gebhart/patrepeval huggingface dataset:
Mitochondrial dysfunction in Parkinson's disease (1999)

The cause of Parkinson's disease (PD) is unknown, but reduced activity of complex I of the electron-transport chain has been implicated in the pathogenesis of both mitochondrial permeability transition pore-induced Parkinsonism and idiopathic PD. We developed a novel model of PD in which chronic, systemic infusion of rotenone, a complex-I inhibitor, selectively kills dopaminergic nerve terminals and causes retrograde degeneration of substantia nigra neurons over a period of months. The distribution of dopaminergic pathology replicates that seen in PD, and the slow time course of neurodegeneration mimics PD more accurately than current models. Our model should enhance our understanding of neurodegeneration in PD. Metabolic impairment depletes ATP, depresses Na+/K(+)-ATPase activity, and causes graded neuronal depolarization. This relieves the voltage-dependent Mg2+ block of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, which is highly permeable to Ca2+. Consequently, innocuous levels of glutamate become lethal via secondary excitotoxicity. Mitochondrial impairment also disrupts cellular Ca2+ homoeostasis. Moreover, the facilitation of NMDA-receptor function leads to further mitochondrial dysfunction. To a large part, this occurs because Ca2+ entering neurons through NMDA receptors has 'privileged' access to mitochondria, where it causes free-radical production and mitochondrial depolarization. Thus there may be a feed-forward cycle wherein mitochondrial dysfunction causes NMDA-receptor activation, which leads to further mitochondrial impairment. In this scenario, NMDA-receptor antagonists may be neuroprotective.
Protein Folding Activities of Escherichia coli Protein Disulfide Isomerase (1994)

DsbA is an Escherichia coli periplasmic protein that mediates disulfide bond formation in newly secreted proteins in vivo. Addition of thiol reagents to purified dsbA reduces its disulfide bond and yields disulfide isomerase activity after removal of the thiol reagent. DsbA can catalyze the conversion of a stable misfolded protein, misfolded IGF-I (mis-IGF-I), to its correctly folded conformation under physiological conditions. This conversion is the result of breaking and re-forming two disulfide bonds. The uncatalyzed rate of this reaction is undetectable. Kinetic analysis of the reaction yielded a Km of 43 microM and a kcat of 0.2 min-1. The oxidized form of dsbA stimulates the oxidative folding of completely reduced IGF-I at pH 7.0. Thus, dsbA has two possible functions depending on its redox state. The reduced form of the protein is a disulfide isomerase while the oxidized protein can assist formation of disulfide bonds in reduced substrates under physiological conditions.
Application of the Mike-11 Flood Forecasting Systems to Tuggerah Lakes (1994)

The MIKE-11 Flood Forecasting System has been applied to a series of three tidal lakes on the Central Coast of New South Wales, where traditional rating-curve based methods of providing flood forecasting is inappropriate due to the influence of tidal effects and the substantial impact of an eroding entrance to the ocean. The paper describes the operation of the Flood Forecast system, and the special aspects of its application to the Tuggerah Lakes system. Operational aspects are also discussed, and the potential for interfaces to CIS and eventual operation as part of a flood evacuation response plan.
The DNA strand of chimeric RNA/DNA oligonucleotides can direct gene repair/conversion activity in mammalian and plant cell-free extracts (2000)

Chimeric oligonucleotides (chimeras), consisting of RNA and DNA bases folded by complementarity into a double hairpin conformation, have been shown to alter or repair single bases in plant and animal genomes. An uninterrupted stretch of DNA bases within the chimera is known to be active in the sequence alteration while RNA residues aid in complex stability. In this study, the two strands were separated in the hope of defining the role each plays in conversion. Using a series of single-stranded oligonucleotides, comprised of all RNA or DNA residues and various mixtures, several new structures have emerged as viable molecules in nucleotide conversion. When extracts from mammalian and plant cells and a genetic readout assay in bacteria are used, single-stranded oligonucleotides, containing a defined number of thioate backbone modifications, were found to be more active than the original chimera structure in the process of gene repair. Single-stranded oligonucleotides containing fully modified backbones were found to have low repair activity and in fact induce mutation. Molecules containing various lengths of modified RNA bases (2'-O-methyl) were also found to possess low activity. Taken together, these results confirm the directionality of nucleotide conversion by the DNA strand of the chimera and further present a novel, modified single-stranded DNA molecule that directs conversion in plant and animal cell-free extracts.
Introduction (2009)

The Russian Revolution set off a political earthquake. In February 1917 the Romanov monarchy tottered; in March it fell. This alone was an event of global significance. Russia and the other Allies were engaged in the Great War against the Central Powers. The Provisional Government, a shifting coalition of liberals and socialists, supplanted Emperor Nicholas II and its ministers proclaimed universal civil rights while assuming responsibility for national defence. They struggled to survive through months of political conflict and confusion. In October they succumbed to a seizure of power by Vladimir Lenin and the Bolsheviks. This second revolution was of still greater importance than the first. The Bolshevik party was dedicated to a more radical brand of socialism than any socialist minister in the Provisional Government had espoused — and the Bolsheviks for this reason were also beginning to call themselves communists in order to distinguish themselves from their more cautious rivals. Decades of agitation and organisation in Europe and North America had not yet given birth to a government composed exclusively of socialists. Bolsheviks in Russia saw themselves as the vanguard of the forces of revolutionary transformation.
30.9 Normally-off computing with crystalline InGaZnO-based FPGA (2014)

An FPGA employing c-axis aligned crystal In-Ga-Zn oxide (CAAC-IGZO) FET [1] based configuration memories (CMs) is known to need no reconfiguration thanks to nonvolatile CMs, shows high operation speed due to boosting effect of pass gates used in routing switches (RS) [2], and easily realizes fine-grained multi-context (FG-MC) architecture [2] because CMs which need very low power to keep the contents can be constructed with a small number of transistors. It would be very difficult to realize all of these features in FPGAs using MRAM [3] or RRAM [4]. These features are very unique to the CAAC-IGZO FPGA.
A Landmark-Based Location Reference Grid for Street Maps. (1979)

Research in cognition and perception has demonstrated that landmarks are useful for orienting travellers in a city. A landmark-based grid reference system for street maps is investigated as a replacement for the conventional system. Locations are referenced to a series of landmarks irregularly spaced throughout the map, each of which is the center of a 2-by-2 grid cell. The cells, labelled by compass quadrant, vary in size depending on distance to adjacent landmarks. The landmark grid relates the map to the landscape, is easily used in a moving car while folded, references locations in the way that directions are given, and fosters familiarity with an area. Potential disadvantages include higher costs because of more drafting time and the research required to insure that depicted landmarks accurately reflect common usage by local residents. A sample of the general population tested the landmark and standard systems using navigation, measurement and visualization tasks. The landmark system allows higher accuracy in less time than existing grids, and assists map users in remembering spatial locations. (Author)
A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides (2004)

The role of endosomal acidification and retrograde transport for the uptake of the highly basic cell-penetrating peptides penetratin, Tat, and oligoarginine was investigated. The effect of a panel of drugs that interfere with discrete steps of endocytosis or Golgi-mediated transport on uptake and cellular distribution of fluorescein-labeled peptide analogues was probed by confocal microscopy, flow cytometry, and fluorescence spectroscopy of whole cell lysates. The analyses were carried out in MC57 fibrosarcoma cells and in HeLa cells. While MC57 fibrosarcoma cells showed some vesicular fluorescence and a pronounced cytoplasmic fluorescence, in HeLa cells little cytoplasmic fluorescence was observed. In MC57 cells the inhibitors of endosomal acidification chloroquine and bafilomycin A1 abolished the release of the peptides into the cytoplasm. Release into the cytosol preserved endosomal integrity. In addition, cellular uptake of the peptides was inhibited by brefeldin A, a compound interfering with trafficking in the trans-Golgi network. In contrast, nordihydroguaiaretic acid, a drug that stimulates the rapid retrograde movement of both Golgi stacks and trans-Golgi network to the endoplasmic reticulum, promoted a cytoplasmic localization of Tat peptides in peptide-pulsed HeLa cells. The effects of these drugs on trafficking shared characteristics with those reported for the trafficking of plant and bacterial toxins, such as cholera toxin, which reach the cytoplasm by means of retrograde transport. A sequence comparison revealed a common stretch of 8-10 amino acids with high sequence homology to the Tat peptide. The structural and functional data therefore strongly suggest a common mechanism of import for cationic cell-penetrating peptides and the toxins.
Optimal Robust Self-Testing by Binary Nonlocal XOR Games (2013)

Self-testing a quantum apparatus means verifying the existence of a certain quantum state as well as the effect of the associated measuring devices based only on the statistics of the measurement outcomes. Robust (i.e., error-tolerant) self-testing quantum apparatuses are critical building blocks for quantum cryptographic protocols that rely on imperfect or untrusted devices. We devise a general scheme for proving optimal robust self-testing properties for tests based on nonlocal binary XOR games. We offer some simplified proofs of known results on self-testing, and also prove some new results.
CTL Recognition of a Bulged Viral Peptide Involves Biased TCR Selection (2005)

MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alphabeta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.
Robust Dynamic Service Composition in Sensor Networks (2012)

Service modeling and service composition are software architecture paradigms that have been used extensively in web services where there is an abundance of resources. They mainly capture the idea that advanced functionality can be realized by combining a set of primitive services provided by the system. Many efforts in web services domain focused on detecting the initial composition, which is then followed for the rest of service operation. In sensor networks, however, communication among nodes is error-prone and unreliable, while sensor nodes have constrained resources. This dynamic environment requires a continuous adaptation of the composition of a complex service. In this paper, we first propose a graph-based formulation for modeling sensor services that maps to the operational model of sensor networks and is amenable to analysis. Based on this model, we formulate the process of sensor service composition as a cost-optimization problem and show that it is NP-complete. Two heuristic methods are proposed to solve the composition problem: the top-down and the bottom-up approaches. We discuss centralized and distributed implementations of these methods. Finally, using ns-2 simulations, we evaluate the performance and overhead of our proposed methods.
Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages (1991)

Activation of coagulation factor X via the intrinsic pathway requires the assembly of factors IXa and VIII on lipid membranes. It is known that the platelet expresses membrane sites for assembly of factors IXa/VIII and promotes efficient factor X activation. We now show that human blood monocytes, but not lymphocytes or polymorphonuclear leukocytes, also express appropriate sites for factors IXa/VIII assembly. The maximal rate of factor X activation by factors IXa (0.75 nM) and VIII (1 unit/ml) assembled on monocytes is similar to the maximal rate on platelets. This rate, adjusted per micromole of lipid phosphorus, is 1636 +/- 358 nM factor Xa/min on monocyte, and 1569 +/- 54 nM factor Xa/min on platelets. At physiologic concentrations of factors X and VIII, the activation rate increases with factor IXa concentration asymptotically approaching a maximum. Half-maximal rate is achieved with 1.0 +/- 0.16 nM factor IXa. Monocytes and macrophages, but not platelets, can express membrane tissue factor and thus promote simultaneous assembly of two distinct factor X-activating protease complexes. In these studies, blood monocytes and alveolar macrophages are used as membrane sources in kinetic experiments comparing factor X activation by intrinsic (factor IXa/VIII) versus extrinsic (factor VII/tissue factor) protease complexes. At plasma concentration of factors VIII and VII, apparent Km on the monocyte is 14.6 +/- 1.4 nM for intrinsic and 117.0 +/- 10.1 nM for extrinsic activation. The apparent Km on alveolar macrophages is 12.1 +/- 1.9 and 90.6 +/- 10.2 nM for intrinsic and extrinsic activation, respectively. Maximal rates on monocytes at saturating concentration of factors IXa, VIII, and VII are 48.0 +/- 11.2 nM factor Xa/min, for intrinsic activation, and 16.5 +/- 5.5 nM factor Xa/min, for extrinsic activation. These data show that the monocyte/macrophage is the only blood-derived cell type with membrane sites for both intrinsic and extrinsic pathway assembly. We have exploited this characteristic of the monocyte/macrophage membrane to demonstrate that factor X activation by the intrinsic pathway protease is more efficient than activation via the extrinsic pathway protease complex.
α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1 (2018)

With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters.
The role of NDRG1 in the pathology and potential treatment of human cancers (2013)

N-myc downstream regulated gene 1 (NDRG1) has been well characterised to act as a metastatic suppressor in a number of human cancers. It has also been implicated to have a significant function in a number of physiological processes such as cellular differentiation and cell cycle. In this review, we discuss the role of NDRG1 in cancer pathology. NDRG1 was observed to be downregulated in the majority of cancers. Moreover, the expression of NDRG1 was found to be significantly lower in neoplastic tissues as compared with normal tissues. The most important function of NDRG1 in inhibiting tumour progression is associated with its ability to suppress metastasis. However, it has also been shown to have important effects on other stages of cancer progression (primary tumour growth and angiogenesis). Recently, novel iron chelators with selective antitumour activity (ie, Dp44mT, DpC) were shown to upregulate NDRG1 in cancer cells. Moreover, Dp44mT showed its antimetastatic potential only in cells expressing NDRG1, making this protein an important therapeutic target for cancer chemotherapy. This observation has led to increased interest in the examination of these novel anticancer agents.
MET inhibition in lung cancer. (2013)

Targeted agents have completely changed cancer treatment strategy, leading it from a "one size fits all" approach to a customized therapy. In this scenario Met, a heterodimere receptor tyrosine kinase deeply involved into embryogenesis and organogenesis, has been introduced many years ago as a potential target for biological agents, becoming "druggable" only in this last period of time. Met can be altered through receptor overexpression, genomic amplification, mutations or alternative splicing, autocrine or paracrine secretion of hepatic growth factor (HGF): these dysregulations stimulate tumorigenesis (in terms of cell-cell detachment, proliferation, invasion, angiogenesis and survival) and metastatization. Met is overexpressed in lung cancer and Met gene amplification can drive the dependency of cell survival and proliferation upon the Met signaling. Both Met overexpression and amplification seem to correlate with poor prognosis. Met amplification is also described to be linked to EGFR acquired resistance. Several Met inhibitors have been tested both in preclinical and human trials, demonstrating activity in lung cancer treatment. This paper aims to summarize data on Met biological function, on its interaction with cell signaling and other pathways and to present data on those Met inhibitors currently under evaluation.
Muscarinic receptor subtypes as potential targets to modulate oligodendrocyte progenitor survival, proliferation, and differentiation (2011)

Acetylcholine (ACh) is a major neurotransmitter but also an important signaling molecule in neuron-glia interactions. Expression of ACh receptors has been reported in several glial cell populations, including oligodendrocytes (OLs). Nonetheless, the characterization of muscarinic receptors in these cells, as well as the description of the cholinergic effects at different stages of OL development, is still incomplete. In this study, we characterized the pattern of expression of muscarinic receptor subtypes in primary cultures of rat oligodendrocyte progenitor cells (OPC) and mature OLs, at both mRNA and protein levels. We found that muscarinic receptor expression is developmentally regulated. M1, M3, and M4 receptors were the main subtypes expressed in OPC, whereas all receptor subtypes were expressed at low levels in mature OLs. Exposure of OPC to muscarine enhanced cell proliferation, an effect mainly due to M1, M3, and M4 receptor subtypes as demonstrated by pharmacological competition with selective antagonists. Conversely, M2 receptor activation impaired OPC survival. In line with the mitogenic activity, muscarinic receptor activation increased the expression of platelet derived growth factor receptor α. Muscarine stimulation increased CX32 and myelin basic protein expression, left unaffected that of myelin proteolipid protein (PLP), and decreased member of the family of epidermal growth factor receptor (EGFR) ErbB3/ErbB4 receptor expression indicating a predominant role of muscarinic receptors in OPC. These findings suggest that ACh may contribute to the maintenance of an immature proliferating progenitor pool and impair the progression toward mature stage. This hypothesis is further supported by increased expression of Notch-1 in OL on muscarinic activation.
Photovoltaic grid-connected inverter using two-switch buck-boost converter (2003)

This paper presents a two-stage photovoltaic grid-connected inverter. The first stage is a two-switch buck-boost circuit that performs various functions; tracking a maximum power point of the photovoltaic array and controlling current using fixed frequency current mode control technique; as well as reforming a direct current waveform to an absolute sinusoidal waveform. The second stage is a H-bridge switch that converts an absolute sinusoidal waveform to a sinusoidal waveform with a low harmonic distortion current and connected to utility. The system configuration is reliable using a single-chip DSP controller. Experimental results satisfy with simulation.
Genetic Factors Associated with Age-Related Macular Degeneration (2011)

Age-related macular degeneration (AMD) is a complex, multifactorial disease associated with environmental and genetic factors. This review emphasizes the clinical impact of the major genetic factors mainly located in the complement factor H gene and on the 10q26 locus, and their current and future implications for the management of AMD.
Pregnenolone Can Protect the Brain from Cannabis Intoxication (2014)

Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation (2001)

Although the standard dose regimen of 20 mg of basiliximab on days 0 and 4 after transplantation appears to be appropriate for the majority of patients with liver transplants, a supplemental dose at the end of the first week may be considered for those with substantial (>10 L) postoperative ascites fluid drainage.
The Waveguide Mach−Zender Interferometer as Atrazine Sensor (1998)

Immunoanalytical techniques used in combination with a highly sensitive Mach-Zender waveguide sensor give a device that is capable of fast on-line monitoring of immunoreactions. The on-line monitoring is especially attractive when the sensor can be used as an environmental probe. It is demonstrated that low concentrations of atrazine can be measured with a sensitivity around the EC limit of 100 ng/L. These measurements are performed with an inhibition technique. In combination with "a dynamic slope method" one complete measurement is done within 10 min. Sensor measurements show the same sensitivity and errors as parallel ELISAs.