gebhart/patrepeval huggingface dataset:
HCN channels (2013)

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises 4 members (HCN1–4) that are expressed in heart and nervous system. HCN channels are activated by membrane hyperpolarization, are permeable to Na+ and K+, and are constitutively open at voltages near the resting membrane potential. In many cases, activation is facilitated by direct interaction with cyclic nucleotides, particularly cyclic adenosine monophosphate (cAMP). The cation current through HCN channels is known as I h; opening of HCN channels elicits membrane depolarization toward threshold for action potential generation, and reduces membrane resistance and thus the magnitude of excitatory and inhibitory postsynaptic potentials. HCN channels have a major role in controlling neuronal excitability, dendritic integration of synaptic potentials, synaptic transmission, and rhythmic oscillatory activity in individual neurons and neuronal networks. These channels participate in mechanisms of synaptic plasticity and memory, thalamocortical rhythms, and somatic sensation. Experimental evidence indicates that HCN channels may also contribute to mechanisms of epilepsy and pain. The physiologic functions of HCN channels and their implications for neurologic disorders have been recently reviewed.1–10 cAMP= : cyclic adenosine monophosphate; CNBD= : cyclic nucleotide-binding domain; DRG= : dorsal root ganglion; EPSP= : excitatory postsynaptic potentials; HCN= : hyperpolarization-activated cyclic nucleotide-gated; LTP= : long-term potentiation; PGE2= : prostaglandin E2; PIP2= : phosphatidylinositol 4,5-bisphosphate; SA= : sinoatrial
Pharmacokinetics and Biodistribution of Nanoparticles (2008)

Nanoparticles show their promise for improving the efficacy of drugs with a narrow therapeutic window or low bioavailability, such as anticancer drugs and nucleic acid-based drugs. The pharmacokinetics (PK) and tissue distribution of the nanoparticles largely define their therapeutic effect and toxicity. Chemical and physical properties of the nanoparticles, including size, surface charge, and surface chemistry, are important factors that determine their PK and biodistribution. The intracellular fate of the nanoparticles after cellular internalization that affects the drug bioavailability is also discussed. Strategies for overcoming barriers for intracellular delivery and drug release are presented. Finally, future directions for improving the PK of nanoparticles and perspectives in the field are discussed.
SRRM2, a Potential Blood Biomarker Revealing High Alternative Splicing in Parkinson's Disease (2010)

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects about five million people worldwide. Diagnosis remains clinical, based on phenotypic patterns. The discovery of laboratory markers that will enhance diagnostic accuracy, allow pre-clinical detection and tracking of disease progression is critically needed. These biomarkers may include transcripts with different isoforms.
The Four-Gate Transistor (2002)

The four-gate transistor or G4-FET combines MOSFET and JFET principles in a single SOI device. Experimental results reveal that each gate can modulate the drain current. Numerical simulations are presented to clarify the mechanisms of operation. The new device shows enhanced functionality, due to the combinatorial action of the four gates, and opens rather revolutionary applications.
Learning with Symmetric Label Noise: The Importance of Being Unhinged (2015)

Convex potential minimisation is the de facto approach to binary classification. However, Long and Servedio [2010] proved that under symmetric label noise (SLN), minimisation of any convex potential over a linear function class can result in classification performance equivalent to random guessing. This ostensibly shows that convex losses are not SLN-robust. In this paper, we propose a convex, classification-calibrated loss and prove that it is SLN-robust. The loss avoids the Long and Servedio [2010] result by virtue of being negatively unbounded. The loss is a modification of the hinge loss, where one does not clamp at zero; hence, we call it the unhinged loss. We show that the optimal unhinged solution is equivalent to that of a strongly regularised SVM, and is the limiting solution for any convex potential; this implies that strong l2 regularisation makes most standard learners SLN-robust. Experiments confirm the SLN-robustness of the unhinged loss.
Site-directed mutagenesis of a predicted cation binding site of sodium-potassium ATPase (1993)

Chemical modification and proteolytic digestion studies have identified a transmembrane glutamic acid residue (E953) of the alpha subunit of the pig kidney Na, K-ATPase as a possible cation binding site [Goldshleger et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6911-6915]. In addition, an adjacent glutamate (E954) is conserved in all species and isoforms and may also be involved in cation binding. To further explore the role of these residues in ion transport, we have utilized a mutagenesis-expression strategy. This approach avoids the introduction of a large chemical moiety into the protein and allows specific amino acid substitutions to be introduced. Glutamic acid residues 955 and 956 of the rat alpha-1 subunit (corresponding to glutamates 953 and 954 of the pig kidney Na, K-ATPase) were replaced separately and together using site-directed mutagenesis of the rat alpha-1 cDNA. The mutant cDNAs were expressed in ouabain-sensitive HeLa cells. This system makes it possible to rapidly identify amino acid substitutions which significantly impair enzyme function, as substitutions which do not affect enzyme activity will yield colonies in the presence of ouabain, while substitutions which severely impair function will prevent or limit growth of the ouabain-sensitive HeLa cells. The amino acid replacements (E955Q, E956Q, E955Q-E956Q, E955D-E956D) all resulted in the growth of ouabain-sensitive cells, demonstrating that the modified Na, K-ATPase in each case was functional. To further study the altered enzymes, ouabain-resistant colonies were isolated and expanded into stable cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
Fabrication Approaches for Generating Complex Micro- and Nanopatterns on Polymeric Surfaces (2008)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFabrication Approaches for Generating Complex Micro- and Nanopatterns on Polymeric SurfacesAránzazu del Campo and Eduard ArztView Author Information Max-Planck-Institut für Metallforschung, Heisenbergstraβe 3, 70569 Stuttgart, Germany Cite this: Chem. Rev. 2008, 108, 3, 911–945Publication Date (Web):February 26, 2008Publication History Received19 June 2006Published online26 February 2008Published inissue 1 March 2008https://pubs.acs.org/doi/10.1021/cr050018yhttps://doi.org/10.1021/cr050018yresearch-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views8185Altmetric-Citations404LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical structure,Lithography,Materials,Polymers,Thin films Get e-Alerts
Anti-FcepsilonRIalpha autoantibodies in autoimmune-mediated disorders. Identification of a structure-function relationship. (1998)

Anti-FcepsilonRIalpha autoantibodies (autoAbs) occur and may be of pathogenetic relevance in a subset of chronic urticaria (CU) patients. To analyze the prevalence and magnitude of the humoral anti-FcepsilonRIalpha response in cohorts of CU patients compared with individuals suffering from classic skin- related (auto)immune diseases, we developed an ELISA system for the measurement of anti-FcepsilonRIalpha autoAbs in nonfractionated serum samples. Results obtained using this assay correlated well with those generated by Western blotting. We found IgG anti-FcepsilonRIalpha autoreactivity in 38% of CU patients but not in atopic dermatitis patients, psoriatics, or healthy individuals. We frequently detected anti-FcepsilonRIalpha autoAbs in pemphigus vulgaris (PV, 39%), dermatomyositis (DM, 36%), systemic lupus erythematosus (SLE, 20%), and bullous pemphigoid (BP, 13%). While the autoAb titers in DM, SLE, BP, and PV were similar to those encountered in CU patients, only anti-FcepsilonRIalpha+ CU serum specimens displayed pronounced histamine-releasing activity. The anti-FcepsilonRIalpha autoAbs in CU patients belong predominantly to the complement-fixing subtypes IgG1 and IgG3, whereas in DM, PV, and BP, they were found to be mainly of the IgG2 or IgG4 subtype. Complement-activating properties of anti-FcepsilonRIalpha autoAbs can indeed be of pathogenetic relevance, because C5a receptor blockade on basophils as well as decomplementation reduced drastically the histamine-releasing capacity of most anti-FcepsilonRIalpha-reactive CU sera. As a consequence, therapeutic efforts in CU should aim at altering not only the quantity but also the complement-activating properties of IgG anti-FcepsilonRIalpha autoAbs.
Expression of complement membrane regulators membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59) in human malignant gliomas. (1996)

Gliomas are malignant brain tumors, which, despite recent progress in surgical and radiological treatment, still have a poor prognosis. Since gliomas apparently resist immunological clearance mechanisms, we became interested in examining bow gliomas resist killing by the human complement system. The resistance of human cells to complement-mediated damage is, in large part, mediated by specific inhibitors of complement:membrane cofactor protein (CD46), decay-accelerating factor (CD55), and protectin (CD59). In the present study we examined the expression of complement regulators in 14 human glioma tumors and in 7 glioma cell lines (U251, U87, HS683, U373, U138, U118, and H2). Protectin was found to be strongly expressed by all glioma tumors and cell lines. Northern blotting analysis demonstrated the typical pattern of four to five protectin mRNAs in the glioma cells. Except for blood vessels, the expression of decay-accelerating factor was weak or absent in the tumors in situ, whereas in the cell lines its expression varied, ranging from negative to intermediate. Membrane cofactor protein was moderately expressed by all the cell lines but only weakly in the tumors. Cell-killing experiments demonstrated that the glioma cell lines were exceptionally resistant to C-mediated lysis. Five of the seven cell lines (U373, HS683, U118, U138, and H2) resisted complement lysis under conditions where most other cell lines were sensitive to killing. Neutralization experiments using specific monoclonal antibodies indicated that protectin was functionally the most important complement regulator in the glioma cells. The killing of the U87 and U251 cells could be significantly increased by a blocking anti-protectin monoclonal antibody, whereas for the other cell lines only moderate or no response was observed. The H2 cell line resisted killing by all antibodies and by complement. These results show that protectin is the most important complement regulator on human glioma cells. The exceptional complement resistance of some glioma cell lines suggests that they may utilize other, hitherto less well characterized, mechanisms to resist complement killing.
Evaluation of a new temperature management system during off-pump coronary artery bypass (2003)

The Arctic Sun system significantly outperformed conventional techniques in achieving and maintaining normothermia during off-pump coronary artery bypass.
The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. (1993)

The adenovirus E1A proteins form complexes with a group of cellular proteins, including a protein of 130 kD. E1A-associated p130 was purified through coimmunoprecipitation with E1A, and sequence data from four tryptic peptides was obtained. Oligonucleotides derived from the peptide sequences were used to clone a 4.85-kb cDNA. The cDNA contained an 1139-amino-acid open reading frame with homology to the retinoblastoma protein and E1A-associated p107 but was more closely related to p107. In vitro-translated p130 bound to E1A, and anti-p130 antibodies detected p130 in immunoblots of E1A immunoprecipitates. p130 was also detected in immunoprecipitates of cyclins A and E and was an efficient substrate in vitro for kinase activities associated with these cyclins. The p130 gene mapped to chromosome 16q12.2-13, a region that undergoes allelic loss in several types of tumors, including hepatocellular, prostate, and breast carcinomas.
CHOROIDAL ANGIOGRAPHY TODAY AND TOMORROW (1992)

Applied Physics Laboratory, Wilmer Ophthalmoligical Institute, Johns Hopkins University and Hospital, Laurel, Maryland
Erythrocyte folate and 5-methyltetrahydrofolate levels decline during 6 months of oral anticoagulation with warfarin (2009)

Dietary fluctuations of vitamin K are detrimental to oral anticoagulant control. Attempts to improve control through the avoidance of vitamin K-rich foods (mainly green vegetables) may inadvertently compromise folate status, itself a risk factor for thromboembolism. We evaluated the effect of a 6-month period of warfarin therapy on folate status in 114 patients using measurements of red-cell folate and 5-methyltetrahydrofolate and plasma folate and total homocysteine. Circulatory levels of phylloquinone, vitamin B12 and methylmalonic acid were also determined. A subset of 45 patients completed 7-day food diaries at the beginning and end of their treatment. There was a significant decrease in total erythrocyte folate (P = 0.005) and 5-methyltetrahydrofolate (P = 0.002) during the study. A concurrent increase in plasma phylloquinone (P = 0.003) was attributed to warfarin-induced perturbation of vitamin K metabolism. No other longitudinal changes were observed. Folate and phylloquinone intakes correlated with each other at baseline (P = 0.024) and after treatment (P = 0.011). Based on robust measurements of erythrocyte folates, patients showed a significant impairment in folate status after 6-month therapy with warfarin. The majority of patients had intakes of folate and phylloquinone below the national average or UK guidelines. The study highlights the need for improved dietary management of patients taking oral anticoagulants.
Development of a third generation intraventricular impedance imaging (III) system: evaluation of hardware design (2002)

Intraventricular Impedance Imaging (III) applies an innovative technique for estimation of cardiac catheter position. It is based on electrical impedance measurements and uses a multi-electrode probe mounted at a tip of a cardiac catheter. After analyzing the previous versions of the III system, a new system hardware realization was proposed, built, and tested. The signal acquisition module is based on AD7850-a highly integrated electronic component. A special protocol was developed for optimal high speed communication between the 32 channel III system and the IBM PC controller. This protocol also significantly reduces the required electronic component count. The results obtained by the prototype evaluation showed that: the proposed realization is working according to expectations, the signal generation provides sufficiently accurate signals, and the system requires 3 ms to generate a set of data-sufficient for real-time 60 Hz determination of catheter position and instantaneous ventricular volume.
Differential Control of Cell Cycle, Proliferation, and Survival of Primary T Lymphocytes by Purine and Pyrimidine Nucleotides (2003)

Purine and pyrimidine nucleotides play critical roles in DNA and RNA synthesis as well as in membrane lipid biosynthesis and protein glycosylation. They are necessary for the development and survival of mature T lymphocytes. Activation of T lymphocytes is associated with an increase of purine and pyrimidine pools. However, the question of how purine vs pyrimidine nucleotides regulate proliferation, cell cycle, and survival of primary T lymphocytes following activation has not yet been specifically addressed. This was investigated in the present study by using well-known purine (mycophenolic acid, 6-mercaptopurine) and pyrimidine (methotrexate, 5-fluorouracil) inhibitors, which are used in neoplastic diseases or as immunosuppressive agents. The effect of these inhibitors was analyzed according to their time of addition with respect to the initiation of mitogenic activation. We showed that synthesis of both purine and pyrimidine nucleotides is required for T cell proliferation. However, purine and pyrimidine nucleotides differentially regulate the cell cycle since purines control both G(1) to S phase transition and progression through the S phase, whereas pyrimidines only control progression from early to intermediate S phase. Furthermore, inhibition of pyrimidine synthesis induces apoptosis whatever the time of inhibitor addition whereas inhibition of purine nucleotides induces apoptosis only when applied to already cycling T cells, suggesting that both purine and pyrimidine nucleotides are required for survival of cells committed into S phase. These findings reveal a hitherto unknown role of purine and pyrimidine de novo synthesis in regulating cell cycle progression and maintaining survival of activated T lymphocytes.
A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins. (1995)

Many integrins recognize short RGD-containing amino acid sequences and such peptide sequences can be identified from phage libraries by panning with an integrin. Here, in a reverse strategy, we have used such libraries to isolate minimal receptor sequences that bind to fibronectin and RGD-containing fibronectin fragments in affinity panning. A predominant cyclic motif, *CWDDG/LWLC*, was obtained (the asterisks denote a potential disulfide bond). Studies using the purified phage and the corresponding synthetic cyclic peptides showed that *CWDDGWLC*-expressing phage binds specifically to fibronectin and to fibronectin fragments containing the RGD sequence. The binding did not require divalent cations and was inhibited by both RGD and *CWDDGWLC*-containing synthetic peptides. Conversely, RGD-expressing phage attached specifically to immobilized *CWDDGWLC*-peptide and the binding could be blocked by the respective synthetic peptides in solution. Moreover, fibronectin bound to a *CWDDGWLC*-peptide affinity column, and could be eluted with an RGD-containing peptide. The *CWDDGWLC*-peptide inhibited RGD-dependent cell attachment to fibronectin and vitronectin, but not to collagen. A region of the beta subunit of RGD-binding integrins that has been previously demonstrated to be involved in ligand binding includes a polypeptide stretch, KDDLW (in beta 3) similar to WDDG/LWL. Synthetic peptides corresponding to this region in beta 3 were found to bind RGD-displaying phage and conversion of its two aspartic residues into alanines greatly reduced the RGD binding. Polyclonal antibodies raised against the *CWDDGWLC*-peptide recognized beta 1 and beta 3 in immunoblots. These data indicate that the *CWDDGWLC*-peptide is a functional mimic of ligand binding sites of RGD-directed integrins, and that the structurally similar site in the integrin beta subunit is a binding site for RGD.
Prosite: a dictionary of sites and patterns in proteins (1991)

Background PROSITE is a compilation of sites and patterns found in protein sequences. The use of protein sequence patterns (or motifs) to determine the function of proteins is becoming very rapidly one of the essential tools of sequence analysis. This reality has been recognized by many authors [1,2]. While there have been a number of recent reports It is for these reasons that we have developed, since 1988, a dictionary of sites and patterns which we call PROSITE.
Stimulation of Gene Expression and Loss of Anular Architecture Caused by Experimental Disc Degeneration–An In Vivo Animal Study (2005)

Experimental moderate disc degeneration is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene expression of disc constituents, catabolic enzymes, and growth factors is stimulated to reestablish disc integrity.
Effects of infliximab therapy on gene expression levels of tumor necrosis factor α, tristetraprolin, T cell intracellular antigen 1, and Hu antigen R in patients with rheumatoid arthritis (2007)

Differences in ABP gene expression may affect TNFalpha gene expression. A higher TIA-1:HuR expression ratio might correlate with the response to infliximab therapy.
Imaging Dopamine Receptors in the Human Brain by Positron Tomography (1983)

Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.
Emerging role of HMGB1 in fibrotic diseases (2014)

High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell-surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.