gebhart/patrepeval huggingface dataset:
Novel targets for the treatment of ACTH-secreting tumors (2006)

Cushing's disease is an endocrine disorder caused by excessive production of ACTH. It represents a major challenge for the physician in terms of accurate diagnosis and efficient treatment. Unless treated, the disease is associated with high morbidity, and ultimately, mortality. In the absence of effective medical therapies, patients with Cushing's disease are usually treated by transsphenoidal pituitary surgery. However, surgery is associated with significant post-operative morbidities and not all patients can be cured by it. In addition to surgical procedures various drugs, such as dopamine agonists and somatostatin analogues, effective in only a limited number of cases, have been employed to treat ACTH-secreting tumors. The therapeutic potential of new generations of these drugs with more selective and long-lasting effects, such as cabergoline and SOM230, has been examined in recent studies. On the other hand, the identification of potential therapeutic targets in pituitary corticotroph tumors, such as the nuclear receptor peroxisome-proliferator-activated receptor -γ (PPARγ) and the retinoic acid receptors (RAR and RXR), provides novel approaches for the treatment of Cushing's disease. However, the ability of the PPARγ ligand rosiglitazone and retinoic acid to treat patients with Cushing's disease still needs to be validated in further clinical studies. Recently, a new study demonstrated the efficacy of the retinoic acid treatment in dogs with Cushing's disease. Since RAR and RXR might have synergistic inhibitory actions with PPARγ ligands, combination therapy with RXR and PPAR γ ligands might allow reduced concentrations of both ligands to be administered therapeutically. A recent in vitro and in vivo study demonstrated the potent antiproliferative and proapoptotic effects of doxazosin, an alpha1-adrenergic receptor antagonist, by mechanisms involving the down-regulation of nuclear factor-κB signalling. The efficiency of doxazosin treatment in patients with Cushing's disease still needs to be tested in clinical trials.
Regioselective One Pot Synthesis of 2‐Alkyl/Aryl‐4H‐benzo[1,4]thiazine‐3‐one via Microwave Irradiation. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines (2014)

A new series of dihydrofolate reductase (DHFR) inhibitors, the 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines, were designed and optimized for antibacterial potency and enzyme selectivity. The most potent inhibitors in this series contained a five-membered heterocycle at the 2-position of the benzimidazole, leading to highly potent and selective compounds that exploit the differences in the size of a binding pocket adjacent to the NADPH cofactor between the bacterial and human DHFR enzymes. Typical of these compounds is 7-((2-thiazol-2-yl)benzimidazol-1-yl)-2,4 diaminoquinazoline, which is a potent inhibitor of S. aureus DHFR (Ki = 0.002 nM) with 46700-fold selectivity over human DHFR. This compound also has high antibacterial potency on Gram-positive bacteria with an MIC versus wild type S. aureus of 0.0125 μg/mL and a MIC versus trimethoprim-resistant S. aureus of 0.25 μg/mL. In vivo efficacy versus a S. aureus septicemia was demonstrated, highlighting the potential of this new series.
Tunable, concurrent multiband, single chain radio architecture for low energy 5G-RANs (2017)

This invited paper considers a key next step in the design of radio architectures aimed at supporting low energy consumption in 5G heterogeneous radio access networks. State-of-the-art mobile radios usually require one RF transceiver per standard, each working separately at any given time. Software defined radios, while spanning a wide range of standards and frequency bands, also work separately at any specific time. In 5G radio access networks, where continuous, multiband connectivity is envisaged, this conventional radio architecture results in high network power consumption. In this paper, we propose the novel concept of a concurrent multiband frequency-agile radio (CM-FARAD) architecture, which simultaneously supports multiple standards and frequency bands using a single, tunable transceiver. We discuss the subsystem radio design approaches for enabling the CM-FARAD architecture, including antennas, power amplifiers, low noise amplifiers and analogue to digital converters. A working prototype of a dual-band CM-FARAD test-bed is also presented together with measured salient performance characteristics.
Chemoinformatics-Based Classification of Prohibited Substances Employed for Doping in Sport (2006)

Representative molecules from 10 classes of prohibited substances were taken from the World Anti-Doping Agency (WADA) list, augmented by molecules from corresponding activity classes found in the MDDR database. Together with some explicitly allowed compounds, these formed a set of 5245 molecules. Five types of fingerprints were calculated for these substances. The random forest classification method was used to predict membership of each prohibited class on the basis of each type of fingerprint, using 5-fold cross-validation. We also used a k-nearest neighbors (kNN) approach, which worked well for the smallest values of k. The most successful classifiers are based on Unity 2D fingerprints and give very similar Matthews correlation coefficients of 0.836 (kNN) and 0.829 (random forest). The kNN classifiers tend to give a higher recall of positives at the expense of lower precision. A naïve Bayesian classifier, however, lies much further toward the extreme of high recall and low precision. Our results suggest that it will be possible to produce a reliable and quantitative assignment of membership or otherwise of each class of prohibited substances. This should aid the fight against the use of bioactive novel compounds as doping agents, while also protecting athletes against unjust disqualification.
Tobacco mosaic virus infection spreads cell to cell as intact replication complexes (2004)

Plant viruses encode movement proteins (MPs) that facilitate cell-cell transport of infection through plasmodesmata. Intracellular and intercellular spread of virus replication complexes (VRCs) of tobacco mosaic virus was followed in intact leaf tissue from 12 to 36 h post infection (hpi) by using confocal microscopy. From 12 hpi, VRCs in primary infected cells were associated with cortical endoplasmic reticulum, and at 14 hpi, exhibited high intracellular mobility ( approximately 160 nm/sec); mobility was slowed between 14 and 16 hpi ( approximately 40 nm/sec), and by 18 hpi, VRCs were stationary, adjacent to plasmodesmata. VRCs traversed the plasmodesmata between 18 and 20 hpi. The process of formation and movement of VRCs was repeated in adjacent cells in 3-4 h vs. 20 h from primary infected cells. The rapid intracellular movement of the VRCs and the spread to adjacent cells was blocked by inhibitors of filamentous actin and myosin, but not by inhibitors of microtubules. We propose a model whereby cell-cell spread of tobamovirus infection is accomplished by subviral replication complexes that initiate TMV replication immediately after entry to adjacent cells.
Plasma phospholipid profiling of a mouse model of anxiety disorder by hydrophilic interaction liquid chromatography coupled to high‐resolution mass spectrometry (2018)

Glycerophospholipids (PLs), as amphipathic small molecules and the main constituents of biological membranes, play an important role in several cellular processes, even though their accurate identification from complex biological samples remains a challenge. In this paper, we report a fast and comprehensive HILIC-ESI-MS method for the analysis of glycerophospholipid classes using high-resolution mass spectrometry in negative mode. The final method enabled the quantitative analysis of 130 endogenous PL species in mouse plasma. The application of the method developed was to find differences of plasma PL composition in a mouse model of anxiety disorder. In the case of four PL classes and 35 PL species, significant differences were observed comparing low anxiety-related behavior with high anxiety-related behavior groups. The most characteristic trend was up-regulation in both the PL classes and PL species, and decreases were only detected in two phosphatidylcholines among 35 species in mice having elevated anxiety.
Transferability of empirical force fields for complex hydrated calcio-silicate layered materials (2014)

The use of empirical force fields is now a standard approach in predicting the properties of hydrated oxides which are omnipresent in both natural and engineering applications. Transferability of force fields to analogous hydrated oxides without rigorous investigations may result in misleading property predictions. Herein, we focus on two common empirical force fields, the simple point charge ClayFF potential and the core–shell potential to study tobermorite minerals, the most prominent family of Calcium–Silicate–Hydrates that are complex hydrated oxides. We benchmark the predictive capabilities of these force fields against first principles results. Although the structural information seem to be in close agreement with DFT results, we find that for higher order properties such as elastic constants, the core-shell potential quantitatively improves upon the simple point charge model and shows a larger degree of transferability to complex materials. In return, to remedy the deficiencies of the simple point charge potential for hydrated calcio-silicates, we suggest using both structural data and elasticity data for potential calibration, a new force field potential, CSH-FF. This reparameterized version of ClayFF is then applied to simulating an atomistic model of cement (Pellenq et al., PNAS, 2009). We demonstrate that this force field improves the predictive capabilities of ClayFF, being considerably less computational intensive than the core-shell model.
Toward a Question Answering Roadmap (2002)

Growth in government investment, academic research, and commercial systems building is motivating a need for increased planning and coordination in the emerging field of question answering (QA). The internationalization of QA research, and the need to move toward a common understanding of resources, tasks and evaluation methods motivate a need to facilitate more rapid and efficient progress. This paper characterizes a range of question answering systems and provides an initial roadmap for future research, including a list of existing resources and ones under development. This roadmap was initiated at the LREC 2002 Workshop on QA and will be updated during the 2003 AAAI Spring Symposium using moderated group brainstorming sessions.
A Bacteria‐Based Remotely Tunable Photonic Device (2016)

The bacteria-based photonic device is analogous to liquid-crystal-based devices where the liquid crystals and an electric field are replaced by magnetic bacteria and a magnetic field, respectively. The controlled orientation of the bacteria in the device is used to tune the intensity and the polarization of the light. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
&lt;title&gt;Optimal unified approach to warping and overlapped block estimation in video coding&lt;/title&gt; (1996)

Among the class of block-based motion estimators, warping prediction and overlapped block motion estimation have emerged recently as two of the most effective inter-frame estimation algorithms. Warping estimation is based on linear operations in the motion field, while overlapped block estimators are based on a linear sum of motion-based estimators in the intensity field. In this paper, we propose a unified framework for estimation of pixel intensities based jointly on warping and overlapped blocks. We motivate our estimator through a discussion of ambiguities in an incomplete (sparsely sampled) motion field; and that different object motions call for resolution of motion ambiguities in either the motion or intensity domain. We offer a means of optimizing the joint estimator simultaneously in intensity and motion domains, thus guaranteeing improved performance compared to warping and overlapped block estimators, which the joint model contains as special cases. Furthermore, the joint framework provides an excellent vehicle for studying the interactions and relative merits of warping and overlapped block estimators in the presence of various motion scenarios.
Chromatid repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids. (1986)

Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed chromatid repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome.
The effect of a physical robot on vocabulary learning (2019)

This study investigates the effect of a physical robot taking the role of a teacher or exercise partner in a language learning exercise. In order to investigate this, an application was developed enabling a 2:nd language learning vocabulary exercise in three different conditions. In the first condition the learner would receive tutoring from a disembodied voice, in the second condition the tutor would be embodied by an animated avatar on a computer screen, and in the final condition the tutor was a physical robotic head with a 3D animated face mask. A Russian language vocabulary exercise with 15 subjects was conducted. None of the subjects reported any Russian language skills prior to the exercises. Each subject were taught a set of 9 words in each of the three conditions during a practice phase, and were then asked to recall the words in a test phase. Results show that the recall of the words practiced with the physical robot were significantly higher than that of the words practiced with the avatar on the screen or with the disembodied voice.
Supplementary Figure from Comprehensive Genome Profiling in Patients With Metastatic Non–Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial (2023)

Supplementary Figure from Comprehensive Genome Profiling in Patients With Metastatic Non–Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial
Loss of <scp><i>Oca2</i></scp> disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes (2013)

Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress.
Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency (2022)

Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. Acid ceramidase deficiency results in lipid accumulation in many tissues and leads to the development of Farber disease (FD). Typical manifestations of classical FD include formation of subcutaneous nodules and joint contractures as well as the development of a hoarse voice. Healthy skin depends on a unique lipid profile to form a barrier that confers protection from pathogens, prevents excessive water loss, and mediates cell-cell communication. Ceramides comprise ~50% of total epidermis lipids and regulate cutaneous homeostasis and inflammation. Abnormal skin development including visual skin lesions has been reported in FD patients, but a detailed study of FD skin has not been performed. We conducted a pathophysiological study of the skin in our mouse model of FD. We observed altered lipid composition in FD skin dominated by accumulation of all studied ceramide species and buildup of abnormal storage structures affecting mainly the dermis. A deficiency of acid ceramidase activity also led to the activation of inflammatory IL-6/JAK/signal transducer and activator of transcription 3 and noncanonical NF-κB signaling pathways. Last, we report reduced proliferation of FD mouse fibroblasts and adipose-derived stem/stromal cells (ASC) along with impaired differentiation of ASCs into mature adipocytes.
Fourier transform spectroscopy with a deformable mirror (2004)

During the in-orbit checkout phase of the Infrared Spectrograph<sup>1</sup> on board The Spitzer Telescope,<sup>2</sup> it was found that the noise of the spectrograph's arrays was correlated with the number of cosmic ray hits. Our analysis reveals that the cause of that effect is most likely due to the algorithms used to correct cosmic ray hits on dark pixels. We also found that the noise characteristics of the pixels that have an illumination that is lower than 1/10 of the full well is artificially raised by the cosmic ray correction by a factor of about 10% if 1% of the pixels are affected by cosmic rays.
Developmental changes in fibroblast growth factor in the chicken embryo limb bud. (1988)

Cell proliferation is a major event during early limb development. Significant levels of growth factor activity, as measured by stimulation of DNA synthesis in mouse BALB/c 3T3 cells, were found in extracts of chicken embryo limb buds at early stages of development. Extracts from stage-18 limbs (3 days of incubation) were 2 to 3 times more potent than were extracts from older stages, namely 22-24 (4 days), 26 (5 days), and 28 (6 days). Basic fibroblast growth factor (bFGF) was measured specifically using an RIA, and the amounts of factor obtained corresponded to the activities measured by the 3T3 cell-growth assay. In addition, most growth factor in the extracts bound with high affinity to heparin-Sepharose columns. Western (immunologic) blotting and immunoprecipitation with an antibody specific for bFGF revealed a protein of identical size to bFGF--i.e., 18 kDa, in the extracts. Thus, a growth factor with the properties of bFGF is present in the early limb, and the level of this factor is highest when proliferation is a predominant cellular event in the developing limb. These and other data suggest that fibroblast growth factor is a key regulatory factor in embryonic growth and morphogenesis.
Three independent mutations in the same exon of the<i>PCCB</i> gene: Differences between Caucasian and Japanese propionic acidaemia (1993)

Propionic acidaemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase (PCC). Enzyme deficiency can result from mutations in either of the non-identical alpha- and beta-subunits. We have screened genomic DNA from patients with defects in the beta-subunit from two ethnic groups (Caucasians and Japanese) and detected three types of mutations in the same exon of the coding sequence of the beta-subunit: an insertion/deletion that replaces 14 nucleotides with 12 nucleotides of unrelated sequence and eliminates an Msp I site; a 3-bp deletion of a single isoleucine codon immediately proximal to that Msp I site; and a C-->T transition in the same Msp I site. The insertion/deletion was detected only in Caucasian patients in 11 of 34 mutant alleles; the C-->T transition was found only in Japanese patients in 4 of 12 mutant alleles. Following digestion of genomic DNA by Msp I, both of these mutations were detected on Southern blots by the presence of a 2.7-kbp band; they can be distinguished from one another by allele-specific oligonucleotide hybridization following PCR amplification. These results underscore the independent origin of the mutations in the two populations and suggest a key role of this exon in the beta-subunit of PCC.
Development of a high stability L-band radiometer for ocean salinity measurements (2004)

An NEDT analysis of a Dicke radiometer with noise diode injection is presented. The analysis is formulated for a calibration that would form separate running averages of receiver noise temperature and of gain in order to minimize the NEDT and maximize the antenna observation duty cycle relative to the reference and noise diode duty cycles. Results are applied to the Aquarius ocean salinity radiometer problem to show that near ideal total-power radiometer performance is possible.