gebhart/patrepeval huggingface dataset:
A cine <i>K</i>-edge subtraction angiographic system for animal studies (1989)

A cine k-edge subtraction imaging system has been constructed for less invasive transvenous angiography research. It utilizes synchrotron radiation and consists of a monochromator, an x-ray television camera with a high-speed shutter, and a data-acquisition and control unit. A 50×60-mm2 monochromatic x ray of about 400 mR/s intensity is produced. The x-ray photon energy is changed by using an oscillating cam mechanism which changes the angle of the crystal with respect to the beam. 16 ms is required to change the photon energy across the k edge for a change up to 800 eV. K-edge subtraction angiography of rats is performed following intravenous injection of materials containing iodine. Dual-energy images are acquired using 17-ms exposures with the same interval. Repetition of this sequence gives a series of k-edge subtraction images. Arteries of 0.3–0.4 mm diam are clearly seen.
Interleukin 6 Mediates Neuroinflammation and Motor Coordination Deficits After Mild Traumatic Brain Injury and Brief Hypoxia in Mice (2013)

Traumatic brain injury (TBI) is a leading cause of mortality and disability. Acute postinjury insults after TBI, such as hypoxia, contribute to secondary brain injury and worse clinical outcomes. The functional and neuroinflammatory effects of brief episodes of hypoxia experienced following TBI have not been evaluated. Our previous studies have identified interleukin 6 (IL-6) as a potential mediator of mild TBI-induced pathology. In the present study, we sought to determine the effects of brief hypoxia on mild TBI and whether IL-6 played a role in the neuroinflammatory and functional deficits after injury. A murine model of mild TBI was induced by a weight drop (500 g from 1.5 cm). After injury, mice were exposed to immediate hypoxia (FIO2 = 15.1%) or normoxia (FIO2 = 21%) for 30 min. Serum and brain samples were analyzed for inflammatory cytokines 24 h after TBI. Neuron-specific enolase was measured as a serum biomarker of brain injury. Evaluation of motor coordination was performed for 5 days after TBI using a rotarod device. In some animals, anti-IL-6 was administered following TBI and hypoxia to neutralize systemic IL-6. Mice undergoing TBI had significant increases in brain injury. Exposure to brief hypoxia after TBI resulted in a more than 5-fold increase in serum neuron-specific enolase. This increase was associated with increases in serum and brain cytokine expression, suggesting that brief hypoxia exacerbates systemic and brain inflammation. Neutralization of IL-6 suppressed postinjury neuroinflammation and neuronal injury. In addition, TBI and hypoxia induced significant motor coordination deficits that were completely abrogated by IL-6 blockade. Exposure to hypoxia after TBI induces neuroinflammation and brain injury. These changes can be mitigated by neutralization of systemic IL-6. Interleukin 6 blockade also corrected the TBI-induced deficit in motor coordination. These data suggest that systemic IL-6 modulates the degree of neuroinflammation and contributes to reduced motor coordination after mild TBI.
Enhanced Power Generation by Optical Solar Reflectors on Geostationary Spinners (1979)

A novel arrangement is proposed to enhance the power generating capabilities of a spin stabilized geostationary satellite (spinner). The unilluminated solar array area of the usual spinner (as sunlight falls on only one side) is illuminated by employing despun optical solar reflectors. The different mechanisms required for implementation of this arrangement are already space proven. The detailed study of this arrangement made by the authors reveals that the practical realization of this concept will enhance the power generating capability of the spinner and simultaneously reduce the weight (per unit power) and cost (per unit power) in such spinners.
On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency (2020)

Here we present the synthesis and evaluation of antibody-drug conjugates (ADCs), for which antibody and drug are non-covalently connected using complementary DNA linkers. These ADCs are composed of trastuzumab, an antibody targeting HER2 receptors overexpressed on breast cancer cells, and monomethyl auristatin E (MMAE) as a drug payload. In this new ADC format, trastuzumab conjugated to a 37-mer oligonucleotide (ON) was prepared and hybridized with its complementary ON modified at 5-end with MMAE (cON-MMAE) in order to obtain trastuzumab-DNA-MMAE. As an advantage, the cON-MMAE was completely soluble in water, which decreases overall hydrophobicity of toxic payload, an important characteristic of ADCs. The stability in the human plasma of these non-engineered ON-based linkers was investigated and showed a satisfactory half-life of 5.8 days for the trastuzumab-DNA format. Finally, we investigated the in vitro cytotoxicity profile of both the DNA-linked ADC and the ON-drug conjugates and compared them with classical covalently linked ADC. Interestingly, we found increased cytotoxicity for MMAE compared to cON-MMAE and an EC50 in the nanomolar range for trastuzumab-DNA-MMAE on HER2-positive cells. Although this proved to be less potent than classically linked ADC with picomolar range EC50, the difference in cytotoxicity between naked payload and conjugated payload was significant when an ON linker was used. We also observed an interesting increase in cytotoxicity of trastuzumab-DNA-MMAE on HER2-negative cells. This was attributed to enhanced non-specific interaction triggered by the DNA strand as it could be confirmed using ligand tracer assay.
Nd:LiNbO/sub 3/ microchip laser with 20 GHz subcarrier (2002)

This paper reports on the development of a 20 GHz mode-locked Nd:LiNbO/sub 3/ microchip laser operating at 1.084 /spl mu/m with an output power greater than 35 mW (CW). With this configuration, a single device simultaneously generates the optical carrier and the microwave subcarrier. A modulation index of 96% was obtained for a driving microwave power of 12.6 dBm at 20 GHz. An information signal up to 8 GHz was also superimposed on the 20 GHz subcarrier using an external modulator.
VEGF siRNA delivered by polycation liposome-encapsulated calcium phosphate nanoparticles for tumor angiogenesis inhibition in breast cancer (2017)

Angiogenesis plays an important role in tumor development and metastasis, and many cancer cells upregulate VEGF expression to promote angiogenesis. Silencing VEGF expression by RNA interference is expected to be a promising strategy to suppress the tumor growth. However, low transfection efficiency and instability are the main barriers for small interfering RNA (siRNA) delivery. In this study, we developed polycation liposome-encapsulated calcium phosphate nanoparticles (PLCP) for siRNA delivery in vivo. VEGF expression silencing effect in MCF-7 cells was investigated by real-time quantitative polymerase chain reaction and Western blot assay. VEGF siRNA mediated by PLCP can reduce 60%-80% VEGF expression in vitro, which was significantly higher than that mediated by Lipofectamine 2000. Furthermore, significant tumor growth and angiogenesis inhibition were observed in MCF-7 xenografts mice when treated with PLCP/VEGF siRNA or combined with doxorubicin. In conclusion, the combination of silencing VEGF expression and chemotherapeutics would be a potential treatment for cancer therapy.
Assessing Text Readability Using Cognitively Based Indices (2008)

Many programs designed to compute the readability of texts are narrowly based on surface‐level linguistic features and take too little account of the processes which a reader brings to the text. This study is an exploratory examination of the use of Coh‐Metrix, a computational tool that measures cohesion and text difficulty at various levels of language, discourse, and conceptual analysis. It is suggested that Coh‐Metrix provides an improved means of measuring English text readability for second language (L2) readers, not least because three Coh‐Metrix variables, one employing lexical coreferentiality, one measuring syntactic sentence similarity, and one measuring word frequency, have correlates in psycholinguistic theory. The current study draws on the validation exercise conducted by Greenfield (1999) with Japanese EFL students, which partially replicated Bormuth's (1971) study with American students. It finds that Coh‐Metrix, with its inclusion of the three variables, yields a more accurate prediction of reading difficulty than traditional readability measures. The finding indicates that linguistic variables related to cognitive reading processes contribute significantly to better readability prediction than the surface variables used in traditional formulas. Additionally, because these Coh‐Metrix variables better reflect psycholinguistic factors in reading comprehension such as decoding, syntactic parsing, and meaning construction, the formula appears to be more soundly based and avoids criticism on the grounds of construct validity.
Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History (2012)

The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ~2.3 million single-nucleotide polymorphisms in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but population structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response; potential adaptive introgression of protection from ultraviolet light; and selection predating modern human diversification, involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history.
Two Forms of NF-kB1 (p105/p50) in Murine Macrophages: Differential Regulation by Lipopolysaccharide, Interleukin-2, and Interferon-γ (1997)

In macrophages, nuclear factor kappa B (NF-kappa B) has been shown to transactivate the promoters of many cytokines, including tumor necrosis factor-alpha (TNF-alpha). We have used the -510 kappa B binding site from the murine TNF-alpha promoter to assay the induction of NF-kappa B in murine macrophages by various stimuli. A basal level of NF-kappa B activity in murine macrophages was detectable, and this activity was enhanced by treatment of these cells with lipopolysaccharide (LPS) or interleukin-2 (IL-2). Interferon-gamma (IFN-gamma), an important regulator of macrophage gene expression, significantly enhanced NF-kappa B activity and altered the apparent molecular weight of the NF-kappa B1-like proteins in LPS-stimulated and IL-2-stimulated murine macrophages. The NRD (NF-kappa B/Rel/Dorsal) complexes induced by LPS and IFN-gamma were further characterized by addition of antisera to electrophoretic mobility shift assay (EMSA) reaction mixtures. NF-kappa B1/p50 was a component of all complexes, whereas RelA/p65 was present in the IFN-gamma/LPS-stimulated activity. IFN-gamma priming or treatment with LPS for 19 h resulted in an upregulation of the larger species of NF-kappa B1/p50. In addition, regulation of the two pools of NF-kappa B1/p50 by IFN-gamma was confirmed by Western immunoblot analysis of cytosolic and nuclear extracts. This is the first demonstration of the presence of two pools of NF-kappa B1/p50 differentially regulated in response to cytokine activation of macrophages.
Involvement of DNA Topoisomerase IIβ in Neuronal Differentiation (2001)

Two isoforms of DNA topoisomerase II (topo II) have been identified in mammalian cells. While topo IIalpha is essential for chromosome segregation in mitotic cells, in vivo function of topo IIbeta remains to be clarified. Here we demonstrate that the nucleoplasmic topo IIbeta, highly expressed in differentiating cerebellar neurons, is the catalytically competent entity operating directly on chromatin DNA in vivo. When the cells reached terminal differentiation, this in vivo activity decreased to a negligible level with concomitant loss of the nucleoplasmic enzyme. Effects of topo II-specific inhibitors were analyzed in a primary culture of cerebellar granule neurons that can mimic the in vivo situation. Only the beta isoform was expressed in granule cells differentiating in vitro. ICRF-193, a catalytic topo II inhibitor, suppressed the transcriptional induction of amphiphysin I which is essential for mature neuronal activity. The effect decreased significantly as the cells differentiate. Expression profiling with a cDNA macroarray showed that 18% of detectable transcripts were up-regulated during the differentiation and one-third of them were susceptible to ICRF-193. The results suggest that topo IIbeta is involved in an early stage of granule cell differentiation by potentiating inducible neuronal genes to become transcribable probably through alterations in higher order chromatin structure.
Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes (1997)

In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.
Anesthetic and ethanol effects on spontaneously opening glycine receptor channels (2002)

Strychnine-sensitive glycine receptors mediate inhibitory neurotransmission occurring in the brain stem and spinal cord. Alcohols, volatile anesthetics and inhaled drugs of abuse are positive allosteric modulators of glycine receptor function, normally enhancing function only in the presence of glycine. A complication in studying allosteric actions on ligand-gated ion channels is in the dissection of their effects on neurotransmitter binding from their effects on channel opening. Mutation of an aspartate residue at position 97 to arginine in the glycine receptor alpha1 subunit simulated the effects of glycine binding, producing receptors that exhibited tonic channel opening in the absence of neurotransmitter; i.e. these receptors demonstrated a dissociation of channel opening from neurotransmitter binding. In these receptors, ethanol, enflurane, chloroform, halothane, 1,1,1-trichloroethane and toluene elicited inward currents in the absence of glycine. We previously identified mutations on ligand-gated ion channels that eliminate ethanol, anesthetic and inhalant actions (such as S267I on alpha1 glycine receptors). The double mutant (D97R and S267I) receptors were both constitutively active and resistant to the enhancing effects of ethanol and enflurane. These data demonstrate that ethanol and volatile anesthetics can affect glycine receptor channel opening independently of their effects on enhancing neurotransmitter binding.
A universal technique for accelerating simulation of scan test patterns (2002)

Scan test patterns are typically generated by ATPG tools which use a zero delay simulation model. These scan test patterns have to be verified using a golden simulator which is approved by the chip foundry with full timing before the patterns are accepted for manufacturing test. This can be very time consuming for many designs because of the size of the test data and the large number of test cycles which have to be simulated. A universal technique for accelerating scan test pattern simulation which can be used for any simulator with any scan cell type from any foundry is proposed. The extensions to test data languages to support universal acceleration of scan pattern simulation are also proposed. Some experiment results are also provided.
Key Mutations Alter the Cytochrome P450 BM3 Conformational Landscape and Remove Inherent Substrate Bias (2013)

Cytochrome P450 monooxygenases (P450s) have enormous potential in the production of oxychemicals, due to their unparalleled regio- and stereoselectivity. The Bacillus megaterium P450 BM3 enzyme is a key model system, with several mutants (many distant from the active site) reported to alter substrate selectivity. It has the highest reported monooxygenase activity of the P450 enzymes, and this catalytic efficiency has inspired protein engineering to enable its exploitation for biotechnologically relevant oxidations with structurally diverse substrates. However, a structural rationale is lacking to explain how these mutations have such effects in the absence of direct change to the active site architecture. Here, we provide the first crystal structures of BM3 mutants in complex with a human drug substrate, the proton pump inhibitor omeprazole. Supported by solution data, these structures reveal how mutation alters the conformational landscape and decreases the free energy barrier for transition to the substrate-bound state. Our data point to the importance of such "gatekeeper" mutations in enabling major changes in substrate recognition. We further demonstrate that these mutants catalyze the same 5-hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 enzyme.
Some Like it Hoax: Automated Fake News Detection in Social Networks (2017)

In recent years, the reliability of information on the Internet has emerged as a crucial issue of modern society. Social network sites (SNSs) have revolutionized the way in which information is spread by allowing users to freely share content. As a consequence, SNSs are also increasingly used as vectors for the diffusion of misinformation and hoaxes. The amount of disseminated information and the rapidity of its diffusion make it practically impossible to assess reliability in a timely manner, highlighting the need for automatic hoax detection systems. As a contribution towards this objective, we show that Facebook posts can be classified with high accuracy as hoaxes or non-hoaxes on the basis of the users who "liked" them. We present two classification techniques, one based on logistic regression, the other on a novel adaptation of boolean crowdsourcing algorithms. On a dataset consisting of 15,500 Facebook posts and 909,236 users, we obtain classification accuracies exceeding 99% even when the training set contains less than 1% of the posts. We further show that our techniques are robust: they work even when we restrict our attention to the users who like both hoax and non-hoax posts. These results suggest that mapping the diffusion pattern of information can be a useful component of automatic hoax detection systems.
Effect of T-T base mismatches on three-arm DNA junctions (1993)

In contrast to four-arm immobile DNA junctions, three-arm DNA junctions have unique structural and dynamic properties consistent with lack of a single dominant conformation. The effect of T-T base mismatches at the branch in a three-arm model junction has been investigated using a combination of electrophoretic mobility measurements, chemical footprinting experiments, and thermodynamic studies. The results indicate that three-arm junctions are only slightly destabilized by a mismatch flanking the branch, relative to four-arm junctions. The effect of a mismatch varies with the sequence and position of the site of the mismatch. Since a three-arm junction with two mismatches flanking the branch is as stable as two junctions each with a single mismatch, the stability of three-arm junctions is not determined by stacking interactions at the branch in a simple way. The properties of three-arm junctions with one or two mismatches are consistent with a picture in which the conformation is the result of several substrates in which base pairs flanking the branch are transiently open, allowing bases to interact with the remaining duplexes.
Alcaligenes eutrophus hydrogenase genes (Hox) (1984)

Mutants of Alcaligenes eutrophus H16 lacking catalytically active soluble hydrogenase (Hos-) grew very slowly lithoautotrophically with hydrogen. Mutants devoid of particulate hydrogenase activity (Hop-) were not affected in growth with hydrogen. The use of Hos- and Hop- mutants as donors of hydrogen-oxidizing ability in crosses with plasmid-free recipients impaired in both hydrogenases (Hox-) resulted in transconjugants which had inherited the plasmid and the phenotype of the donor. This indicates that the structural genes which code for the hydrogenases reside on plasmid pHG1. The Hox function of one class of Hox- mutants could not be restored by conjugation. These mutants exhibited a pleiotropic phenotype since they were unable to grow with hydrogen and also failed to grow heterotrophically with nitrate (Hox- Nit-). Nitrate was scarcely utilized as electron acceptor or as nitrogen source. Hox- Nit- mutants did not act as recipients but could act as donors of the Hox character. Transconjugants derived from those crosses were Hox+ Nit+, indicating that the mutation which leads to the Hox- Nit- phenotype maps on the chromosome. Apparently, the product of a chromosomal gene is involved in the expression of plasmid-encoded Hox genes. We observed that the elimination of plasmid pHG1 coincided with the occurrence of multiple resistances to various antibiotics. Since Hox+ transconjugate retained the antibiotic-resistant phenotype, we conclude that this property is not directly plasmid associated.
Polarization recovery in optical polarization shift-keying systems (1997)

For the first time, a solution to the problem of recovering and tracking the signal constellation at the receiver side for binary and octonary digital optical transmission systems employing the modulation of polarization (POLSK) is proposed and analyzed. The effect of two recovery algorithms on the system performance is evaluated in terms of power penalty induced at P(e)=10/sup -9/, acquisition and tracking speed, and hardware complexity. The results show that very small penalties are obtainable in practical situations by properly designing the recovery algorithms.
Interaction of hsp70 with unfolded proteins: effects of temperature and nucleotides on the kinetics of binding. (1991)

Circular dichroism and HPLC gel filtration were used to show that cytosolic hsp70 is thermally stable but undergoes a conformational transition (midpoint, 43 degrees C; 57 degrees C in the presence of ATP or ADP) leading to oligomerization. hsp70 binds to unfolded, but not to folded, proteins in a temperature-dependent manner; complex formation is significant only at physiologically relevant temperatures. hsp70 binds ADP more tightly than ATP to form a binary complex, which binds to the unfolded protein more rapidly than free hsp70. ADP also inhibits the ATP-induced dissociation of the hsp70-protein complex. A regulatory role for the hsp70-nucleotide binary complexes is proposed.