gebhart/patrepeval huggingface dataset:
Multifunctional, Ultra‐Flyweight, Synergistically Assembled Carbon Aerogels (2013)

All carbon aerogels (up to 1000 cm(3)) with ultralow density (down to 0.16 mg cm(-3)) and temperature-invariant (-190-900 °C) super-elasticity are fabricated by facile assembling of commercial carbon nanotubes (CNTs) and chemically-converted giant graphene sheets, on the basis of the synergistic effect between elastic CNTs ribs and giant graphene cell walls.
A Polymorphism in the Protease-Like Domain of Apolipoprotein(a) Is Associated With Severe Coronary Artery Disease (2007)

The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.
Relaxed Polar Codes (2017)

Polar codes are the latest breakthrough in coding theory, as they are the first family of codes with explicit construction that provably achieve the symmetric capacity of binary-input discrete memoryless channels. Polar encoding and successive cancellation decoding have the complexities of N log N , for code length N. Although, the complexity bound of N log N is asymptotically favorable, we report in this work methods to further reduce the encoding and decoding complexities of polar coding. The crux is to relax the polarization of certain bit-channels without performance degradation. We consider schemes for relaxing the polarization of both very good and very bad bit-channels, in the process of channel polarization. Relaxed polar codes are proved to preserve the capacity achieving property of polar codes. Analytical bounds on the asymptotic and finite-length complexity reduction attainable by relaxed polarization are derived. For binary erasure channels, we show that the computation complexity can be reduced by a factor of six, while preserving the rate and error performance. We also show that relaxed polar codes can be decoded with significantly reduced latency. For additive white Gaussian noise channels with medium code lengths, we show that relaxed polar codes can have lower error probabilities than conventional polar codes, while having reduced encoding and decoding computation complexities.
A digital filterbank hearing aid-design, implementation and evaluation (1991)

A digital filterbank that can be used in a hearing aid is proposed. Complementary interpolated linear phase impulse-response filters are used to minimize the number of multiplications per sample. The filterbank has eight bands, each with sidelobes of about 40 dB. It can be realized with a total of 27 multiplications. If a multiplication with 0.5 is implemented as a shift, then the total will be 19. The hearing aid was implemented on a general-purpose digital signal processor for real-time evaluations. A portable processor system based on Texas TMS320E25 was constructed for testing under real-world conditions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of naloxone on the analgesic activity of methadone in a 1:10 oral combination; Time and cost of flirting with the null hypothesis in tests of equivalence (1974)

The effect of oral naloxone on the analgesic efficacy and side effects of oral methadone was examined in one hundred patients with postoperative pain. Doses of methadone of 5 mg and 15 mg were compared with combinations containing the same amount of methadone plus one‐tenth as much naloxone. No consistent or statistically significant effect of naloxone was detected on analgesia, sedation, or side effects. However, the statistical power of this study was low, its chance of detecting a real difference of 20% being at best 10%. To increase this chance to 95%, nearly 4,500 subiects would be needed. This analysis has implications for the general problem of testing drug equivalence.
Deep bilateral learning for real-time image enhancement (2017)

Performance is a critical challenge in mobile image processing. Given a reference imaging pipeline, or even human-adjusted pairs of images, we seek to reproduce the enhancements and enable real-time evaluation. For this, we introduce a new neural network architecture inspired by bilateral grid processing and local affine color transforms. Using pairs of input/output images, we train a convolutional neural network to predict the coefficients of a locally-affine model in bilateral space. Our architecture learns to make local, global, and content-dependent decisions to approximate the desired image transformation. At runtime, the neural network consumes a low-resolution version of the input image, produces a set of affine transformations in bilateral space, upsamples those transformations in an edge-preserving fashion using a new slicing node, and then applies those upsampled transformations to the full-resolution image. Our algorithm processes high-resolution images on a smartphone in milliseconds, provides a real-time viewfinder at 1080p resolution, and matches the quality of state-of-the-art approximation techniques on a large class of image operators. Unlike previous work, our model is trained off-line from data and therefore does not require access to the original operator at runtime. This allows our model to learn complex, scene-dependent transformations for which no reference implementation is available, such as the photographic edits of a human retoucher.
MTH1 Substrate Recognition—An Example of Specific Promiscuity (2016)

MTH1 (NUDT1) is an oncologic target involved in the prevention of DNA damage. We investigate the way MTH1 recognises its substrates and present substrate-bound structures of MTH1 for 8-oxo-dGTP and 8-oxo-rATP as examples of novel strong and weak binding substrate motifs. Investigation of a small set of purine-like fragments using 2D NMR resulted in identification of a fragment with weak potency. The protein-ligand X-Ray structure of this fragment provides insight into the role of water molecules in substrate selectivity. Wider fragment screening by NMR resulted in three new protein structures exhibiting alternative binding configurations to the key Asp-Asp recognition element of the protein. These inhibitor binding modes demonstrate that MTH1 employs an intricate yet promiscuous mechanism of substrate anchoring through its Asp-Asp pharmacophore. The structures suggest that water-mediated interactions convey selectivity towards oxidized substrates over their non-oxidised counterparts, in particular by stabilization of a water molecule in a hydrophobic environment through hydrogen bonding. These findings may be useful in the design of inhibitors of MTH1.
Form birefringence of SiO_2/Ta_2O_5 periodic multilayers (1985)

Dielectric multilayers consisting of alternating layers of SiO2 and Ta2O5 with a period as short as 42 nm are fabricated by sputtering. Their birefringent properties are analyzed by polarization-dependent etalon characteristics. Principal refractive indices and birefringence are controlled by the layer thickness ratio and are in good agreement with the theory. An extremely large birefringence of Δn = 0.13, close to the theoretical maximum, is achieved. A relatively short period compared to the wavelength of light contributes to low dispersion. These multilayers are potentially useful as artificial birefringent media in integrated optics.
Developing FGFR4 Inhibitors As Potential Anti-Cancer Agents Via In Silico Design, Supported by In Vitro and Cell-Based Testing (2013)

Fibroblast growth factor receptor-4 (FGFR4) is a tyrosine kinase with a range of important physiological functions. However, it is also frequently mutated in various cancers and is now generating significant interest as a potential therapeutic target. Unfortunately, biochemical characterization of its role in disease, and further evaluation as a drug target is hampered by lack of a specific inhibitor. We aimed to discover new inhibitors for FGFR4 ab initio using a strategy combining in silico, in vitro and cell-based assays. We used the homologous FGFR1 to calculate docking scores of a chemically-diverse library of approximately 2000 potential kinase inhibitors. Nineteen potential inhibitors and ten randomly- selected negative controls were taken forward for in vitro FGFR4 kinase assays. All compounds with good docking scores significantly inhibited FGFR4 kinase activity, some with sub-micromolar (most potent being V4-015 with an IC(50) of 0.04 μM). Four of these compounds also demonstrated substantial activity in cellular assays using the FGFR4- overexpressing breast carcinoma cell line, MDA-MB453. Through immunoblot assays, these compounds were shown to block the phosphorylation of the FGFR4 adaptor protein, FGFR substrate protein-2α (FRS2α). The most potent compound to date, V4-015, suppressed proliferation of MDA-MB453 cells at sub-micromolar concentrations, activated the pro-apoptotic caspases 3/7 and inhibited cellular migration. While achieving complete selectivity of this compound for FGFR4 will require further lead optimization, this study has successfully identified new chemical scaffolds with unprecedented FGFR4 inhibition capacities that will support mechanism of action studies and future anti-cancer drug design.
Identification of a Lipid Peroxidation Product as a Potential Trigger of the p53 Pathway (2005)

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 can trigger apoptosis in many cell types, including neurons. We found that this nuclear protein was significantly phosphorylated when human neuroblastoma SH-SY5Y cells were exposed to in vitro oxidized polyunsaturated fatty acids. To identify an oxidized lipid that induces p53 phosphorylation, we conducted a screening of lipid peroxidation products in human neuroblastoma SH-SY5Y cells and identified 4-oxo-2-nonenal (ONE), a recently identified aldehyde originating from the peroxidation of omega6 polyunsaturated fatty acids, as a potential inducer of the p53 phosphorylation. We also found that ONE induced the phosphorylation of ataxia telangiectasia-mutated, which plays an essential role in transmitting DNA damage signals by the phosphorylation of p53. In addition, exposure of the cells to ONE resulted in an accumulation of ubiquitinated proteins and in a significant inhibition of proteasome activities, suggesting that ONE acted on the ubiquitin-proteasome pathway, a regulatory mechanism of p53 turnover. In addition, the observation that the ONE-induced p53 response was associated with the induction of apoptosis suggested that ONE activated the p53-dependent apoptosis mechanism via activation of the p53 signaling pathway and down-regulation of the p53 turnover. Finally, we observed that the ONE-2'-deoxyguanosine adduct, 7-(2-oxo-heptyl)-substituted 1,N(2)-etheno-2'-deoxyguanosine, was accumulated in the spinal cord motor neurons of patients with sporadic amyotrophic lateral sclerosis. These data may suggest the potential critical role for ONE in the induction of a neuronal apoptosis program during oxidative processes.
Storing Certificates in the Domain Name System (DNS) (1999)

and their authenticity demonstrated by certificates. A CERT resource record (RR) is defined so that such certificates and related certificate revocation lists can be stored in
Modular assembly of proteins on nanoparticles (2018)

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold-sulfur bonds (Au-S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond.
149. Dithiols. Part XII. The alkaline hydrolysis of acetylated hydroxy-thiols: a new reaction for the formation of cyclic sulphides (1952)

L. W. C. Miles and L. N. Owen, J. Chem. Soc., 1952, 817 DOI: 10.1039/JR9520000817
Structural basis of SARS-CoV-2 spike protein induced by ACE2 (2020)

Abstract Motivation The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. Results Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.
Operational Characteristics of a High Purity Germanium Photon Spectrometer Cooled by a Closed-Cycle Cryogenic Refrigerator (1973)

Experience with several (commercially available) miniature closed-cycle refrigerators used to cool a high purity germanium photon detector is reported. While maintaining good resolution, closed-cycle cooling has resulted in a versatile photon spectrometer with long storage times, variable length run times, and freedom from the need for a liquid nitrogen supply. The demonstrated resolution and background levels indicate the concept to be especially useful for field measurements in problems of general radioisotope detection and in some applications of on-line x-ray fluorescence.
Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. (1996)

Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (.O2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and .O2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no .O2- was seen. With cells in L-Arg-free medium, we observed .O2- formation that increased as the cytosolic L-Arg levels decreased, while NO generation declined. .O2- formation was virtually abolished by the specific NOS blocker, N-nitro-L-arginine methyl ester (L-NAME). Nitrotyrosine, a specific nitration product of peroxynitrite, accumulated in L-Arg-depleted cells but not in control cells. Activation by A23187 was cytotoxic to L-Arg-depleted, but not to control cells, with marked lactate dehydrogenase release. The cytotoxicity was largely prevented by either superoxide dismutase or L-NAME. Thus, with reduced L-Arg availability NOS elicits cytotoxicity by generating .O2- and NO that interact to form the potent oxidant peroxynitrite. Regulating arginine levels may provide a therapeutic approach to disorders involving .O2-/NO-mediated cellular injury.
Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy (2012)

Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-κB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset-specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF-induced signaling provide a molecular explanation for GM-CSF-dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF-differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF-dependent DC-based strategies to regulate immunity.
Electro-optic Charon polymeric microring modulators (2008)

We propose and demonstrate a new type of electro-optic polymeric microring resonators, where the shape of the transmission spectrum is controlled by losses and phase shifts induced at the asymmetric directional coupler between the cavity and the bus waveguide. The theoretical analysis of such Charon microresonators shows, depending on the coupler design, three different transmission characteristics: normal Lorentzian dips, asymmetric Fano resonances, and Lorentzian peaks. The combination of the active azo-stilbene based polyimide SANDM2 surrounded by the hybrid polymer Ormocomp allowed the first experimental demonstration of electro-optic modulation in Charon microresonators. The low-loss modulators (down to 0.6 dB per round trip), with a radius of 50 microm, were produced by micro-embossing and exhibit either highly asymmetric and steep Fano resonances with large 43-GHz modulation bandwidth or strong resonances with 11-dB extinction ratio. We show that Charon microresonators can lead to 1-V half wave voltage all-polymer micrometer-scale devices with larger tolerances to coupler fabrication limitations and wider modulation bandwidths than classical ring resonators.
Rhetorical Relations, Action and Intentionality in Conversation (1993)

This paper contains all investigation of the relationship between rhetorical relations and intentions. Rhetorical relations are claimed to I)e actions, and thus the proper objects of intentions, although some relations may occur Im independent of intentions. Explicit identification of particular relations is shown to he not always necessary when this intn&amp;apos;mation can be cal)tnred in other ways, nevertheless, relations are o[&amp;apos;tela useful both in planning and recognition.
Is Mammography Adequate for Screening Women with Inherited BRCA Mutations and Low Breast Density? (2008)

It is necessary to add MRI to mammography for screening women with BRCA mutations even if their breast density is low.
Time-frequency distributions of subdural EEG at epileptic seizure onset (2002)

A high-frequency signal occurring at epileptic seizure onset is investigated using time-frequency methods. This signal is extracted from the background activity by repeated forward and inverse Gabor transformations. The generation sites of this signal are determined by displaying the average signal power values with a 3-D anatomical image obtained from MRI scans.
Induction of Skin Tanning by Subcutaneous Administration of a Potent Synthetic Melanotropin (1991)

-A significant parabolic curve of skin darkening activity was noted in subjects with skin type I or II (P less than .001) and with skin type III or IV (P much less than .001) who were given NDP. No darkening occurred in the subjects who were given a placebo. Peak changes were seen 1 to 3 weeks after therapy was completed. CONCLUSION--Human skin darkens as a response to a synthetic melanotropin given by subcutaneous injection. Skin tanning appears possible without potentially harmful exposure to ultraviolet radiation.
Masking by Tones vs Noise Bands (1959)

In a previous study it was proposed that tonal masking arose mainly from the cochlear activity pattern of the masking tone, modified by the formation of beats between the signal and masking tones. The present study casts further light on these proposed mechanisms by comparing the masking effects of pure tones of 500, 1000, 2000, and 4000 cps at 60 and 80 db SL with 13 octave bands of noise of equal intensities and centered at the same frequencies. The results show that the noise bands produce about the same amount of extended masking despite the absence of any possible aural harmonic distortion, but greater direct masking due to the elimination of beats. Furthermore, the noise-masking curves join the tone-masking curves at the second peak in the latter, providing strong additional support for the proposed mechanisms of auditory masking.
A Better Platinum-Based Anticancer Drug Yet to Come? (2010)

In attempts to overcome the drawbacks of cisplatin - severe toxicity, drug resistance and poor oral bioavailability - the development of platinum-based drugs has progressed from carboplatin and oxaliplatin to the newest generation of drugs, such as satraplatin, picoplatin and the multinuclear platinum complex BBR3464 (triplatin). Despite encouraging preclinical in vitro and in vivo results, outcomes of clinical trials of these coordination complexes remained below expectations. Biased rationale underlying the drug design along with in vitro and in vivo preclinical tests with inadequate predictive power seem to have eventually resulted in the selection of drug candidates of limited clinical activity. The nature of the active species generated in vivo, uptake, efflux, intracellular trafficking and detailed mechanisms involved in chemoresistance of platinum drugs in vivo are topics that need further investigation to provide clues for the rational formulation of new drugs. Insufficient diffusion in tumor tissues is likely to constitute an important limiting step in the treatment of solid tumors with platinum compounds. Preclinical assays with improved predictive power for the clinical outcome of the compounds should be based on more representative tumor models, such as resistant primary cancer cell lines, spheroids and orthotopic xenograft models, respectively. Finally, use of new pharmaceutical formulations and bifunctional complexes, as well as their selection by decisive preclinical tests, are expected to result in the generation of platinum-based anticancer drugs with the potential to achieve clinical activity even in multidrug-resistant tumors.