gebhart/patrepeval huggingface dataset:
Remote power delivery for hybrid integrated bio-implantable electrical stimulation system (2005)

In this work, a remote power delivery system to charge rechargeable batteries that power a Bio-implanted Electrical Stimulation System (BESS) is first described. A loosely coupled inductive transmitter and receiver system has been used to power a bio-implanted gastric pacer. The receiver coil, rechargeable batteries, battery charging chip and the chip containing stimulation circuitry form a hybrid integrated microsystem. A design methodology for this Remote Power Delivery System (RPDS) is proposed. The BESS chip is also designed for electrical stimulation. It is a special IC chip which takes power from the rechargeable batteries and provides output pulses of 9.9 V amplitude at a frequency of 103 Hz and a duty cycle of 5%. The BESS chip contains a battery switching circuit and a pulse conditioning circuit which first provides pulses of 3 V amplitude. It also has an internal charge pump and a pulse booster circuit to boost the pulse amplitude to 9.9 V. Hybrid packaging is considered for integrating the implantable electrical stimulation circuitry and the remote power delivery system. Screen printed interconnects are used to integrate the BESS chip, the battery charging chip, discrete components and the receiver circuit of the RPDS.
Identification of one exon deletion of intestinal alkaline sphingomyelinase in colon cancer HT-29 cells and a differentiation-related expression of the wild-type enzyme in Caco-2 cells (2004)

Sphingomyelin (SM) metabolism in the gut has been implicated in colonic tumorigenesis. Intestinal alkaline sphingomyelinase (alk-SMase) hydrolyses SM in the intestinal content and at the brush border. The enzyme activity is decreased in the tissues of human colorectal tumours. This study examines whether site or chain-mutation of alk-SMase occurs in colon cancer HT-29 cells and Caco-2 cells. Total RNA was isolated and the cDNA of alk-SMase was amplified by RT-PCR. The size of the cDNA from HT-29 cells was smaller than that of the wild-type cDNA. DNA sequencing identified a deletion of exon 4 in alk-SMase cDNA in HT-29 cells. No mutation in genomic alk-SMase DNA from exon 3 to 5 was identified. The exon 4 deletion was caused by a shift of RNA splice site in chromosome 17q25. In Caco-2 cells, no mutation of alk-SMase cDNA was identified. Transient expression in COS-7 cells showed that the enzyme from the cDNA in HT-29 cells had little alk-SMase activity whereas that in Caco-2 cells was as active as the wild-type alk-SMase. The deleted region included residue His353, which is predicted to form a substrate-binding site of alk-SMase. H353A substitution resulted in a protein with no alk-SMase activity. In monolayer cultured Caco-2 cells and HT-29 cells the alk-SMase activities were low. However, to culture the cells under polarizing conditions increased alk-SMase activity and reduced SM level in Caco-2 cells. The alk-SMase activity varied in parallel with alkaline phosphatase activity. In conclusion, we identified an inactive deletion in alk-SMase in HT-29 cells, and a differentiation-related expression of the enzyme in Caco-2 cells. The results provide a molecular mechanism related to previous findings of reduced alk-SMase activity in human colon cancers.
Phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases: A pharmacokinetic (PK)-pharmacodynamic (PD) study to identify the optimal therapeutic dose regimen (2005)

3028 Background: AEE788 is an orally active, small-molecule, multitargeted kinase inhibitor with potent inhibitory activity against multiple tyrosine kinases, including EGFR, HER2, and VEGFR2. This phase I study is being conducted to assess its safety, PK, PD, maximum tolerated dose, and optimal biologic dose in pts with advanced solid tumors. Methods: AEE788 was given PO at 25, 50, 100, 150, 225, 300, 400, 450, 500, and 550 mg/day in 28-day cycles to 3–6 pt cohorts. 24-hr PK profiles were performed on days 1, 15, 28. PK parameters of AEE788 and AQM674 (active metabolite) were computed by model-independent methods. PD markers were analyzed in skin (SK), wound and tumor (TU) biopsies pre- and post-treatment. Emax models were used to characterize concentration-effect relationships. % change in PD markers (%dE=100*1-Et/Eo) were computed, Eo and Et are pre- and post-treatment. Emax and IC50 were estimated by non-linear least squares regression, and doses corresponding to 80% Emax were computed. Results: 69 pts were treated with a median of 2 cycles (range <1–10). AEE788 and AQM674 concentrations varied widely and increased with dose and duration. IC50 values were estimated for pEGFR (42nM), pMAPK (38nM), Ki67 (7nM) in SK and pEGFR (28nM), pMAPK (22nM) in TU; 80% Emax was achieved with 100–300 mg/day. Conclusions: A dose-dependent inhibition of EGFR signaling in SK and TU was observed; profound receptor inhibition is achieved with ≥ 300 mg/day. As expected, inhibition of endothelial pMAPK and Ki67 occurs at higher doses than EGFR inhibition (≥ 300 mg). Exposure dependent effects were observed and estimated IC50 values agree with preclinical data. Integration of PK, PD, and clinical response will suggest a potentially therapeutic regimen for further clinical evaluation. Model development will continue as more data become available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Aventis, Bristol-Myers Squibb, Lilly Oncology, Merck KgaA (A), Novartis, Pfizer, Pharma Mar, Roche, Roche (A) Novartis Aventis, Novartis, Pfizer, Roche ILEX Oncology, Novartis
The interplay between the effectiveness of the grass‐endophyte mutualism and the genetic variability of the host plant (2010)

Neotyphodium endophytic fungi, the asexual state of Epichloë species, protect cool-season grasses against stresses. The outcomes of Neotyphodium-grass symbioses are agronomically relevant as they may affect the productivity of pastures. It has been suggested that the mutualism is characteristic of agronomic grasses and that differential rates of gene flow between both partners' populations are expected to disrupt the specificity of the association and, thus, the mutualism in wild grasses. We propose that compatibility is necessary but not sufficient to explain the outcomes of Neotyphodium-grass symbiosis, and advance a model that links genetic compatibility, mutualism effectiveness, and endophyte transmission efficiency. For endophytes that reproduce clonally and depend on allogamous hosts for reproduction and dissemination, we propose that this symbiosis works as an integrated entity where gene flow promotes its fitness and evolution. Compatibility between the host plant and the fungal endophyte would be high in genetically close parents; however, mutualism effectiveness and transmission efficiency would be low in fitness depressed host plants. Increasing the genetic distance of mating parents would increase mutualism effectiveness and transmission efficiency. This tendency would be broken when the genetic distance between parents is high (out-breeding depression). Our model allows for testable hypotheses that would contribute to understand the coevolutionary origin and future of the endophyte-grass mutualism.
RATE PARAMETERS FOR THE QUENCHING OF SINGLET OXYGEN BY WATER‐SOLUBLE AND LIPID‐SOLUBLE SUBSTRATES IN AQUEOUS AND MICELLAR SYSTEMS (1981)

Abstract— The laser flash photolysis method has been used to determine the bimolecular rate constants for the reaction between O 2 ( 1 Δ 9 ) and several lipid‐soluble and water‐soluble substrates. Values for lipid‐soluble substrates have been obtained using aqueous dispersions of surfactants above the critical micelle concentration with 1,3 diphenylisobenzofuran as monitor of singlet oxygen. Under these conditions the hydrophobic substances are solubilized by the micellar phase. For substrates which are water‐soluble, 9,10‐anthracene dipropionic acid disodium salt was used as singlet oxygen monitor. For several substances, the values obtained are comparable to the values found in homogeneous nonaqueous solutions. In cases where significant differences have been found these have been rationalized according to the individual case. The only major unexpected result concerned β‐carotene which, in micellar dispersion, failed to react at all with O 2 ( 1 Δ 9 ) This may be due to multi‐molecular aggregations occurring in the polar medium. The work described herein shows clearly that, under appropriate conditions, singlet oxygen kinetics can be effectively followed in aqueous solutions by time resolved methods. The indiscriminate use of β‐carotene as a quencher of O 2 ( 1 Δ 9 )in mainly aqueous media is questioned.
Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in mice (2006)

Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease, lesions are predominantly found in the optic nerves and spinal cord but not the brain. The immunological bases of the different forms of MS are unknown. We previously generated myelin oligodendrocyte glycoprotein-specific (MOG-specific) TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that a large proportion of these mice develop spontaneous isolated optic neuritis. We have now crossed the TCRMOG mice with MOG-specific Ig heavy-chain knock-in mice (IgHMOG mice; also referred to as Th mice), in which one-third of the B cells are specific for MOG. In these mice, MOG-specific B cells are very efficient in presenting MOG to the transgenic T cells and undergo class switching to IgG1 in the presence of the transgenic T cells. Sixty percent of TCRMOG x IgHMOG mice spontaneously developed a severe form of experimental autoimmune encephalomyelitis (EAE). Histological examination of the CNS revealed a selective distribution of meningeal and parenchymal inflammatory lesions in the spinal cord and optic nerves. Thus, CNS antigen-specific T and B cells cooperate to induce a distinct clinicopathologic EAE pattern that closely replicates human Devic disease.
Suggestions for a Total Elasto-Dynamic Intervertebral Disc Prosthesis (1981)

The essential considerations to be taken for the design of a composite elasto-dynamic intervertebral disc prosthesis (IDP) are discussed, and a disc implant, supposedly satisfying the demands for surgical and biomechanical applicability and biocompatibility, are outlined. The suggested IDP implant is composed of an elastic kernel, covered in a two-components telescoping shell, situated in a polymer slit-tube fundament, after preparation fixed to the respective vertebral bodies of the respective motion segment with bone cement. The approach to a lumbar motion segment is suggested to be by way of an abdominal and retroperitoneal incision and exploration.
Analysis Tool Web Services from the EMBL-EBI (2013)

Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods.
Comprehensive in vivo Mapping of the Human Basal Ganglia and Thalamic Connectome in Individuals Using 7T MRI (2012)

Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD), essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS). Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR) and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI). This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric disorders, in individual human subjects.
The human alpha 2-macroglobulin receptor: identification of a 420-kD cell surface glycoprotein specific for the activated conformation of alpha 2-macroglobulin. (1990)

Ligand affinity chromatography was used to purify a cell surface alpha 2-macroglobulin (alpha 2M) receptor. Detergent extracts of human placenta were applied to an affinity matrix consisting of alpha 2M, previously reacted with methylamine, coupled to Sepharose. Elution with EDTA specifically released polypeptides with apparent molecular masses of 420 and 39 kD. In some preparations, small amounts of a 90-kD polypeptide were observed. The 420- and 39-kD polypeptides appear specific for the forms of alpha 2M activated by reaction with proteinases or methylamine and do not bind to an affinity matrix consisting of native alpha 2M coupled to Sepharose. Separation of these two polypeptides was accomplished by anion exchange chromatography, and binding activity was exclusively associated with the 420-kD polypeptide. The purified 420-kD protein binds to the conformationally altered forms of alpha 2M that are known to specifically interact with alpha 2M receptors and does not bind to native alpha 2M. Binding of the 420-kD polypeptide to immobilized wheat germ agglutinin indicates that this polypeptide is a glycoprotein. The cell surface localization of the 420-kD glycoprotein was confirmed by affinity chromatography of extracts from surface radioiodinated fibroblasts. These properties suggest that the 420-kD polypeptide is a cell surface receptor for the activated forms of alpha 2M.
Functional Analysis of PIK3CA Gene Mutations in Human Colorectal Cancer (2005)

Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer. Most of the mutations cluster at hotspots within the helical and kinase domains. Whereas H1047R, one of the hotspot mutants, is reported to have elevated lipid kinase activity, the functional consequences of other mutations have not been examined. In this study, we examined the effects of colon cancer-associated PIK3CA mutations on the lipid kinase activity in vitro, activation of the downstream targets Akt and p70S6K in vivo and NIH 3T3-transforming ability. Of eight mutations examined, all showed increased lipid kinase activity compared with wild-type p110alpha. All the mutants strongly activated Akt and p70S6K compared with wild-type p110alpha as determined by immunoblotting using phospho-specific antibodies. These mutants also induced morphologic changes, loss of contact inhibition, and anchorage-independent growth of NIH 3T3 cells. The hotspot mutations examined in this study, E542K, E545K, and H1047R, all had high enzymatic and transforming activities. These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.
Optomechanics in an ultrahigh-Q two-dimensional photonic crystal cavity (2010)

We demonstrate an ultrahigh-Q slotted two-dimensional photonic crystal cavity capable of obtaining strong interaction between the internal light field and the mechanical motion of the slotted structure. The measured optical quality factor is Q=1.2×106 for a cavity with an effective modal volume of Veff=0.04(λ)3. Optical transduction of the thermal motion of the fundamental in-plane mechanical resonance of the structure (νm=151 MHz) is performed, from which a zero-point motion optomechanical coupling rate of g∗/2π=320 kHz is inferred. Dynamical back-action of the optical field on the mechanical motion, resulting in cooling and amplication of the mechanical motion, is also demonstrated.
Neural Relational Inference for Interacting Systems (2018)

Interacting systems are prevalent in nature, from dynamical systems in physics to complex societal dynamics. The interplay of components can give rise to complex behavior, which can often be explained using a simple model of the system's constituent parts. In this work, we introduce the neural relational inference (NRI) model: an unsupervised model that learns to infer interactions while simultaneously learning the dynamics purely from observational data. Our model takes the form of a variational auto-encoder, in which the latent code represents the underlying interaction graph and the reconstruction is based on graph neural networks. In experiments on simulated physical systems, we show that our NRI model can accurately recover ground-truth interactions in an unsupervised manner. We further demonstrate that we can find an interpretable structure and predict complex dynamics in real motion capture and sports tracking data.
Concepts as knowledge handles in collaborative document management (2003)

With the increasing availability of electronic documents, it is essential that people can navigate through document spaces for information effectively through an index, in a collaborative manner. We describe a system that supports the collaborative construction of indexes of concepts rather than terms. In a concept index, a concept can be described by more than one term, phrase, arbitrary text piece, and other concepts. These concepts can be structured and associated with one another without strict restrictions. Software agents work in the background to find occurrences of concepts in a document collection, enabling users to navigate documents based on concepts. Users can extract concepts by simply highlighting pieces of text while browsing documents. Through collaborative index construction, a user benefits from contributions of other users, and the system enables a group of users to collaboratively manage information.
Seizures Decrease Postnatal Neurogenesis and Granule Cell Development in the Human Fascia tDentata (2002)

These results indicate that severe seizures during early childhood are associated with anatomic signs of decreased postnatal granule cell neurogenesis (PSA NCAM IR) and aberrant mossy fiber axon connections (neo-Timm's) without evidence of seizure-induced cell death (TUNEL). In humans, these results support the concept that seizures do not damage existing neurons, but adversely affect processes involved with normal postnatal neuronal development such as neurogenesis and axon formation. Such alterations probably negatively affect normal brain development, and/or promote epileptogenesis.
Resolvin D1 binds human phagocytes with evidence for proresolving receptors (2010)

Endogenous mechanisms that act in the resolution of acute inflammation are essential for host defense and the return to homeostasis. Resolvin D1 (RvD1), biosynthesized during resolution, displays potent and stereoselective anti-inflammatory actions, such as limiting neutrophil infiltration and proresolving actions. Here, we demonstrate that RvD1 actions on human polymorphonuclear leukocytes (PMNs) are pertussis toxin sensitive, decrease actin polymerization, and block LTB(4)-regulated adhesion molecules (beta2 integrins). Synthetic [(3)H]-RvD1 was prepared, which revealed specific RvD1 recognition sites on human leukocytes. Screening systems to identify receptors for RvD1 gave two candidates--ALX, a lipoxin A(4) receptor, and GPR32, an orphan--that were confirmed using a beta-arrestin-based ligand receptor system. Nuclear receptors including retinoid X receptor-alpha and peroxisome proliferator-activated receptor-alpha, -delta, -gamma were not activated by either resolvin E1 or RvD1 at bioactive nanomolar concentrations. RvD1 enhanced macrophage phagocytosis of zymosan and apoptotic PMNs, which increased with overexpression of human ALX and GPR32 and decreased with selective knockdown of these G-protein-coupled receptors. Also, ALX and GPR32 surface expression in human monocytes was up-regulated by zymosan and granulocyte-monocyte-colony-stimulating factor. These results indicate that RvD1 specifically interacts with both ALX and GPR32 on phagocytes and suggest that each plays a role in resolving acute inflammation.
Autophagy-induced tumor dormancy in ovarian cancer (2008)

Autophagy--a process of "self-eating" that involves enzymatic digestion and recycling of cellular constituents in response to stress--contributes to both cancer cell death and survival. In this issue of the JCI, Lu et al. report that controlled induction of tumor suppressor gene aplasia Ras homolog member I (ARHI) results in autophagic cell death of human ovarian cancer cells in vitro (see the related article beginning on page 3917). However, within xenograft tumors in mice, multiple factors within the tumor microenvironment switched ARHI-induced autophagy to a mechanism of tumor cell survival, leading to tumor dormancy. Since ARHI expression is suppressed in the majority of breast and ovarian cancers but is high in premalignant lesions, ARHI-induced autophagy could be manipulated for therapeutic benefit.