gebhart/patrepeval huggingface dataset:
A Key Role for Old Yellow Enzyme in the Metabolism of Drugs by Trypanosoma cruzi (2002)

Trypanosoma cruzi is the etiological agent of Chagas' disease. So far, first choice anti-chagasic drugs in use have been shown to have undesirable side effects in addition to the emergence of parasite resistance and the lack of prospect for vaccine against T. cruzi infection. Thus, the isolation and characterization of molecules essential in parasite metabolism of the anti-chagasic drugs are fundamental for the development of new strategies for rational drug design and/or the improvement of the current chemotherapy. While searching for a prostaglandin (PG) F(2alpha) synthase homologue, we have identified a novel "old yellow enzyme" from T. cruzi (TcOYE), cloned its cDNA, and overexpressed the recombinant enzyme. Here, we show that TcOYE reduced 9,11-endoperoxide PGH(2) to PGF(2alpha) as well as a variety of trypanocidal drugs. By electron spin resonance experiments, we found that TcOYE specifically catalyzed one-electron reduction of menadione and beta-lapachone to semiquinone-free radicals with concomitant generation of superoxide radical anions, while catalyzing solely the two-electron reduction of nifurtimox and 4-nitroquinoline-N-oxide drugs without free radical production. Interestingly, immunoprecipitation experiments revealed that anti-TcOYE polyclonal antibody abolished major reductase activities of the lysates toward these drugs, identifying TcOYE as a key drug-metabolizing enzyme by which quinone drugs have their mechanism of action.
A fullerene alloy based photovoltaic blend with a glass transition temperature above 200 °C (2017)

Solar cells based on a glass-forming ternary blend of C<sub>60</sub>, C<sub>70</sub> and PTB7 display a high power conversion efficiency above 5% up to an annealing temperature of 180 °C. The excellent thermal stability correlates with a high glass transition temperature of 224 °C.
Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation (2017)

Somatic hypermutation (SHM) plays a critical role in the maturation of antibodies, optimizing recognition initiated by recombination of V(D)J genes. Previous studies have shown that the propensity to mutate is modulated by the context of surrounding nucleotides and that SHM machinery generates biased substitutions. To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional human antibody repertoires and developed mGSSP (method for gene-specific substitution profile), a method to construct amino acid substitution profiles from next-generation sequencing-determined B cell transcripts. We demonstrated that these gene-specific substitution profiles (GSSPs) are unique to each V gene and highly consistent between donors. We also showed that the GSSPs constructed from functional antibody repertoires are highly similar to those constructed from antibody sequences amplified from non-productively rearranged passenger alleles, which do not undergo functional selection. This suggests the types and frequencies, or mutational space, of a majority of amino acid changes sampled by the SHM machinery to be well captured by GSSPs. We further observed the rates of mutational exchange between some amino acids to be both asymmetric and context dependent and to correlate weakly with their biochemical properties. GSSPs provide an improved, position-dependent alternative to standard substitution matrices, and can be utilized to developing software for accurately modeling the SHM process. GSSPs can also be used for predicting the amino acid mutational space available for antigen-driven selection and for understanding factors modulating the maturation pathways of antibody lineages in a gene-specific context. The mGSSP method can be used to build, compare, and plot GSSPs; we report the GSSPs constructed for 69 common human V genes (DOI: 10.6084/m9.figshare.3511083) and provide high-resolution logo plots for each (DOI: 10.6084/m9.figshare.3511085).
Immunogenicity of the Envelope Surface Unit of Human Endogenous Retrovirus K18 in Mice (2022)

The triggers for the development of multiple sclerosis (MS) have not been fully understood to date. One hypothesis proposes a viral etiology. Interestingly, viral proteins from human endogenous retroviruses (HERVs) may play a role in the pathogenesis of MS. Allelic variants of the HERV-K18 env gene represent a genetic risk factor for MS, and the envelope protein is considered to be an Epstein-Barr virus-trans-activated superantigen. To further specify a possible role for HERV-K18 in MS, the present study examined the immunogenicity of the purified surface unit (SU). HERV-K18(SU) induced envelope-specific plasma IgG in immunized mice and triggered proliferation of T cells isolated from these mice. It did not trigger phenotypic changes in a mouse model of experimental autoimmune encephalomyelitis. Further studies are needed to investigate the underlying mechanisms of HERV-K18 interaction with immune system regulators in more detail.
Modulation Transfer Functions of Low Power Telescopes (1988)

The modulation transfer functions (MTF's) of 131 low power Galilean and Pechan roof prism Keplerian telescopes comprising 20 models from 7 vendors were measured. MTF results are compared according to model, by type (Galilean or Keplerian), and magnification. Measurements were made on-axis and at the +/- 0.7 field angles. In addition to measuring tangential and radial MTF's some devices were tested with target grating azimuths of 45 degrees and 135 degrees. We also measured the effect of 3 and 6.4 mm exit pupil diameters on the MTF, and compared a color-corrected with a non-color-corrected design in monochromatic and white light. Galilean telescopes exhibited superior MTF's compared to Keplerian designs. The MTF's of Galilean telescopes tested on-axis with vertical and horizontal gratings were equivalent, as expected of rotationally symmetrical devices. However, similarly tested Keplerian telescopes exhibited significantly higher MTF's with vertical gratings. Tests at +/- 0.7 field angles showed that the tangential MTF's of Galilean telescopes were consistently poorer than radial MTF's, but the opposite was true for Keplerian telescopes. The comparatively poorer results obtained with the Keplerian telescopes are due to image doubling and deviation errors of the roof prisms that are dependent on the azimuthal orientation of the prism roof edge. Failure to adopt and maintain the same orientation of hand-held prism monoculars may result in experiencing a variable sharpness of image each time that they are used. Prism deviations of binocular devices must be controlled to avoid vertical disparities.
Replicability of 1H MR spectroscopic imaging in mild traumatic brain injury (2023)

1 H-MRS has the potential to provide biomarkers for mild traumatic brain injury (mTBI), a diagnosis in which damage is often imaging-occult, but a lack of replicability and reproducibility studies hampers clinical translation. Here, we tested the replicability of previous MRSI results in mTBI with a different patient cohort. Five out of seven hypotheses were consistent with previous work, with key findings of globally diffuse white matter (WM) injury and limited gray matter injury. However, we report differences in choline and creatine, not N -acetyl-aspartate. Correlations were found between metabolite levels in WM and both symptomatology and neuropsychological testing.
On Evaluating the Generalization of LSTM Models in Formal Languages (2018)

Recurrent Neural Networks (RNNs) are theoretically Turing-complete and established themselves as a dominant model for language processing. Yet, there still remains an uncertainty regarding their language learning capabilities. In this paper, we empirically evaluate the inductive learning capabilities of Long Short-Term Memory networks, a popular extension of simple RNNs, to learn simple formal languages, in particular $a^nb^n$, $a^nb^nc^n$, and $a^nb^nc^nd^n$. We investigate the influence of various aspects of learning, such as training data regimes and model capacity, on the generalization to unobserved samples. We find striking differences in model performances under different training settings and highlight the need for careful analysis and assessment when making claims about the learning capabilities of neural network models.
Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV). (1987)

A T-cell tropic lentivirus of macaques the simian immunodeficiency virus (SIV), has morphologic, growth, and antigenic properties that indicate that it is related to the human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Six juvenile macaques developed persistent lymphadenopathy (greater than 3 months in duration) after inoculation with SIV. The histologic appearance of the lymph nodes was characterized by marked follicular hyperplasia with abundant proliferative B cells infiltrating into the paracortex. The number of T8-positive lymphocytes equaled or exceeded the number of T4-positive lymphocytes in the paracortex. These findings, in association with immunologic abnormalities and a previously observed fatal immunodeficiency syndrome in SIV-infected macaques, provide further evidence of the importance of SIV-induced disease in macaques as a model for the study of AIDS.
Asymmetric Synthesis of Quaternary α- and β-Amino Acids and β-Lactams via Proline-Catalyzed Mannich Reactions with Branched Aldehyde Donors (2004)

[reaction: see text] L-Proline-catalyzed direct asymmetric Mannich reactions of N-PMP protected alpha-imino ethyl glyoxylate with various alpha,alpha-disubstituted aldehydes affords quaternary beta-formyl alpha-amino acid derivatives with excellent yields and enantioselectivities. The Mannich products are further converted to the corresponding quaternary alpha- and beta-amino acids and beta-lactams.
Water-Soluble Antitumor Agents. I. Synthesis and Biological Activity of 6-S-Aminoacyloxymethyl Mercaptopurine Derivatives. (1995)

In an attempt to improve the effectiveness and bioavailability of 6-mercaptopurine, various kinds of water-soluble analogues, such as 6-S-aminoacyloxymethyl mercaptopurine derivatives (3a--m) and 6-S,9-disubstituted derivates (7a,b and 9a,b), were synthesized. These compounds were evaluated for activity to augment antitumor immunity by using a double grated tumor system. Antitumor activities against solid tumors (sarcoma 180 and colon 26) were also evaluated. Many compounds exhibited potent activities in both test systems. In particular, the aminopropionate derivative (3a) and the L-glutamate derivative (3f) showed significant enhancement of antitumor immunity together with potent antitumor activities.
Engaging in Civic Life: Confucianism, Republicanism, and Ordinary Chinese in the 1940s (2015)

Journal of Anthropology and Archaeology is a peer-reviewed international journal, which publishes original papers promoting theoretical, methodological and empirical developments in the discipline of socio-cultural anthropology.
Approximate Learning of Dynamic Models (1998)

Inference is a key component in learning probabilistic models from partially observable data. When learning temporal models, each of the many inference phases requires a traversal over an entire long data sequence; furthermore, the data structures manipulated are exponentially large, making this process computationally expensive. In [2], we describe an approximate inference algorithm for monitoring stochastic processes, and prove bounds on its approximation error. In this paper, we apply this algorithm as an approximate forward propagation step in an EM algorithm for learning temporal Bayesian networks. We provide a related approximation for the backward step, and prove error bounds for the combined algorithm. We show empirically that, for a real-life domain, EM using our inference algorithm is much faster than EM using exact inference, with almost no degradation in quality of the learned model. We extend our analysis to the online learning task, showing a bound on the error resulting ...
Supplementary Figure 3 from Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells (2023)

Supplementary Figure 3 from Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells
PDF optimized parametric vector quantization of speech line spectral frequencies (2002)

A computationally efficient, high quality, vector quantization scheme based on a parametric probability density function (PDF) is developed for encoding speech line spectral frequencies (LSF). For this purpose, speech LSFs are modeled as i.i.d realizations of a multivariate normal mixture density. The mixture model parameters are efficiently estimated from the training data using the expectation maximization (EM) algorithm. The estimated density is suitably quantized using transform coding and bit-allocation techniques for both fixed rate and variable rate systems. Source encoding using the resultant codebook involves no searches and its computational complexity is minimal and independent of the rate of the system. Experimental results show that the proposed scheme provides 2-3 bits gain over conventional MSVQ schemes. The proposed memoryless quantizer is enhanced to form a quantizer with memory. The quantizer with memory provides transparent quality speech at 20 bits/frame.
Transient receptor potential vanilloid 1, substance P and reactive oxygen species mediate ethanol – induced gastric injury in mice (2008)

Background and aims. Ingestion of elevated amounts of ethanol (EtOH) can cause hemorrhagic ulceration of the stomach in humans and experimental animals by mechanisms that are incompletely understood. Although previous report showed that coadministration of neurokinin 1 receptor (NK1) agonist aggravated and NK1 receptor antagonists prevent ethanol-induced gastric lesions, the mechanisms by which ethanol releases substance P (SP) and SP damages the mucosa are unknown. We recently reported that ethanol by lowering the threshold temperature for channel activation, stimulate TRPV1 and cause the release of sensory neuropeptides. Thus, we hypothesized that ethanol activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to release SP, which stimulates epithelial NK1 receptors to generate damaging reactive oxygen species. Methods and results. SP release was measured from&#13;\nsegments of mouse stomach, and lesions were assessed by macroscopic and microscopic examination of whole stomach. Reactive oxygen species were detected using dichlorofluorescein-diacetate, and NK1 receptors were localized by immunofluorescence. Ethanol stimulated SP release, and antagonism of transient receptor potential vanilloid 1 prevented this effect. High dose ethanol caused lesions, and TRPV1 antagonism and NK1 receptor antagonism or genetic deletion of NK1 receptor inhibited lesion formation. Co-administration of low, innocuous doses of ethanol and SP caused lesions by a TRPV1-independent but NK1 receptor-dependent process. Ethanol, capsaicin and SP stimulated generation of reactive oxygen species by superficial gastric epithelial cells, expressing NK1 receptors, by a NK1 receptor-dependent mechanism. Diverse reactive oxygen species scavengers (acorbic acid, lipolic acid and n-acetyl cysteine) ameliorated lesions induced by a high ethanol dose or a low ethanol dose plus SP. Conclusions. Present results indicate that gastric lesions are caused by an initial detrimental effect of ethanol, which is damaging only if associated with TRPV1 activation and SP release from sensory nerves. SP, by stimulation of NK1 receptors on gastric epithelial cells cause the release of and tissue damaging reactive oxygen species.
Development of a New Physical Model for Experimental Assessment of Expandable Casing Technology Effect on Wellbore Cement Integrity (2013)

The focus of this novel research was to develop a physical model and apply an experimental approach to explore the effect of casing expansion technology on wellbore cement integrity.
Synthesis of Galbulimima Alkaloid 13 (2006)

Galbulimima alkaloid 13 is isolated from the bark of the Galbulimima belgraveana tree. Noteworthy in this synthesis are (a) a radical cyclization to synthesize the cyclopentane ring in E and (b) an enamine addition strategy to construct the strained 1-hydroxy-bicyclo[3.2.1]octane core. This work established the absolute stereo­chemistry of the target.
Photocatalytic Activity Inhibition by ZnO-SiO<sub>2</sub> Nanocomposites Synthesized by Sonochemical Method (2015)

Here, ZnO particles and ZnO-SiO 2 nanocomposites synthesized by sonochemical method under continuous ultrasound irradiation were reported. For an hour ultrasound irradiated by ultrasonic horn at atmospheric condition, nanorods and spherical structures with crystalline sizes 33 and 17 nm were obtained for ZnO and ZnO-SiO 2 , respectively, revealed that silica inhibited the particles and crystal growth. FTIR analysis also indicated that silica covered the ZnO particles. In addition, photocatalytic activity was also inhibited by silica in which ZnO without and with silica had degradation rate 69% and 48%, respectively, to degrade methylene blue solution under direct sunlight irradiation for an hour. The addition of SiO 2 to ZnO gives an advantage in some application to avoid excessive degradation by controlling their photocatalytic activity.
Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques (2015)

Bitter taste receptors (TAS2R proteins) allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC), in 333 Japanese macaques (Macaca fuscata) from 9 local populations in Japan. We identified a PTC "non-taster" TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area), at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb) from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.
Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood (2015)

Viral load measurements are an essential tool for the long-term clinical care of hum an immunodeficiency virus (HIV)-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use. In this paper, we perform reverse-transcription loop-mediated isothermal amplification (RT-LAMP) on minimally processed HIV-spiked whole blood samples with a microfluidic and silicon microchip platform, and perform fluorescence measurements with a consumer smartphone. Our integrated assay shows amplification from as few as three viruses in a ~ 60 nL RT-LAMP droplet, corresponding to a whole blood concentration of 670 viruses per µL of whole blood. The technology contains greater power in a digital RT-LAMP approach that could be scaled up for the determination of viral load from a finger prick of blood in the clinical care of HIV-positive individuals. We demonstrate that all aspects of this viral load approach, from a drop of blood to imaging the RT-LAMP reaction, are compatible with lab-on-a-chip components and mobile instrumentation.
Effect of Hydrogen and External Donor on Propylene Polymerization Kinetics with a 4th‐Generation Ziegler‐Natta Catalyst (2012)

Abstract Apparent kinetic rate constants and activation energies for catalyst activation, deactivation, and propylene propagation with a 4th‐generation Ziegler‐Natta catalyst are estimated. The rate of polymerization in the presence of donor and hydrogen is higher than in their absence. Catalyst activation and propagation rate constants increase with the addition of hydrogen, likely because hydrogen frees 2–1‐terminated dormant sites. The deactivation term was the highest without electron donor, presumably because the nonspecific sites deactivate faster than the specific sites. Apparent activation energies for catalyst activation, deactivation, and propagation are not significantly influenced by the presence of hydrogen or external donor, indicating that they do not affect these mechanisms substantially. magnified image
P3‐333: SYSTEMIC INFLAMMATION, SELECTIVE DEGRADATION OF LARGE‐SCALE FUNCTIONAL BRAIN NETWORKS, AND AMYLOID DEPOSITION (2019)

Systemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer's disease, but inflammation's effect on distributed brain networks is unclear. Using the BIOCARD cohort, we examined the relationship between systemic inflammation and functional connectivity within five large-scale cognitive networks and evaluated the role of cortical amyloid and APOE ε4 status. Blood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 175 participants (mean age: 65±9; 62% women; 77% were cognitively normal), and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 134 participants also underwent 11C Pittsburgh compound-B (PiB) PET imaging to assess cortical amyloid burden. Using linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with reduced connectivity within the Default Mode (β=−20.9; 95% CI: −36.3, -5.5) and the Dorsal Attention Networks (β=−23.0; 95% CI: −39.0, -7.1) (see Table 1 and Figures 1-2). These associations were not accounted for (mediated) by cortical amyloid, and the strength of these associations did not vary by amyloid status (amyloid+/amyloid-). The association between higher Inflammatory Index and reduced Default Mode connectivity extended to amyloid-negative and cognitively normal participants (Table 2). We found a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated significantly greater reductions in Default Mode and Dorsal Attention Network connectivity compared to ε4-negative participants (Table 3). The Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (i.e., Control, Limbic, and Salience/Ventral Attention networks).