gebhart/patrepeval huggingface dataset:
Neural basis of opioid-induced respiratory depression and its rescue (2021)

Opioid-induced respiratory depression (OIRD) causes death following an opioid overdose, yet the neurobiological mechanisms of this process are not well understood. Here, we show that neurons within the lateral parabrachial nucleus that express the µ-opioid receptor (PBL <sup><i>Oprm1</i></sup> neurons) are involved in OIRD pathogenesis. PBL <sup><i>Oprm1</i></sup> neuronal activity is tightly correlated with respiratory rate, and this correlation is abolished following morphine injection. Chemogenetic inactivation of PBL <sup><i>Oprm1</i></sup> neurons mimics OIRD in mice, whereas their chemogenetic activation following morphine injection rescues respiratory rhythms to baseline levels. We identified several excitatory G protein-coupled receptors expressed by PBL <sup><i>Oprm1</i></sup> neurons and show that agonists for these receptors restore breathing rates in mice experiencing OIRD. Thus, PBL <sup><i>Oprm1</i></sup> neurons are critical for OIRD pathogenesis, providing a promising therapeutic target for treating OIRD in patients.
Aroma Precursors and Methylpyrazines in Underfermented Cocoa Beans Induced by Endogenous Carboxypeptidase (2008)

Cocoa-specific aroma precursors and methylpyrazines in underfermented cocoa beans obtained from fermentation induced by indigenous carboxypeptidase have been investigated. Fermentation conditions and cocoa bean components were analyzed during 0 to 3 d of fermentation. Underfermented cocoa beans were characterized as having hydrophilic peptides and free hydrophobic amino acids much higher than unfermented ones. These 2 key components of cocoa aroma precursors may be produced from the breakdown of proteins and polypeptides by endogenous carboxypeptidase during the fermentation process. The enzyme was activated during fermentation. Polypeptides of 47, 31, and 19 kDa were observed in the samples throughout the 3-d fermentation period; however, only the first 2 polypeptides were remarkably reduced during fermentation. Since the 1st day of fermentation, underfermented cocoa beans contained methylpyrazines, a dominant group of cocoa-specific aroma. This might be due to microbial activities during fermentation, observed through a decrease of pH value and an increase of temperature of cocoa beans. The concentration of tetramethylpyrazines was significantly increased during the 3 d of fermentation. This may increase the cocoa-specific flavor to the beans.
In Situ Measurement of the Plane-Strain Modulus of the Solid Electrolyte Interphase on Lithium-Metal Anodes in Ionic Liquid Electrolytes (2018)

We present an experimental approach for in situ measurement of elastic modulus of the solid electrolyte interphase (SEI), which is formed from reactions between a lithium thin-film [on a polydimethylsiloxane (PDMS) substrate] and a room-temperature ionic liquid (RTIL) electrolyte. The SEI forms under a state of compressive stress, which causes buckling of the sample surface. In situ atomic force microscopy is used to measure the dominant wavelength of the wrinkled surface topography. A mechanics analysis of strain-induced elastic buckling instability of a stiff thin film on a soft substrate is used to determine the plane strain modulus of the SEI from the measured wavelength. The measurements are performed for three RTIL electrolytes: 1-butyl 1-methylpiperidinium bis(trifluoromethylsulfonyl)imide (P<sub>14</sub> TFSI) without any lithium salt, 1.0 M lithium bis(trifluoromethylsulfonyl)imide (Li TFSI) in P<sub>14</sub> TFSI, and 1.0 M lithium bis(fluorosulfonyl)imide (Li FSI) in P<sub>14</sub> TFSI to investigate the influence of lithium salts on the plane strain modulus of the SEI. The measurements yield plane-strain moduli of approximately 1.3 GPa for no-salt P<sub>14</sub> TFSI and approximately 1.6 GPa for 1.0 M Li TFSI in P<sub>14</sub> TFSI and 1.0 M Li FSI in P<sub>14</sub> TFSI. The experimental technique presented here eliminates some of the uncertainties associated with traditional SEI mechanical characterization approaches and offers a platform to engineer an SEI with desired mechanical properties by approaches that include altering the electrolyte composition.
High-resolution Detector for Neutron Diffraction and Quantification of Subsurface Residual Stress (2019)

High-resolution Detector for Neutron Diffraction and Quantification of Subsurface Residual Stress Stuart R. Miller, Matthew S.J.Marshall, Megan Wart, Pijush Bhattacharya, Stephen Puplampu, Matthew Seals, Dayakar Penumadu, Rick Riedel, Vivek V. Nagarkar Abstract. We have developed a new high-resolution large-area detector for neutron diffraction imaging, specifically for the measurement of subsurface residual stress in engine components. […]
Learning Multivariate Shapelets with Multi-Layer Neural Networks (2018)

Shapelets are discriminative subsequences extracted from timeseries data.Classifiers using shapelets have proven to achieve performances competitive to state-of-the-art methods, while enhancing the model's interpretability.While a lot of research has been done for univariate time-series shapelets, extensions for the multivariate setting have not yet received much attention.To extend shapeletsbased classification to a multidimensional setting, we developed a novel architecture for shapelets learning, by embedding them as trainable weights in a multi-layer Neural Network.We also investigated a novel initialization strategy for the shapelets, based on meaningful multidimensional motif discovery using the Matrix Profile, a recently proposed time series analysis tool.Results on seven benchmark datasets show how the proposed architecture generalize the classification task to non-linear decision boundaries and allow for the extraction of interpretable multidimensional shapelets, while achieving competitive performance.
<title>Real-time portal imaging devices operating on high-pressure gaseous electronic principles</title> (1995)

A novel real-time portal imaging scanning detector, based on high-pressure gaseous electronics principles and operating up to 60 atmospheres, is presented and the predicted performance of this detector is analyzed. The idea is to utilize high pressure gaseous electronics imaging detectors operating in the saturation regime, aimed at improving image performance characteristics in real time portal imaging. As a result, beam localization errors are controlled, identified and corrected accurately and the patient radiotherapy treatment becomes more effective.
Effects of carbon nanotube fillers on the curing processes of epoxy resin‐based composites (2006)

Abstract The effects of different grades of carbon nanotubes on the curing of a typical epoxy resin (EPIKOTE™ resin 862 and EPIKURE™ curing agent W) were examined via differential scanning calorimetry. It was found that nanotubes could initiate cure at lower temperatures, while the overall curing process was slowed as evidenced by lower total heat of reaction and lower glass transition temperatures of the cured nanocomposites compared to neat epoxy. This finding is practically important as it is essential to have a consistent degree of cure when the properties of thermosets with nanoinclusions are compared to neat resins. It was also found that the inclusion of carbon nanotubes might induce the thermal degradation of epoxy composites at lower temperatures. Morphological analysis done with scanning electron microscopy revealed good dispersion of nanotubes within the epoxy matrix. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:5248–5254, 2006
Tuning parameters of the expected reciprocal rank (2012)

There are several popular IR metrics based on an underlying user model. Most of them are parameterized. Usually parameters of these metrics are chosen on the basis of general considerations and not validated by experiments with real users. Particularly, the parameters of the Expected Reciprocal Rank measure are the normalized parameters of the DCG metric, and the latter are chosen in an ad-hoc manner. We suggest two approaches for adjusting parameters of the ERR model by analyzing real users behaviour: one based on a controlled experiment and another relying on search log analysis. We show that our approaches generate parameters that are largely different from the commonly used parameters of the ERR model.
A Note on Design Decisions of a Formalization of the OCL (2002)

We compare several formal and informal approaches to define the semantics of the Object Constraint Language (OCL). This comparison reveals a number of minor and major design problems to be settled in upcoming versions of the OCL standard. We review these problems in the context of our work of providing a formal semantics of OCL through an conservative embedding in HOL using the Isabelle theorem prover.
Wide‐Range Color Tuning of Narrowband Emission in Multi‐resonance Organoboron Delayed Fluorescence Materials through Rational Imine/Amine Functionalization (2021)

Establishing a simple and versatile design strategy to finely modulate emission colors while retaining high luminescence efficiency and color purity remains an appealing yet challenging task for the development of multi-resonance-induced thermally activated delayed fluorescence (MR-TADF) materials. Herein, we demonstrate that the strategic introduction of electron-withdrawing imine and electron-donating amine moieties into a versatile boron-embedded 1,3-bis(carbazol-9-yl)benzene skeleton enables systematic hypsochromic and bathochromic shifts of narrowband emissions, respectively. By this method, effective electroluminescence color tuning was accomplished over a wide visible range from deep-blue to yellow (461-571 nm), using the same MR molecular system, without compromising very narrow spectral features. Deep-blue to yellow organic light-emitting diodes with maximum external quantum efficiencies as high as 19.0-29.2 % and superb color purity could be produced with this family of color-tunable MR-TADF emitters.
Characterization of Molecular Interactions between ACP and Halogenase Domains in the Curacin A Polyketide Synthase (2011)

Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are large multidomain proteins present in microorganisms that produce bioactive compounds. Curacin A is such a bioactive compound with potent anti-proliferative activity. During its biosynthesis the growing substrate is bound covalently to an acyl carrier protein (ACP) that is able to access catalytic sites of neighboring domains for chain elongation and modification. While ACP domains usually occur as monomers, the curacin A cluster codes for a triplet ACP (ACP(I)-ACP(II)-ACP(III)) within the CurA PKS module. We have determined the structure of the isolated holo-ACP(I) and show that the ACPs are independent of each other within this tridomain system. In addition, we have determined the structure of the 3-hydroxyl-3-methylglutaryl-loaded holo-ACP(I), which is the substrate for the unique halogenase (Hal) domain embedded within the CurA module. We have identified the interaction surface of both proteins using mutagenesis and MALDI-based identification of product formation. Amino acids affecting product formation are located on helices II and III of ACP(I) and form a contiguous surface. Since the CurA Hal accepts substrate only when presented by one of the ACPs within the ACP(I)-ACP(II)-ACP(III) tridomain, our data provide insight into the specificity of the chlorination reaction.
Allosteric Modulators of the CB 1 Cannabinoid Receptor: A Structural Update Review (2016)

In 2005, the first evidence of an allosteric binding site at the CB<sub>1</sub>R was provided by the identification of three indoles of the company Organon that were allosteric enhancers of agonist binding affinity and, functionally, allosteric inhibitors of agonist activity. Since then, structure-activity relationships of indoles as CB<sub>1</sub>R modulators have been reported. Targeting the allosteric site on CB<sub>1</sub>R, new families structurally based on urea and on 3-phenyltropane analogs of cocaine have been discovered as CB<sub>1</sub>R-negative allosteric modulators (NAMs), respectively, by Prosidion and by the Research Triangle Park. Endogenous allosteric ligands of different nature have been identified more recently. Thus, the therapeutic neuroprotection application of lipoxin A4, an arachidonic acid derivative, as an allosteric enhancer of CB<sub>1</sub>R activity has been confirmed <i>in vivo</i>. It was also the case of the steroid hormone, pregnenolone, whose negative allosteric effects on <i>Δ</i><sup>9</sup>-tetrahydrocannabinol (<i>Δ</i><sup>9</sup>-THC) were reproduced <i>in vivo</i> in a behavioral tetrad model and in food intake and memory impairment assays. Curiously, the peroxisome proliferator-activated receptor-γ agonist fenofibrate or polypeptides such as pepcan-12 have been shown to act on the endocannabinoid system through CB<sub>1</sub>R allosteric modulation. The mechanistic bases of the effects of the phytocannabinoid cannabidiol (CBD) are still not fully explained. However, there is evidence that CBD behaves as an NAM of <i>Δ</i><sup>9</sup>-THC- and 2-AG. Allosteric modulation at CB<sub>1</sub>R offers new opportunities for therapeutic applications. Therefore, further understanding of the chemical features required for allosteric modulation as well as their orthosteric probe dependence may broaden novel approaches for fine-tuning the signaling pathways of the CB<sub>1</sub>R.
Production Rules for Stereo Acquisition (2011)

This paper gives an overview on the framework of production rules that are required for the acquisition of adequate stereo content. It is well known that if stereo is not produced properly, consequences for the human 3-D perception might be eye strain and visual fatigue. Therefore, to avoid discomfort, stereographers use a production grammar that reflects extensive knowledge and experience in the fields of 3-D perception, stereo geometry, video technology, and content creation. Some of these rules are of heuristic nature, and others are motivated by perceptual, geometric, or technical aspects. The application of these rules at the set usually results in time-consuming manual work for rigging and adjusting stereo cameras before shooting. Against this background the paper reviews relevant aspects of 3-D perception, the fundamentals of stereo geometry, and the main rules of stereo production. Finally, it describes the functionality of camera assistance systems that have recently been proposed for stereo acquisition and production in order to ease the work of stereographers at the set and, with it, to save time and to make stereo productions more efficient.
Experimental Methods in Economics and Political Science: The Design and Testing of Policy Options (1994)

[Introduction] &#13;\nDesigner markets are becoming a reality: theoretical developments in economics and political science are now being combined with advances in laboratory technology to produce new uses of basic science and a new approach to policy. In essence the approach is similar to that of engineering, in which scientific principles and practical knowledge from laboratory experiments arc used to design systems or devices to perform a specific function. The new research efforts can be understood as involving a design methodology in the truest sense of the&#13;\nword. Policy issues are first cast as problems of decision process design and the architectures of decision mechanisms are then built on basic&#13;\nresearch foundations. Refinements and adjustments to institutions, organizations and procedures - which provide strength and desirability to a policy process - are then added as a result of the practical experience provided by laboratory experimentation and testing. The practical experience and testing are achieved by involving real people in controlled exercises that carefully replicate the constraints, the freedom for individual initiative, and the potential rewards of the process under test.
Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner (2020)

A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.
Are Inappropriate Relationships Inappropriate (2014)

Reiter’s lecture focused on relationships that society considers inappropriate and demonstrated how there are varying degrees of inappropriateness. The talk also highlighted how labeling a relationship as inappropriate has the power to impact people’s behaviors in ways that might not be helpful.
Structure–Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent (2017)

Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.
Performance of 200 V CMOS compatible auxiliary cathode lateral insulated gate transistors (2002)

The authors report the performance of various anode-shorted auxiliary cathode lateral insulated gate transistor (ACLIGT) structures fabricated using a 2.5 mu m digital CMOS compatible HVIC process. The reverse breakdown voltage of the ACLIGT is comparable to that of an equivalent anode shorted lateral insulated gate transistor (LIGT). The results indicate that, by placing an auxiliary cathode and an extended p-buried layer of an anode-shorted LIGT, the holes flowing into the p-well can be diverted to overcome the latch-up problems of the LIGT in an ACLIGT. The LIGT shows latch-up at 140 mA, which corresponds to a current density of 340 A/cm/sup 2/ while the ACLIGT structures do not show latch-up. The measured turn-off characteristics of the ACLIGT reveal a turn-off time of less than 250 ns while an equivalent LIGT shows a turn-off time of 350 ns.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Clinically Translatable Immune-based Classification of HPV-associated Head and Neck Cancer with Implications for Biomarker-Driven Treatment Deintensification and Immunotherapy (2022)

Abstract Purpose Human papillomavirus-associated (HPV + ) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America. There is significant interest in treatment de-escalation for these patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict the survival of patients with newly diagnosed HPV + HNSCC. Methods We created a prognostic score (UWO3) that was successfully validated in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Transcriptomic data from two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. Results A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival at 5 years to the immune desert (HR= 9.0, 95% CI 3.2–25.5, P =3.6×10 −5 ) and mixed (HR=6.4, 95%CI 2.2–18.7, P =0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. Conclusions The UWO3 immune score could enable biomarker-driven clinical decision-making for patients with HPV + HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies, while the inferior outcomes of the immune desert patients suggest the potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned.
Design of Polydiacetylene-Phospholipid Supramolecules for Enhanced Stability and Sensitivity (2012)

We present polydiacetylene (PDA) liposome assemblies with various phospholipids that have different headgroup charges and phase transition temperatures (T(m)). 10,12-Pentacosadiynoic acid (PCDA)-epoxy was used as a base PDA monomer and the insertion of highly charged phospholipids resulted in notable changes in the size of liposome and reduction of the aggregation of PDA liposome. Among the various phospholipids, the phospholipid with a moderate T(m) demonstrated enhanced stability and sensitivity, as measured by the size and zeta potential over storage time, thermochoromic response, and transmission electron microscopy images. By combining these results, we were able to detect immunologically an antibody of bovine viral diarrhea virus over a wide dynamic range of 0.001 to 100 μg/mL.
Supplementary Figure S5 from The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects (2023)

&lt;p&gt;JQ1 and panobinostat do not cooperatively regulate GSK3β and Aurora A expression, and LIN28B does not regulate Aurora A expression.&lt;/p&gt;
ChemInform Abstract: The C4 Hydroxyl Group of Phorbol Esters Is Not Necessary for Protein Kinase C Binding. (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.