gebhart/patrepeval huggingface dataset:
Antigenic Analysis of Nonstructural Protein (NSP) 4 of Group A Avian Rotavirus Strain PO‐13 (2003)

In order to analyze the antigenic structure of nonstructural protein (NSP) 4 of group A avian rotavirus strain PO-13, 25 monoclonal antibodies (MAbs) against NSP4 expressed in Escherichia coli were produced. All MAbs reacted with NSP4 on Western blotting, indicating that they recognized sequential epitopes. To determine the antigenic sites (ASs) recognized by the produced MAbs, seven truncated NSP4s were expressed in E. coli. Western blotting analysis showed that there are at least four major ASs on PO-13 NSP4, designated as AS I located in amino acids (aa) 151 to 169, AS II (aa 136 to 150), AS III (aa 112 to 133) and AS IV (aa 1 to 24). Two MAbs reacted exclusively with AS III encompassing the region that has been reported to be an enterotoxin domain. MAbs against ASs II, III and IV reacted with all avian rotaviruses tested by indirect immunofluorescent antibody assays. MAbs against AS I reacted with turkey strains, Ty-1 and Ty-3, but not with a chicken strain, Ch-1. Nine of 11 MAbs against AS II cross-reacted with NSP4 of mammalian rotavirus strains with different NSP4 genotypes. These results suggest that AS II on NSP4 is widely conserved among a variety of rotaviruses.
Towards Extracting Semantically Meaningful Key Frames From Personal Video Clips: From Humans to Computers (2008)

Extracting key frames from video is of great interest in many applications, such as video summary, video organization, video compression, and prints from video. Key frame extraction is not a new problem but existing literature has focused primarily on sports or news video. In the personal or consumer video space, the biggest challenges for key frame selection are the unconstrained content and lack of any pre-imposed structures. First, in a psychovisual study, we conduct ground truth collection of key frames from video clips taken by digital cameras (as opposed to camcorders) using both first- and third-party judges. The goals of this study are to: 1) create a reference database of video clips reasonably representative of the consumer video space; 2) identify consensus key frames by which automated algorithms can be compared and judged for effectiveness, i.e., ground truth; and 3) uncover the criteria used by both first- and third-party human judges so these criteria can influence algorithm design. Next, we develop an automatic key frame extraction method dedicated to summarizing consumer video clips acquired from digital cameras. Analysis of spatio-temporal changes over time provides semantically meaningful information about the scene and the camera operator's general intents. In particular, camera and object motion are estimated and used to derive motion descriptors. A video clip is segmented into homogeneous parts based on major types of camera motion (e.g., pan, zoom, pause, steady). Dedicated rules are used to extract candidate key frames from each segment. In addition, confidence measures are computed for the candidates to enable ranking in semantic relevance. This method is scalable so that one can produce any desired number of key frames from the candidates. Finally, we demonstrate the effectiveness of our method by comparing the results with two alternative methods against the ground truth agreed by multiple judges.
Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells (1987)

Changes in cytoplasmic calcium concentration ([Ca2+]i) activate numerous cellular processes thus mediating the effects of a number of hormones, but whether this mechanism is involved in the activation of osteoblasts by parathyroid hormone (PTH) remains uncertain. To examine this question, [Ca2+]i has been measured in suspensions of UMR 106 cells, a rodent osteosarcoma cell line with an osteoblastic phenotype. Basal [Ca2+]i was 137 +/- 3.7 nM (n = 60) and after the addition of rat PTH-(1-34) [rPTH-(1-34)] there was a rapid, dose-related increase with return to base line within 1 min. Half-maximal stimulation was produced by 5 X 10(-8) M rPTH-(1-34). Complexing of intracellular calcium by EGTA addition immediately before that of rPTH did not affect the calcium transient; neither did MnCl2 (10(-4) M) nor diltiazem (10(-4) M). Verapamil (10(-5) M) reduced the [Ca2+]i peak height after rPTH to 0.48 +/- 0.14 of control (n = 7). 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoic acid and dantrolene both reduced the [Ca2+]i response to rPTH (0.65 +/- 0.08 and 0.29 +/- 0.13 of control, respectively). Forskolin (10(-6) and 10(-5) M) produced a slight [Ca2+]i transient smaller in amplitude than seen with PTH. It is concluded that PTH mobilizes an intracellular calcium pool in these osteoblastlike cells, and the predominant mechanism for this is independent of cAMP.
Isolation and characterization of gelatinase granules from human neutrophils (1994)

We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation. Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients. We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from human neutrophils; in particular, it allows separation of specific and gelatinase granules. This allows us to characterize these two granule populations with regard to their content of membrane proteins, which become incorporated into the plasma membrane during exocytosis. We found that gelatinase granules, defined as peroxidase-negative granules containing gelatinase but lacking lactoferrin, contain 50% of total cell gelatinase, with the remaining residing in specific granules. Furthermore, we found that 20% to 25% of both the adhesion protein Mac-1 and the NADPH-oxidase component cytochrome b558 is localized in gelatinase granules. Although no qualitative difference was observed between specific granules and gelatinase granules with respect to cytochrome b558 and Mac-1, stimulation of the neutrophil with FMLP resulted in a selective mobilization of the least dense peroxidase-negative granules, ie, gelatinase granules, which, in concert with secretory vesicles, furnish the plasma membrane with Mac-1 and cytochrome b558. This shows that gelatinase granules are functionally important relative to specific granules in mediating early inflammatory responses.
Ultrafast dynamic ellipsometry of laser driven shock waves (2008)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.
A new electrochemically graded hydroxyapatite coating for osteosynthetic implants promotes implant osteointegration in a rat model (2002)

Hydroxyapatite (HAP) is widely used as an osteoconductive coating for orthopedic implants. So far standard coating methods like plasma spraying produce a relatively thick coating layer (>30 microm). In addition, the chemical structure of the HAP may be altered because of the heating throughout the coating process. This may have negative effects on the coating stability, implant fixation, and induction of bone formation. The relatively thick layer may detach from the implant with the risk of wear debris. In the present study the potential of a newly developed HAP coating of implants on osteointegration was investigated in a rat model. The coating method, based on an electrochemical process, is applied in a graded manner and results in a biodegradable HAP coating with a thickness of approximately 2 mum. Coated versus uncoated titanium Kirschner wires (1.4-mm diameter) were inserted into the medullary cavity of the right femora of 5-month old female Sprague Dawley rats (n=36) in a retrograde fashion. Throughout an experimental period of 2 months the osteointegration was traced radiologically. After this time the animals were sacrificed and the implant integration was tested biomechanically with the use of a push-out test. To analyze the bone-implant interface, histological sections (80 mum) were investigated with an image analyzing system. The biomechanical testing revealed a significantly higher implant fixation in the group treated with the HAP-coated implant (shear strength: 27.8 +/- 6.7 MPa) compared to control (shear strength: 8.08 +/- 3.4 MPa). The histological analyses demonstrated a better ingrowth of the implants in the HAP group with significantly more direct bone-implant contacts compared to the control group. The results demonstrate that the HAP coating promotes implant osteointegration in a rat model.
Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity—Opportunity for Repurposed Chemotherapy of COVID-19 Infection (2020)

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG - residues with predicted or expected low pK<sub>a</sub> by neighboring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related <i>coronaviridae: SARS-CoV and MERS. Finally, w</i>e identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.
A high-resolution multiple-crystal multiple-reflection diffractometer (1989)

A high-resolution multiple-reflection diffractometer has been built to study crystals distorted by epitaxy and defects in nearly perfect crystals. The diffractometer combines the merits of the two-crystal four-reflection monochromator (to define a narrow wavelength range with a tailless reflectivity profile) and an analyser crystal to select the angular range diffracted from the sample crystal. The diffractometer is operated in two modes. In the first the sample and analyser rotations are coupled to obtain near-perfect rocking curves from distorted crystals, and in the second mode the two axes are uncoupled to obtain a diffraction space map for studying the diffuse scattering. The simulation of these profiles and maps based on dynamical theory is presented. The former allows complex structures to be analysed and the latter case, by deconvolving the dynamical scattering in these maps, permits a complete interpretation of the kinematic scattering.
Exploring T Cell Reactivity to Gliadin in Young Children with Newly Diagnosed Celiac Disease (2014)

Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin peptides to CD4 T cells in the small intestine. Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low circulating frequencies and heterogeneity in response to gliadin epitopes. We investigated the peripheral T cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated CD. Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones previously derived from intestinal biopsies of CD patients. These recombinant proteins and a panel of α- and γ-gliadin peptides were used to assess T cell responses from the peripheral blood. Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T cell responses to α-gliadin than γ-gliadin peptides with a single deamidated α-gliadin peptide able to identify 60% of CD children. We conclude that it is possible to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring proliferative responses.
Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis (2019)

Tumour necrosis factor (TNF)-α is a key mediator of inflammation in rheumatoid arthritis, and its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug, leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single-cell technology have enabled the characterization of many leucocyte subsets. Studying the blood immunophenotype may therefore, define biomarker profiles relevant to each individual patient's disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs.
The Mouse Extracellular Signal-regulated Kinase 2 Gene (1997)

ERK2 (extracellular-signal regulated kinase 2, also known as p42 mitogen-activated protein kinase) is an integral member of the mitogen-activated protein kinase cascade that is crucial for many cellular events such as proliferation and differentiation. Here, we determined the genomic organization of the Erk2 gene and characterized its promoter. The Erk2 gene spans over 60 kilobases, and the coding region is split into eight exons. In the coding region, exon-intron organization was exactly conserved between the two mouse genes for ERK2 and ERK1 except one junction shifted by one nucleotide. Primer extension and S1 nuclease analyses identified two major transcription start sites located at -219 and -223 relative to the translation start site. The 5'-flanking sequence lacked TATA box but contained a CCAAT box located approximately 60 base pairs upstream of transcription start sites. Sequencing of the 5'-flanking region also revealed potential cis-acting elements for multiple transcriptional regulatory factors including Sp1, zif268, Ets, CREB, and PuF sites. The promoter activity of the 5'-flanking region was examined using chloramphenicol acetyltransferase as a reporter gene. Transient transfection experiments using Chinese hamster ovary cells defined a maximal promoter activity in a 371-base pair region immediately upstream of the translation start site. Furthermore, we demonstrated, using mouse P19 embryonal carcinoma cells, that this 371-base pair sequence is likely to be sufficient to confer the transcriptional activation of the ERK2 promoter during the retinoic acid-induced differentiation of P19 cells.
Motion and Structure Estimation Using Fusion of Inertial and Vision Data for Helmet Tracker (2010)

For weapon cueing and Head-Mounted Display (HMD), it is essential to continuously estimate the motion of the helmet. The problem of estimating and predicting the position and orientation of the helmet is approached by fusing measurements from inertial sensors and stereo vision system. The sensor fusion approach in this paper is based on nonlinear filtering, especially expended Kalman filter(EKF). To reduce the computation time and improve the performance in vision processing, we separate the structure estimation and motion estimation. The structure estimation tracks the features which are the part of helmet model structure in the scene and the motion estimation filter estimates the position and orientation of the helmet. This algorithm is tested with using synthetic and real data. And the results show that the result of sensor fusion is successful.
Metabolic engineering with Dof1 transcription factor in plants: Improved nitrogen assimilation and growth under low-nitrogen conditions (2004)

Utilization of transcription factors might be a powerful approach to modification of metabolism for a generation of crops having superior characteristics because a single transcription factor frequently regulates coordinated expression of a set of key genes for respective pathways. Here, we apply the plant-specific Dof1 transcription factor to improve nitrogen assimilation, the essential metabolism including the primary assimilation of ammonia to carbon skeletons to biosynthesize amino acids and other organic compounds involving nitrogen in plants. Expressing Dof1 induced the up-regulation of genes encoding enzymes for carbon skeleton production, a marked increase of amino acid contents, and a reduction of the glucose level in transgenic Arabidopsis. The results suggest cooperative modification of carbon and nitrogen metabolisms on the basis of their intimate link. Furthermore, elementary analysis revealed that the nitrogen content increased in the Dof1 transgenic plants (approximately 30%), indicating promotion of net nitrogen assimilation. Most significantly, the Dof1 transgenic plants exhibit improved growth under low-nitrogen conditions, an agronomically important trait. These results highlight the great utility of transcription factors in engineering metabolism in plants.
Synthesis of 5-Fluoropyrimidine Nucleotides as Sensitive NMR Probes of RNA Structure (2007)

Enzymatic synthesis methods for the fluorinated 5'-triphosphate analogues 5F-UTP and 5F-CTP have been developed to facilitate 19F-labeling of RNAs for biophysical studies. HIV-2 TAR RNAs were synthesized using these analogues by in vitro transcription reactions using T7 RNA polymerase. The uniform incorporation of 5F-U or 5F-C analogues into HIV-2 TAR RNA transcripts does not significantly alter the RNA structure or thermodynamic stability. Fluorine observed homonuclear 19F-19F and heteronuclear 19F-1H NOE experiments providing selective distance information are presented and discussed. The availability of efficient synthesis of 5F-UTP, and for the first time, 5F-CTP, will facilitate the use of 5F-labeled RNAs in structural, ligand binding, and dynamic studies of RNAs using the advantages of 19F-labeling.
Can Epileptic Seizures be Predicted? Evidence from Nonlinear Time Series Analysis of Brain Electrical Activity (1998)

We evaluate the capability of nonlinear time series analysis to extract features from brain electrical activity (EEG) predictive of epileptic seizures. Time-resolved analysis of the EEG recorded in 16 patients from within the seizure-generating area of the brain indicate marked changes in nonlinear characteristics for up to several minutes prior to seizures as compared to other states or recording sites. If interpreted as a loss of complexity in brain electrical activity these changes could reflect the hypothesized continuous increase of synchronization between pathologically discharging neurons and allow one to study seizure-generating mechanisms in humans.
Tumor Necrosis Factor Blockade in Rheumatoid Arthritis (1996)

Advances in the understanding of basic disease mechanisms in rheumatoid arthritis (RA) are leading to the development of new, rational therapies. In one widely accepted view of disease pathogenesis, RA is initiated and possibly maintained by an immune response involving the recognition by T cells of an autoantigen (yet uncharacterized) in the context of a specific &quot;shared epitope&quot; HLA-DR~ gene product (l ), with consequent T-cell activation and the initiation of an inflammatory cascade. Although cytokines may be involved in the initiating immune response, they are particularly important in the subsequent processes of inflammation and it is to this level that anticytokine therapy is primarily directed.
Low O 2 tensions and the prevention of differentiation of hES cells (2005)

Early-stage mammalian embryos develop in a low O(2) environment (hypoxia). hES cells, however, are generally cultured under an atmosphere of 21% O(2) (normoxia), under which conditions they tend to differentiate spontaneously. Such conditions may not be the most suitable, therefore, for hES cell propagation. Here we have tested two hypotheses. The first hypothesis was that hES cells would grow as well under hypoxic as under normoxic conditions. The second hypothesis was that hypoxic culture would reduce the amount of spontaneous cell differentiation that occurs in hES colonies. Both hypotheses proved to be correct. Cells proliferated as well under 3% and 5% O(2) as they did under 21% O(2), and growth was only slightly reduced at 1% O(2). The appearance of differentiated regions as assessed morphologically, biochemically (by the production of human chorionic gonadotropin and progesterone), and immunohistochemically (by the loss of stage-specific embryonic antigen-4 and Oct-4 and gain of stage-specific embryonic antigen-1 marker expression) was markedly reduced under hypoxic conditions. In addition, hES cell growth under hypoxia provided enhanced formation of embryoid bodies. Hypoxic culture would appear to be necessary to maintain full pluripotency of hES cells.
Identification of a Δ4 Fatty Acid Desaturase fromThraustochytrium sp. Involved in the Biosynthesis of Docosahexanoic Acid by Heterologous Expression inSaccharomyces cerevisiae and Brassica juncea (2001)

The existence of Delta 4 fatty acid desaturation in the biosynthesis of docosahexanoic acid (DHA) has been questioned over the years. In this report we describe the identification from Thraustochytrium sp. of two cDNAs, Fad4 and Fad5, coding for Delta 4 and Delta 5 fatty acid desaturases, respectively. The Delta 4 desaturase, when expressed in Saccharomyces cerevisiae, introduced a double bond at position 4 of 22:5(n-3) and 22:4(n-6) resulting in the production of DHA and docosapentanoic acid. The enzyme, when expressed in Brassica juncea under the control of a constitutive promoter, desaturated the exogenously supplied substrate 22:5(n-3), resulting in the production of DHA in vegetative tissues. These results support the notion that DHA can be synthesized via Delta 4 desaturation and suggest the possibility that DHA can be produced in oilseed crops on a large scale.