gebhart/patrepeval huggingface dataset:
EXTH-17. SELECTIVE, NON-COMPETITIVE DRD2/3 ANTAGONISM BY IMIPRIDONE ONC206 IS EFFECTIVE IN TUMORS WITH DOPAMINE RECEPTOR DYSREGULATION (2018)

Dopamine receptor D2 (DRD2) is a G protein-coupled receptor that is overexpressed in several cancers and its antagonism has been shown to cause anti-cancer effects. ONC201, an imipridone small molecule, is a DRD2/3 antagonist in Phase II advanced cancer clinical trials. We evaluated the binding target and anti-tumor activity of ONC206, a chemical derivative of ONC201. Experimental GPCR profiling with β-Arrestin recruitment assays revealed that ONC206 selectively antagonizes dopamine receptors DRD2 and DRD3. ONC206 exhibited a Ki of ~320nM for DRD2 with complete specificity across human GPCRs at doses that resulted in complete inhibition. Schild analyses of ONC206 in cAMP and β-Arrestin recruitment assays revealed hallmarks of non-competitive DRD2 antagonism, unlike antipsychotics that act as competitive and often non-selective antagonists. Shotgun mutagenesis across DRD2 identified 7 residues within and outside of the orthosteric binding site that are critical for ONC206-mediated antagonism. While 6 mutated residues were also critical for ONC201-mediated antagonism, the impact and magnitude of different mutants varied between the two compounds and one of the mutated residues was unique to ONC206 in an allosteric location. In vitro profiling of ONC206 in >1000 GDSC cancer cell lines revealed broad nanomolar efficacy (GI50 <78-889nM). TCGA and tissue microarrays analyses revealed that malignant DRD2 expression was highest in pheochromocytoma, high grade gliomas, neuroblastoma and medulloblastoma with nanomolar in vitro ONC206 sensitivity. A DRD2+/DRD5- RNA expression signature in the GDSC panel predicted significantly enhanced ONC206 sensitivity. ONC206 reduced the viability of normal human fibroblasts at micromolar doses (GI50 > 5µM), suggesting a wide therapeutic window. Robust inhibition of tumor growth was observed with weekly oral ONC206 (50mg/kg) in subcutaneous xenografts of cholangiocarcinoma, a dopamine-secreting bile duct tumor with DRD2 overexpression. Thus, imipridone ONC206 acts as a selective non-competitive DRD2/3 antagonist at nanomolar concentrations with efficacy in tumors with dopamine receptor pathway dysregulation.
Humor Detection in English-Hindi Code-Mixed Social Media Content : Corpus and Baseline System (2018)

The tremendous amount of user generated data through social networking sites led to the gaining popularity of automatic text classification in the field of computational linguistics over the past decade. Within this domain, one problem that has drawn the attention of many researchers is automatic humor detection in texts. In depth semantic understanding of the text is required to detect humor which makes the problem difficult to automate. With increase in the number of social media users, many multilingual speakers often interchange between languages while posting on social media which is called code-mixing. It introduces some challenges in the field of linguistic analysis of social media content (Barman et al., 2014), like spelling variations and non-grammatical structures in a sentence. Past researches include detecting puns in texts (Kao et al., 2016) and humor in one-lines (Mihalcea et al., 2010) in a single language, but with the tremendous amount of code-mixed data available online, there is a need to develop techniques which detects humor in code-mixed tweets. In this paper, we analyze the task of humor detection in texts and describe a freely available corpus containing English-Hindi code-mixed tweets annotated with humorous(H) or non-humorous(N) tags. We also tagged the words in the tweets with Language tags (English/Hindi/Others). Moreover, we describe the experiments carried out on the corpus and provide a baseline classification system which distinguishes between humorous and non-humorous texts.
ChemInform Abstract: Investigation of the N‐Arylation of Various Substituted Indoles Using Microwave‐Assisted Technology. (2009)

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cardiovascular interactions assessed via conditional joint transfer entropy in patients developing atrial fibrillation after coronary artery bypass graft surgery (2016)

Assigned the universe of knowledge Ω as composed by one target and two exogenous signals, the conditional joint transfer entropy (CJTE), assessing the amount of information jointly transferred from the two sources to the target that can be uniquely linked to one of the two sources, was found useful to study cardiovascular control. We propose the assessment of CJTE from systolic arterial pressure (SAP) and respiration (R) to heart period (HP) conditioned on R (CJTESAP, R→HP|R) along the baroreflex, and from HP and R to SAP conditioned on R (CJTEHP, R→SAP|R) along the feedforward mechanical pathway, in 134 patients undergoing coronary artery bypass graft surgery before (PRE) and after (POST) the induction of general anesthesia. In this group 38 patients developed atrial fibrillation (AF) after surgery, while the remaining individuals did not (noAF, n=96). Both CJTESAP, R→HP|R and CJTEHP, R→SAP|R distinguished AF from noAF individuals in the PRE condition, suggesting an impairment of HP-SAP closed-loop regulation in AF group and the possibility to identify subjects at higher risk to develop post-surgery AF.
Combining multiuser diversity and WCDMA transmit diversity models (2002)

Currently there are a number of proposals to extend third generation wireless systems to handle asymmetrical, packet– oriented services requiring high downlink capacities. One such scheme is the high speed downlink packet access (HSDPA) developed within 3GPP WCDMA standardization. This paper studies the performance of multiuser diversity introduced by a certain HSDPA scheduler together with different closed–loop transmit diversity schemes.
ASpoGAMo: Automated Sports Game Analysis Models (2009)

Abstract. We propose automated sport game models as a novel technical means for the analysis of team sport games. The basic idea is that automated sport game models are based on a conceptualization of key notions in such games and probabilistically derived from a set of previous games. In contrast to existing approaches, automated sport game models provide an analysis that is sensitive to their context and go beyond simple statistical aggregations allowing objective, transparent and meaningful concept definitions. Based on automatically gathered spatio-temporal data by a computer vision system, a model hierarchy is built bottom up, where context-sensitive concepts are instantiated by the application of machine learning techniques. We describe the current state of implementation of the ASPOGAMO system including its computer vision subsystem that realizes the idea of automated sport game models. Their usage is exemplified with an analysis of the final of the soccer World Cup 2006.
Eye Tracking for Everyone (2016)

From scientific research to commercial applications, eye tracking is an important tool across many domains. Despite its range of applications, eye tracking has yet to become a pervasive technology. We believe that we can put the power of eye tracking in everyone's palm by building eye tracking software that works on commodity hardware such as mobile phones and tablets, without the need for additional sensors or devices. We tackle this problem by introducing GazeCapture, the first large-scale dataset for eye tracking, containing data from over 1450 people consisting of almost 2.5M frames. Using GazeCapture, we train iTracker, a convolutional neural network for eye tracking, which achieves a significant reduction in error over previous approaches while running in real time (10-15fps) on a modern mobile device. Our model achieves a prediction error of 1.71cm and 2.53cm without calibration on mobile phones and tablets respectively. With calibration, this is reduced to 1.34cm and 2.12cm. Further, we demonstrate that the features learned by iTracker generalize well to other datasets, achieving state-of-the-art results. The code, data, and models are available at http://gazecapture.csail.mit.edu.
Supplementary Data from MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer (2023)

Supplementary Data from MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Physical models for electron transport in graphene nanoribbons and their junctions (2008)

Physics-based equivalent circuit models are presented for armchair and zigzag graphene nanoribbons (GNRs), and their conductances have been benchmarked against those of carbon nanotubes and copper wires. It is demonstrated that GNRs that have large coherence length behave like waveguides for electrons. This poses both challenges and opportunities for designing graphene nanoelectronic circuits.
The Association of Aspirin Use With Age-Related Macular Degeneration (2013)

Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.
Mechanism of the Antiviral Activity of New Aurintricarboxylic Acid Analogues (1996)

Various new aurintricarboxylic acid (ATA) polymer analogues have been evaluated for their antiviral activity against a wide array of DNA and RNA viruses, and their mechanism of action against human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1). Most of the polymers exhibited marked antiviral activity against a variety of enveloped viruses, but not against non-enveloped viruses. The ATA polymers displayed the most pronounced activity against HIV-1, HCMV and human herpesvirus type 6 (HHV-6). Their action against HCMV and HIV could be ascribed to inhibition of the initial attachment of virus particles to the cells. Using radiolabelled virus, we proved that the polymers inhibit the binding of HCMV to HEL fibroblasts. By flow cytometric analysis, we demonstrated that these new polymers interfere with (i) the binding of OKT4A monoclonal antibody (mAb) to the cellular CD4 receptor, (ii) the binding of anti-gp120 mAb to HIV-1 glycoprotein (gp) 120, and (iii) the adsorption of HIV-1 virions and recombinant HIV-1gp120 (rgp120) to MT-4 cells. The presence of a salicylic acid substituent on the central bridging carbon in the parent compound ATA seems to play an important role in the anti-HIV activity of these ATA related polymer analogues.
Comparison of resistance-based and inductance-based self-sensing control for surface permanent magnet machine using high frequency signal injection (2011)

This paper presents injection-based self-sensing (position sensorless) control methods for surface permanent magnet (SPM) machines with highly symmetric rotors. Two suitable position-dependent spatial saliency signals are compared. The two signals relate to inductance variation due to stator tooth saturation and resistance variation due to high frequency (HF) eddy current losses. Finite element analysis (FEA) is performed to investigate the properties of two saliency signals in different SPM machines. Implementation methods as well as advantages for closed-loop self-sensing control are discussed. This paper includes experimental comparative evaluation of resistance-based versus inductance-based closed-loop self-sensing control performance in a SPM machine using concentrated windings.
Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study (2022)

Cerebral glucose hypometabolism is a typical hallmark of Alzheimer's disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [<sup>18</sup>F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [<sup>18</sup>F]PI-2620 for tau deposition, [<sup>18</sup>F]DPA-714 for TSPO expression associated with neuroinflammation, and [<sup>18</sup>F]UCB-H for synaptic density in a transgenic tauopathy mouse model. Seven-month-old rTg4510 mice (n = 8) and non-transgenic littermates (n = 8) were examined in a small animal PET scanner with the tracers listed above. Hypometabolism was observed throughout the forebrain of rTg4510 mice. Tau pathology, increased TSPO expression, and synaptic loss were co-localized in the cortex and hippocampus and correlated with hypometabolism. In the thalamus, however, hypometabolism occurred in the absence of tau-related pathology. Thus, cerebral hypometabolism was associated with two regionally distinct forms of molecular pathology: (1) characteristic neuropathology of the Alzheimer-type including synaptic degeneration and neuroinflammation co-localized with tau deposition in the cerebral cortex, and (2) pathological changes in the thalamus in the absence of other markers of AD pathophysiology, possibly reflecting downstream or remote adaptive processes which may affect functional connectivity. Our study demonstrates the feasibility of a multitracer approach to explore complex interactions of distinct AD-pathomechanisms in vivo in a small animal model. The observations demonstrate that multiple, spatially heterogeneous pathomechanisms can contribute to hypometabolism observed in AD mouse models and they motivate future longitudinal studies as well as the investigation of possibly comparable pathomechanisms in human patients.
Wide Dynamic Range in Tunable Electrochromic Bragg Stacks from Doped Semiconductor Nanocrystals (2019)

Abstract Electrochromic properties can be enhanced by constructing photonic architectures, in which the reflectance contributes to optical modulation along with the intrinsic dynamic absorptivity of the material. However, optimization of reflectance is challenging without a rational design approach. Here, electrochemically tunable Bragg reflectors are demonstrated that are tuned to be highly transparent in the “off” state, achieving synergistic dynamic optical modulation of absorption and reflection in the visible and near‐infrared range. These Bragg stacks are composed of alternating doped semiconductor nanocrystal (NC) layers of 5 nm sized oxygen vacancy‐doped WO 3− x and 15 nm sized 0.4 at% Sn:In 2 O 3 NCs. Combining judicious NC selection and processing optimization with guidance from optical simulations, optimized Bragg stacks are implemented for electrochromic window applications. NCs with high absorption coefficients are essential for strong transmission modulation, though this characteristic limits the dynamic range of the Bragg reflectance. Optimal reflectance modulation including a highly transparent “off” state is confirmed with in situ reflectance and transmittance measurement. More broadly, ligand‐stripped NCs can enable fabrication of complex device architectures on low‐cost flexible substrates. These results guide the design rules for accessing different types of doped semiconductor NC‐based tunable Bragg stacks, an exemplary photonic structure, over a broad wavelength range.
NMR and X-ray Investigations of a Plastic Crystalline Phase in MBBA (1985)

Abstract Wideline and high resolution NMR studies have been carried out on MBBA in its isotropic, nematic and solid phases. Isotropic and nematic phase spectra correspond to what has been reported earlier. In the solid phase, contrary to expectations, very intense narrow signals similar to signals of the isotropic phase have been observed for the first time at temperatures close to the solid ↔ nematic phase transition temperature. This indicates rapid reorientational or translational motion in the system. The X-ray results however confirm the existence of translational order. The results are interpreted as indicative of the existence of a plastic crystalline phase in MBBA.
Dinuclear Nickel–Ruthenium Complexes as Functional Bio‐Inspired Models of [NiFe] Hydrogenases (2007)

Abstract Three new dinuclear nickel ruthenium complexes, namely [Ni(xbsms)Ru( p ‐cymene)Cl] + , [Ni(emi)Ru(CO) 2 Cl 2 ] 2– and [Ni(emi)Ru( p ‐cymene)Cl] – [H 2 xbsms = 1,2‐bis(4‐mercapto‐3,3‐dimethyl‐2‐thiabutyl)benzene, H 2 emi = N , N′ ‐ethylenebis(2‐mercaptoisobutyramide], have been synthesized and fully characterized as models of the active site of[NiFe] hydrogenases. The three‐dimensional structure of [Ni(xbsms)Ru( p ‐cymene)Cl] + reveals a nickel center in a square‐planar dithioether‐dithiolate environment that is connected to a ruthenium moiety via a Ni(μ‐SR) 2 Ru bridge. These complexes catalyze hydrogen evolution by electroreduction of the weakly acidic Et 3 NH + ions in dimethylformamide and are therefore among the first bio‐inspired functional models of [NiFe] hydrogenases. The catalytic activity of these new complexes is explained by the existence of a cooperative effect between the metal centers and is further related to their electronic properties. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Characterization and Optimization of a Red-Shifted Fluorescence Polarization ADP Detection Assay (2009)

ATP depletion and ADP formation are generic detection methods used for the identification of kinase and other ATP-utilizing enzyme inhibitors in high-throughput screening campaigns. However, the most widely used nucleotide detection approaches require high ATP consumption rates or involve the use of coupling enzymes, which can complicate the selection of lead compounds. As an alternative, we have developed the Transcreener (BellBrook Labs, Madison, WI) platform, which relies on the direct immunodetection of nucleotides. Here we describe the development of antibodies with >100-fold selectivity for ADP versus ATP, which enable robust detection of initial velocity rates (Z' > 0.7 at 10% substrate consumption) at ATP concentrations ranging from 0.1 microM to 1,000 microM in a competitive fluorescence polarization (FP) immunoassay. Competitive binding experiments indicate similar affinities for other nucleotide diphosphates, including 2' -deoxy ADP, GDP, and UDP. The antibody-tracer complex and the red-shifted, ratiometric FP signal are stable for at least 24 h at room temperature, providing suitable conditions for high-throughput screening. A method for calculating a kinase ATP Km with this FP immunoassay is also presented. The Transcreener ADP assay provides a simple, generic assay platform for inhibitor screening and selectivity profiling that can be used for any ADP-generating enzyme.
Nonclassical Antigen-Processing Pathways Are Required for MHC Class II–Restricted Direct Tumor Recognition by NY-ESO-1–Specific CD4+ T Cells (2013)

Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157-170 peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment.
Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy (2012)

We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) of EMT6 tumors established in the ears of BALB/c mice. 24 h following intravenous (IV) administration of 1 μmol kg(-1) HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue. Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution. Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1(+)/CD11b(+) leukocytes and major histocompatibility complex class II (MHC-II)(+) cells in vivo. Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1(+) cells in response to therapy. The maximum accumulation of Gr1(+) cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point. Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1(+ )cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status. Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils. At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed. Co-localization analysis reveals an increase in the fraction of Gr1(+) cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype.
Supplementary Data from Pharmacokinetic Analysis and Phase 1 Study of MRX-1024 in Patients Treated with Radiation Therapy with or without Cisplatinum for Head and Neck Cancer (2023)

Supplementary Data from Pharmacokinetic Analysis and Phase 1 Study of MRX-1024 in Patients Treated with Radiation Therapy with or without Cisplatinum for Head and Neck Cancer