gebhart/patrepeval huggingface dataset:
PaperSpace (2006)

Here we present PaperSpace a computer vision based document management system that allows users to combine paper and digital documents. Using PaperSpace users can locate paper copies of printed digital documents, retrieve digital versions of paper documents and fluidly move between digital and paper documents. The system works by tracking 2D identity and operation codes printed in the margins of each page of the document. Users can activate commands by selecting the command from the command bar at the bottom of each document. Through an informal evaluation we found that all users felt our system would be valuable in helping them organize their cluttered desk and manage digital and paper documents better.
Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives (2020)

Blocking the MDM2/X-P53 protein-protein interaction has been widely recognized as an attractive therapeutic strategy for the treatment of cancers. Numerous small-molecule MDM2 inhibitors have been reported since the release of the structure of the MDM2-P53 interaction in 1996, SAR405838, NVP-CGM097, MK-8242, RG7112, RG7388, DS-3032b, and AMG232 currently undergo clinical evaluation for cancer therapy. This review is intended to provide a comprehensive and updated overview of MDM2 inhibitors and proteolysis targeting chimera (PROTAC) degraders with a particular focus on how these inhibitors or degraders are identified from starting points, strategies employed, structure-activity relationship (SAR) studies, binding modes or co-crystal structures, biochemical data, mechanistic studies, and preclinical/clinical studies. Moreover, we briefly discuss the challenges of designing MDM2/X inhibitors for cancer therapy such as dual MDM2/X inhibition, acquired resistance and toxicity of P53 activation as well as future directions.
Vascular Smooth Muscle Cell Differentiation to an Osteogenic Phenotype Involves TRPM7 Modulation by Magnesium (2010)

Arterial calcification, common in vascular diseases, involves vascular smooth muscle cell (VSMC) transformation to an osteoblast phenotype. Clinical studies suggest that magnesium may prevent this, but mechanisms are unclear. We assessed whether increasing magnesium levels reduce VSMC calcification and differentiation and questioned the role of the Mg(2+) transporter, transient receptor potential melastatin (TRPM)7 cation channels in this process. Rat VSMCs were exposed to calcification medium in the absence and presence of magnesium (2.0 to 3.0 mmol/L) or 2-aminoethoxy-diphenylborate (2-APB) (TRPM7 inhibitor). VSMCs from mice with genetically low (MgL) or high-normal (MgH) [Mg(2+)](i) were also studied. Calcification was assessed by von Kossa staining. Expression of osteocalcin, osteopontin, bone morphogenetic protein (BMP)-2, BMP-4, BMP-7, and matrix Gla protein and activity of TRPM7 (cytosol:membrane translocation) were determined by immunoblotting. Calcification medium induced osteogenic differentiation, reduced matrix Gla protein content, and increased expression of the sodium-dependent cotransporter Pit-1. Magnesium prevented calcification and decreased osteocalcin expression and BMP-2 activity and increased expression of calcification inhibitors, osteopontin and matrix Gla protein. TRPM 7 activation was decreased by calcification medium, an effect reversed by magnesium. 2-APB recapitulated the VSMC osteoblastic phenotype in VSMCs. Osteocalcin was increased by calcification medium in VSMCs and intact vessels from MgL but not MgH, whereas osteopontin was increased in MgH, but not in MgL mice. Magnesium negatively regulates vascular calcification and osteogenic differentiation through increased/restored TRPM7 activity and increased expression of anticalcification proteins, including osteopontin, BMP-7, and matrix Gla protein. New molecular insights are provided whereby magnesium could protect against VSMC calcification.
Polynomial expansion of severely aberrated wave fronts (1987)

The optimization of an optical system is generally carried out by minimizing the wave-front aberrations, the x and y transverse aberrations, or a combination of both. In the last-named, most general case, the optimization implies the treatment of a large number of functions of quite a different nature. We propose to use, together with the Zernike polynomials that orthogonalize the wave-front aberrations, a new set of wave-front polynomials that orthogonalize the transverse aberrations. These polynomials turn out to be a simple linear combination of Zernike polynomials. The combination of these two sets of wave-front polynomials with proper weighting yields the possibility of optimizing the frequency response of both slightly and severely aberrated systems in a formally identical way. The advantage of the method is that one does not have to leave the domain of the wave-front aberration to characterize an optical system, even when severe aberrations are present. The polynomials that minimize the transverse aberrations yield optimum response at very low frequencies; other linear combinations of Zernike polynomials are shown to maximize the frequency response at relatively high spatial frequencies.
THE EFFECTS OF AROMATIC AMINO ACID DERIVATIVES ON THE EXCITABILITY OF AN IDENTIFIABLE GIANT NEURONE OF THE AFRICAN GIANT SNAIL (<i>Achatina fulica</i> Férussac) (1980)

1 The effects of derivatives of aromatic amino acids on the excitability of an identifiable giant neurone (TAN, tonically autoactive neurone) of the African giant snail (Achatina fulica Férussac) were examined. 2 The following substances had marked inhibitory effects on TAN using bath application: N-beta-phenylpropionyl-L-Tyr and N-beta-phenylpropionyl-L-Trp (critical concentration, 3 x 10(-7) M), N-beta-phenylpropionyl-L-Phe, N-cinnamoyl-DL-Trp and N-phenoxyacetyl-L-Trp (critical concentration, 10(-5) to 3 x 10(-5) M). However, N-beta-phenylpropionyl-D-Tyr and N-beta-phenylpropionyl tyramine had no effect. 3 Microdrop (150 micrometers in diameter) application of N-beta-phenylpropionyl-L-Tyr or N-beta-phenylpropionyl-l-trp containing about 100 pg resulted in marked inhibitory effects on TAN. The effect was observed in Ca2+-free, Mg2+-rich (24 mM) solution. Substitution of Cl- by acetate did not alter the response. This indicates that the two substances act directly on the TAN membrane and not via synaptic influences, and that the inhibition produced by the two substances is not due to the permeability increase of the TAN membrane to Cl-.
Applications of smart antennas in cellular networks (2003)

Many cellular telephone networks are in the midst of migrating from analog to digital radio air interfaces. This paper examines the network performance of smart antenna architectures designed for current dual-mode AMPS and CDMA cellular networks. The proposed smart antenna approach is implemented as a non-invasive add-on to existing base stations with the goal of addressing many of the fundamental performance limitations that exist within these networks. Traditionally smart antennas are used to improve capacity by increasing traffic channel carrier-to-interference (C/I) ratios, resulting in tightened frequency reuse for FDMA networks. In this paper the focus is turned instead to non-traditional methods for phased-array antenna deployments to improve capacity in CDMA networks through traffic load balancing, handoff management and network-wide interference control.
[Nephrotoxicity of amphotericin B]. (2002)

Amphotericin B is widely used for severe life threatening fungal infections. Its use is limited by a dose-dependent nephrotoxicity manifested by a reduction in glomerular filtration rate and tubular dysfunction. An elevated creatinine associated with amphotericin B is not only a marker for renal dysfunction but is also linked to a substantial risk for the use of hemodialysis and a higher mortality rate; therefore amphotericin B nephrotoxicity is not a benign complication and its prevention is essential. Several manipulations have been proposed to try and minimize amphotericin B induced nephrotoxicity. Systematic hydration is crucial to minimize amphotericin B. Mannitol or intralipids administration were once suggested as protective based on anecdotal observational reports. Small prospective and randomized trials, however did not support a protective effect. Three new formulations have been developed in an attempts to improse both efficacy and tolerability: amphotericin B in lipid complex (ABLC, Abelcet). Colloidal dispersion (ABCD, Amphotec and amphotericin B liposome (Ambisome). Three prospectives randomized studies have clearly shown that Ambisome is less nephrotoxic than amphotericin B. Unfortunately the only randomized trial comparing Abelcet with amphotericin B is an open-label treatment of invasive candidiasis which was presented 5 years ago but never published as a full paper. Furthermore in a recent multicenter double-blind study it has been shown that Ambisome has a better safety profile than Abelcet with less chills/rigors and less nephrotocixity.
Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas" (1993)

The spatial memory functions of the monkey's prefrontal cortex were examined with oculomotor delayed-response (ODR) paradigms that required the animal to remember the spatial location of peripheral visual cues, while maintaining fixation on a central visual target during the presentation of each cue and during a subsequent 1.5-8 sec delay period. Four rhesus monkeys received unilateral or serial prefrontal lesions in and around the principal sulcus after they reached criterion performance on the ODR tasks. Unilateral lesions disrupted the performance of memory-guided eye movements to spatial cues in the visual field contralateral to the hemisphere in which the lesion was placed. Memory-guided eye movements to ipsilateral cues were mildly affected by unilateral lesions, and these lesions had little or no effect on performance in visually guided control tasks. With addition of a second lesion in the opposite hemisphere, the deficit was extended to include the opposite hemifield. The impairment was characterized by eye movements of inappropriate direction, and, excepting the one lesion that extended into the frontal eye field region of the arcuate sulcus, saccadic reaction times and velocities were the same before and after the lesions. The effect of the lesions was delay dependent: performance was rarely altered at the shortest (1.5 sec) delay but became progressively worse as the delay period was lengthened. The present results strengthen the evidence that the delayed-response deficits of monkeys with prefrontal lesions are caused by failure to maintain a transient memory "trace" in working memory, and indicate for the first time that working memory mechanisms are lateralized: memories for visuo-spatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. These findings provide evidence for the concept of mnemonic hemianopias and mnemonic scotomas, that is, memory deficits for particular hemifields or visual field locations, unaccompanied by simple sensory or motor deficits.
Nature of the Active Site in Surface-Enhanced Raman Scattering (1983)

Experiments involving competitive and cooperative adsorption of pyridine, ${\mathrm{Cl}}^{\ensuremath{-}}$, SC${\mathrm{N}}^{\ensuremath{-}}$, and Tl, and voltage induced resonance shifting show that the largest surface-enhanced Raman scattering intensity comes from complexes of these species adsorbed on defects which cover less than 3% of the Ag surface. The resonance is attributed to charge transfer excitation from Ag to pyridine and from SC${\mathrm{N}}^{\ensuremath{-}}$ to Ag which is communicated to all vibrations of the complex.
The Interaction of FABP with Kapα (2015)

Gene-activating lipophilic compounds are carried into the nucleus when loaded on fattyacid-binding proteins (FABP). Some of these proteins are recognized by the -Karyopherin (Kap) through its nuclear localization signal (NLS) consisting of three positive residues that are not in a continuous sequence. The Importin system can distinguish between FABP loaded with activating and non-activating compounds. In the present study, we introduced molecular dynamics as a tool for clarifying the mechanism by which FABP4, loaded with activating ligand (linoleate) is recognized by Kap. In the first phase, we simulated the complex between Kap IBB (termed "Armadillo") that was crystallized with two NLS hepta-peptides. The trajectory revealed that the crystal-structure orientation of the peptides is rapidly lost and new interactions dominate. Though, the NLS sequence of FABP4 is cryptic, since the functional residues are not in direct sequence, implicating more than one possible conformation. Therefore, four possible docked conformations were generated, in which the NLS of FABP4 is interacting with either the major or the minor sites of Kap, and the N ! C vectors are parallel or anti-parallel. Out of these four basic starting positions, only the FABP4-minor site complex exhibited a large number of contact points. In this complex, the FABP interacts with the minor and the major sites, suppressing the self-inhibitory interaction of the Kap, rendering it free to react with Kap. Finally, we propose that the transportable conformation generated an extended hydrophobic domain which expanded out of the boundary of the FABP4, allowing the loaded linoleate to partially migrate out of the FABP into a joint complex in which the Kap contributes part of a combined binding pocket.
Design and Implementation for Universal Digital Flight Simulation Platform (2008)

Aiming at the need of combat training and verifying the advanced flight control law,a sort of universal digital flight simulation platform is proposed in this paper.The structure of the flight simulation platform is introduced.The dynamic model of airplane and universal flight simulation database is constructed,and the function of each module and method to establish each module are fully illustrated.A validation in this platform for a sort of UAV is made.The simulation result shows that the platform acquires good visual effect and accurate parameters,simulating real flight well.
Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology (2010)

Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial experimental and pre-clinical evidence showing that the S protein is a promising lead for vaccines and therapeutics. Previously we generated a panel of monoclonal antibodies (mAbs) to whole inactivated SARS-CoV which neutralize the virus in vitro. Here, we define their specificity and affinity, map several of their epitopes and lastly characterise chimeric versions of them. Our data show that the neutralizing mAbs bind to the angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD) of the SARS S protein. Three of the chimeric mAbs retain their binding specificity while one conformational mAb, F26G19, lost its ability to bind the S protein despite high level expression. The affinity for recombinant S is maintained in all of the functional chimeric versions of the parental mAbs. Both parental mAb F26G18 and the chimeric version neutralize the TO R2 strain of SARS-CoV with essentially identical titres (2.07 and 2.47 nM, respectively). Lastly, a comparison with other neutralizing mAbs to SARS-CoV clearly shows that the dominance of a 33 amino acid residue loop of the SARS-CoV RBD is independent of repertoire, species, quaternary structure, and importantly, the technology used to derive the mAbs. In cases like this, the dominance of a compact RBD antigenic domain and the central role of the S protein in pathogenesis may inherently create immunoselection pressure on viruses to evolve more complex evasion strategies or die out of a host species. The apparent simplicity of the mechanism of SARS-CoV neutralization is in stark contrast to the complexity shown by other enveloped viruses.
MIN6 Is Not a Pure Beta Cell Line but a Mixed Cell Line with Other Pancreatic Endocrine Hormones (2009)

MIN6 cells retains glucose-stimulated insulin secretion (GSIS) as isolated islets. We comprehensively evaluated the gene expression and production of other islet hormones in MIN6 cells. Islet hormones were demonstrated by immunohistochemical staining and measured by ELISA. The gene expression profiles of MIN6 cells were compared with those in the mouse islets obtained by the laser capture micro-dissection (LCM). MIN6 cells excreted insulin, glucagon, somatostatin and ghrelin. They expressed mRNAs of insulin I and II, proglucagon, somatostatin, pancreatic polypeptide (PP) and ghrelin which were shown in the mouse pancreatic islet core and periphery obtained by LCM. A variety of genes closely related to the islet hormone producing cells were expressed in MIN6. Confocal laser scanning microscopy revealed that MIN6 cells included not only insulin positive cells but also insulin and glucagon or somatostin double positive cells. Glucagon, somatostatin and ghrelin were detectable in the culture medium. The present study clearly demonstrated that MIN6 produce pancreatic endocrine cells. It would be possible to use this cell line as a model to research the development, cell differentiation and function of pancreatic islets.
A one step synthesis of 4‐substituted imidazoles. An important observation when <i>N</i>‐alkylating imidazoles (1988)

Abstract Imidazoles substituted in the 2‐position with methyl, 1e , phenyl, 1a , 2‐imidazole, 1b‐d , or t ‐butyldiphenylsilyl, If, react with soft electrophiles 2 to give modest yields of 4(5)‐ C ‐alkylated‐imidazoles 3 and N ‐alkylated products 5. These two products are readily separated by flash chromatography.
Optimal design for antireflective tapered two-dimensional subwavelength grating structures (1995)

Techniques for the design of continuously tapered two-dimensional (2D) subwavelength surface-relief grating structures for broadband antireflection surfaces are investigated. It has been determined that the Klopfenstein taper [ Proc. IRE44, 31 ( 1956)] produces the optimum graded-index profile with the smallest depth for any specified minimum reflectance. A technique is developed to design the equivalent tapered subwavelength surface-relief grating structure by use of 2D effective-medium theory. An optimal Klopfenstein tapered 2D subwavelength grating is designed to reduce the Fresnel reflections by 20 dB over a broad band from an air–substrate (ns = 3.0) interface. The performance is verified by use of both a 2D effective-medium-theory simulation algorithm and rigorous coupled-wave analysis. These structures are also shown to achieve this low reflectance over a wide field of view (θFOV > 110°). The pyramidal spatial profile, which has generally been assumed to produce the optimal broadband antireflection grating structure, is shown to require a significantly larger depth to achieve the same performance as a Klopfenstein-designed tapered antireflection grating structure.
<b>Recombination in mycobacteria</b> (1996)

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) is thought to infect a quarter of the world's population and accounts for 3 million deaths each year. Leprosy, caused by Mycobacterium leprae continues to afflict millions. In many countries, the incidence of TB is increasing due to its association with acquired immune deficiency syndrome (AIDS) and the emergence of multidrug resistance strains of tubercle bacilli. Genes that encode major antigens, enzymes, potential virulence determinants and drug resistance in mycobacteria have been isolated and characterized; however, further genetic analysis of pathogenic mycobacteria has been severely hampered by the difficulty in precisely defining the phenotype of both wild-type and mutant genes by utilizing homologous recombination to perform allele exchange. Recombination mechanisms have been intensely studied in Escherichia coli but it is unclear how far mechanistic pathways elucidated in this species are applicable to other organisms, such as mycobacteria. The aim of this review is to examine what is currently known about homologous recombination in mycobacteria. A model is proposed to account for both low levels of homologous recombination and high levels of illegitimate recombination found in the tubercle bacillus.
Reactivity of Carbonyl-Functionalized Phosphaalkenes RC(O)P=C(NMe2)2 (R = tBu, Ph) towards Electrophiles (1999)

The reaction of the carbonyl-functionalized phosphaalkenes RC(O)P=C(NMe2)2 [R = tBu (2a), Ph (2b)] with protic acids and alkylating reagents occurred at the two-coordinate phosphorus atom to give the phosphanyl-substituted carbocations 3a,b and 4a,b. In contrast, treatment with Me3SiOSO2CF3 resulted in attack at the oxygen atom by the silyl group, and the formation of [RC(OSiMe3)=PC(NMe2)2]SO3CF3 (5a,b). Similarly, the Lewis acids B(C6F5)3, Al(tBu)2Cl and AlMe3 were ligated to the oxygen atom of the carbonyl group. Two equivalents of GaMe3 were added to the oxygen and phosphorus atom of the phosphaalkene to yield the thermolabile complexes [RC(OGaMe3)=P(GaMe3)C(NMe2)2] (10a,b). In contrast, one molecule of InMe3 was bound to the phosphorus center of the phosphorus compound. Reaction of the phosphaalkenes with [Ni(CO)4], [Fe2(CO)9] or [{(Z)-cyclooctene}Cr(CO)5] also took place at the pnictogen atom, resulting in complexes of the type [RC(O)P{M(CO)n}C(NMe2)2] (R = tBu, Ph; M = Ni, n = 3; Fe, n = 4; Cr, n = 5). The chemical transformations reported here underline the versatile chemistry of phosphaalkenes and emphasize a relationship between carbonyl-functionalized phosphaalkenes and the well-investigated class of phosphorus ylides. X-ray structures of compounds 6b, 7b*, 10a, 11a and 12a are reported.
Comparison of Radix Angelicae pubescentis and Substitutes - Constituents and Inhibitory Effect on 5-lipoxygenase and Cyclooxygenase (1998)

AbstractVarious samples of Radix Angelicae pubescentis (Duhuo) and substitutes from the genera Angelica, Heracleum (Umbelliferae), and Aralia (Araliaceae) were analyzed for their constituents and inhibitory effect on cyclooxygenase (COX-1) and 5-lipoxygenase (5-LO). HPLC analysis showed that osthol, columbianedin, columbianetin acetate, and angelol-type coumarins are the principal constituents of the n -hexane and dichloromethane extracts of the roots of Angelica pubescens f. biserrata. The constituents of the substitutes from Angelica and Heracleum species were found to be mainly furanocoumarins and falcarindiol. No coumarins were detected in Aralia cordata. The presence of fatty acids (linoleic acid) could be confirmed by GC in Duhuo and the substitutes. All the species showed inhibitory effects on COX-1 and 5-LO. Linoleic acid turned out to be the most active constituent in the extract exerting COX-1 inhibition and also had strong inhibitory activity on 5-LO. Osthol was another major inhibitor of 5-LO in Radix Angelicae pubescentis, while in the substitutes falcarindiol was mainly responsible for the 5-LO inhibitory effect, except in Aralia cordata which also contained other polyacetylene derivatives.