gebhart/patrepeval huggingface dataset:
Abstract B05: Discovery, validation and targeting of novel synthetic lethal interactions in academic drug discovery (2017)

Abstract The identification of novel oncology targets for small molecule drug discovery is becoming increasingly challenging despite 10-15% of the human genome estimated to be druggable. The literature is an important source of novel targets; however, several recent reports by pharma and academia have indicated that approximately 11-55% of published studies are irreproducible. Moreover, oncology drug attrition rates are extremely poor, with 66% of candidates in Phase III clinical trials not achieving approval. This is reflected by increasing failure rates of drug development projects in Phase II, from 72% in 2006-2007 to 82% in 2008-2009. These failures have been attributed to lack of efficacy, thus highlighting the critical requirement for new novel drug targets that demonstrate clear promise of clinical efficacy through predictive in vitro and in vivo models. Furthermore, it is important to prioritize and pursue targets that are most likely to bind a small molecule inhibitor with high infinity. We sought to utilize the wealth of unvalidated genomic data now available in the public domain by developing a bioinformatic pipeline founded on the collateral vulnerability hypothesis, which is based on the concept of synthetic lethality and exploits the co-occurrence of deletions of genes flanking tumor suppressors that are lost during the course of tumor evolution. We can then target the paralogs of these genes if together they belong to gene families with essential predicted function, thereby exploiting a vulnerability of the cancer cells with these losses. Here, we describe our industry-standard approaches to the target validation of the output generated from lung adenocarcinoma data, and present the validation and de-validation of several novel targets predicted by the collateral vulnerability pipeline, including SMARCA2, KMT2C, and SETD1B. Citation Format: H. Nikki March, Phil Chapman, Elizabeth Blaikley, Catherine A. Eberlein, Mark Cockerill, Samantha Hitchin, Ian D. Waddell, Donald Ogilvie. Discovery, validation and targeting of novel synthetic lethal interactions in academic drug discovery [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B05.
Supplementary Table 2 from Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G<sub>2</sub>–M Cell-Cycle Progression (2023)

&lt;p&gt;PDF file - 45K, Information about TaqMan assays used in RT-qPCR&lt;/p&gt;
Supplementary Figure 1 from A Smac Mimetic Rescue Screen Reveals Roles for Inhibitor of Apoptosis Proteins in Tumor Necrosis Factor-α Signaling (2023)

Supplementary Figure 1 from A Smac Mimetic Rescue Screen Reveals Roles for Inhibitor of Apoptosis Proteins in Tumor Necrosis Factor-α Signaling
Re-Inventing Building Energy Codes as Technology and Market Drivers (2010)

Global climate change, with a time frame of decades not years, encourages policy makers to pay more attention to new construction in addition to the retrofitting of existing buildings and to upgrading the efficiency of fast-turnover appliances and lighting. Increased interest in advanced building energy codes is reflected in proposed federal legislation to set multiyear energy code targets leading to zero-energy buildings. The expectation of continuous, staged improvements in building codes – coupled with voluntary market transformation – can help drive long-term demand for energy-efficient building designs, construction materials, and installed equipment. For building energy codes to serve as market-drivers not just followers, we need to revitalize the code development process; strengthen incentives and mandates for code adoption, compliance, and enforcement; and encourage beyond-code building practices. Increasingly stringent goals for energy codes will challenge current processes of code development, adoption, compliance, and enforcement, and may require a transition from prescriptive to performancebased code compliance, or perhaps a mixed system. In the future, incorporating “building life-cycle performance” into energy codes would require accounting for building or component lifetimes and reaching beyond the design stage to address construction quality, acceptance testing, long-term performance, and the role of occupants. Beyond today’s common metric, annual energy use per square meter of floor space, future codes could address: electricity load shape and demand-responsiveness, environmental impacts, embodied energy, metrics based on occupancy instead of (or in addition to) conditioned floorspace, code requirements or credits for features that enable future technology upgrades, subdivision- and community-scale energy systems, “locational” efficiency, and “progressive efficiency” criteria that require higher performance from larger homes and buildings.
Princeton Sound Kitchen Open Source Software Report (2001)

The Princeton Sound Kitchen is a repository of open source software for computer music written by graduate students and professors of the computer science and music departments at Princeton University.This studio report describes some recent open source software that has been added to this repository.These projects include computer music tools developed at the Music Department of Princeton as well as audio synthesis and recognition tools developed at the Computer Science Department.All the software is open source, uses standard cross-platform free software and has been tested in a variety of operating system and hardware configurations.
Height control for small periodic structures using x-ray radiography (2016)

We report on a method to characterize the height of periodic x-ray absorbing structures.Such structures are used for example in grating-based x-ray interferometry.In contrast to other techniques, our approach allows for a non-destructive determination of the height based on a few transmission measurements.It can be used with conventional laboratory-based x-ray setups and is therefore of great interest at the application sites of the structures, as it allows further characterization without the need of additional hardware.Here we present the principle of the method, show first results acquired with an absorption grating and compare them with theoretical calculations and those obtained using a destructive method.
Response of soil fauna to land use intensification in a global meta-analysis (2023)

Land use intensification, particularly a shift from extensively to intensively managed agroecosystems is often seen as one of the main drivers of global biodiversity decline and is considered the main factor applying pressure on soil biodiversity. When confronted with future land use change, understanding the responses of soil biodiversity to different land use regimes is decisive for adequate land management. However, there is still substantial uncertainty about how consistently different taxonomic groups respond to land use intensification. Oftentimes, different taxa show divergent responses to more intense land use regimes, and the community composition is rarely correlated with land use intensity, which may suggest that the drivers of community composition may not be the same as drivers of diversity. The mechanisms that determine the response of different taxa to land use intensification may be regulated by changes in the plant community and abiotic environmental drivers. We systematically assessed and quantified through meta-analysis the effects of land use intensification on soil organisms in global agroecosystems and analyzed the dependence of these effects on abiotic factors such as soil properties (organic matter, pH, nutrient and water availability, texture) and climatic zone.
Domain engineered switchable strain states in ferroelectric (011) [Pb(Mg1/3Nb2/3)O3](1−x)-[PbTiO3]x (PMN-PT, x≈0.32) single crystals (2011)

The ferroelectric properties of (011) [Pb(Mg1/3Nb2/3)O3](1−x)-[PbTiO3]x (PMN-PT, x≈0.32) single crystals with focus on piezoelectric strain response were reported. Two giant reversible and stable remanent strain states and tunable remanent strain properties are achieved by properly reversing the electric field from the depolarized direction. The unique piezoelectric strain response, especially along the [100] direction, mainly stems from the non-180° ferroelectric polarization reorientation in the rhombohedral phase crystal structure. Such giant strain hysteresis with tunable remanent strain properties may be useful for magnetoelectric based memory devices as well as a potential candidate for other applications.
Geometric Partitioning Mode in Versatile Video Coding: Algorithm Review and Analysis (2020)

This paper presents an overview of the geometric partitioning mode (GPM) algorithm that is a part of the most recent Versatile Video Coding (VVC) standard. The GPM algorithm aims to increase the partitioning precision of moving objects using non-rectangular and asymmetric rectangular partitions on top of the conventional rectangular block partitioning structure of VVC. Novel features of GPM contributing to the increase in coding efficiency and the reduction in encoder and decoder complexity are detailed and analyzed in this paper. Evaluated with VVC test model version 8.0 under the joint video experts team common test conditions, experimental results show that the presented GPM algorithm provides luma Bjøntegaard Delta rate reduction of 0.70% for random access and of 1.55% for low delay with B slices configurations, with roughly 3% to 5% additional encoding time and negligible decoder runtime change. Furthermore, as GPM provides more precise partitions for the boundaries of the moving objects, an improvement of visual quality is seen in GPM coded sequences.
Feasibility of cardiovascular magnetic resonance derived coronary wave intensity analysis (2016)

This proof of concept study demonstrated that CMR may be used to perform coronary WIA non-invasively with reasonable reproducibility compared to invasive WIA. The technique potentially allows WIA to be performed in a wider range of patients and pathologies than those who can be studied invasively.
Demonstration of multi‐channel 80 Gbit/s integrated transmitter and receiver for wavelength‐division multiplexing passive optical network and fronthauling applications (2016)

The performance evaluation of a multi‐channel transmitter that employs an arrayed reflective electroabsorption modulator‐based photonic integrated circuit and a low‐power driver array in conjunction with a multi‐channel receiver incorporating a pin photodiode array and integrated arrayed waveguide grating is reported. Due to their small footprint, low power consumption and potential low cost, these devices are attractive solutions for future mobile fronthaul and next generation optical access networks. A BER performance of &lt;10 −9 at 10.3 Gbit/s per channel is achieved over 25 km of standard single mode fibre. The transmitter/receiver combination can achieve an aggregate bit rate of 82.4 Gbit/s when eight channels are active.
Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis (2012)

This study reports a global glycoproteomic analysis of pancreatic cancer cells that describes how flux through the sialic acid biosynthetic pathway selectively modulates a subset of N-glycosylation sites found within cellular proteins. These results provide evidence that sialoglycoprotein patterns are not determined exclusively by the transcription of biosynthetic enzymes or the availability of N-glycan sequons; instead, bulk metabolic flux through the sialic acid pathway has a remarkable ability to increase the abundance of certain sialoglycoproteins while having a minimal impact on others. Specifically, of 82 glycoproteins identified through a mass spectrometry and bioinformatics approach, ≈ 31% showed no change in sialylation, ≈ 29% exhibited a modest increase, whereas ≈ 40% experienced an increase of greater than twofold. Increased sialylation of specific glycoproteins resulted in changes to the adhesive properties of SW1990 pancreatic cancer cells (e.g. increased CD44-mediated adhesion to selectins under physiological flow and enhanced integrin-mediated cell mobility on collagen and fibronectin). These results indicate that cancer cells can become more aggressively malignant by controlling the sialylation of proteins implicated in metastatic transformation via metabolic flux.
Opposing Effects of Oxygen Regulation on Kallistatin Expression: Kallistatin as a Novel Mediator of Oxygen‐Induced HIF‐1‐eNOS‐NO Pathway (2017)

Oxidative stress has both detrimental and beneficial effects. Kallistatin, a key component of circulation, protects against vascular and organ injury. Serum kallistatin levels are reduced in patients and animal models with hypertension, diabetes, obesity, and cancer. Reduction of kallistatin levels is inversely associated with elevated thiobarbituric acid-reactive substance. Kallistatin therapy attenuates oxidative stress and increases endothelial nitric oxide synthase (eNOS) and NO levels in animal models. However, kallistatin administration increases reactive oxygen species formation in immune cells and bacterial killing activity in septic mice. High oxygen inhibits kallistatin expression via activating the JNK-FOXO1 pathway in endothelial cells. Conversely, mild oxygen/hyperoxia stimulates kallistatin, eNOS, and hypoxia-inducible factor-1 (HIF-1) expression in endothelial cells and in the kidney of normal mice. Likewise, kallistatin stimulates eNOS and HIF-1, and kallistatin antisense RNA abolishes oxygen-induced eNOS and HIF-1 expression, indicating a role of kallistatin in mediating mild oxygen's stimulation on antioxidant genes. Protein kinase C (PKC) activation mediates HIF-1-induced eNOS synthesis in response to hyperoxia/exercise; thus, mild oxygen through PKC activation stimulates kallistatin-mediated HIF-1 and eNOS synthesis. In summary, oxidative stress induces down- or upregulation of kallistatin expression, depending on oxygen concentration, and kallistatin plays a novel role in mediating oxygen/exercise-induced HIF-1-eNOS-NO pathway.
Isolation of circulating tumor cells (2022)

Circulating tumor cells (CTCs) enter the vasculature from solid tumors and disseminate widely to initiate metastases. Mining the metastatic-enriched molecular signatures of CTCs before, during, and after treatment holds unique potential in personalized oncology. Their extreme rarity, however, requires isolation from large blood volumes at high yield and purity, yet they overlap leukocytes in size and other biophysical properties. Additionally, many CTCs lack EpCAM that underlies much of affinity-based capture, complicating their separation from blood. Here, we provide a comprehensive introduction of CTC isolation technology, by analyzing key separation modes and integrated isolation strategies. Attention is focused on recent progress in microfluidics, where an accelerating evolution is occurring in high-throughput sorting of cells along multiple dimensions.
Numerical simulations of carotid MRI quantify the accuracy in measuring atherosclerotic plaque components in vivo (2013)

Current clinical MRI can quantify carotid plaques but shows limitations for thin FC thickness quantification. These limitations could influence the reliability of carotid MRI for assessing plaque rupture risk associated with FC thickness. Overall, MRI simulations provide a feasible methodology for assessing segmentation and quantification accuracy, as well as for improving scan protocol design.
ChemInform Abstract: Base Induced Reaction of an Azetidin‐2‐one: Formation of a Novel [1,4]‐Diazepinedione. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Elucidation of Factors Affecting the Electronic Structures of Magnesium(II) and Zinc(II) Tetraarylporphyrin Radical Cations (1995)

Abstract A series of magnesium and zinc tetraarylporphyrins and their porphyrinoxidized derivatives were studied by UV/Vis, ESR, and resonance Raman spectroscopy at various temperatures. The series included tetra( meta ‐dichlorophenyl)porphyrinatozinc ( 5 ), tetra( ortho ‐dichlorophenyl)porphyrinatozinc ( 6 ), tetra( ortho ‐difluorophenyl)porphyrinatozinc and ‐magnesium ( 9 and 10 ), and tetra(pentafluorophenyl)porphyrinatozinc and ‐magnesium ( 7 and 8 ). The radical cations ( 3a ‐ 10a ) were isolated by chemical one‐electron oxidation of their neutral precursors ( 3 ‐ 10 ). Despite the structural similarity of all these radicals, their electronic ground state varied within the series. The position of the chloro groups was found to play a key role. While the radical cation of the meta ‐dichloro‐substituted derivative 5a exhibited A 2u spectroscopic features, the ortho ‐dichlorophenyl derivative ( 6a ) showed A 1u spectral features. Radicals of the fluoro‐substituted porphyrins, especially that of 10 , were found to have state‐admixed ( A 1u / A 2u ) electronic structures, and the relative contributions of the two states was found to vary with temperature and to depend on the axial ligand. The results indicate that the fluoro‐substituted porphyrins are primarily A 2u at low temperature, even though their room temperature spectroscopic features resemble those of A 1u cations. The elucidation of factors that affect the electronic structures of the radicals in the present series is helpful in providing a greater understanding of the spin‐spin interactions in the intermediates of heme‐dependant enzymatic reactions and their synthetic analogues.
Supplementary Table S2 from Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer (2023)

&lt;p&gt;- PDF file 86K, Supplementary Table S2. BNC1 and ADAMTS1 Gene expression changes in pancreatic cancers from previously published microarray dataset&lt;/p&gt;
Anti-kindling achieved by stimulation targeting slow synaptic dynamics (2009)

The presented stimulation strategies and the results of our modeling study might have strong implications in the context of deep brain stimulation.
Use of human leukocyte‐specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys (1994)

The rhesus monkey (Macaca mulatta) is an important experimental animal frequently utilized for studies of infectious diseases, immunity, hematopoiesis, and transplantation. Since the structure of cell surface molecules is phylogenetically conserved, monoclonal antibodies raised against human leukocyte antigens can sometimes recognize the homologous determinant on monkey leukocytes. To facilitate better utilization of this animal model, we tested 89 commercially available monoclonal antibodies which define 27 human cell surface antigens for reactivity with rhesus monkey PBL. Certain antigens which delineate clinical useful lymphocyte subsets such as CD2, CD4, CD8, CD14, CD16, CD20, and MHC class II are apparently well conserved since most human cell-specific antibodies identified the homologous cell subset in monkeys. However, other antigens such as CD3, CD19, CD45, and CD56 were identified infrequently by human cell-specific antibodies. FITC-modification of antibodies which had no effect on their binding to human cells occasionally inhibited antibody binding to monkey cells. Nevertheless, an adequate number of cross-reactive monoclonal antibodies was identified to allow gating of lymphocytes for accurate flow cytometric analysis and quantitation of the major lymphocyte subsets of the rhesus monkey. The T lymphocyte subset distribution in blood and lymphoid tissue of rhesus monkeys was similar to man. However, the B subset was significantly larger in monkeys. The daily variation in absolute PBL subset size was marked and found to be due mainly to daily fluctuations in total lymphocyte number.
Modiolides A and B, Two New 10-Membered Macrolides from a Marine-Derived Fungus (2003)

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.
Placental Growth Factor Promotes Atherosclerotic Intimal Thickening and Macrophage Accumulation (2005)

Local adenoviral PlGF2 delivery promotes atherogenic neointima formation in hypercholesterolemic rabbits, and PlGF is required for macrophage infiltration in early atherosclerotic lesions in apoE(-/-) mice. These findings support a novel role for PlGF in the pathogenesis of atherosclerotic disease.
Merger of dynamic two-photon and phosphorescence lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors (2019)

This study demonstrates a versatile and highly contextual FaST-PLIM method for phosphorescence lifetime-based oxygen imaging in living animal tumor immunology models. The initial results of this method application to ALL and solid lung tumor models highlight the importance of oxygen supply for the maintenance of intratumoral T cell migration, define a 5 mmHg local oxygen concentration threshold for TIL motility, and demonstrate efficacy of supplementary oxygen breathing in TIL motility enhancement coincident with reduction of tumor hypoxia.
GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2) (2017)

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.
Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection (2020)

Our results indicate that tacrolimus treatment has a significant impact directly on KCs and on TREM1, thereby compromising their capacity to fend off infections.