gebhart/patrepeval huggingface dataset:
Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fcγ receptors (2016)

The immunotherapeutic catumaxomab targets EpCAM positive cancers and is approved for the treatment of peritoneal carcinomatosis. To assess the safety of intravenous applications a phase 1 clinical trial was initiated. Treatment of EpCAM positive tumor patients with catumaxomab caused dose dependent hepatitis as evidenced by significant elevations in serum alanine- and aspartate aminotransferases, bilirubin, γGT and induction of the acute phase C-reactive protein (CRP) and the cytokines IL6 and IL8. The first patient receiving 10μg catumaxomab experienced fatal acute liver failure which led to the termination of the study. Immmunopathology revealed catumaxomab to bind via its Fc-fragment to FcγR-positive Kupffer cells to stimulate CRP, chemokine and cytokine release. The observed CD3+T-cell margination at activated hepatic macrophages exacerbated T-cell mediated cytotoxicity. Strikingly, the combined Kupffer/T-cell responses against liver cells did not require hepatocytes to be EpCAM-positive. Catumaxomab's off-target activity involved T-cell mediated lysis of the granzyme B cell death pathway and the molecular interaction of hepatic sinusoidal macrophages with T-cells induced cytolytic hepatitis. Although the bile ducts were surrounded by densely packed lymphocytes these rarely infiltrated the ducts to suggest an intrahepatic cholestasis as the cause of hyperbilirubinaemia. Lastly, evidence for the programming of memory T-cells was observed with one patient that succumbed to his cancer six weeks after the last catumaxomab infusion. In conclusion, our study exemplifies off-target hepatotoxicity with molecularly targeted therapy and highlights the complexities in the clinical development of immunotherapeutic antibodies.
Evaluation of Polydimethylsiloxane as an Alternative in the Endoscopic Treatment of Vesicoureteral Reflux (1994)

Endoscopic correction of vesicoureteral reflux is an attractive alternative to open repair. In terms of effectiveness and long-term successful results polytetrafluoroethylene (Polytef) is the most reliable injectable product. However, legitimate concerns regarding particle migration still exist for polytetrafluoroethylene. Polydimethylsiloxane (Macroplastique) was evaluated as an alternative to polytetrafluoroethylene. Seven mongrel female dogs underwent endoscopic suburothelial injections of 0.35 to 0.50 cc polydimethylsiloxane paste by the O'Donnell technique to a unilateral nonrefluxing ureteral orifice. To facilitate migratory surveillance the paste was mixed with 57carbon monoxide radiolabeled 80 microns. microspheres and injected in 5 of the 7 animals. Animals were sacrificed at 1, 3 and 6-month intervals. All major organs were retrieved and processed. After intensive histological evaluation the remaining tissue underwent dissolution and centrifugation in sodium hypochlorite. The resulting insoluble pellet was further analyzed. In dogs injected with radiolabeled paste tissue samples and insoluble pellets of each organ system were analyzed for gamma counts. Smears of the insoluble pellets of all animals were examined on light and phase contrast microscopy. At autopsy no gross abnormalities were noted. Tissue reaction at injection sites revealed a well encapsulated foreign body reaction with predominantly giant cells, fibroblasts and collagen deposition. Limited local migration of polydimethylsiloxane particles into the periureteral lymphatics of 1 animal sacrificed at 1 month was noted and a single particle visually indistinguishable from polydimethylsiloxane also was found within the splenic capsule. The endoscopic procedure in this animal was complicated in that 2 separate injections were required and histological evaluation confirmed that the injections were performed uniquely deep into the bladder muscularis. Radioactive counts and dissolution of all major organ systems demonstrated no migration in the remaining 6 animals. Endoscopic subureteral injection of polydimethylsiloxane is technically feasible, and it may prove to be biocompatible and without risk of distant migration if injected correctly.
What sensory signals are about (1998)

Journal Article What sensory signals are about Get access Crawford L. Elder Crawford L. Elder University of ConnecticutU-54 Storrs, CT 06269-2054, USAelder@uconnvm.uconn.edu Search for other works by this author on: Oxford Academic Google Scholar Analysis, Volume 58, Issue 4, October 1998, Pages 273–276, https://doi.org/10.1093/analys/58.4.273 Published: 01 October 1998
Accuracy of Various HumanNAT2SNP Genotyping Panels to Infer Rapid, Intermediate and Slow Acetylator Phenotypes (2011)

A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non-European ancestry.
Hydrogen Sulfide Protects HT22 Neuronal Cells from Oxidative Stress (2006)

Hydrogen sulfide (H2S) is a neuromodulator in the brain and a relaxant for smooth muscle. H2S protects primary cortical neurons from oxidative stress by increasing the intracellular concentrations of glutathione, the major antioxidant in cells. However, changes in glutathione alone are not sufficient to account for full protection in all types of nerve cells. H2S is here shown to protect an immortalized mouse hippocampal cell line from oxidative glutamate toxicity by activating ATP-dependent K+ (KATP) and Cl- channels, in addition to increasing the levels of glutathione. The present study therefore identifies a novel pathway for H2S protection from oxidative stress.
Creating Sustainable Cyberinfrastructures (2015)

In this paper we report the results of a qualitative research study of the GENI cyberinfrastructure: a program of four federated cyberinfrastructures. Drawing on theories of stakeholder positioning, we examine how different GENI stakeholders attempt to enlist new participants in the cyberinfrastructures of GENI, and leverage existing relationships to create sustainable infrastructure. This study contributes to our understanding of how cyberinfrastructures emerge over time through processes of stakeholder alignment, enrollment, and through synergies among stakeholder groups. We explore these issues to better understand how cyberinfrastructures can be designed to sustain over time.
Genomic Organization of the Mouse Gene for Lung Surfactant Protein D (1999)

Lung surfactant protein (SP)-D belongs to the family of soluble collagenous C-type lectins, named collectins. SP-D participates in the local innate immune defense of the lung, eliciting various effector functions by acting as a pattern recognition receptor for the carbohydrate structures on inhaled microorganisms and particulate matter. This work describes the isolation and characterization of the mouse SP-D gene (Sftpd), which spans 8 exons over 14 kb of sequence and shows an overall organization similar to other collectin genes. The complete 5' untranslated region of the messenger RNA, absent from the published complementary DNA for mouse SP-D, was also cloned and is shown to be encoded by a single exon. Analysis of 3.5 kb of 5' flanking nucleotide sequence for Sftpd is described and reveals positional conservation of a number of transcription factor binding sites on comparison of Sftpd with the human SP-D gene and the bovine conglutinin gene. In addition, a single copy SP-D-like gene has been shown to be present in mammals, birds, and amphibians but is absent in fish. An atypical, rodent-specific, long terminal repeat of retroviral origin containing a minisatellite that has become inserted in Sftpd is described. Three new polymorphic microsatellites are also described, one of which is just 160 base pairs upstream of Sftpd. This microsatellite was used to map the gene to the central region of chromosome 14; fine-scale mapping indicates that it lies in a 5. 64-centimorgan area between D14Mit45 and D14Mit60. This will allow the easy identification of the collectin gene cluster and aid in the construction of a physical map over this region.
Adaptation to Hydrogen Sulfide of Oxygenic and Anoxygenic Photosynthesis among Cyanobacteria (1986)

Four different types of adaptation to sulfide among cyanobacteria are described based on the differential toxicity to sulfide of photosystems I and II and the capacity for the induction of anoxygenic photosynthesis. Most cyanobacteria are highly sensitive to sulfide toxicity, and brief exposures to low concentrations cause complete and irreversible cessation of CO(2) photoassimilation. Resistance of photosystem II to sulfide toxicity, allowing for oxygenic photosynthesis under sulfide, is found in cyanobacteria exposed to low H(2)S concentrations in various hot springs. When H(2)S levels exceed 200 muM another type of adaptation involving partial induction of anoxygenic photosynthesis, operating in concert with partially inhibited oxygenic photosynthesis, is found in cyanobacterial strains isolated from both hot springs and hypersaline cyanobacterial mats. The fourth type of adaptation to sulfide is found at H(2)S concentrations higher than 1 mM and involves a complete replacement of oxygenic photosynthesis by an effective sulfide-dependent, photosystem II-independent anoxygenic photosynthesis. The ecophysiology of the various sulfide-adapted cyanobacteria may point to their uniqueness within the division of cyanobacteria.
Body Posture and Mode of Locomotion in Early Pleistocene Hominids (1971)

Assumptions concerning the carriage of fossil primates play a considerable role in most discussions of human evolution. Such assertions may be reliable to a very high degree, since there exists a causal relationship between mechanical stresses acting in a bone during locomotion and its shape and structure. The stresses in a bone are determined by relatively few characteristics: the relative forces of the muscles, lengths of their lever arms, as well as points of application and directions of external forces. Whereas the former can be assumed to have certain values and then be treated as known factors, the latter depend on the body’s posture and the method of locomotion of the animal in question. Analyses of this type are used to improve our knowledge about Early Pleistocene hominids from East and South Africa. The investigation is based primarily on the foot and leg bones from Olduvai Gorge.
Protection against generalized autoimmunity of the nervous system (GANS), a novel animal model with combined features of EAE, EAN and EAU by a recombinant HIV-1 Tat37–72peptide-based multiple T cell epitope vaccine (1997)

A new model of multi-compartment auto-immune disease has been established to analyze the effects of polyvalent recombinant peptide vaccines. A synthetic gene encoding major pathogenic determinants for Lewis rats of guinea pig myelin basic protein (MBP68-84), bovine interphotoreceptor retinoid binding protein (IRBP1169-1191), and bovine P2 protein (P2,53-78) was used to induce Generalized Autoimmunity of the Nervous System (GANS), which is characterized by development of auto-immune infiltration of the brain and spinal cord, the eyes, the pineal organ and the peripheral nerves. Thus, this model integrates the prominent features of three auto-immune diseases: experimental autoimmune encephalomyelitis (EAE), neuritis (EAN) and uveitis (EAU). In this study, GANS was used to study the effect of HIV-1 Tat37-72 targeting peptide on vaccination by recombinant polyvalent T cell auto-antigen vaccine. Depending on the route of administration, the recombinant vaccine effectively protects against the development of auto-immune nervous system inflammation.
Surfactant protein C peptides with salt-bridges (“ion-locks”) promote high surfactant activities by mimicking the α -helix and membrane topography of the native protein (2014)

Background. Surfactant protein C (SP-C; 35 residues) in lungs has a cationic N-terminal domain with two cysteines covalently linked to palmitoyls and a C-terminal region enriched in Val, Leu and Ile. Native SP-C shows high surface activity, due to SP-C inserting in the bilayer with its cationic N-terminus binding to the polar headgroup and its hydrophobic C-terminus embedded as a tilted, transmembrane α-helix. The palmitoylcysteines in SP-C act as 'helical adjuvants' to maintain activity by overriding the β-sheet propensities of the native sequences. Objective. We studied SP-C peptides lacking palmitoyls, but containing glutamate and lysine at 4-residue intervals, to assess whether SP-C peptides with salt-bridges ("ion-locks") promote surface activity by mimicking the α-helix and membrane topography of native SP-C. Methods. SP-C mimics were synthesized that reproduce native sequences, but without palmitoyls (i.e., SP-Css or SP-Cff, with serines or phenylalanines replacing the two cysteines). Ion-lock SP-C molecules were prepared by incorporating single or double Glu(-)-Lys(+) into the parent SP-C's. The secondary structures of SP-C mimics were studied with Fourier transform infrared (FTIR) spectroscopy and PASTA, an algorithm that predicts β-sheet propensities based on the energies of the various β-sheet pairings. The membrane topography of SP-C mimics was investigated with orientated and hydrogen/deuterium (H/D) exchange FTIR, and also Membrane Protein Explorer (MPEx) hydropathy analysis. In vitro surface activity was determined using adsorption surface pressure isotherms and captive bubble surfactometry, and in vivo surface activity from lung function measures in a rabbit model of surfactant deficiency. Results. PASTA calculations predicted that the SP-Css and SP-Cff peptides should each form parallel β-sheet aggregates, with FTIR spectroscopy confirming high parallel β-sheet with 'amyloid-like' properties. The enhanced β-sheet properties for SP-Css and SP-Cff are likely responsible for their low surfactant activities in the in vitro and in vivo assays. Although standard (12)C-FTIR study showed that the α-helicity of these SP-C sequences in lipids was uniformly increased with Glu(-)-Lys(+) insertions, elevated surfactant activity was only selectively observed. Additional results from oriented and H/D exchange FTIR experiments indicated that the high surfactant activities depend on the SP-C ion-locks recapitulating both the α-helicity and the membrane topography of native SP-C. SP-Css ion-lock 1, an SP-Css with a salt-bridge for a Glu(-)-Lys(+) ion-pair predicted from MPEx hydropathy calculations, demonstrated enhanced surfactant activity and a transmembrane helix simulating those of native SP-C. Conclusion. Highly active SP-C mimics were developed that replace the palmitoyls of SP-C with intrapeptide salt-bridges and represent a new class of synthetic surfactants with therapeutic interest.
Guided Self-Assembly of Symmetric Diblock Copolymer Films on Chemically Nanopatterned Substrates (2000)

Self-assembled films of octadecyltrichlorosilane were patterned with regions of different chemical functionality using extreme ultraviolet interferometric lithography. Unexposed regions of the imaging layers remain terminated in methyl groups, and exposed regions are modified so as to be terminated with polar, oxygen-containing terminal groups. Thin films of symmetric poly(styrene-b-methyl methacrylate) were deposited on the substrates and annealed. Unexposed and exposed regions are preferentially wet by the polystyrene block and poly(methyl methacrylate) block of the copolymer, respectively. The dimensions of the grating patterns on the substrate had periods (Ls) from 1400 to ∼60 nm. If Ls ≫ Lo (Lo = bulk lamellar period of the block copolymer), then the surface pattern was replicated in the topography of the polymer film with a maximum difference in film thickness of 1/2Lo on adjacent regions. The topographic pattern of the polymer film was a result of lamellae oriented parallel to the substrate with symmetric wetting on unexposed regions (thickness = nLo) and with asymmetric wetting on exposed regions (thickness = (n + 1/2)Lo). As the dimension of Ls approached Lo, the replication of the surface pattern in the topography of the film continued to be observed, but with decreasing difference in thickness over adjacent exposed and unexposed regions. For a surface pattern with Ls ≈ Lo, the lamellae oriented perpendicular to the substrate and were macroscopically aligned with the surface pattern.
Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions (1989)

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
Development of automatic techniques for segmentation of brain tissues from multispectral MR images (2002)

Automatic segmentation of brain tissues from multispectral magnetic resonance (MR) images (acquired as relaxation time T/sub 1/, T/sub 2/, and proton density P/sub D/ weighted by selecting appropriate settings of T/sub E/ and T/sub R/, the spin-echo delay time and repetition time of a pulse sequence) requires automating the following steps: (1) compensation for image-intensity variation of a same tissue type induced by radiofrequency inhomogeneity across field-of-view; (2) stripping away image pixels which represent skull and scalp; and (3) estimation of model parameters (or training samples) such as image-intensity mean and variance for each tissue type and correlation coefficients for that tissue type among the three spatially-registered images (acquired in a very short time period). This proposed automatic approach first strips away the pixels of skull and scalp. The stripping is performed by detecting radially the pixels of inner-skull margin from the T/sub 2/ weighted transaxial image and applying the detected margin to remove the pixels of skull and scalp in the T/sub 1/ and P/sub D/ weighted transaxial images as well. The approach then determines the intensity-variation map within the margin from each stripped image and compensates for the variation by dividing that image by the determined map. Finally the approach estimates the model parameters by fitting the image data into a multivariate mixture. The fitting is performed by a maximum-likelihood estimator. The above three steps have been successfully implemented by a computer. The automatic approach was tested by a set of three MR images acquired by a 1.5 Tesla whole body scanner from a head. The removal of skull and scalp was very satisfactory. The compensation for the intensity variation improved significantly the estimation of model parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 (2000)

Tumor necrosis factor alpha (TNFalpha) inhibits insulin action, in part, through serine phosphorylation of IRS proteins; however, the phosphorylation sites that mediate the inhibition are unknown. TNFalpha promotes multipotential signal transduction cascades, including the activation of the Jun NH(2)-terminal kinase (JNK). Endogenous JNK associates with IRS-1 in Chinese hamster ovary cells. Anisomycin, a strong activator of JNK in these cells, stimulates the activity of JNK bound to IRS-1 and inhibits the insulin-stimulated tyrosine phosphorylation of IRS-1. Serine 307 is a major site of JNK phosphorylation in IRS-1. Mutation of serine 307 to alanine eliminates phosphorylation of IRS-1 by JNK and abrogates the inhibitory effect of TNFalpha on insulin-stimulated tyrosine phosphorylation of IRS-1. These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function.
The histamine H3-receptor: A target for developing new drugs (1992)

At the beginning of this century histamine was only considered as a mediator of allergic conditions. Indeed, histamine proved to be a very spasmogenic agent of e.g. airway smooth muscle, and intensive research had resulted in the development of several potent “antihistaminergics” (e.g. mepyramine), which were useful in inhibiting various symptoms of allergic conditions.
Towards Activity Databases: Using Sensors and Statistical Models to Summarize People's Lives. (2006)

Automated reasoning about human behavior is a central goal of artificial intelligence. In order to engage and intervene in a meaningful way, an intelligent system must be able to understand what humans are doing, their goals and intentions. Furthermore, as social animals, people’s interactions with each other underlie many aspects of their lives: how they learn, how they work, how they play and how they affect the broader community. Understanding people’s interactions and their social networks will play an important role in designing technology and applications that are “socially-aware”. This paper introduces some of the current approaches in activity recognition which use a variety of different sensors to collect data about users ’ activities, and probabilistic models and relational information that are used to transform the raw sensor data into higher-level descriptions of people’s behaviors and interactions. The end result of these methods is a richly structured dataset describing people’s daily patterns of activities and their evolving social networks. The potential applications of such datasets include mapping patterns of information-flow within an organization, predicting the spread of disease within a community, monitoring the health and activity-levels of elderly patients as well as healthy adults, and allowing “smart environments ” to respond proactively to the needs and intentions of their users. 1