gebhart/patrepeval huggingface dataset:
Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. (2009)

Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13-60 years of age and had lesions with a duration of 15-90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less than 30 days of illness. Patients with classic ulcerative ACL (n = 120) had ulcerated classic lesions, longer duration, larger lesions, and higher levels of interferon-gamma and tumor necrosis factor-alpha (P < or = 0.01 for all comparisons). Ulcerated lesions were associated with a lower treatment failure rate compared with early ACL (25.8% versus 75.0%; P < 0.001). Early treatment of ACL does not prevent lesion ulceration and is associated with higher rates of treatment failure.
Design of State Space Controllers for Industrial Twin Shaft Gas Turbines (2005)

This paper depicts the development of a new control strategy for industrial gas turbines to improve the control accuracy in the entire operating range. In the first step, a complex mathematical model has been developed, which is implemented into the controller dynamic simulation. An automatic operating point dependent linearization process permits the model to be displayed in a linear state space description. Three established controller design procedures have been applied to the process. In the past, only a small number of state space control designs have been presented for industrial gas turbines. These approaches use low order mathematical descriptions, which often do not describe the system behavior in detail. This paper presents a controller design for a more detailed mathematic model of the 15th order. It is indicated, that certain controller designs are difficult to realize or even fail. These effects result from unfavourable numerical conditions (depending on the operating point) in combination with the high order of the approximated linear system description. The tested pole placement designs show favorable closed loop system dynamic behavior and were improved by adding an integrating part to the controller.
A distributed multi-agent system for switching optimization in low-voltage power grids (2017)

Information and communication technology plays a crucial role in increasing reliability and efficiency of our critical infrastructure. This paper presents a distributed multi-agent system for switching optimization in low-voltage power grids. As opposed to centralized approaches, the overall optimization procedure is not implemented in a single node but emerges from the behavior and interaction of the participating agents. Thereby, the communication strictly follows a predefined interaction protocol. Losses are reduced by balancing loads among all available transformers. Based on a small distribution network, an exemplary optimization run is discussed in detail. Furthermore, FNCS, a state-of-the-art co-simulation framework, is used to evaluate the actual potential for energy saving.
Supplementary Material for: Development of a Hypoallergenic Recombinant Parvalbumin for First-in-Man Subcutaneous Immunotherapy of Fish Allergy (2017)

<b><i>Background:</i></b> The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. <b><i>Objectives: </i></b>Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. <b><i>Methods:</i></b><i>Escherichia coli</i>-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. <b><i>Results:</i></b> Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)<sub>3</sub>-adsorbed drug product demonstrated at least 20 months of stability. <b><i>Conclusion:</i></b> The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.
ISSCR 2013: Back to Bean Town (2013)

The International Society for Stem Cell Research 11(th) Annual Meeting was held in Boston in June 2013, bringing together just over 4000 attendees. An emphasis on therapeutic applications in many talks reflected the maturation of the stem cell field from its origins in basic science to one that is beginning to show therapeutic promise.
Development and characterization of human immortalized cell-based multicellular spheroidal blood-brain barrier model (2018)

[Introduction] The blood-brain barrier (BBB), which is formed by brain microvascular endothelial cells (BMECs) together with brain pericytes (BPCs) and astrocytes, strictly controls the drug traffic between the blood and brain. For evaluation of drug permeability across the BBB in humans, in vitro BBB model is a useful experimental tool. Multicellular spheroid (MCS) culture system is a promising method for development of highly functional in vitro BBB models. To develop such MCS-BBB model, immortalized cells are useful in terms of their scalability and functionality, and accordingly we have recently established human conditionally immortalized BMECs (HBMEC/ci18), astrocytes (HASTR/ci35), and BPCs (HBPC/ci37). Therefore, in this study, we aimed to develop a human immortalized cell-based MCS-BBB model and characterize their BBB properties.
Association of dopamine transporter gene variants with childhood ADHD features in bipolar disorder (2012)

Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) exhibit remarkably high rates of comorbidity, as well as patterns of familial co-segregation. Epidemiological data suggests that these disorders either share a common genetic architecture or that ADHD features in BD may represent an etiologically distinct subtype. We previously used the Wender Utah Rating Scale (WURS) to assess ADHD features in BD families and identified three heritable factors relating to impulsivity, mood instability, and inattention. Linkage analysis revealed a LOD score of 1.33 for the inattention factor on 5p15.3 near the dopamine transporter gene (DAT1), which has been associated with both BD and ADHD. Pharmacological evidence also suggests a role for DAT in both disorders. We have now evaluated the association of ten DAT1 variants for the WURS total score and factors in an overlapping sample of 87 BD families. Significant associations for three SNPs were observed across the WURS measures, notably for a SNP in intron 8 with the WURS total score (P = 0.007) and for variants in introns 9 and 13 with mood instability (P = 0.009 and 0.004, respectively). Analysis of an independent sample of 52 BD cases and 46 healthy controls further supported association of the intron 8 variant with mood instability (P = 0.005), and a combined analysis confirmed the associations of this SNP with WURS total score. Impulsivity and mood instability (P = 0.002, 0.007, and 8 × 10(-4), respectively). These data suggest that variants within DAT1 may predispose to a subtype of BD characterized by early prodromal features that include attentional deficits.
Different Finite Element Strategies to Satisfy Clinical and Engineering Requirements in Modeling a Novel Percutaneous Device (2012)

By taking into account patient-specific properties, finite element (FE) models can aid in the optimization of the devices’ mechanical performances, accelerating the time of development and reducing testing costs. Patient-specific cardiovascular modeling can also drive the development of novel devices [1], by means of anatomical elements that are more representative than animal surrogates [2], and integrating standard in vitro tests with patient-specific loading conditions [3]. Transcatheter heart valve implantation can particularly benefit from a modeling approach. In the field of treatment of valve dysfunctions, percutaneous techniques are relatively new or under development, and modeling tools can contribute to improve these procedures (e.g. design modifications or different routes for device insertion) and increase patient safety in the early introduction of new devices into clinical practice. For a feasible clinical application, computational methods need to be fully validated against physical data, to take into account patient-specific properties, and to provide results in a short time. Instead, from an engineering perspective, models can cost-effectively aid the design phase by improving preclinical testing with more realistic loading conditions for accurate simulation of mechanical behaviour and prediction of durability. This study aims to identify optimal modeling strategies to respond to both clinical and engineering requirements. As a case study, simulations were conducted on a new percutaneous pulmonary valve implantation (PPVI) device [4] tested within a patient-specific right ventricular outflow tract model.
IN SITU CHEMICAL CHARACTERIZATION OF THE MOTILE TO SESSILE TRANSITION OF PSEDOMONAS AERUGINOSA COMMUNITIES (2018)

\\textit{Pseudomonas aeruginosa} is a Gram-negative opportunistic pathogen which infects more than 50,000 people each year in the United States alone. Its abilities to move, colonize surfaces, and develop biofilms give rise to the high resistance to antimicrobial treatment. One type of motility employed by \\textit{P. aeruginosa} is swarming motility, where bacterial cells undergo physical and metabolic alterations. Swarming has been studied by many researchers but the knowledge on its chemical composition that relates to the transition between the motile and sessile biofilm stages are still lack. Here we apply confocal Raman microscopy (CRM) to examine \\textit{P. aeruginosa} wild-type PA14 (a virulent strain isolated from a burn wound) under swarming and biofilm conditions.\n\n\n\nThe comparison between the swarming and biofilm samples indicates different molecules linked to the motile to sessile transition, revealing their community-specific chemical features. While the \\textit{Pseudomonas} quinolone signal (PQS) is found in swarm colonies and biofilms, the \\textit{N}-oxide quinolines (4-hydroxy-2-heptylquinoline-\\textit{N}-oxide,2-nonyl-4-hydroxyquinoline, etc.) are present in higher abundance and are synthesized and secreted much earlier in swarm colonies. Moreover, a closer investigation spanning from the center to the edge of a swarm colony shows high abundance of PQS at the center while \\textit{N}-oxides dominate the edge of the colony. The results provide insights into the chemical profile change occurring during the motile to sessile transition in \\textit{P. aeruginosa}, and demonstrate the broad application of CRM in biomolecular imaging.\n\n\n\n\n\n\\begin{wrapfigure}{r}{0pt} \n\n\\includegraphics[scale=0.8]{image_file.eps} \n\n\\end{wrapfigure}
Etiological Expression of Heat Shock Protein 70 (HSP70) in Human Endothelial Cells With Hemodynamic Shear Stress (1999)

Abstract The expression of heat shock protein 70 (hsp70) and the polymerization of the actin cytoskeleton of human umbilical vein endothelial cells (HUVECs) were investigated with the endothelial cell-extracellular matrix system and the laminar flow chamber appratus. Shear stress-induced polymerization of the actin cytoskeleton of HUVEC was summarized with the formation of the ‘dense peripheral band’ after 5 min exposure of flow, shear-induced focal contact formation at the proximal periphery, and the aligned actin microfilament formation to the direction of flow. In contrast to the intranucleous expression of hsp70 with the conventioanl heat shock, perinuclear expression of hsp70 was detected with the laser scanning confocal microscope and the western blotting of HUVECs exposed to 15 dyne/cm2 shear stress for 1 hour. Expression of hsp70 in perinuclear region increased with proportional to the magnitude of shear stress. The polymerization of cytoplasmic actin cytoskeleton and the cytoplasmic expression of hsp70 may prevent the cellular damage from the pathophysiological stimulus that initiate vascular cell disease, such as the atherosclerosis. Consequently, three-dimensional intracellular expression and the localization of protein and organelles play an important role in the signal transduction generated by the mechanical cue, such as fluid shear stress.
Cobalt complexes with α-amino acid ligands catalyze the incorporation of CO<sub>2</sub>into cyclic carbonates (2023)

Arguably one of the largest research areas involving carbon dioxide (CO<sub>2</sub>) fixation is the coupling of CO<sub>2</sub> to epoxides to form cyclic carbonates and polycarbonates. In this sense, there is an ever-increasing demand for the development of higher-performing catalytic systems that could counterbalance sustainability and energy efficiency in the production of cyclic carbonates. The use of abundant first-row transition metals combined with naturally occurring amino acids may be an ideal catalytic platform to fulfill this demand. Nevertheless, detailed information on the interactions between metal centers and natural products as catalysts in this transformation is lacking. Here a series of Co(III) amino acid catalysts operating in a binary system showed outstanding performance for the coupling reaction of epoxides and CO<sub>2</sub>. Nine new complexes of the type <i>trans</i>(<i>N</i>)-[Co(aa)<sub>2</sub>(bipy)]Cl (aa: ala, asp, lys, met, phe, pro, ser, tyr, and val) were used to explore the structure-activity relationship influenced by the complex outer coordination sphere, and its effect on the catalytic activity in the coupling reaction of CO<sub>2</sub> and epoxides.
Ti$_3$C$_2$T$_x$ MXene Enabled All-Optical Nonlinear Activation Function for On-Chip Photonic Deep Neural Networks (2021)

Neural networks are one of the first major milestones in developing artificial intelligence systems. The utilisation of integrated photonics in neural networks offers a promising alternative approach to microelectronic and hybrid optical-electronic implementations due to improvements in computational speed and low energy consumption in machine-learning tasks. However, at present, most of the neural network hardware systems are still electronic-based due to a lack of optical realisation of the nonlinear activation function. Here, we experimentally demonstrate two novel approaches for implementing an all-optical neural nonlinear activation function based on utilising unique light-matter interactions in 2D Ti$_3$C$_2$T$_x$ (MXene) in the infrared (IR) range in two configurations: 1) a saturable absorber made of MXene thin film, and 2) a silicon waveguide with MXene flakes overlayer. These configurations may serve as nonlinear units in photonic neural networks, while their nonlinear transfer function can be flexibly designed to optimise the performance of different neuromorphic tasks, depending on the operating wavelength. The proposed configurations are reconfigurable and can therefore be adjusted for various applications without the need to modify the physical structure. We confirm the capability and feasibility of the obtained results in machine-learning applications via an Modified National Institute of Standards and Technology (MNIST) handwritten digit classifications task, with near 99% accuracy. Our developed concept for an all-optical neuron is expected to constitute a major step towards the realization of all-optically implemented deep neural networks.
Value of electrical stimulation and high frequency oscillations (80–500 Hz) in identifying epileptogenic areas during intracranial EEG recordings (2009)

Areas showing epileptic HFOs colocalize with those reacting to ES. HFOs may represent a pathologic correlate of regions showing an ES response; both phenomena suggest a more widespread epileptogenicity.
A spectral multi-domain technique for analysis of chemically reacting flows (1987)

A technique is presented which models the chemical kinetics and flow kinematics of a nonionized air mixture passing through a fully resolved shock wave, thus alleviating the need for artificial viscosity. The quasi-one-dimensional Navier-Stokes equations and the species conversation equation are the governing equations. The validity of the multidomain Navier-Stokes algorithm is demonstrated via comparison with experiment.
Qué son las scoping reviews y por qué son importantes en tesis doctorales (2021)

Presentación de las características principales de las scoping reviews, en sí mismas, y también en comparación con las systematic reviews. Usos en tesis doctorales y en nuevas investigaciones. Protocolos principales. Fases y estrategias de aplicación. Ventajas e inconvenientes. Referencias principales y recursos web.
Supplementary Tables from The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell–Mediated Immunotherapies (2023)

&lt;p&gt;Supplementary tables&lt;/p&gt;
Small Molecules Restore Azole Activity Against Drug-Tolerant and Drug-Resistant <i>Candida</i> Isolates (2022)

ABSTRACT Each year, fungi cause more than 1.5 billion infections worldwide and have a devastating impact on human health, particularly in immunocompromised individuals or patients in intensive care units. The limited antifungal arsenal and emerging multidrug resistant species necessitate the development of new therapies. One strategy for combating drug resistant pathogens is the administration of molecules that restore fungal susceptibility to approved drugs. Accordingly, we carried out a screen to identify small molecules that could restore the susceptibility of pathogenic Candida species to azole antifungals. This screening effort led to the discovery of novel 1,4-benzodiazepines that restore fluconazole susceptibility in resistant isolates of Candida albicans , as evidenced by 100-1000-fold potentiation of fluconazole activity. This potentiation effect was also observed in azole-tolerant strains of C. albicans and in other pathogenic Candida species. The 1,4-benzodiazepines selectively potentiated different azoles, but not other approved antifungals. A remarkable feature of the potentiation was that the combination of the compounds with fluconazole was fungicidal, whereas fluconazole alone is fungistatic. Interestingly, the potentiators were not toxic to C. albicans in the absence of fluconazole, but inhibited virulence-associated filamentation of the fungus. We found that the combination of the potentiators and fluconazole significantly enhanced host survival in a Galleria mellonella model of systemic fungal infection. Taken together, these observations validate a strategy wherein small molecules can restore the activity of highly used anti-infectives that have lost potency. IMPORTANCE In the last decade, we have been witnessing a higher incidence of fungal infections, due to an expansion of the fungal species capable of causing disease ( e.g ., Candida auris ), as well as increased antifungal drug resistance. Among human fungal pathogens, Candida species are a leading cause of invasive infections and are associated with high mortality rates. Infections by these pathogens are commonly treated with azole antifungals, yet the expansion of drug-resistant isolates have reduced their clinical utility. In this work, we describe the discovery and characterization of small molecules that potentiate fluconazole and restore the susceptibility of azole-resistant and azole-tolerant Candida isolates. Interestingly, the potentiating 1,4-benzodiazepines were not toxic to fungal cells but inhibited their virulence-associated filamentous growth. Furthermore, combinations of the potentiators and fluconazole decreased fungal burdens and enhanced host survival in a Galleria mellonella model of systemic fungal infections. Accordingly, we propose the use of novel antifungal potentiators as a powerful strategy for addressing the growing resistance of fungi to clinically approved drugs.
Anatomical variability predicts individual differences in transcranial electric stimulation motor threshold (2013)

We have proposed that the current amplitude in electroconvulsive therapy (ECT) be lowered to produce stimulation closer to the neural activation threshold and individualized to account for anatomical variability across patients. A novel approach to individualize the ECT current amplitude could be via motor threshold (MT) determination with transcranial electric stimulation (TES) applied through the ECT electrodes instead of the fixed high current approach. This study derives an estimate of the electric field (E-field) neural activation threshold and tests whether individual differences in TES MT are explained by anatomical variability measurements and simulations in individual head models. The E-field distribution induced by a right unilateral (RUL) ECT electrode configuration was computed in subject-specific finite element head models of four nonhuman primates (NHPs) for whom MT was measured. By combining the measured MTs and the computed E-field maps, the neural activation threshold is estimated to be 0.45 ± 0.07 V/cm for 0.2 ms stimulus pulse width. The individual MT was correlated with the electrode-to-cortex distance under the superior electrode (R(2)=.96, p=.022) as well as with the simulated electrode-current/induced-E-field ratio (R(2)=.95, p=.026), indicating that both anatomical measurements and computational models could predict the individual current requirements for transcranial stimulation. These findings could be used with realistic human head models and in clinical studies to explore novel ECT dosing paradigms, and as a new noninvasive means to determine individual dosage requirement with ECT.