gebhart/patrepeval huggingface dataset:
Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype (1991)

Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace 125I-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.
都市の若者は"出会い系"で人生のパートナーを探す ("日本人化"するインド人の暮らし--まさか日本人が読むとは思わなかったインド二大誌の記事で読み解く!) -- (変化する若者の結婚観) (2009)

Rotational effects on the nonlinear sliding friction of a damped dimer moving over a substrate are studied within a largely one-dimensional model. The model consists of two masses connected rigidly, internally damped, and sliding over a sinusoidal (substrate) potential while being free to rotate in the plane containing the masses and the direction of sliding. Numerical simulations of the dynamics performed by throwing the dimer with an initial center of mass velocity along the substrate direction show a richness of phenomena including the appearance of three separate regimes of motion. The orientation of the dimer performs tiny oscillations around values that are essentially constant in each regime. The constant orientations form an intricate pattern determined by the ratio of the dimer length to the substrate wavelength as well as by the initial orientations chosen. Corresponding evolution of the center of mass velocity consists, respectively, of regular oscillations in the first and the third regimes, but a power law decay in the second regime; the center of mass motion is effectively damped in this regime because of the coupling to the rotation. Depending on the initial orientation of the dimer, there is considerable variation in the overall behavior. For small initial angles to the vertical, an interesting formal connection can be established to earlier results known in the literature for a vibrating, rather than rotating, dimer. But for large angles, on which we focus in the present paper, quite different evolution occurs. Some of the numerical observations are explained successfully on the basis of approximate analytical arguments but others pose puzzling problems.
High Affinity Binding between Lipoprotein Lipase and Lipoproteins Involves Multiple Ionic and Hydrophobic Interactions, Does Not Require Enzyme Activity, and Is Modulated by Glycosaminoglycans (2000)

Lipoprotein lipase (LPL) physically associates with lipoproteins and hydrolyzes triglycerides. To characterize the binding of LPL to lipoproteins, we studied the binding of low density lipoproteins (LDL), apolipoprotein (apo) B17, and various apoB-FLAG (DYKDDDDK octapeptide) chimeras to purified LPL. LDL bound to LPL with high affinity (K(d) values of 10(-12) m) similar to that observed for the binding of LDL to its receptors and 1D1, a monoclonal antibody to LDL, and was greater than its affinity for microsomal triglyceride transfer protein. LDL-LPL binding was sensitive to both salt and detergents, indicating the involvement of both hydrophobic and hydrophilic interactions. In contrast, the N-terminal 17% of apoB interacted with LPL mainly via ionic interactions. Binding of various apoB fusion peptides suggested that LPL bound to apoB at multiple sites within apoB17. Tetrahydrolipstatin, a potent enzyme activity inhibitor, had no effect on apoB-LPL binding, indicating that the enzyme activity was not required for apoB binding. LDL-LPL binding was inhibited by monoclonal antibodies that recognize amino acids 380-410 in the C-terminal region of LPL, a region also shown to interact with heparin and LDL receptor-related protein. The LDL-LPL binding was also inhibited by glycosaminoglycans (GAGs); heparin inhibited the interactions by approximately 50% and removal of trace amounts of heparin from LPL preparations increased LDL binding. Thus, we conclude that the high affinity binding between LPL and lipoproteins involves multiple ionic and hydrophobic interactions, does not require enzyme activity and is modulated by GAGs. It is proposed that LPL contains a surface exposed positively charged amino acid cluster that may be important for various physiological interactions of LPL with different biologically important molecules. Moreover, we postulate that by binding to this cluster, GAGs modulate the association between LDL and LPL and the in vivo metabolism of LPL.
Boosting chaperone-mediated autophagy in vivo mitigates α-synuclein-induced neurodegeneration (2013)

α-Synuclein levels are critical to Parkinson's disease pathogenesis. Wild-type α-synuclein is degraded partly by chaperone-mediated autophagy, and aberrant α-synuclein may act as an inhibitor of the pathway. To address whether the induction of chaperone-mediated autophagy may represent a potential therapy against α-synuclein-induced neurotoxicity, we overexpressed lysosomal-associated membrane protein 2a, the rate-limiting step of chaperone-mediated autophagy, in human neuroblastoma SH-SY5Y cells, rat primary cortical neurons in vitro, and nigral dopaminergic neurons in vivo. Overexpression of the lysosomal-associated membrane protein 2a in cellular systems led to upregulation of chaperone-mediated autophagy, decreased α-synuclein turnover, and selective protection against adenoviral-mediated wild-type α-synuclein neurotoxicity. Protection was observed even when the steady-state levels of α-synuclein were unchanged, suggesting that it occurred through the attenuation of α-synuclein-mediated dysfunction of chaperone-mediated autophagy. Overexpression of the lysosomal receptor through the nigral injection of recombinant adeno-associated virus vectors effectively ameliorated α-synuclein-induced dopaminergic neurodegeneration by increasing the survival of neurons located in the substantia nigra as well as the axon terminals located in the striatum, which was associated with a reduction in total α-synuclein levels and related aberrant species. We conclude that induction of chaperone-mediated autophagy may provide a novel therapeutic strategy in Parkinson's disease and related synucleinopathies through two different mechanisms: amelioration of dysfunction of chaperone-mediated autophagy and lowering of α-synuclein levels.
Increased Expression of Serum Amyloid A in Glaucoma and Its Effect on Intraocular Pressure (2008)

These findings indicate that SAA, which is an acute-phase apolipoprotein that plays important roles in infection, inflammation, and tissue repair, may contribute to the pathogenic changes to the TM in glaucoma.
INO-4995 Therapeutic Efficacy Is Enhanced with Repeat Dosing in Cystic Fibrosis Knockout Mice and Human Epithelia (2009)

Progressive lung damage in cystic fibrosis (CF) has been linked to inadequate airway mucosal hydration. We previously demonstrated that an inositol tetrakisphosphate analog, 1-O-octyl-2-O-butyryl-myo-inositol 3,4,5,6-tetrakisphosphate octakis(propionoxymethyl)ester (INO-4995), regulates airway secretory and absorptive processes, affecting mucosal hydration by prolonged (24 h) inhibition of Na(+) and fluid absorption in CF human nasal epithelia (CFHNE). The objectives of this study were to further assess clinical potential of INO-4995 in CF through ascertaining in vivo activity in mice with CF, determining the effects of repeated administration on potency and determining cytoplasmic half-life. Uptake and metabolism of [(3)H]INO-4995 was monitored with HPLC to calculate intracellular half-life. INO-4995 was administered in vitro repeatedly over 4 to 8 days to CFHNE. Fluid absorption was assessed by blue dextran exclusion, and basal short-circuit current was measured in Ussing chambers. INO-4995 (1-100 microg/kg) was dosed intranasally either as a single dose or once per day over 4 days to gut-corrected CF mice. [(3)H]INO-4995 was rapidly taken up by epithelial cultures and converted to the active drug, which had a half-life of 40 hours. Repeated daily application of INO-4995 to CFHNE lowered the effective concentration for inhibition of fluid absorption and amiloride-sensitive short-circuit current in cultured CFHNE, and reduced nasal potential difference to nearly control levels in gut-corrected CF mice. Ca(2+)-activated Cl(-) channel activity was also boosted in cultures. Mouse nasal levels fell from abnormal levels to within 2 muA of normal with repeated exposure to 0.8 microg/kg over 4 days. These data support further development of INO-4995 for the treatment of CF.
Systemic lupus erythematosus relapse with lupus cystitis. (1996)

A 45-year-old woman who had been diagnosed as having systemic lupus erythematosus (SLE) at the age of 28 years and who had been in remission developed severe urinary frequency, watery diarrhea, vomiting and weight loss. She also developed acute renal failure and her serological examination was consistent with active SLE. She had a markedly decreased urinary bladder capacity of 20 ml with hydroureteronephrosis. Histopathological study of her urinary bladder biopsy specimen showed mucosal edema, infiltration by lymphocytes and granulocytes, and deposition of IgA in the epithelium and submucosal region. We diagnosed this as a case of lupus cystitis. The patient's symptoms were alleviated by bilateral nephrostomy and corticosteroid therapy. In the present episode the patient showed none of the usual symptoms of SLE. This case and others reported in the literature show that lupus cystitis presents with specific signs and symptoms and therefore, this syndrome may represent a specific clinical manifestation of SLE.
Uncompensated Blood Loss Is Not Tolerated During Acute Normovolemic Hemodilution in Anesthetized Pigs (1998)

Anesthetized pigs with extremely low hemoglobin levels (one third of normal) showed poor tolerance to blood loss >10 mL/kg. A decreasing arterial blood pressure, a decreasing oxygen saturation in the venous blood, and an increase in arterial blood lactate concentration were useful indicators of blood loss.
Enhancing and Diminishing Gene Function in Human Embryonic Stem Cells (2004)

It is widely recognized that gain- and loss-of-function approaches are essential for understanding the functions of specific genes, and such approaches would be particularly valuable in studies involving human embryonic stem (hES) cells. We describe a simple and efficient approach using lipofection to transfect hES cells, which enabled us to generate hES cell lines expressing naturally fluorescent green or red proteins without affecting cell pluripotency. We used these cell lines to establish a means of diminishing gene function using small interfering (si)RNAs, which were effective at knocking down gene expression in hES cells. We then demonstrated that stable expression of siRNA could knock down the expression of endogenous genes. Application of these gain- and loss-of-function approaches should have widespread use, not only in revealing the developmental roles of specific human genes, but also for their utility in modulating differentiation.
Site-Specific Recombination of Bacteriophage P22 Does Not Require Integration Host Factor (1999)

Site-specific recombination by phages lambda and P22 is carried out by multiprotein-DNA complexes. Integration host factor (IHF) facilitates lambda site-specific recombination by inducing DNA bends necessary to form an active recombinogenic complex. Mutants lacking IHF are over 1,000-fold less proficient in supporting lambda site-specific recombination than wild-type cells. Although the attP region of P22 contains strong IHF binding sites, in vivo measurements of integration and excision frequencies showed that infecting P22 phages can perform site-specific recombination to its maximum efficiency in the absence of IHF. In addition, a plasmid integration assay showed that integrative recombination occurs equally well in wild-type and ihfA mutant cells. P22 integrative recombination is also efficient in Escherichia coli in the absence of functional IHF. These results suggest that nucleoprotein structures proficient for recombination can form in the absence of IHF or that another factor(s) can substitute for IHF in the formation of complexes.
Expansion of the Antigenic Repertoire of a Single T Cell Receptor upon T Cell Activation (2001)

Activated T cells and their naive precursors display different functional avidities for peptide/MHC, but are thought to have identical antigenic repertoires. We show that, following activation with a cognate mimotope (NRP), diabetogenic CD8(+) T cells expressing a single TCR (8.3) respond vigorously to numerous peptide analogs of NRP that were unable to elicit any responses from naive 8.3-CD8(+) T cells, even at high concentrations. The NRP-reactive, in vivo activated CD8(+) cells arising in pancreatic islets of nonobese diabetic mice are similarly promiscuous for peptide/MHC, and paradoxically this promiscuity expands as the aviditiy of the T cell population for NRP/MHC increases with age. Thus, activation and avidity maturation of T lymphocyte populations can lead to dramatic expansions in the range of peptides that elicit functional T cell responses.
CTLA4 Blockade Broadens the Peripheral T-Cell Receptor Repertoire (2014)

CTLA4 blockade with tremelimumab diversifies the peripheral T-cell pool, representing a pharmacodynamic effect of how this class of antibodies modulates the human immune system.
Comparison of Soluble Guanylate Cyclase Stimulators and Activators in Models of Cardiovascular Disease Associated with Oxidative Stress (2012)

Soluble guanylate cyclase (sGC), the primary mediator of nitric oxide (NO) bioactivity, exists as reduced (NO-sensitive) and oxidized (NO-insensitive) forms. We tested the hypothesis that the cardiovascular protective effects of NO-insensitive sGC activation would be potentiated under conditions of oxidative stress compared to those of NO-sensitive sGC stimulation. The cardiovascular effects of the NO-insensitive sGC activator GSK2181236A [a low, non-depressor dose, and a high dose which lowered mean arterial pressure (MAP) by 5-10 mmHg] and those of equi-efficacious doses of the NO-sensitive sGC stimulator BAY 60-4552 were assessed in (1) Sprague Dawley rats during coronary artery ischemia/reperfusion (I/R) and (2) spontaneously hypertensive stroke prone rats (SHR-SP) on a high salt/fat diet (HSFD). In I/R, neither compound reduced infarct size 24 h after reperfusion. In SHR-SP, HSFD increased MAP, urine output, microalbuminuria, and mortality, caused left ventricular hypertrophy with preserved ejection fraction, and impaired endothelium-dependent vasorelaxation. The low dose of BAY 60-4552, but not that of GSK2181236A, decreased urine output, and improved survival. Conversely, the low dose of GSK2181236A, but not that of BAY 60-4552, attenuated the development of cardiac hypertrophy. The high doses of both compounds similarly attenuated cardiac hypertrophy and improved survival. In addition to these effects, the high dose of BAY 60-4552 reduced urine output and microalbuminuria and attenuated the increase in MAP to a greater extent than did GSK2181236A. Neither compound improved endothelium-dependent vasorelaxation. In SHR-SP isolated aorta, the vasodilatory responses to the NO-dependent compounds carbachol and sodium nitroprusside were attenuated by HSFD. In contrast, the vasodilatory responses to both GSK2181236A and BAY 60-4552 were unaltered by HSFD, indicating that reduced NO-bioavailability and not changes in the oxidative state of sGC is responsible for the vascular dysfunction. In summary, GSK2181236A and BAY 60-4552 provide partial benefit against hypertension-induced end-organ damage. The differential beneficial effects observed between these compounds could reflect tissue-specific changes in the oxidative state of sGC and might help direct the clinical development of these novel classes of therapeutic agents.
Security Concerns in Minimum Storage Cooperative Regenerating Codes (2016)

Here, we revisit the problem of exploring the secrecy capacity of minimum storage cooperative regenerating (MSCR) codes under the (l <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2 l2</sub> )-eavesdropper model, where the eavesdropper can observe the data stored on l <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> nodes and the repair downloads of an additional l <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> nodes. Compared to minimum storage regenerating (MSR) codes which support only single node repairs, MSCR codes allow efficient simultaneous repairs of multiple failed nodes, referred to as a repair group. However, the repair data sent from a helper node to another failed node may vary with different repair groups or the sets of helper nodes, which would inevitably leak more data information to the eavesdropper and even render the storage system unable to maintain any data secrecy. In this paper, we introduce and study a special category of MSCR codes, termed “stable” MSCR codes, where the repair data from any one helper node to any one failed node is required to be independent of the repair group or the set of helper nodes. Our main contributions include: 1) Demonstrating that two existing MSCR codes inherently are not stable and thus have poor secrecy capacity; 2) Converting one existing MSCR code to a stable one, which offers better secrecy capacity when compared to the original one; and 3) Employing information theoretic analysis to characterize the secrecy capacity of stable MSCR codes in certain situations.
New approach for fault location on transmission lines without requiring line parameters (2008)

This paper presents a new numerical algorithm for fault location on transmission lines. It does not require line parameters, which is a radical step forward compared to the existing approaches, which require this information, so the algorithm can be considered as a settings-free algorithm. Line parameters are only approximately constant; they differ with the loading and weather conditions. Thus, an approach which does not require them would be more robust, accurate and flexible, than those approaches that do require line parameter information to determine the location to the fault. This is essential for the fast and secure elimination of faults on transmission lines, and, consequently, the solution leading to a significant improvement of the quality of the energy supply. The new algorithm uses synchronised data sampling at both line terminals, which is a prerequisite for the successful algorithm application. The paper presents the results of the initial algorithm testing through the use of ATP-EMTP simulations.
Building Rome in a day (2011)

We present a system that can reconstruct 3D geometry from large, unorganized collections of photographs such as those found by searching for a given city (e.g., Rome) on Internet photo-sharing sites. Our system is built on a set of new, distributed computer vision algorithms for image matching and 3D reconstruction, designed to maximize parallelism at each stage of the pipeline and to scale gracefully with both the size of the problem and the amount of available computation. Our experimental results demonstrate that it is now possible to reconstruct city-scale image collections with more than a hundred thousand images in less than a day.
Activation of c-Jun N-Terminal Kinase, a Potential Therapeutic Target in Autoimmune Arthritis (2020)

The c-Jun-N-terminal kinase (JNK) is a critical mediator involved in various physiological processes, such as immune responses, and the pathogenesis of various diseases, including autoimmune disorders. JNK is one of the crucial downstream signaling molecules of various immune triggers, mainly proinflammatory cytokines, in autoimmune arthritic conditions, mainly including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The activation of JNK is regulated in a complex manner by upstream kinases and phosphatases. Noticeably, different subtypes of JNKs behave differentially in immune responses. Furthermore, aside from biologics targeting proinflammatory cytokines, small-molecule inhibitors targeting signaling molecules such as Janus kinases can act as very powerful therapeutics in autoimmune arthritis patients unresponsiveness to conventional synthetic antirheumatic drugs. Nevertheless, despite these encouraging therapies, a population of patients with an inadequate therapeutic response to all currently available medications still remains. These findings identify the critical signaling molecule JNK as an attractive target for investigation of the immunopathogenesis of autoimmune disorders and for consideration as a potential therapeutic target for patients with autoimmune arthritis to achieve better disease control. This review provides a useful overview of the roles of JNK, how JNK is regulated in immunopathogenic responses, and the potential of therapeutically targeting JNK in patients with autoimmune arthritis.
I/Q mismatch cancellation for MIMO-OFDM systems (2005)

MIMO-OFDM systems are gaining prominence in high data rate applications due to their increased spectral efficiency, in MIMO-OFDM systems, I/Q mismatch causes interference between the frequency mirror subcarriers. This can significantly degrade and limit the performance of the system. We present a mathematical analysis of the effects of I/Q gain, delay and phase mismatches in MIMO-OFDM systems. We show the impact of I/Q mismatch when more antennas are added. We also derive a linear optimal solution to cancel all three I/Q mismatches and an RLS based adaptive filter for the same. We show simulation results and results on an experimental testbed.
PCR Technology: Principles and Applications for DNA Amplification (1989)

This introductory guide covers the basic methodology, research applications, and medical applications of PCR technology, emphasizing the practical aspects of the technique. Every chapter is written by pioneers in the field and most include detailed protocols and favourite PCR recipes.