gebhart/patrepeval huggingface dataset:
Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization (2019)

Abstract μ‐Opioid receptors (μ‐ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ‐ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ‐OR antagonist E‐p ‐nitrocinnamoylamino‐dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single‐molecule imaging of μ‐ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ‐ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ‐ORs interact with each other to form short‐lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ‐OR pharmacology at single‐molecule level.
A design approach for dual-polarized multiband frequency selective surfaces using fractal elements (2002)

We propose a technique for the design of multiband frequency selective surfaces (FSSs) that is based on the use of fractal screen elements. We demonstrate the design methodology by exploiting the self-similarity of the crossbar fractal to implement a tri-band FSS. Another benefit of this design approach, in addition to its multiband performance, is that the frequency response of both the TE and TM modes are exactly the same, owing to the symmetry in the tree-like fractal structure of the screen elements. Dielectric loading effects have been considered for practical implementation of designs with coverage exceeding two bands.
Stationary bubble formation and cavity collapse in wedge-shaped hoppers (2016)

The hourglass is one of the apparatuses familiar to everyone, but reveals intriguing behaviors peculiar to granular materials, and many issues are remained to be explored. In this study, we examined the dynamics of falling sand in a special form of hourglass, i.e., a wedge-shaped hopper, when a suspended granular layer is stabilized to a certain degree. As a result, we found remarkably different dynamic regimes of bubbling and cavity. In the bubbling regime, bubbles of nearly equal size are created in the sand at a regular time interval. In the cavity regime, a cavity grows as sand beads fall before a sudden collapse of the cavity. Bubbling found here is quite visible to a level never discussed in the physics literature and the cavity regime is a novel phase, which is neither continuous, intermittent nor completely blocked phase. We elucidate the physical conditions necessary for the bubbling and cavity regimes and develop simple theories for the regimes to successfully explain the observed phenomena by considering the stability of a suspended granular layer and clogging of granular flow at the outlet of the hopper. The bubbling and cavity regimes could be useful for mixing a fluid with granular materials.
Effects of ball pad configuration on joint reliability in BGA chip-scale packages (2005)

The drive for thinner, lighter, smaller semiconductor packages has produced not only a variety of advanced package configurations but numerous packaging concerns, including joint reliability, moisture-induced reliability, warpage, and coplanarity. One critical concern is the joint reliability of unique ball pad configurations in chip-scale packages (CSPs) rendered by the advancement of the micro-via technologies. This study examines the effects of ball pad configurations on solder joint integrity and reliability, with its focus on a conventional pad versus a via-defined pad configuration on bismaleimide triazine (BT) and flex interposers. The assessment of board-level reliability was correlated to solder ball shear tests and a simplified analytical model for further insights into the failure mechanism.
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas (2016)

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.
Low-frequency backscatter from dense submerged bubble clouds. (1992)

The frequency-dependent characteristics of the acoustic backscatter from submerged bubble clouds was studied using both conventional and parametric sound sources. The clouds, all of which possessed a characteristic length scale of 0.5 m, a void fraction of order 10−3, and a mean bubble radius of approximately 1.5 mm, were generated 39.2 m beneath the surface of a freshwater lake (Lake Seneca, NY) using an array of hypodermic needles driven with pulsed flow of compressed air. Backscattering target strengths were measured for frequencies ranging from 300 Hz to 14 kHz. Results obtained using conventional and parametric sources were comparable, with target strengths falling in the +1 to −10-dB range. Several peaks were observed in the target strength versus frequency data. Low-frequency (less than 1 kHz) results exhibit elevated target strengths throughout, with evidence of a broad peak at approximately 500 Hz. Results obtained over the entire range of frequencies will be compared with theoretical predictions based on coherent, resonance scattering (≳1 kHz) and coherent, off-resonance scattering (&amp;lt;1 kHz) and collective bubble oscillations (&amp;lt;1 kHz). [Work supported by ONR, ONT, AEAS, and NUSC/IR.]
Measurement of hadronic event shapes in multijet final states at $sqrt{s}=13$ TeV with the ATLAS detector (2020)

A measurement of event-shape variables in proton$-$proton collisions at large momentum transfer is presented using data collected at $\sqrt{s} = 13$ TeV with the ATLAS detector at the Large Hadron Collider. Six event-shape variables calculated using hadronic jets are studied in inclusive multijet events using data corresponding to an integrated luminosity of 139 fb$^{-1}$. Measurements are performed in bins of jet multiplicity and in different ranges of the scalar sum of the transverse momenta of the two leading jets, reaching scales beyond 2 TeV. These measurements are compared with predictions from Monte Carlo event generators containing leading-order or next-to-leading order matrix elements matched to parton showers simulated to leading-logarithm accuracy. At low jet multiplicities, shape discrepancies between the measurements and the Monte Carlo predictions are observed. At high jet multiplicities, the shapes are better described but discrepancies in the normalisation are observed.
Quantitative signal analysis in pulsed resonant photoacoustics (1997)

The pulsed excitation of acoustic resonances was studied by means of a high-Q photoacoustic resonator with different types of microphone. The signal strength of the first radial mode was calculated by the basic theory as well as by a modeling program, which takes into account the acoustic impedances of the resonator, the acoustic filter system, and the influence of the microphone coupling on the photoacoustic cavity. When the calculated signal strength is used, the high-Q system can be calibrated for trace-gas analysis without a certified gas mixture. The theoretical results were compared with measurements and show good agreement for different microphone configurations. From the measured pressure signal (in pascals per joule), the absorption coefficient of ethylene was calculated; it agreed within 10% with literature values. In addition, a Helmholtz configuration with a highly sensitive 1-in. (2.54-cm) microphone was realized. Although the Q factor was reduced, the sensitivity could be increased by the Helmholtz resonator in the case of pulsed experiments. A maximum sensitivity of the coupled system of 341 mV/Pa was achieved.
Functionalization and molecular dynamics study of carboxy‐terminated poly(1‐vinylpyrrolidin‐2‐one): A potential soluble carrier of biomolecules (2008)

Abstract The reactivity of carboxy‐terminated poly(1‐vinylpyrrolidin‐2‐one) (PVP‐COOH) 40‐mers 1 with various small bi‐functionalized molecules has been investigated. A number of new differently functionalized PVP 3–11 have been successfully obtained demonstrating that the presence of the bulky PVP chain did not hamper the reactivity of the carboxy group. This would imply that in solution the carboxyl group is not buried inside the coil, but well exposed to the solvent, as further confirmed by a molecular dynamics conformational study. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1683–1698, 2008
Improved Protocol for the Diastereoselective Cyclopropanation of Alkenes using Geminal Dizinc Carbenoids: A Study on the Effect of Zinc Iodide (2004)

Abstract A mixture of ZnI 2 , EtZnI·2OEt 2 and CHI 3 produces a gem ‐dizinc carbenoid that is an efficient cyclopropanating reagent. The presence of ZnI 2 allows for shorter reaction times and cleaner reactions, particularly with less reactive substrates. This modification improves the scope of the reaction and it raises important mechanistic issues about this reaction. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
Anisotropic Effects on the Thermoelectric Properties of Highly Oriented Electrodeposited Bi2Te3 Films (2016)

Highly oriented [1 1 0] Bi2Te3 films were obtained by pulsed electrodeposition. The structure, composition, and morphology of these films were characterized. The thermoelectric figure of merit (zT), both parallel and perpendicular to the substrate surface, were determined by measuring the Seebeck coefficient, electrical conductivity, and thermal conductivity in each direction. At 300 K, the in-plane and out-of-plane figure of merits of these Bi2Te3 films were (5.6 ± 1.2)·10(-2) and (10.4 ± 2.6)·10(-2), respectively.
Phase-slope and group-dispersion calculations in the frequency domain by simple optical low-coherence reflectometry (2003)

We report a new method by which phase slope and group dispersion can be calculated with a simple optical low-coherence reflectometer to quantify physiological conditions. A discrete-time signal processing algorithm based on the first and second derivatives of the phase with respect to wave number was developed from discrete-time Fourier properties. The algorithm avoids the 2pi ambiguity associated with most phase unwrapping. Experimental data collected by use of well-characterized optical materials validated the algorithm, which was minimally sensitive to phase noise. The group dispersion of bovine cornea was measured at various hydrations and was significantly dependent on hydration. The results suggest that group dispersion is an indicator of corneal alterations.
Figure S6 from Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia (2023)

&lt;p&gt;Figure S6.Identification of biomarker of response to ABBV-744/venetoclax therapy.&lt;/p&gt;
1,2-Cyclic Sulfamidates as Versatile Precursors to Thiomorpholines and Piperazines (2003)

[reaction: see text] 1,2-Cyclic sulfamidates undergo regiospecific nucleophilic displacement with either methyl thioglycolate or alpha-amino esters, followed by lactamization (thermal, base-mediated, or cyanide-catalyzed), to give thiomorpholin-3-ones and piperazin-2-ones.
Autoactivation of the Epstein-Barr Virus Oncogenic Protein LMP1 during Type II Latency through Opposite Roles of the NF-κB and JNK Signaling Pathways (2006)

Epstein-Barr virus (EBV) is associated with several human malignancies where it expresses limited subsets of latent proteins. Of the latent proteins, latent membrane protein 1 (LMP1) is a potent transforming protein that constitutively induces multiple cell signaling pathways and contributes to EBV-associated oncogenesis. Regulation of LMP1 expression has been extensively described during the type III latency of EBV. Nevertheless, in the majority of EBV-associated tumors, the virus is commonly found to display a type II latency program in which it is still unknown which viral or cellular protein is really involved in maintaining LMP1 expression. Here, we demonstrate that LMP1 activates its own promoter pLMP1 through the JNK signaling pathway emerging from the TES2 domain. Our results also reveal that this activation is tightly controlled by LMP1, since pLMP1 is inhibited by LMP1-activated NF-kappaB signaling pathway. By using our physiological models of EBV-infected cells displaying type II latency as well as lymphoblastoid cell lines expressing a type III latency, we also demonstrate that this balanced autoregulation of LMP1 is shared by both latency programs. Finally, we show that this autoactivation is the most important mechanism to maintain LMP1 expression during the type II latency program of EBV.
Unique Self‐Anhydride Formation in the Degradation of Cytidine‐5′‐monophosphosialic Acid (CMP‐Neu5Ac) and Cytidine‐5′‐diphosphosialic Acid (CDP‐Neu5Ac) and its Application in CMP‐sialic Acid Analogue Synthesis (2011)

Sialyloligosaccharides are synthesised by various glycosyltransferases and sugar nucleotides. All of these nucleotides are diphosphate compounds except for cytidine-5'-monophosphosialic acid (CMP-Neu5Ac). To obtain an insight into why cytidine-5'-diphosphosialic acid (CDP-Neu5Ac) has not been used for the sialyltransferase reaction and why it is not found in biological organisms, the compound was synthesised. This synthesis provided the interesting finding that the carboxylic acid moiety of the sialic acid attacks the attached phosphate group. This interaction yields an activated anhydride between carboxylic acid and the phosphate group and leads to hydrolysis of the pyrophosphate linkage. The mechanism was demonstrated by stable isotope-labelling experiments. This finding suggested that CMP-Neu5Ac might also form the corresponding anhydride structure between carboxylic acid and phosphate, and this seems to be the reason why CMP-Neu5Ac is acid labile in relation to other sugar nucleotides. To confirm the role of the carboxylic acid, CMP-Neu5Ac derivatives in which the carboxylic acid moiety in the sialic acid was substituted with amide or ester groups were synthesised. These analogues clearly exhibited resistance to acid hydrolysis. This result indicated that the carboxylic acid of Neu5Ac is associated with its stability in solution. This finding also enabled the development of a novel chemical synthetic method for CMP-Neu5Ac and CMP-sialic acid derivatives.
Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology (2016)

Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC → CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1-the main output region for CA2-correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden.<b>SIGNIFICANCE STATEMENT</b> This study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach-informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data-helps tease out the relative contribution of Lewy pathology to memory dysfunction in the disease. Levels of Lewy pathology were found to be highest in the hippocampal CA2 subregion and entorhinal cortex, implicating a potentially overlooked circuit in disease pathogenesis. However, correlation with memory performance was strongest with CA1. This unexpected finding suggests that Lewy pathology must reach a critical burden across hippocampal circuitry to contribute to memory dysfunction beyond that related to other factors, notably coexisting Alzheimer's disease tau pathology.
PI4K2A deficiency in an intellectual disability, epilepsy, myoclonus, akathisia syndrome (2018)

We report a family of Saudi Arabian ancestry with two children presenting with global developmental delay, dystonia, disturbed sleep, and heat intolerance. By genome sequencing, we identified a nonsense variant in the first exon of <i>PI4K2A</i> that was homozygous in both affected individuals and was absent from, or heterozygous in, seven unaffected siblings. <i>PI4K2A</i> is highly expressed in the brain and a mouse model displays a neurological phenotype, implicating <i>PI4K2A</i> as a new disease gene for a neurological disorder.
Induction of chromosome damage by ultraviolet light and caffeine: Correlation of cytogenetic evaluation and flow karyotype (1982)

Asynchronously growing cells of a M3-1 Chinese hamster line were ultraviolet (UV) irradiated (lambda = 254 nm) with UV fluences up to 7.5 J/m(2). After irradiation cells were incubated with or without 2 mM caffeine for 20 hr, then mitotic cells were selected by mechanical shaking. Their chromosomes were isolated, stained with Hoechst 33258 and chromomycin A3, and measured flow cytometrically. While the fluorescence distributions of chromosomes (flow karyo-types) from cells treated with UV alone or with caffeine alone were very similar to those of untreated controls, the flow karyo-types of UV + caffeine-treated cells showed a debris continuum that increased with increasing UV fluence suggesting an increased number of chromosome fragments. Visual evaluation of metaphase plates revealed that the percentage of cells with chromosome damage also increased steadily with increasing UV fluence. A high degree of correlation was observed between the relative magnitude of the debris level from flow karyotypes and the percentage of cells with chromosome damage and with generalized chromosomes shattering, respectively, as determined from metaphase spreads.
Machine learning prediction and tau-based screening identifies potential Alzheimer’s disease genes relevant to immunity (2022)

With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand the ever-growing omics data to enhance early diagnosis, map complex disease networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph and evidence paths transformed into vectors by metapath matching. We extracted features between specific genes and diseases, then trained and optimized our model using XGBoost, termed MPxgb(AD). To determine our MPxgb(AD) prediction performance, we examined the top twenty predicted genes through an experimental screening pipeline. Our analysis identified potential AD risk genes: FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2. FRRS1 and FAM92B are considered dark genes, while CTRAM, SCGB3A1, and TMEFF2 are connected to TREM2-TYROBP, IL-1β-TNFα, and MTOR-APP AD-risk nodes, suggesting relevance to the pathogenesis of AD.
Synthesis and Photophysical Properties of Benzotriazole-Derived Unnatural α-Amino Acids (2019)

The synthesis of a new class of benzotriazole-derived α-amino acid is described using a highly efficient nucleophilic aromatic substitution of ortho-fluoronitrobenzenes with l-3-aminoalanine and a polymer-supported nitrite reagent-mediated diazotization and cyclization of the subsequent 1,2-aryldiamines as the key steps. Further functionalization of the benzotriazole unit by preparation of halogenated analogues and Suzuki–Miyaura cross-coupling with aryl boronic acids allowed the synthesis of α-amino acids with conjugated side chains. Analysis of the photophysical properties of these α-amino acids revealed that incorporation of electron-rich substituents results in charge-transfer-based, fluorescent compounds with MegaStokes shifts.
Spiro-oxindole Piperidines and 3-(Azetidin-3-yl)-1H-benzimidazol-2-ones as mGlu2 Receptor PAMs (2019)

Starting from two weak mGlu<sub>2</sub> receptor positive allosteric modulator (PAM) HTS hits (<b>4</b> and <b>5</b>), a molecular hybridization strategy resulted in the identification of a novel spiro-oxindole piperidine series with improved activity and metabolic stability. Scaffold hopping around the spiro-oxindole core identified the 3-(azetidin-3-yl)-1<i>H</i>-benzimidazol-2-one as bioisoster. Medicinal chemistry optimization of these two novel chemotypes resulted in the identification of potent, selective, orally bioavailable, and brain penetrant mGluR<sub>2</sub> PAMs.