gebhart/patrepeval huggingface dataset:
Influence of Food Intake and Formulation on the Pharmacokinetics and Metabolism of Bosentan, a Dual Endothelin Receptor Antagonist (2002)

The purpose of the study was to investigate the effect of food intake on the pharmacokinetics and metabolism as well as the relative bioavailability of bosentan. Sixteen healthy male subjects were treated in a randomized, four-way, crossover design with single oral doses of 125 mg bosentan, given as one tablet (with or without food), two tablets of 62.5 mg (with food), and a suspension (without food). The pharmacokinetic parameters of bosentan (and also three of its metabolites) were very similar after the four treatments: geometric means for Cmax and AUC0-infinity, ranged from 1.3 to 1.6 microg/ml and from 7.8 to 8.9 microg x h/ml, respectively, and median t(max) from 3.0 to 4.0 hours. The bioavailability of the 125 mg tablet relative to that of the suspension, both given fasted, was 102%. In the presence of food, Cmax and AUC0-max increased by 22% and 10%, respectively, whereas the two 62.5 mg tablets were bioequivalent to the 125mg tablet, both under fed conditions. The pharmacokinetics of the metabolites was independent of the treatment administered. In conclusion, bosentan bioavailability from the newly developed 125 mg tablet formulation is similar to that of the suspension, and food intake does not influence its pharmacokinetics to a clinically relevant extent.
Antisense Oligonucleotide-Mediated Reduction of HDAC6 Does Not Reduce Tau Pathology in P301S Tau Transgenic Mice (2021)

Acetylation of tau protein is dysregulated in Alzheimer's Disease (AD). It has been proposed that acetylation of specific sites in the KXGS motif of tau can regulate phosphorylation of nearby residues and reduce the propensity of tau to aggregate. Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme involved in deacetylation of multiple targets, including tau, and it has been suggested that inhibition of HDAC6 would increase tau acetylation at the KXGS motifs and thus may present a viable therapeutic approach to treat AD. To directly test the contribution of HDAC6 to tau pathology, we intracerebroventricularly injected an antisense oligonucleotide (ASO) directed against HDAC6 mRNA into brains of P301S tau mice (PS19 model), which resulted in a 70% knockdown of HDAC6 protein in the brain. Despite a robust decrease in levels of HDAC6, no increase in tau acetylation was observed. Additionally, no change of tau phosphorylation or tau aggregation was detected upon the knockdown of HDAC6. We conclude that HDAC6 does not impact tau pathology in PS19 mice.
Malignant Transformation of Condyloma Acuminatum: A Light Microscopic and Ultrastructural Study (1974)

Three cases of condyloma acuminatum with malignant transformation, and ultrastructural details of one, are reported. Carcinoma developed wim unusual rapidity in the sessile papillomas. Aggregates of uniform, spherical, 45–50-millimicron particles, suggestive of papova viruses, were detected in the nuclei of a few cells in one benign condyloma. Similar particles were not found in the condyloma showing malignant transformation from the same patient. In the neoplastic epithelium there were peculiar multinucleated, syncytial giant cells. Ultrastructurally, the nuclei of the giant cells often manifested ring-shaped nucleoli, characteristic of resting cells, which may not contribute to the further growth of the neoplasm.
A random dynamical systems approach to filtering in large-scale networks (2010)

The paper studies the problem of filtering a discrete-time linear system observed by a network of sensors. The sensors share a common communication medium to the estimator and transmission is bit and power budgeted. Under the assumption of conditional Gaussianity of the signal process at the estimator (which may be ensured by observation packet acknowledgements), the conditional prediction error covariance of the optimum mean-squared error filter is shown to evolve according to a random dynamical system (RDS) on the space of non-negative definite matrices. Our RDS formalism does not depend on the particular medium access protocol (randomized) and, under a minimal distributed observability assumption, we show that the sequence of random conditional prediction error covariance matrices converges in distribution to a unique invariant distribution (independent of the initial filter state), i.e., the conditional error process is shown to be ergodic. Under broad assumptions on the medium access protocol, we show that the conditional error covariance sequence satisfies a Markov-Feller property, leading to an explicit characterization of the support of its invariant measure. The methodology adopted in this work is sufficiently general to envision this application to sample path analysis of more general hybrid or switched systems, where existing analysis is mostly moment-based.
Automated Assessment of the Quality of Depression Websites (2005)

Depression websites of different evidence-based quality can be differentiated using an automated system. If replicable, generalizable to other health conditions and deployed in a consumer-friendly form, the automated procedure described here could represent an important advance for consumers of Internet medical information.
Evaluating the Impact of Proposed OpenMP 5.0 Features on Performance, Portability and Productivity (2018)

We investigate how specialization mechanisms proposed for OpenMP 5.0 -- specifically, the metadirective and declare variant directives -- may be deployed in a real-life code, using the miniMD benchmark from the Mantevo suite. Additionally, we develop an OpenMP 4.5 implementation of miniMD that achieves a performance portability of 59.35% across contemporary CPU and GPU hardware, discuss the processes of porting and enabling this code, and show that the use of specialization would enable our code to be expressed in a significantly more compact form, with implications for productivity.
Development and Validation of a Chromatographic Ultraviolet Method for the Quantification of Isavuconazole in Human Plasma Samples (2018)

Cozzi, Valeria BiolSciD*; Baldelli, Sara ChemD*; Castoldi, Simone BiotechD*; Clementi, Emilio MD†,‡; Cattaneo, Dario PhD* Author Information
Fluorescent labels and their use in separations (2023)

Compositions are provided comprising sets of fluorescent labels carrying pairs of donor and acceptor dye molecules, designed for efficient excitation of the donors at a single wavelength and emission from the acceptor in each of the pairs at different wavelengths. The different molecules having different donor-acceptor pairs can be modified to have substantially the same mobility under separation conditions, by varying the distance between the donor and acceptor in a given pair. Particularly, the fluorescent compositions find use as labels in sequencing nucleic acids.
Molecular Testing for Treatment of Metastatic Non-Small Cell Lung Cancer: How to Implement Evidence-Based Recommendations (2015)

The recent discovery of relevant biomarkers has reshaped our approach to therapy selection for patients with non-small cell lung cancer. The unprecedented outcomes demonstrated with tyrosine kinase inhibitors in molecularly defined cohorts of patients has underscored the importance of genetic profiling in this disease. Despite published guidelines on biomarker testing, successful tumor genotyping faces significant hurdles at both academic and community-based practices. Oncologists are now faced with interpreting large-scale genomic data from multiple tumor types, possibly making it difficult to stay current with practice standards in lung cancer. In addition, physicians' lack of time, resources, and face-to-face opportunities can interfere with the multidisciplinary approach that is essential to delivery of care. Finally, several challenges exist in optimizing the amount and quality of tissue for molecular testing. Recognizing the importance of biomarker testing, a series of advisory boards were recently convened to address these hurdles and clarify best practices. We reviewed these challenges and established recommendations to help optimize tissue acquisition, processing, and testing within the framework of a multidisciplinary approach.
A multi-band internal antenna for all commercial mobile communication bands and 802.11a/b/g/n WLAN (2011)

An internal antenna for mobile phones with small volume is proposed. The proposed antenna is based on a planar inverted F-antenna (PIFA) with a coupled feeding structure. The proposed antenna realized on a printed circuit board to reduce fabrication costs. The coupled feeding structure helps the antenna have broadband characteristic which includes all commercial service bands, GSM850 / GSM900 / GPS / GSM1800 / GSM1900 / WCDMA2100 / 802.11b/g / LTE2600 (824–2690 MHz) as well as 802.11a/n (5150–5825 MHz). The antenna gain is in the range of −0.1–3.5 dBi over 824–2690 MHz and 2.3–2.8 dBi over 5150–5825 MHz. And the antenna efficiency is in the range of 615150–93 % over 8245150–2690 MHz and 695150–81 % over 51505150–5825 MHz. In addition, the effect of SAM head phantom is tested using a simulation. As a result, it was verified that the performance does not change significantly. The total size including system circuit area and no-ground area is 100 5150× 40 × 0.8 mm3. The SAR results for the proposed antenna are presented as proper values. As a result, the designed antenna is suitable for small mobile devices and slim wireless applications.
Preparation and Characterization of Poly(3-arylthiophene)s (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and Characterization of Poly(3-arylthiophene)sDouglas J. Guerrero, Xiaoming Ren, and J. P. FerrarisCite this: Chem. Mater. 1994, 6, 8, 1437–1443Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://doi.org/10.1021/cm00044a049RIGHTS & PERMISSIONSArticle Views347Altmetric-Citations71LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
A Specific Multi-Nutrient Diet Reduces Alzheimer-Like Pathology in Young Adult AβPPswe/PS1dE9 Mice (2012)

Diet is an important lifestyle factor implicated in the etiology of Alzheimer's disease (AD), but so far it is not fully elucidated to which nutrients the suggested protective effect of diet can be attributed. Recent evidence obtained in the amyloid-β 1-42 (Aβ(42)) infusion model in rats has shown that a multi-nutrient intervention known as Fortasyn™ Connect (FC) may protect the central cholinergic system against Aβ(42)-induced toxicity. FC comprises the nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid (DHA), eicosapentaenoic acid, uridine-mono-phosphate (UMP), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium. In order to investigate whether the combined administration of these nutrients may also affect AD-like pathology, we now evaluated the effects of the FC diet intervention in the transgenic AβPP(swe)/PS1(dE9) mouse model with endogenous Aβ production. In addition we evaluated the effects of diets containing the individual nutrients DHA and UMP and their combination in this model. Between the age of 3 and 6 months, FC diet decreased brain Aβ levels and amyloid plaque burden in the hippocampus of AβPP/PS1 mice. The FC diet also reduced ongoing disintegrative degeneration in the neocortex, as indicated by Amino Cupric Silver staining. Although all three DHA-containing diets were equally effective in changing brain fatty acid profiles, diets differentially affected amyloid-related measures, indicating that effects of DHA may depend on its dietary context. The current data, showing that dietary enrichment with FC reduces AD-like pathology in AβPP/PS1 mice, confirm and extend our previous findings in the Aβ(42) infusion model and favor the combined administration of relevant nutrients.
Model-Based Threat Assessment for Avoiding Arbitrary Vehicle Collisions (2010)

This paper presents a model-based algorithm that estimates how the driver of a vehicle can either steer, brake, or accelerate to avoid colliding with an arbitrary object. In this algorithm, the motion of the vehicle is described by a linear bicycle model, and the perimeter of the vehicle is represented by a rectangle. The estimated perimeter of the object is described by a polygon that is allowed to change size, shape, position, and orientation at sampled time instances. Potential evasive maneuvers are modeled, parameterized, and approximated such that an analytical expression can be derived to estimate the set of maneuvers that the driver can use to avoid a collision. This set of maneuvers is then assessed to determine if the driver needs immediate assistance to avoid or mitigate an accident. The proposed threat-assessment algorithm is evaluated using authentic data from both real traffic conditions and collision situations on a test track and by using simulations with a detailed vehicle model. The evaluations show that the algorithm outperforms conventional threat-assessment algorithms at rear-end collisions in terms of the timing of autonomous brake activation. This is crucial for increasing the performance of collision-avoidance systems and for decreasing the risk of unnecessary braking. Moreover, the algorithm is computationally efficient and can be used to assist the driver in avoiding or mitigating collisions with all types of road users in all kinds of traffic scenarios.
Online Assessment of Driving Riskiness via Smartphone-Based Inertial Measurements (2020)

Assessing the driving-style from dynamic data is a well established line of research, which has tackled the description of risky behaviours, the profiling of energy-consumption habits, and the detection of different driver's characteristics from the analysis of motion data. In the last years, as smartphone ownership has become widespread, such an assessment has been increasingly relying on the measurements taken from the inertial sensors on board of the smartphone itself. This work stands in this context, and it aims to design a 4-dimensional driving-style assessment for insurance purposes. The main contribution is adding, to more common proxies of risky-driving, the dimension of smartphone usage, the detection of which is performed through an appropriate processing of smartphone-based inertial sensors, thus not relying on privacy-sensitive monitoring of phone usage behavior. Physics-based, fine-grained dynamic features are used to classify the overall riskiness of the driving-style, thus providing a comprehensive insight into the most discriminating features. The study is based on experimental data, collected over more than five thousands kilometers of varied car trips.
Single-Event Effects Induced on Atom Switch-based Field-Programmable Gate Array (2019)

Single-event effects (SEEs) of atom switches (ASs) embedded on 40-nm complementary metal-oxide-semiconductor (CMOS) are investigated with both heavy-ion and pulsed laser irradiation. In the evaluation of an AS-based field-programmable gate array (AS-FPGA), ASs show immunity against the irradiation and there is no change of the state of ASs both in a cross-bar switch and memory in lookup tables (LUTs). ASs are not supposed to make any single-event transient (SET) noise when the ions hit. However, the CMOS layer shows SETs, and new approaches are proposed to solve the SET in CMOS, especially for AS-FPGA application.
Abstract SY42-03: Systematic interrogation of cancer dependencies and synthetic lethal interactions (2019)

Abstract Although molecular profiling of human tumors is becoming increasingly routine, the use of this data to guide remains limited to a subset of patients. To complement genome characterization studies, we have used genome scale gain and loss of function approaches to identify genes required for cell survival and transformation. Specifically, we have performed systematic studies to interrogate rare alleles found altered in cancer genomes and used advances in synthetic gene synthesis to prospectively interrogate all possible alleles of known cancer genes. In parallel, we have performed both genome scale RNAi and CRISRP-Cas9 screens in hundreds of cancer cell lines to identify differentially essential genes and the context that specifies gene dependency. Integrating these studies with genome characterization of human tumors and protein-protein interaction databases facilitates the identification of genes and pathways required for the survival of specific cancer subtypes. These studies allow us to define a global cancer dependencies map, which will help further operationalize precision cancer medicine. Citation Format: William C. Hahn. Systematic interrogation of cancer dependencies and synthetic lethal interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY42-03.
Total Synthesis of Violaceoid A and (−)- and (+)-Violaceoid B (2018)

The first total synthesis of violaceoid A, a cytotoxic agent, and the asymmetric total synthesis of (-)- and (+)-violaceoid B are reported. The precursor was accessed by desymmetrization of a substituted quinol moiety, and the racemic secondary alcohol was kinetically resolved using a chiral nucleophilic catalyst. The asymmetric synthesis of (-)- and (+)-violaceoid B elucidated the absolute configuration of the naturally occurring violaceoid B. Synthetic violaceoid A inhibited the growth of human breast cancer cell lines MCF-7 and Hs 578T at concentrations of less than 100 μM, while ( S)- and ( R)-violaceoid B were inactive.
Introduction: Intolerance, Power, and Epistemology (2022)

In 1522, the Knights’ Revolt kicked off the Wars of Religion. Half a millennium later, intolerance is rife, and important questions about it have yet to be answered. It is a pleasure to be able to introduce a symposium that addresses some of these questions, although of course it does not fully resolve them. Fallibilism may cast enough doubt on the validity of one’s own beliefs that it undermines the self-confident, Marcusean desire to suppress antithetical beliefs. But as Friedman points out in her paper, “Early Modern Epistemologies of Religious Toleration,” fallibilism, an epistemological stance, does not necessarily map onto a tolerationist policy stance. The many logical possibilities created by Friedman’s separation of fallibilist epistemologies and tolerationist attitudes from tolerant policies are not, of course, exhausted by the combinations that we find in Castellio’s, Calvin’s, and Franck’s thought.
Phenotype characterization of human melanoma cells resistant to dabrafenib (2017)

In the present study, the phenotype of melanoma cells resistant to dabrafenib (a B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B-RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3 different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they were characterized by cytofluorometric analysis, Ion Torrent technology, immunofluorescence and biochemistry. All dabrafenib-resistant cells showed, in addition to a re-activation of MAPK signaling, morphological changes compared to their sensitive counterparts, accompanied by an increase in CD90 (mesenchymal marker) expression and a decrease in E-cadherin (epithelial marker) expression, suggesting an epithelial-to-mesenchymal-like phenotypic transition. However, melanoma cells with TGF-β1-induced epithelial-to-mesenchymal transition (EMT) were more sensitive to dabrafenib treatment compared to the sensitivity noted in the non-TGF‑β1‑induced EMT melanoma cells, suggesting that TGF-β1-induced EMT was not associated with dabrafenib resistance. Although dabrafenib-resistant cells exhibited increased cell motility and E-cadherin/vimentin reorganization, as expected in EMT, all of them showed unvaried E-cadherin mRNA and unchanged Snail protein levels, while Twist1 protein expression was decreased with the exception of A375 dabrafenib-resistant melanoma cells, where it was unaffected. These findings suggest a distinct active EMT-like process adopted by melanoma cells under drug exposure. Furthermore, dabrafenib-resistant cells exhibited stem cell-like features, with Oct4 translocation from the cytoplasm to peri-nuclear sites and nuclei, and increased CD20 expression. In conclusion, our data, in addition to confirming that resistance to dabrafenib is dependent on re-activation of MAPK signaling, suggest that this resistance is linked to a distinct active EMT-like process as well as stem-cell features adopted by melanoma cells.
Molecular Design of Thermally Activated Delayed‐Fluorescent Emitters Using 2,2′‐Bipyrimidine as the Acceptor in Donor–Acceptor Structures (2017)

Donor-acceptor-donor (D-A-D)-type thermally activated delayed fluorescence (TADF) emitters 5,5'-bis{4-[9,9-dimethylacridin-10(9H)-yl]phenyl}-2,2'-bipyrimidine (Ac-bpm) and 5,5'-bis[4-(10H-phenoxazin-10-yl)phenyl]-2,2'-bipyrimidine (Px-bpm), based on the 2,2'-bipyrimidine accepting unit, were developed and their TADF devices were fabricated. The orthogonal geometry between the donor unit and the 2,2'-bipyrimidine accepting core facilitated a HOMO/LUMO spatial separation, thus realizing thermally activated delayed fluorescence. The exhibited electroluminescence ranged from green to yellow, depending on the donor unit, with maximum external quantum efficiencies of up to 17.1 %.
A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis (2014)

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.