gebhart/patrepeval huggingface dataset:
Nerve growth factor metabolic dysfunction in Down’s syndrome brains (2014)

Basal forebrain cholinergic neurons play a key role in cognition. This neuronal system is highly dependent on NGF for its synaptic integrity and the phenotypic maintenance of its cell bodies. Basal forebrain cholinergic neurons progressively degenerate in Alzheimer's disease and Down's syndrome, and their atrophy contributes to the manifestation of dementia. Paradoxically, in Alzheimer's disease brains, the synthesis of NGF is not affected and there is abundance of the NGF precursor, proNGF. We have shown that this phenomenon is the result of a deficit in NGF's extracellular metabolism that compromises proNGF maturation and exacerbates its subsequent degradation. We hypothesized that a similar imbalance should be present in Down's syndrome. Using a combination of quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting and zymography, we investigated signs of NGF metabolic dysfunction in post-mortem brains from the temporal (n = 14), frontal (n = 34) and parietal (n = 20) cortex obtained from subjects with Down's syndrome and age-matched controls (age range 31-68 years). We further examined primary cultures of human foetal Down's syndrome cortex (17-21 gestational age weeks) and brains from Ts65Dn mice (12-22 months), a widely used animal model of Down's syndrome. We report a significant increase in proNGF levels in human and mouse Down's syndrome brains, with a concomitant reduction in the levels of plasminogen and tissue plasminogen activator messenger RNA as well as an increment in neuroserpin expression; enzymes that partake in proNGF maturation. Human Down's syndrome brains also exhibited elevated zymogenic activity of MMP9, the major NGF-degrading protease. Our results indicate a failure in NGF precursor maturation in Down's syndrome brains and a likely enhanced proteolytic degradation of NGF, changes which can compromise the trophic support of basal forebrain cholinergic neurons. The alterations in proNGF and MMP9 were also present in cultures of Down's syndrome foetal cortex; suggesting that this trophic compromise may be amenable to rescue, before frank dementia onset. Our study thus provides a novel paradigm for cholinergic neuroprotection in Alzheimer's disease and Down's syndrome.
Oxidative Lipidomics of γ-Radiation-Induced Lung Injury: Mass Spectrometric Characterization of Cardiolipin and Phosphatidylserine Peroxidation (2011)

Oxidative damage plays a significant role in the pathogenesis of γ-radiation-induced lung injury. Endothelium is a preferred target for early radiation-induced damage and apoptosis. Given the newly discovered role of oxidized phospholipids in apoptotic signaling, we performed oxidative lipidomics analysis of phospholipids in irradiated mouse lungs and cultured mouse lung endothelial cells. C57BL/6NHsd female mice were subjected to total-body irradiation (10 Gy, 15 Gy) and euthanized 24 h thereafter. Mouse lung endothelial cells were analyzed 48 h after γ irradiation (15 Gy). We found that radiation-induced apoptosis in vivo and in vitro was accompanied by non-random oxidation of phospholipids. Cardiolipin and phosphatidylserine were the major oxidized phospholipids, while more abundant phospholipids (phosphatidylcholine, phosphatidylethanolamine) remained non-oxidized. Electrospray ionization mass spectrometry analysis revealed the formation of cardiolipin and phosphatidylserine oxygenated molecular species in the irradiated lung and cells. Analysis of fatty acids after hydrolysis of cardiolipin and phosphatidylserine by phospholipase A(2) revealed the presence of mono-hydroperoxy and/or mono-hydroxy/mono-epoxy, mono-hydroperoxy/mono-oxo molecular species of linoleic acid. We speculate that cyt c-driven oxidations of cardiolipin and phosphatidylserine associated with the execution of apoptosis in pulmonary endothelial cells are important contributors to endothelium dysfunction in γ-radiation-induced lung injury.
Development of an Algorithm for Reconstructing a Comprehensive Pathway Model: Application to &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; (2015)

The generation of bioactive products by microbial bioprocesses is important for drug discovery, functional food development, and other beneficial purposes. Many pathways contribute to the production of these bioactive compounds, but important knowledge for improving productivity still remains in hidden pathways. Recently, an abundance of knowledge about metabolic pathways has been accumulated in metabolic pathway databases, such as BioCyc and KEGG. Many by-products are chemically transformed and actually used in other enzymatic reactions. In this work, we developed an algorithm for the reconstruction of a comprehensive genetic pathway model from a known metabolic pathway database. This model considers the interactions of the by-products, in addition to the main products. Furthermore, we developed a method for the construction of a comprehensive pathway model in a specific organism. In this study, we reconstructed a Saccharomyces cerevisiae model. From this model, the pathways among enzymes that contributed to galactose metabolism were explored. Using S. cerevisiae DNA microarray data, the activated pathways were found among the explored pathways.
Optimized deghosting of over/under towed-streamer data in the presence of noise (2008)

Seismic exploration is widely used to locate geologic formations for hydrocarbon accumulations. In a typical marine seismic survey, one or more marine seismic streamers are towed behind a survey vessel. As the streamers are towed, acoustic signals, commonly referred to as “shots,” are produced by the seismic source. These travel down through the water column into strata beneath the water bottom surface, where they are reflected from the various geologic formations and travel back to the sea surface. One well-known marine seismic problem is that these upgoing waves are then reflected with inverted polarity at the sea surface because of the air/water interface. Hence, the sensors in the seismic streamer cable record not only the desired wavefield (i.e., the upgoing wave-reflected signal from various subterranean geologic formations), but also their reflections from the sea surface (the downgoing wave). The undesired downgoing reflected signal is known as the “receiver ghost.” Depending on the incidence angle of the upgoing wavefield and depth of the streamer cable, the interference between the upgoing and downgoing wavefields creates nulls or notches in the recorded spectrum. As illustrated in Figure 1, these notches reduce the useful bandwidth of the spectrum especially at increasing streamer depths.
Heterojunction Modification for Highly Efficient Organic–Inorganic Perovskite Solar Cells (2014)

Organic-inorganic perovskites, such as CH3NH3PbX3 (X=I, Br, Cl), have emerged as attractive absorber materials for the fabrication of low cost high efficiency solar cells. Over the last 3 years, there has been an exceptional rise in power conversion efficiencies (PCEs), demonstrating the outstanding potential of these perovskite materials. However, in most device architectures, including the simplest thin-film planar structure, a current-voltage response displays an "anomalous hysteresis", whereby the power output of the cell varies with measurement time, direction and light exposure or bias history. Here we provide insight into the physical processes occurring at the interface between the n-type charge collection layer and the perovskite absorber. Through spectroscopic measurements, we find that electron transfer from the perovskite to the TiO2 in the standard planar junction cells is very slow. By modifying the n-type contact with a self-assembled fullerene monolayer, electron transfer is "switched on", and both the n-type and p-type heterojunctions with the perovskite are active in driving the photovoltaic operation. The fullerene-modified devices achieve up to 17.3% power conversion efficiency with significantly reduced hysteresis, and stabilized power output reaching 15.7% in the planar p-i-n heterojunction solar cells measured under simulated AM 1.5 sunlight.
Updates on the Origin of Life (2012)

Loren Williams from the Georgia Tech Center for Ribosomal Origins and Evolution joins us to discuss new developments in the chemical search for the origin of life on earth.
An Unbiased Linkage Approach Reveals That the p53 Pathway Is Coupled to NK Cell Maturation (2017)

Natural killer cells constitute potent innate lymphoid cells that play a major role in both tumor immunosurveillance and viral clearance via their effector functions. A four-stage model of NK cell functional maturation has been established according to the expression of CD11b and CD27, separating mature NK (mNK) cells into distinct populations that exhibit specific phenotypic and functional properties. To identify genetic factors involved in the regulation of NK cell functional maturation, we performed a linkage analysis on F<sub>2</sub> (B6.Rag1<sup>-/-</sup> × NOD.Rag1<sup>-/-</sup> intercross) mice. We identified six loci on chromosomes 2, 4, 7, 10, 11, and 18 that were linked to one or more mNK cell subsets. Subsequently, we performed an in silico analysis exploiting mNK cell subset microarray data, highlighting various genes and microRNAs as potential regulators of the functional maturation of NK cells. Together, the combination of our unbiased genetic linkage study and the in silico analysis positions genes known to affect NK cell biology along the specific stages of NK cell functional maturation. Moreover, this approach allowed us to uncover a novel candidate gene in the regulation of NK cell maturation, namely <i>Trp53</i> Using mice deficient for <i>Trp53</i>, we confirm that this tumor suppressor regulates NK cell functional maturation. Additional candidate genes revealed in this study may eventually serve as targets for the modulation of NK cell functional maturation to potentiate both tumor immunosurveillance and viral clearance.
Self-timed router with virtual channel control (2023)

Systems, apparatuses, and methods for implementing an asynchronous router with virtual channel (VC) control. The asynchronous router may support multiple VCs for connections to other routers. The asynchronous router may include an interface unit on each switch boundary, with each interface unit including a data merge unit. The data merge unit may include a full detector unit for each VC, with the full detector unit counting the number of flits sent out on a respective VC and counting the number of credits released by the successor router. Whenever the successor router has no credits available, the full detector unit will assert the full signal to prevent any input requests from requesting to transmit over that particular VC. When the full signal is asserted, a timer unit may be activated to repeatedly check if any credits have been released in the successor router.
Flight simulator experiments to determine human reaction to aircraft motion environments (1974)

An analysis of human response to aircraft motion is presented using data obtained on the NASA Flight Research Center's Jetstar aircraft. The purpose of these tests was to explore the relationship of vertical and transverse accelerations to human comfort as well as obtain information on the maximum comfortable bank angle for commercial aircraft operations. A preliminary study was also conducted to establish the importance or lack thereof of the low frequency content of aircraft motion due to natural turbulence. An effort has been made to model these data and comparisons with appropriate sources are made.
Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma (2016)

Proteasome-regulated NF-κB has been shown to be important for cell survival in T-cell lymphoma and Hodgkin lymphoma models. Several new small-molecule proteasome inhibitors are under various stages of active preclinical and clinical development. We completed a comprehensive preclinical examination of the efficacy and associated biologic effects of a second-generation proteasome inhibitor, ixazomib, in T-cell lymphoma and Hodgkin lymphoma cells and in vivo SCID mouse models. We demonstrated that ixazomib induced potent cell death in all cell lines at clinically achievable concentrations. In addition, it significantly inhibited tumor growth and improved survival in T-cell lymphoma and Hodgkin lymphoma human lymphoma xenograft models. Through global transcriptome analyses, proteasomal inhibition showed conserved overlap in downregulation of cell cycle, chromatin modification, and DNA repair processes in ixazomib-sensitive lymphoma cells. The predicted activity for tumor suppressors and oncogenes, the impact on "hallmarks of cancer," and the analysis of key significant genes from global transcriptome analysis for ixazomib strongly favored tumor inhibition via downregulation of MYC and CHK1, its target genes. Furthermore, in ixazomib-treated lymphoma cells, we identified that CHK1 was involved in the regulation of MYC expression through chromatin modification involving histone H3 acetylation via chromatin immunoprecipitation. Finally, using pharmacologic and RNA silencing of CHK1 or the associated MYC-related mechanism, we demonstrated synergistic cell death in combination with antiproteasome therapy. Altogether, ixazomib significantly downregulates MYC and induces potent cell death in T-cell lymphoma and Hodgkin lymphoma, and we identified that combinatorial therapy with anti-CHK1 treatment represents a rational and novel therapeutic approach. Cancer Res; 76(11); 3319-31. ©2016 AACR.
A comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus (2009)

Despite early and more aggressive therapy in sTTP, mortality was higher and the time to complete remission were longer, suggesting that sTTP is more severe. The tempo of development of TTP in SLE patients was slower.
Tissue oxygen saturation predicts response to breast cancer neoadjuvant chemotherapy within 10 days of treatment (2018)

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC = 0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO2 to surrounding tissue StO2 are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer.
CRISPRi-mediated metabolic engineering of E. coli for O-methylated anthocyanin production (2017)

An E. coli strain was engineered for production of the specialty anthocyanin P3G using the abundant and comparatively inexpensive flavonol precursor, (+)-catechin. Furthermore, dCas9-mediated transcriptional repression of metJ alleviated a limiting SAM pool size, enhancing titers of the methylated anthocyanin product. While microbial production of P3G and other O-methylated anthocyanin pigments will likely be valuable to the food industry as natural food and beverage colorants, we expect that the strain constructed here will also prove useful to the ornamental plant industry as a platform for evaluating putative anthocyanin O-methyltransferases in pursuit of bespoke flower pigment compositions.
Quantitative analysis of Doppler flow spectra in the lower limb arteries (2003)

A computer processing method was developed to analyze lower limb Doppler signals, extract diagnostic features from Doppler spectrograms, and classify the severity of the arterial disease. A pattern recognition method (Bayes model) was used to discriminate between nonhemodynamically significant (<50% diameter reduction) and hemodynamically significant (<50% diameter reduction) stenoses. The features investigated were based on spectral broadening and on the power of the spectrogram in various frequency bands. The performance of the pattern recognition method was compared to that of conventional biplane contrast angiograms read by experienced angioradiologists. Results showed a percentage of correct classification of 85%. Sensitivity was 77%, and specificity was 90%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Direct Oxidation of Alkylamines by YBa2Cu3O7-δ:  A Key Step in the Formation of Self-Assembled Monolayers on Cuprate Superconductors (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDirect Oxidation of Alkylamines by YBa2Cu3O7-δ: A Key Step in the Formation of Self-Assembled Monolayers on Cuprate SuperconductorsJin Zhu, Chad A. Mirkin, Robert M. Braun, and Nicholas WinogradView Author Information Department of Chemistry, Northwestern University 2145 Sheridan Rd., Evanston, Illinois 60201 Department of Chemistry, The Pennsylvania State University University Park, Pennsylvania 16802 Cite this: J. Am. Chem. Soc. 1998, 120, 20, 5126–5127Publication Date (Web):May 7, 1998Publication History Received29 December 1997Revised9 April 1998Published online7 May 1998Published inissue 1 May 1998https://pubs.acs.org/doi/10.1021/ja974348ehttps://doi.org/10.1021/ja974348erapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views268Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amines,Granular materials,Layers,Monolayers,Superconductors Get e-Alerts
InP based active and passive components for communication systems at 2&#x03BC;m (2014)

Progress on active and passive photonic components (high speed lasers, detectors, modulators, waveguides, optical hybrids, arrayed waveguide grating mux/demux) operating at wavelengths around 2 microns are described.
Search for pair-produced heavy quarks decaying toWqin the two-lepton channel at(s)=7  TeVwith the ATLAS detector (2012)

Search for pair-produced heavy quarks decaying to Wq in the two-lepton channel at ffiffi p s 7 TeV with the ATLAS detector
Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015)

The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.
Classifying neuronal subclasses of the cerebellum through constellation pharmacology (2015)

A pressing need in neurobiology is the comprehensive identification and characterization of neuronal subclasses within the mammalian nervous system. To this end, we used constellation pharmacology as a method to interrogate the neuronal and glial subclasses of the mouse cerebellum individually and simultaneously. We then evaluated the data obtained from constellation-pharmacology experiments by cluster analysis to classify cells into neuronal and glial subclasses, based on their functional expression of glutamate, acetylcholine, and GABA receptors, among other ion channels. Conantokin peptides were used to identify N-methyl-d-aspartate (NMDA) receptor subtypes, which revealed that neurons of the young mouse cerebellum expressed NR2A and NR2B NMDA receptor subunits. Additional pharmacological tools disclosed differential expression of α-amino-3-hydroxy-5-methyl-4-isoxazloepropionic, nicotinic acetylcholine, and muscarinic acetylcholine receptors in different neuronal and glial subclasses. Certain cell subclasses correlated with known attributes of granule cells, and we combined constellation pharmacology with genetically labeled neurons to identify and characterize Purkinje cells. This study illustrates the utility of applying constellation pharmacology to classify neuronal and glial subclasses in specific anatomical regions of the brain.