gebhart/patrepeval huggingface dataset:
An acetylation switch controls TDP-43 function and aggregation propensity (2015)

TDP-43 pathology is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Although a critical role for TDP-43 as an RNA-binding protein has emerged, the regulation of TDP-43 function is poorly understood. Here, we identify lysine acetylation as a novel post-translational modification controlling TDP-43 function and aggregation. We provide evidence that TDP-43 acetylation impairs RNA binding and promotes accumulation of insoluble, hyper-phosphorylated TDP-43 species that largely resemble pathological inclusions in ALS and FTLD-TDP. Moreover, biochemical and cell-based assays identify oxidative stress as a signalling cue that promotes acetylated TDP-43 aggregates that are readily engaged by the cellular defense machinery. Importantly, acetylated TDP-43 lesions are found in ALS patient spinal cord, indicating that aberrant TDP-43 acetylation and loss of RNA binding are linked to TDP-43 proteinopathy. Thus, modulating TDP-43 acetylation represents a plausible strategy to fine-tune TDP-43 activity, which could provide new therapeutic avenues for TDP-43 proteinopathies.
Ctp1<sup>CtIP</sup> and Rad32<sup>Mre11</sup> Nuclease Activity Are Required for Rec12<sup>Spo11</sup> Removal, but Rec12<sup>Spo11</sup> Removal Is Dispensable for Other MRN-Dependent Meiotic Functions (2009)

The evolutionarily conserved Mre11/Rad50/Nbs1 (MRN) complex is involved in various aspects of meiosis. Whereas available evidence suggests that the Mre11 nuclease activity might be responsible for Spo11 removal in Saccharomyces cerevisiae, this has not been confirmed experimentally. This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11). Furthermore, we show that the CtIP homologue Ctp1 is required for Rec12(Spo11) removal, confirming functional conservation between Ctp1(CtIP) and the more distantly related Sae2 protein from Saccharomyces cerevisiae. Finally, we show that the MRN complex is required for meiotic recombination, chromatin remodeling at the ade6-M26 recombination hot spot, and formation of linear elements (which are the equivalent of the synaptonemal complex found in other eukaryotes) but that all of these functions are proficient in a rad50S mutant, which is deficient for Rec12(Spo11) removal. These observations suggest that the conserved role of the MRN complex in these meiotic functions is independent of Rec12(Spo11) removal.
Transformer-isolated gate drive design for SiC JFET phase-leg module (2011)

In order to take full advantage of the SiC devices' high-temperature and high-frequency capabilities, a transformer isolated gate driver is designed for the SiC JFET phase leg module to achieve a fast switching speed of 26V/ns and a small cross-talking voltage of 4.2V in a 650V and 5A inductive load test. Transformer isolated gate drive circuits suitable for high-temperature applications are compared with respect to different criteria. Based on the comparison, an improved edge triggered gate drive topology is proposed. Then, using the proposed gate drive topology, special issues in the phase-leg gate drive design are discussed. Several strategies are implemented to improve the phase-leg gate drive performance and alleviate the cross-talking issue. Simulation and experimental results are given for verification purposes.
Mechanism of action of antifungals and combination therapy (1995)

Abstract Biochemical studies have identified a number of potential targets for antifungal chemotherapy, including cell wall synthesis, membrane sterol biosynthesis, nucleic acid synthesis, metabolic inhibition and macromolecular biosynthesis. The inhibition of cell wall synthesis would be in theory highly specific since only fungal cells build their cell wall with chitin and glucan. Despite this defined specificity, none of the clinically available drugs act there. Most antifungals interfere with enzymatic steps involved in the complicated synthesis of ergosterol. Allylamines interfere with the squalene epoxidation leading to an intracellular accumulation of squalene. The imidazole and triazole derivatives interact with the cytochrom P-450-dependent C14-demethylase system. C14-methyl-sterols like lanosterol are accumulated within the fungal cell. Under treatment of morpholine derivatives like amorolfine, ignosterol a sterol containing a Δ14 double bond is accumulated. Amorolfine inhibits two steps in the pathway of ergosterol biosynthesis namely the Δ14 reductase and the Δ7,8 isomerase. Amorolfine possesses a broad antimycotic spectrum against fungi pathogenic to plants and humans. The drug not only inhibits the fungal growth, it also shows a strong fungicidal activity which is both concentration- and time-dependent. The fungicidal activity against dermatophytes is in the same order as the one of terbinafine. Amorolfine also shows good fungicidal activity against yeasts, dimorphic and dematiaceous fungi. Amorolfine exerts synergistic activity in combination with several other antifungals such as ketoconazole, terbinafine, itraconazole and griseofulvin. The fungistatic activity of all these antifungals against dermatophytes is slightly increased by addition of amorolfine. The synergistic effect seen in vitro is, however, more pronounced in an animal model. Combination therapy of amorolfine with terbinafine, itraconazole and griseofulvin was studied in a murine trichophytosis model. Murine trichophytosis is self-healing, the course of infection reaches a plateau on day 7 and declines thereafter throughout the second week. Mice infected with trichophyton and treated with various antifungal drugs generally responded to the treatment in a dose-dependent manner, showing a significant reduction in the appearance of mycotic foci in comparison to untreated animals. The combinations of amorolfine with griseofulvin, terbinafine, itraconazole and fluconazole were always more efficient than the individual drug treatment alone, provided that the single therapy is not overwhelmingly efficacious per se. Antagonism was never observed.
Pickering Interfacial Catalysis for Biphasic Systems: From Emulsion Design to Green Reactions (2015)

Pickering emulsions are surfactant-free dispersions of two immiscible fluids that are kinetically stabilized by colloidal particles. For ecological reasons, these systems have undergone a resurgence of interest to mitigate the use of synthetic surfactants and solvents. Moreover, the use of colloidal particles as stabilizers provides emulsions with original properties compared to surfactant-stabilized emulsions, microemulsions, and micellar systems. Despite these specific advantages, the application of Pickering emulsions to catalysis has been rarely explored. This Minireview describes very recent examples of hybrid and composite amphiphilic materials for the design of interfacial catalysts in Pickering emulsions with special emphasis on their assets and challenges for industrially relevant biphasic reactions in fine chemistry, biofuel upgrading, and depollution.
Prostaglandin E2 production by rabbit urinary bladder (1980)

Synthesis of prostaglandin E2 (PGE2) by rabbit bladder was examined. PGE2 synthesis was assessed by thin-layer chromatographic analysis after conversion of [14C]-arachidonic acid to [14C]PGE2 or by a specific radioimmunoassay technique. Intact bladder and microsomes prepared from the bladder transitional epithelium (mucosal) layer and the outer vesicular layer demonstrated synthesis of PGE2. PGE2 synthesis was increased by arachidonic acid and blocked by indomethacin. When the inside medium (bathing the transitional epithelium) contained [14C]arachidonic acid, no detectable radioactivity was observed in the outside medium (bathing the outer layer). Conversely, when the outside medium contained [14C]arachidonic acid, no detectable radioactivity was observed in the inside medium. In addition, [14C]arachidonic acid was incorporated only into tissue directly exposed to bathing media containing the label. These results demonstrate that the rabbit bladder can synthesize PGE2 and that the PGE2- synthesizing systems of the transitional epithelium and outer layer of bladder may be distinct.
Fast thermo-optical switch based on SOI waveguides (2003)

Thermo-optical silicon-on-insulator (SOI) waveguide switch has been fabricated and characterized. The switch is based on a 2x2 Mach-Zehnder interferometer and 9 microns thick ridge waveguides. The extinction ratio of the switch is 17 dB with ultra-slow modulation and it is limited by the unoptimized directional coupler lengths. Thermo-optical switching with conventional on/off modulation was demonstrated up to 10 kHz. The average power consumption was 150 mW and the extinction ratio was 15 dB in 10 kHz square wave modulation. By using a novel modulation principle the maximum frequency was rised up to 167 kHz, while still maintaining the 15 dB extinction ratio in square wave modulation. With random binary modulation at 167 kHz frequency (3 μs per bit) the extinction ratio remained above 13 dB and the average power consumption was 590 mW. The obtained frequency limits for square wave modulation correspond to a maximum of 1% deviation from the attainable extinction ratio limits. With less strict extinction ratio requirements the maximum frequencies can be much higher. The new modulation method can be used to radically speed up interferometric switches with a tolerable increase in the power consumption.
A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology (2012)

An animal's ability to navigate through space rests on its ability to create a mental map of its environment. The hippocampus is the brain region centrally responsible for such maps, and it has been assumed to encode geometric information (distances, angles). Given, however, that hippocampal output consists of patterns of spiking across many neurons, and downstream regions must be able to translate those patterns into accurate information about an animal's spatial environment, we hypothesized that 1) the temporal pattern of neuronal firing, particularly co-firing, is key to decoding spatial information, and 2) since co-firing implies spatial overlap of place fields, a map encoded by co-firing will be based on connectivity and adjacency, i.e., it will be a topological map. Here we test this topological hypothesis with a simple model of hippocampal activity, varying three parameters (firing rate, place field size, and number of neurons) in computer simulations of rat trajectories in three topologically and geometrically distinct test environments. Using a computational algorithm based on recently developed tools from Persistent Homology theory in the field of algebraic topology, we find that the patterns of neuronal co-firing can, in fact, convey topological information about the environment in a biologically realistic length of time. Furthermore, our simulations reveal a "learning region" that highlights the interplay between the parameters in combining to produce hippocampal states that are more or less adept at map formation. For example, within the learning region a lower number of neurons firing can be compensated by adjustments in firing rate or place field size, but beyond a certain point map formation begins to fail. We propose that this learning region provides a coherent theoretical lens through which to view conditions that impair spatial learning by altering place cell firing rates or spatial specificity.
Dynamic reconstruction of 3D structure and 3D motion (2002)

This paper presents a computational scheme for reconstructing 3D structure, 3D motion and complete surfaces from instantaneous image motion based on multiple frames. The scheme is motivated by psychophysical observations and designed to achieve efficient, robust and flexible behavior. The scheme consists of multiple interacting stages. At the structure-from-motion stage, relative depths and 3D velocities are estimated by minimizing the error in fit to the instantaneous 2D motion measurements and the overall deviation from rigidity. This nonlinear optimization is achieved by an efficient two-stage iterative algorithm. The temporal integration stage based on Kalman filtering effectively improves the 3D structure over multiple frames. The global motion of the observer or each constituent object can be computed at a later stage by using the estimated 3D velocities. The surface reconstruction stage reconstructs complete 3D surfaces, which can further stabilize the 3D structure recovery. The scheme can account for a number of psychophysical findings that include the perceptual demonstrations explored by Ramachandran et al. (Husain et al. 1989, Lappin et al. 1980) regarding interactions between two superimposed cylinders, and the experimental results using displays of moving points with short lifetimes (28, 55).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Page frame segmentation for contextual advertising in print on demand books (2009)

The Web, TV and print publishing are the top three advertisement media. With the technology breakthroughs in digital printing, scanning and data processing, print on demand emerges into a multi-billion dollar business that is due to revolutionize the traditional publishing industry.
CRFs form protein–protein interactions with each other and with members of the cytokinin signalling pathway in Arabidopsis via the CRF domain (2011)

Cytokinin is a plant hormone essential for growth and development. The elucidation of its signalling pathway as a variant of the bacterial two-component signalling system (TCS) has led to a better understanding of how this hormone is involved in general plant processes. A set of cytokinin-regulated transcription factors known as cytokinin response factors (CRFs) have been described as a potential branch emanating from the TCS, yet little is known about how CRFs actually interact with each other and with members of the TCS pathway. Here the interactions of CRF proteins (CRF1-CRF8) using the yeast two-hybrid system and bimolecular fluorescence complementation in planta assays are described. It was found that CRFs are readily able to form both homo- and heterodimers with each other. The first analysis of CRF versus TCS pathway protein interactions is also provided, which indicates that CRFs (CRF1-CRF8) are able specifically to interact directly with most of the Arabidopsis histidine-phosphotransfer proteins (AHP1-AHP5) further solidifying their link to the cytokinin signalling pathway. In addition, the region of CRF proteins involved in these interactions was mapped and it was determined that the clade-specific CRF domain alone is sufficient for these interactions. This is the first described function for the CRF domain in plants.
Poly(p-Oxybenzoyl Systems): Homopolymer for Coatings; Copolymers for Compression and Injection Molding (1974)

Development work has been going on for several years at The Carborundum Company on p-oxybenzoyl polymer systems. The early work mainly focused on the homopolymer (EKONOL).1,2,3 This polymer has excellent thermal stability and also very good friction and wear properties and has found use recently as an additive to PTFE for molded shapes and coatings. The homopolymer however is very difficult to fabricate by itself and this has led to the development of copolymer systems which retain the excellent thermal stability of the homopolymer; but have sufficient flow for compression and injection molding. Para-hydroxybenzoic acid (PHBA) by itself does not have sufficient reactivity to permit the growth of a polymer to any useful molecular weight. This has been overcome by using the phenyl ester of PHBA. With a slow controlled heating to temperatures of 320-340°C, this monomer has sufficient reactivity to build the molecular weight to a useful level. However,
Serial MRI evaluation of cardiac structure and function in mice after reperfused myocardial infarction (2002)

This study evaluated the utility of cardiac MRI for assessing the impact of myocardial infarction (MI) on cardiac structure and function in mice following reperfused 1- or 2-hr occlusions of the left anterior descending coronary artery (LAD). When assessed 1 day after MI, the left ventricular ejection fraction (LVEF) had declined by more than half, and remained depressed for the duration of the study. Furthermore, MI initiated dramatic increases in both LV end-systolic volume (LVESV) and end-diastolic volume (LVEDV), with a greater than threefold increase in LVESV and a twofold increase in LVEDV by 4 weeks post-MI. Transmural LV wall thickening (WTh) analysis revealed that noninfarcted myocardium in the remote septal region exhibited an early deficit in contractile function after MI that transiently resolved by day 7, only to be followed by a late phase of dysfunction that became fully manifest by day 28 post-MI. In conclusion, MRI allows the serial assessment of cardiac structure and function after MI in mice, with a resolution adequate to document both regional and temporal changes. The application of these imaging techniques in transgenic and knock-out mice will greatly expedite research aimed at defining the functional roles of individual genes in the pathophysiology of LV remodeling (LVR) after reperfused MI.
Performance of joints in steel storage pallet racks (2000)

Performance of pallet racking systems depends upon the efficiency of beam-end-connectors, which provide, together with column bases, sources of stiffness for down-aisle stability. Knowledge of the actual joint behaviour under static and seismic loading is of fundamental importance for a suitable definition of simplified moment-rotation joint relationships to use into design of semi-continuous frames. This paper presents the preliminary results of research activities currently in progress in Italy focused on static and seismic behaviour of pallet racking beam-to-column joints. 1.
Language Analysis and Tools for Ambiguous Input Streams (2004)

Automatically generated lexers and parsers for programming languages have a long history. Although they are well-suited for many languages, many widely-used generators, among them Flex and Bison, fail to handle input stream ambiguities that arise in embedded languages, in legacy languages, and in programming by voice. We have developed Blender, a combined lexer and parser generator that enables designers to describe many classes of embedded languages and to handle ambiguities in spoken input and in legacy languages. We have enhanced the incremental lexing and parsing algorithms in our Harmonia framework to analyze lexical, syntactic and semantic ambiguities. The combination of better language description and enhanced analysis provides a powerful platform on which to build the next generation of language analysis tools.
DP<sub>2</sub>receptor antagonists in development (2010)

Considerable progress has been made in the development of selective DP(2) antagonists and initial indications are that they could prove a useful new option in the treatment of asthma. More comprehensive clinical results that will shortly become available will further clarify their therapeutic potential and also indicate the possibility of their use in the treatment of chronic obstructive pulmonary disease.
CXCR2 and RET Single Nucleotide Polymorphisms in Pancreatic Cancer (2008)

Enhanced angiogenesis and perineural invasion are markers of poor prognosis in patients with pancreatic cancer. Systemic therapies for pancreatic cancer have been largely ineffective, and thus improved, targeted therapies are needed. Single nucleotide polymorphisms (SNP) are DNA sequence variations that result in vast diversity of disease susceptibility and response to disease. CXCR2 is an important mediator of CXC chemokine-induced angiogenesis and is upregulated in pancreatic cancer. In a preclinical corneal micropocket assay, treatment of pancreatic cancer cell lines that express CXCR2 with anti-CXCR2 antibody inhibited angiogenesis. To date, there have not been any CXCR2 SNP associated with pancreatic cancer, but CXCR2 SNP has been postulated to be associated with angiogenesis in systemic sclerosis. The receptor tyrosine kinase encoded by the RET gene and its ligand glial derived neurotrophic factor (GDNF) are upregulated in pancreatic cancer. In vitro treatment of pancreatic cancer cell lines that express RET with anti-RET antibody or RET siRNA-inhibited GDNF-induced invasiveness. G691S RET SNP has been previously shown to be associated with enhanced pancreatic cancer invasiveness. We suggest that molecular profiling of each patient's tumor for G691S RET SNP, potentially CXCR2 SNP, and also other yet-to-be identified SNP associated with pancreatic cancer will allow for both improved understanding of individual prognosis and allow for utilization of more personalized, targeted adjuvant therapies.
Nyström-Clenshaw-Curtis quadrature for integral equations with discontinuous kernels (2002)

A new highly accurate numerical approximation scheme based on a Gauss type Clenshaw-Curtis quadrature for Fredholm integral equations of the second kind <disp-formula content-type="math/mathml"> \[ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="x left-parenthesis t right-parenthesis plus integral Subscript a Superscript b Baseline k left-parenthesis t comma s right-parenthesis x left-parenthesis s right-parenthesis d s equals y left-parenthesis t right-parenthesis comma"> <mml:semantics> <mml:mrow> <mml:mi>x</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>t</mml:mi> <mml:mo stretchy="false">)</mml:mo> <mml:mo>+</mml:mo> <mml:msubsup> <mml:mo>∫</mml:mo> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi>a</mml:mi> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi>b</mml:mi> </mml:mrow> </mml:msubsup> <mml:mi>k</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>t</mml:mi> <mml:mo>,</mml:mo> <mml:mi>s</mml:mi> <mml:mo stretchy="false">)</mml:mo> <mml:mi>x</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>s</mml:mi> <mml:mo stretchy="false">)</mml:mo> <mml:mi>d</mml:mi> <mml:mi>s</mml:mi> <mml:mo>=</mml:mo> <mml:mi>y</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>t</mml:mi> <mml:mo stretchy="false">)</mml:mo> <mml:mo>,</mml:mo> </mml:mrow> <mml:annotation encoding="application/x-tex">x(t)+\int ^{b}_{a}k(t,s)x(s)ds=y(t),</mml:annotation> </mml:semantics> </mml:math> \] </disp-formula> whose kernel <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="k left-parenthesis t comma s right-parenthesis"> <mml:semantics> <mml:mrow> <mml:mi>k</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>t</mml:mi> <mml:mo>,</mml:mo> <mml:mi>s</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:mrow> <mml:annotation encoding="application/x-tex">k(t,s)</mml:annotation> </mml:semantics> </mml:math> </inline-formula> is either discontinuous or not smooth along the main diagonal, is presented. This scheme is of spectral accuracy when <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="k left-parenthesis t comma s right-parenthesis"> <mml:semantics> <mml:mrow> <mml:mi>k</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>t</mml:mi> <mml:mo>,</mml:mo> <mml:mi>s</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:mrow> <mml:annotation encoding="application/x-tex">k(t,s)</mml:annotation> </mml:semantics> </mml:math> </inline-formula> is infinitely differentiable away from the diagonal <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="t equals s"> <mml:semantics> <mml:mrow> <mml:mi>t</mml:mi> <mml:mo>=</mml:mo> <mml:mi>s</mml:mi> </mml:mrow> <mml:annotation encoding="application/x-tex">t = s</mml:annotation> </mml:semantics> </mml:math> </inline-formula>. Relation to the singular value decomposition is indicated. Application to integro-differential Schrödinger equations with nonlocal potentials is given.