gebhart/patrepeval huggingface dataset:
Novel N-Arylpyrazolo[3,2-c]-Based Ligands for the Glucocorticoid Receptor:  Receptor Binding and in Vivo Activity (2004)

A novel series of selective ligands for the human glucocorticoid receptor (hGR) are described. Preliminary structure-activity relationships were focused on substitution at C-1 and indicated a preference for 3-, 4-, and 5-substituted aromatic and benzylic groups. The resulting analogues, e.g., 18 and 34, exhibited excellent affinity for hGR (IC(50) 1.9 nM and 2.8 nM, respectively) and an interesting partial agonist profile in functional assays of transactivation (tyrosine aminotransferase, TAT, and glutamine synthetase, GS) and transrepression (IL-6). The most potent compounds described in this study were the tertiary alcohol derivatives 21 and 25. These candidates showed highly efficacious IL-6 inhibition versus dexamethasone. The thiophenyl analogue 25 was evaluated in vivo in the mouse LPS challenge model and showed an ED(50) = 4.0 mg/kg, compared to 0.5 mg/kg for prednisolone in the same assay.
A Study of Flame-Vortex Interactions in the Presence of Residual Gases (2008)

In this work the effects of residual combustion products from a prior injection on flame extinction characteristics in a Diesel fuel pulse are investigated through a fundamental study. A numerical code with sixth-order accurate spatial discretization and multiple-step chemical kinetics is used to simulate flame-vortex interactions under Diesel conditions in the presence of residual combustion product mixtures. The results indicate that there is a balance between the heating effect of the high-temperature combustion products that enhance flame stability and the dilution effect of the reduced oxygen concentration, which promotes extinction. These counteracting aspects of the entrained combustion products can lead to an ideal dwell time between multiple injection events for optimum benefits in flame stability.
Low-pressure Cs-Ba discharge. I. Model development (1995)

A transient model of a low-pressure Cs-Ba diode which operates in a collisionless Knudsen mode is developed and benchmarked with experimental measurements. The model couples the external circuit to the plasma discharge in the diode. The model calculates the electron energy, plasma density, densities of ground state and first four excited states of neutral Cs atoms, sheath potentials, Cs coverage on the electrode surfaces, forward voltage drop, and discharge current as functions of time, as well as the current-voltage (I-V) characteristic of the diode. Calculated terminal voltage and current characteristics are in good agreement with experimental values.
Identifying patterns in amyotrophic lateral sclerosis progression from sparse longitudinal data (2022)

The clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought to determine whether there were common patterns of disease progression that could aid in the design and analysis of clinical trials. We developed an approach based on a mixture of Gaussian processes to identify clusters of patients sharing similar disease progression patterns, modeling their average trajectories and the variability in each cluster. We show that ALS progression is frequently nonlinear, with periods of stable disease preceded or followed by rapid decline. We also show that our approach can be extended to Alzheimer's and Parkinson's diseases. Our results advance the characterization of disease progression of ALS and provide a flexible modeling approach that can be applied to other progressive diseases.
Ofranogene obadenovec (VB-111), an anti-cancer gene therapy in combination with bevacizumab to improve overall survival compared to bevacizumab monotherapy in patients with rGBM: A phase 2 historically controlled trial. (2016)

2074 Background: Ofranergene obadenovec (VB-111) is a gene-therapy specifically targeting angiogenic endothelial cells thereby leading to tumor starvation. Safety and efficacy of VB-111 in combination with bevacizumab (BEV) were evaluated in recurrent Glioblastoma (rGBM) patients in this Phase 2 study and were compared to pooled BEV data generated using meta-analysis. Methods: VB-111 was administered at 1x1013 viral particles bimonthly until progression, followed by BEV standard of care (limited exposure cohort). The protocol was amended to add BEV 10mg/Kg biweekly combined with VB-111 bimonthly, until further progression (continuous exposure cohort). A systematic literature review identified reports of rGBM BEV monotherapy published between 1.1.2009 and 30.11.2015. Data were pooled in a meta-analysis and served as historical controls for comparison of VB-111 extended exposure cohort. Results: 46 patients at 4 sites received up to 13 doses of VB-111. Upon further progression, 24 received VB-111 with BEV, 22 were treated with BEV as standard of care. VB-111 was safe and well-tolerated alone and combined with BEV. Median OS was 59 weeks for continuous exposure versus 33 weeks for limited exposure cohort (p = 0.048). Eight reports of BEV monotherapy were identified, with a total of 694 rGBM patients. VB-111 continuous exposure had superior OS compared to the pooled meta-analysis of BEV monotherapy, 59 versus 39 weeks (p = 0.0295, log-rank test), with a Hazard Ratio of 0.62 (95% CI: 0.40-0.96). Of 46 patients who received VB-111, 25 patients spiked a fever post- dosing of VB-111 at least once, which was associated with increased median OS of 64 weeks versus 34 weeks among patients without fever (p = 0.03). Conclusions: VB-111 was safe and well-tolerated alone and combined with BEV in rGBM patients. VB-111 continuous exposure significantly increased OS compared to a historical BEV meta-analysis controls, and compared to VB-111 limited exposure. Toxicities were as expected in this population. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway. Clinical trial information: NCT01260506.
Effects of angular range on lesion margin assessment in contrast-enhanced digital breast tomosynthesis (2019)

Contrast-Enhanced Digital Breast Tomosynthesis (CEDBT) provides quasi three-dimensional contrast enhancement of breast lesions and has been investigated for breast cancer detection and lesion assessment. The acquisition geometry of CEDBT may affect its ability to detect and assess contrast-enhanced lesions. In this study, we investigate the effects of angular range of CEDBT on lesion margin assessment. The CIRS BR3D phantom with iodine inserts was imaged for four angular ranges between 15 and 45 degrees with same total glandular dose using a prototype CEDBT system. The artifact spread functions of iodine objects with various sizes were measured. The detectability of iodine objects overlaid in the depth direction with different separation distances was evaluated using signal-difference-to-noise ratio. Clinical images of malignant lesions were acquired with 25 projections over approximately 50 degrees, and CEDBT for various angular ranges were generated using a subset or all of the projection images and were assessed for lesion margins. Our results show that increasing angular range of CEDBT improves the separation of overlapping iodine signals in phantom images, and the margins of malignant mass lesions are better identified. In conclusion, CEDBT with wide angular range may improve lesion characterizations, e.g. lesion size, morphology and location, and provide better performance than contrast enhanced digital mammography (CEDM) for applications such as guidance of biopsy and evaluation of treatment response.
Corrigendum: (N‐Phosphinoamidinate)cobalt‐Catalyzed Hydroboration: Alkene Isomerization Affords Terminal Selectivity (2016)

In Figure 1, <5% conversion of 2c to 3 when using 1-Fe was presented in the originally published manuscript. We have observed in subsequent repeat experiments that under these conditions 2c is transformed into a mixture of 3 (≈80%) and internal hydroboration products (≈20%). Though the source of poor catalytic performance originally observed for 1-Fe is unclear at present, it is possible that catalyst poisoning by an impurity in a commercial substrate may play a role. The authors apologize for any confusion caused as a result.1 Figure 2 Octene isomerization/hydroboration reactions catalyzed by 1-Fe and 1-Co and employing HBPin (conversions given on the basis of NMR spectroscopic data).
ChemInform Abstract: Conversion of Azides into Diazo Compounds in Water. (2014)

Abstract A new phosphinoester mediates the conversion of azides into diazo compounds in phosphate buffer at pH 7.0.
Pausing a stir: heterogeneous catalysis in “dry water” (2010)

The highly distributed gas–liquid interface in “dry water” powder can be used to greatly increase the kinetics of a gas–liquid heterogeneous catalytic hydrogenation, in the absence of any applied mixing.
B5GEMINI: Digital Twin Network for 5G and Beyond (2022)

Digital Twin Network (DTN) is a new technology that builds on the concept of Digital Twins (DT) to create a virtual representation of the physical objects of a telecommunications network. DTN bridges physical and virtual spaces to enable coordination and synchronization of physical parts while eliminating the need to directly interact with them. In this work, we present B5GEMINI a DTN for 5G and beyond networks that makes an extensive use of artificial intelligence (AI). First, we present the infrastructural and architectural components that support B5GEMINI. Next, we explore five paradigmatic use cases where AI can leverage B5GEMINI for building new AI-powered applications. Finally, we identify the main components of the AI ecosystem of B5GEMINI.
Supplementary Data from Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis (2023)

Supplementary Data from Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis
Knowledge, attitudes, beliefs and behaviours of older adults about pneumococcal immunization, a Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN) investigation (2014)

These results indicate healthcare recommendation significantly influenced vaccine uptake in this population of older adults. Measures to encourage healthcare providers to offer the vaccine may help increase coverage.
Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions (2013)

TWEAK binds to hFn14 by surface plasmon resonance (View interaction) xeFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction) TWEAK binds to xeFn14 by surface plasmon resonance (View interaction) hFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction).
Intermolecular Stereospecific Substitution of Underivatized Enantioenriched Secondary Alcohols by Organocatalysis (2019)

The stereospecific substitution of non-derivatized and non-allylic enantioenriched alcohols with only water as a by-product would enable the use of readily available alcohols as substrates for green and sustainable transformations. However, the poor leaving group ability of the OH group has hampered the development of such a process. Denton and co-workers recently described the use of (2-hydroxybenzyl)diphenylphosphine oxide as a catalyst of a redox-neutral and zero-waste-generating Mitsunobu reaction. This innovative process constitutes the first intermolecular stereospecific substitution of non-allylic alcohols, and might find industrial applications.
An electrical micro Coulter approach toward the characterization of size tunable microbubbles produced by a flow focusing microfluidic device (2017)

Micro Coulter Particle Counters (μCPCs) are a class of microfluidic devices that achieve electrical detection of particles through a sensing zone. An unsolved problem in operating flow focusing microfluidic devices (FFMDs) and researching potential point-of-use applications is the requirement for observation under a high speed microscopy setup. By integrating a μCPC into an FFMD, we demonstrate the electrical detection of microbubbles (MBs) as progress towards eventual use in a point-of-use application involving an FFMD placed on a catheter tip.
A dual molecular analogue tuner for dissecting protein function in mammalian cells (2016)

Loss-of-function studies are fundamental for dissecting gene function. Yet, methods to rapidly and effectively perturb genes in mammalian cells, and particularly in stem cells, are scarce. Here we present a system for simultaneous conditional regulation of two different proteins in the same mammalian cell. This system harnesses the plant auxin and jasmonate hormone-induced degradation pathways, and is deliverable with only two lentiviral vectors. It combines RNAi-mediated silencing of two endogenous proteins with the expression of two exogenous proteins whose degradation is induced by external ligands in a rapid, reversible, titratable and independent manner. By engineering molecular tuners for NANOG, CHK1, p53 and NOTCH1 in mammalian stem cells, we have validated the applicability of the system and demonstrated its potential to unravel complex biological processes.
Alkylating analogs of bradykinin (1975)

Three analogs of bradykinin have been synthesized which bear a bromoacetyl function on the alpha-amino group or on an anilinic amino group at position 5 or 8. It was hoped that one or more of these analogs might act as an irreversible bradykinin antagonist or as a long-acting converting enzyme inhibitor. Although none of the analogs exhibited the desired pharmacological properties, the methods described for the synthesis and characterization of peptides bearing anilinic bromoacetyl groups are of potential utility in the development of antagonists of other tyrosine--or phenylalanine--containing peptides.
Performance of visual tasks from contour information (2010)

A recently proposed visual aid for patients with a restricted visual field (tunnel vision) combines a see-through head-mounted display (HMD) and a simultaneous minified contour view of the wide field image of the environment. Such a widening of the effective visual field is helpful for tasks such as visual search, mobility and orientation. The sufficiency of contours (outlines of the objects in the image) for performing everyday visual tasks by human observers is of major importance for this application, as well as for other applications, and for basic understanding of human vision. Due to their efficient properties as good object descriptors, contours are widely used in computer vision applications, and therefore many methods have been developed for automatic extraction of them from the image. The purpose of this research is to examine and compare the use of different types of automatically created contours, and contour representations, for practical everyday visual operations using commonly observed images. The visual operations include visual searching for items such as keys, remote control, etc. Considering different recognition levels, identification of an object is distinguished from detection (when it is not clearly identified). Some new non-conventional visual-based contour representations were developed for this purpose. Experiments were performed with normal vision subjects, by superposing contours of the wide-field of the scene, over a narrow field (see-through) background. Results show that about 85% success is obtained by for searched object identification when the best contour versions are employed.
Sub-nanometer Copper Clusters as Alternative Catalysts for the Selective Oxidation of Methane to Methanol with Molecular O2 (2022)

The partial oxidation of methane to methanol with molecular O<sub>2</sub> at mild reaction conditions is a challenging process, which is efficiently catalyzed in nature by enzymes. As an alternative to the extensively studied Cu-exchanged zeolites, small copper clusters composed by just a few atoms appear as potential specific catalysts for this transformation. Following previous work in our group that established that the reactivity of oxygen atoms adsorbed on copper clusters is closely linked to cluster size and morphology, we explore by means of DFT calculations the ability of bidimensional (2D) and three-dimensional (3D) Cu<sub>5</sub> and Cu<sub>7</sub> clusters to oxidize partially methane to methanol. A highly selective Eley-Rideal pathway involving homolytic C-H bond dissociation and a non-adsorbed radical-like methyl intermediate is favored when bicoordinated oxygen atoms, preferentially stabilized at the edges of 2D clusters, are available. Cluster morphology arises as a key parameter determining the nature and reactivity of adsorbed oxygen atoms, opening the possibility to design efficient catalysts for partial methane oxidation based on copper clusters.
Desferrioxamine for Stimulation of Fracture Healing and Revascularization in a Bone Defect Model (2012)

Abstract : Our study explored local delivery of deferroxamine with and without bone allograft as a means to accelerate fracture healing in a tibia defect model of the rat. Experimental groups in the first study included: control, CS: calcium sulfate annulus around spacer at defect, CS/DBA: CS implant and demineralized bone allograft (DBA); CS/DFO: DFO (300 g) loaded CS implant, CS/DFO/DBA: DFO loaded CS implant with DBA allograft. Experimental groups in the second study included: control, DBA, LDFO/ DBA: DBA soaked with DFO (10 g), H-DFO/DBA: DBA soaked with DFO (100ug). Fractures were evaluated at 6 weeks postinjury for radiographic cortical bridging, CT mineralized callus volume and torsional properties. The bulk CS annulus was found to impair healing compared to the control in the 1st study. In the 2nd study L-DFO/DBA was found to increase cortical bridging and torsional strength relative to the control. Bulk form CS is not an effective method of delivery of DFO to stimulate fracture healing. Low dosage DFO treatment directly to DBA was found to enhance the ability of DBM to stimulate fracture healing, while higher dosage DFO treatment of DBA was not effective.
Performance of High-Speed Downlink Packet Access in Coexistence With Dedicated Channels (2007)

The joint third-generation system performance of high-speed downlink packet access (HSDPA) and Release 99 (Rel'99) dedicated channels (DCH) is studied. Given such a scenario, the optimal sharing of the cell carrier transmit power between HSDPA and DCH, which is conditioned on a certain number of channelization codes that are reserved for HSDPA transmission, is addressed. Detailed network-performance results are shown from a comprehensive dynamic system-level simulator, which includes a simulation of many cells and users, and a detailed modeling of layer 1 to layer 3. Compared to a scenario without HSDPA, the total cell throughput can be increased by 69% by allocating five high-speed physical downlink shared channel codes and 35% of the maximum cell transmit power to HSDPA transmission. These results are obtained for a macrocellular scenario with best effort packet data services. Furthermore, it is demonstrated that part of this capacity gain comes from better utilization of the available cell transmit power since less power control headroom must be reserved for HSDPA. The presented performance results reflect the expected performance improvement from gradually introducing HSDPA in an existing Rel'99 wideband code-division multiple-access network
Effects of Eliminating Pyruvate Node Pathways and of Coexpression of Heterogeneous Carboxylation Enzymes on Succinate Production by Enterobacter aerogenes (2014)

Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production.
Physicochemical Trapping of Neurotransmitters in Polymer-Mediated Gold Nanoparticle Aggregates for Surface-Enhanced Raman Spectroscopy (2019)

Because of the sharp distance dependence of surface-enhanced Raman spectroscopy (SERS), analyte molecules that do not exhibit strong affinity for Au/Ag often elude detection. New methods of integrating such analytes with SERS substrates are required to circumvent this limitation and expand the sensitivity of SERS to new molecules and applications. We communicate here a solution-phase, capture agent-free method of aggregating Au nanospheres in the presence of five neurotransmitters (dopamine, epinephrine, norepinephrine, serotonin, and histamine) and preventing sedimentation by encapsulating the aggregated nanospheres with polyvinylpyrrolidone, thereby trapping the neurotransmitters in close proximity to the Au nanospheres and enabling SER detection. The primary advantages of this physicochemical trapping method, which is generalizable to analytes beyond the scope of this work, are the high signal-to-noise ratio and spectral consistency down to nM levels. Normal Raman spectra and density functional theory calculations corroborate the accuracy of the spectra. Spectra collected over a wide range of concentrations were used to construct adsorption isotherms for all five neurotransmitters, from which adsorption dissociation constants were calculated, spanning from 5.7 × 10<sup>-4</sup> M to 1.7 × 10<sup>-10</sup> M. We expect this method to produce high quality SER spectra of any molecule with an Au affinity known or expected (based on functional groups) to be within that range. Our results have implications for plasmonic detection of these neurotransmitters, particularly for mixtures of those that exhibited disparate Au affinity in our study. We also present evidence that this method produces spectra of sufficient resolution to explore hypotheses related to surface adsorption behavior.