LDL particles fusion-competent compared to controls. N-Terminal sequencing of cathepsin cleavage fragments from apolipoprotein B-100 revealed an abundance of enzyme-specific cleavage sites located in almost all structurally and functionally essential regions. Since the cleavage sites superimpose well with results from substrate specificity studies, they might be useful for the development of cathepsin-specific inhibitors and substrates.
Serotonin (5-HT) Activation of Immortalized Hypothalamic Neuronal Cells Through the 5-HT1B Serotonin Receptor (2012)

Serotonin [or 5-hydroxytryptamine or (5-HT)] has been implicated as a key modulator in energy homeostasis and a primary focus in the treatment of obesity. There is growing evidence that 5-HT, acting through the 5-HT 1B receptor (5-HT(1B)R) in the paraventricular nucleus of the hypothalamus (PVN), is important to this regulation. However, there is some contention as to whether 5-HT(1B)R action occurs directly on PVN neurons or indirectly via inhibitory inputs into the PVN. To address these questions, we used a novel clonal, hypothalamic neuronal cell model, adult mouse hypothalamic-2/30 (mHypoA-2/30), expressing a PVN-specific marker, single-minded homolog 1, as well as a complement of PVN neuropeptides, including TRH, vasopressin, ghrelin, nucleobindin-2, and galanin. Adult mouse hypothalamic-2/30 neurons were also found to express the 5-HT(1B)R and 5-HT 6 receptor, but not 2C, all previously linked to feeding regulation. Direct serotonergic stimulation (100 nm to 10 μm) of these neurons resulted in dose-dependent cFos activation. 5-HT (10 μm) suppressed forskolin-induced cAMP levels and induced a rise in intracellular Ca(2+) through ER Ca(2+) release, effects that were mimicked by the 5-HT(1B)R agonists, CGS12066B and CP93129, and that were attenuated in the presence of the 5-HT(1B)R-specific inhibitors, GR55562 and isamoltane hemifumarate. Modest transcriptional changes in ghrelin and nucleobindin-2 were also observed in response to 100 nm and 10 μm 5-HT, respectively. These findings support the model wherein 5-HT action through the 1B receptor subtype occurs directly on PVN neurons, leading to potential modification of neuronal transcriptional and secretory machinery.
Boresight Calibration of Mobile Laser Scanner Using an External Fixture (2016)

Abstract The boresight misalignment of a mobile laser scanning system is a major source of error for point cloud data and cannot be measured directly. This paper presents a new boresight calibration method for a mobile laser scanner system that uses an external fixture with a simple checkerboard pattern. The boresight angles are determined by minimizing the differences between the measured relative distances of the intersection points of the squares in a checkerboard fixture with the corresponding actual distances in the fixture. Experimental results from scanning the checkerboard pattern on the fixture show that the calibrated values of the boresight angles match the manufacturer’s values within 0.22 cm. Using this simple checkerboard fixture in the field prevents surveyors from having to rely on roadway features or setting control targets and provides for an alternative approach for the boresight calibration of a mobile laser scanner system.
X-Ray crystal structure of W(CCMe<sub>3</sub>)(CHCMe<sub>3</sub>)(CH<sub>2</sub>CMe<sub>3</sub>)(Me<sub>2</sub>PCH<sub>2</sub>CH<sub>2</sub>PMe<sub>2</sub>), an ordered five-co-ordinate tungsten(<scp>VI</scp>) complex with metal–alkyl, metal–alkylidene, and metal–alkylidyne linkages (1979)

An -ray structural analysis of the complex W( [[triple bond, length half m-dash]] CCMe)( [[double bond, length half m-dash]] CHCMe)(CHCMe)(MePCHCHPMe) shows a distorted five-co-ordinate geometry about the tungsten atom.
&amp;#945;-Synuclein and the Pathogenesis of Parkinsons Disease (2004)

Lesions known as Lewy bodies (LBs) and Lewy neurites (LNs) characterise brains of Parkinson's disease (PD) patients. Intracellular aggregation of alpha-synuclein (alpha-syn) appears to play a key role in the generation of LBs and LNs. Such aggregation in the presence of redox metals may initiate Fenton reaction-mediated generation of reactive oxygen species (ROS). ROS thus generated may result in cytotoxic mechanisms such as the induction of DNA single-strand breaks.
Transfected MDCK Cell Line with Enhanced Expression of CYP3A4 and P-Glycoprotein as a Model To Study Their Role in Drug Transport and Metabolism (2012)

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions.
THE ECOLOGIES OF HUMAN IMMUNE FUNCTION (2005)

Immune function is notoriously complex, and current biomedical research elaborates this complexity by focusing on the cellular and molecular mechanisms that characterize immune defenses. However, the human immune system is a product of natural selection that develops and functions in whole organisms that are integral parts of their surrounding environments. A population-level, cross-cultural, adaptationist perspective is therefore a necessary complement to the micro levels of analysis currently favored by biomedical immunology. Prior field-based research on human immunity is reviewed to demonstrate the relevance of cultural ecological factors, with an emphasis on the ecologies of nutrition, infectious disease, reproduction, and psychosocial stress. Common themes and anthropological contributions are identified in an attempt to promote future research in human ecological immunology that integrates theory and method for a more contextualized understanding of this important physiological system.
Constitutive Expression of GATA4 Dramatically Increases the Cardiogenic Potential of D3 Mouse Embryonic Stem Cells (2016)

The transcription factor GATA binding protein 4 (GATA4) is a vital regulator of cardiac programming that acts by inducing the expression of many different genes involved in cardiomyogenesis. Here we generated a D3 mouse embryonic stem cell line that constitutively expresses high levels of GATA4 and show that these cells have dramatically increased cardiogenic potential compared to an eGFP-expressing control cell line. Embryoid bodies (EB) derived from the D3-GATA4 line displayed increased levels of cardiac gene expression and showed more abundant cardiomyocyte differentiation than control eGFP EB. These cells and two additional lines expressing lower levels of GATA4 provide a platform to screen previously untested cardiac genes and gene combinations for their ability to further increase the efficiency of cardiomyocyte differentiation beyond that achieved by transgenic GATA4 alone. Non-integrative delivery of identified gene combinations will aid in the production of differentiated cells for the treatment of ischemic cardiomyopathy.
Heat transfer with condensation at a steam-water interface in a horizontal channel. (1991)

Condensation of steam on a subcooled water layer was studied in a cocurrent horizontal channel at atmospheric pressure through experimental and numerical analysis. The liquid and vapor Reynolds numbers, based on hydraulic diameters, were varied experimentally from 6900 to 21900 and from 7700 to 19700, respectively. The experimental results showed promotion of heat transfer by the existence of interfacial waves. The numerical analysis predicted a heat transfer coefficient lower than the experimental results. This discrepancy can be explained by the fact that the numerical results showed decay of turbulent viscosity near the interface because of severe restriction of turbulent values.
Pathological Characterization of Male Wistar Rats From The Gerontology Research Center (1993)

Male Wistar rats aged 6-26 months were obtained from the colony of The Gerontology Research Center of the National Institute on Aging, and pathological profiles were assessed. One hundred animals were sacrificed at 6, 12, 18, 21, 24, and 26 months and used for cross-sectional determinations; also, 150 animals were followed longitudinally and sacrificed when clinical signs of moribundity appeared. Renal disease contributed the most common pathology observed in both studies (found in over 70% of the animals examined), with neoplasms a secondary problem (pituitary tumors were by far the most prevalent, with adenomas present in approximately 20% of the animals). This analysis represents the first complete pathological characterization of this commonly used rat model for aging research, and offers an opportunity for comparison with other rat strains.
An indicator cell assay for blood-based diagnostics (2017)

Abstract We have established proof of principle for the Indicator Cell Assay Platform™ (iCAP™), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients’ blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, cost-effective disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value=3.81E-6) and correctly identified samples from a murine Huntington’s disease model as non-carriers of ALS. In a preliminary human disease assay, the iCAP detected early stage Alzheimer’s disease with 72% cross-validated accuracy (p-Value=3.10E-3). For both assays, iCAP features were enriched for disease-related genes, supporting the assay’s relevance for disease research.
Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins (2018)

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on <i>L</i> and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here) from the protein distribution densities in the LD space defined by ln(<i>L</i>) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.
Tachykinin receptors in GtoPdb v.2023.1 (2023)

Tachykinin receptors (provisional nomenclature as recommended by NC-IUPHAR [91]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin α, neuromedin L), neurokinin B (NKB; previously known as neurokinin β, neuromedin K), neuropeptide K and neuropeptide γ (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in in vitro pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.
ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion (2012)

In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the regulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progression. Here, we report that ERK3 interacted with and phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity in lung cancer cells. Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to invade and form tumors in the lung in a xenograft mouse model. In addition, ERK3 was found to be highly upregulated in human lung carcinomas. Our study identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylation. As such, ERK3 protein kinase may be an attractive target for therapeutic treatment of invasive lung cancer.
Supplementary Figure 2 from Active CREB1 Promotes a Malignant TGFβ2 Autocrine Loop in Glioblastoma (2023)

&lt;p&gt;A graph showing the quantification of tumor growth in GBM PDX models expressing shCREB1.&lt;/p&gt;
Sequential Dynamics of Stearoyl-CoA Desaturase-1(SCD1)/Ligand Binding and Unbinding Mechanism: A Computational Study (2021)

Stearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases, including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as an apoprotein. The modeling of SCD1:fatty acid interactions suggests that: (1) SCD1:CoA moiety interactions open the substrate-binding tunnel, (2) SCD1 stabilizes a substrate conformation favorable for desaturation, and (3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.
ChemInform Abstract: Discovery of Novel 1H‐Imidazol‐2‐yl‐pyrimidine‐4,6‐diamines as Potential Antimalarials. (2010)

Abstract Newly synthesized title compounds (I) show potent activity against the erythrocyte‐stage of Plasmodium falciparum, the most causative agent of malaria.
Modeling Concrete Structures Under Impact Loading: Applicability of Three Material Models (2009)

Advances in computational mechanics and computer hardware made it easier to model complex engineering structures under high rate loading. In this paper, three concrete material models are presented and utilized in simulating concrete structures under impact loading. To verify the models, exiting impact tests on concrete bridge rails were used and presented as well. One of the material models was further used to evaluate pier column under high rate loading. The three material models are available in LS-DYNA commercial finite element code and they are materials type 72R3, 84 and 159. The results indicate that damage profile and impact force estimate can be captured within reasonable accuracy using simple input concrete models. However, further small scale tests will definitely add to the accuracy of such model
Supplementary Figure 3 from Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas (2023)

Supplementary Figure 3 from Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas
Expression and Purification Methods for the Production of Recombinant Human Complement Component C2 (2013)

Human complement component C2 is a critical factor of the classical complement pathway. Here we provide a method for the production of recombinant human C2 (rhC2) protein for research purposes. The human complement component C2 (hC2) is cloned from a human cDNA library by polymerase chain reaction and inserted in a mammalian expression vector (Martini et al., BMC Immunol 11:43, 2010). Transient transfection is utilized to express hC2 in a mammalian cell line, and the expressed C2 is harvested from the conditioned media. rhC2 is purified from the conditioned media by sequential steps of cation exchange and affinity column chromatography. The purified hC2 is characterized for protein purity, stability, and enzymatic activity. The recombinant hC2 activity is tested in a complement activation ELISA assay that measures classical, alternative, and lectin complement pathway activity in C2-depleted serum.
First M87 Event Horizon Telescope Results. II. Array and Instrumentation (2019)

Abstract The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ∼1.3 mm, EHT angular resolution ( λ / D ) is ∼25 μ as, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s −1 , exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.
Heavy Quark Production at the H1 Experiment at HERA (2011)

Heavy Quark Production at HERA with H1Andreas B
Variability of repeated facial nerve electroneurography in healthy subjects (1998)

The symmetry of facial evoked compound potentials postulated by Esslen and Fisch is not supported by these data. As have other investigators, the authors found significant left-right differences in healthy subjects. Furthermore, they showed for the first time that the amplitude ratio is not constant in every individual at repeated measurements. In light of these data, prognosis of facial palsy based on electroneurographic data alone seems doubtful.