gebhart/patrepeval huggingface dataset:
Direct Observation of Multiple Tautomers of Oxythiamine and their Recognition by the Thiamine Pyrophosphate Riboswitch (2013)

Structural diversification of canonical nucleic acid bases and nucleotide analogues by tautomerism has been proposed to be a powerful on/off switching mechanism allowing regulation of many biological processes mediated by RNA enzymes and aptamers. Despite the suspected biological importance of tautomerism, attempts to observe minor tautomeric forms in nucleic acid or hybrid nucleic acid-ligand complexes have met with challenges due to the lack of sensitive methods. Here, a combination of spectroscopic, biochemical, and computational tools probed tautomerism in the context of an RNA aptamer-ligand complex; studies involved a model ligand, oxythiamine pyrophosphate (OxyTPP), bound to the thiamine pyrophosphate (TPP) riboswitch (an RNA aptamer) as well as its unbound nonphosphorylated form, oxythiamine (OxyT). OxyTPP, similarly to canonical heteroaromatic nucleic acid bases, has a pyrimidine ring that forms hydrogen bonding interactions with the riboswitch. Tautomerism was established using two-dimensional infrared (2D IR) spectroscopy, variable temperature FTIR and NMR spectroscopies, binding isotope effects (BIEs), and computational methods. All three possible tautomers of OxyT, including the minor enol tautomer, were directly identified, and their distributions were quantitated. In the bound form, BIE data suggested that OxyTPP existed as a 4'-keto tautomer that was likely protonated at the N1'-position. These results also provide a mechanistic framework for understanding the activation of riboswitch in response to deamination of the active form of vitamin B1 (or TPP). The combination of methods reported here revealing the fine details of tautomerism can be applied to other systems where the importance of tautomerism is suspected.
Thoracic Microendoscopic Discectomy (2005)

In Brief Study Design. Feasibility analysis of percutaneous posterolateral thoracic microendoscopic discectomy in a human cadaver model. Objective. To describe a new, minimally invasive, posterolateral approach to the thoracic spine for the treatment of disc herniations. Summary of Background. Thoracoscopic discectomy offers surgeons direct ventral access to thoracic disc herniations but requires entry into the chest. Many surgeons favor a posterolateral approach to the thoracic spine, thereby avoiding morbidity associated with entry into the thoracic cavity. By adapting minimal access surgical techniques to the thoracic spine, effective treatment of thoracic disc herniations should be possible and may help expedite recovery. Methods. Two cadaveric human torsos were used. Using simple adaptations of our standard lumbar microendoscopic discectomy technique, endoscopic discectomies were performed throughout the mid and lower thoracic spine. Operative time was recorded. The extent of the discectomy as well as the extent of bony removal was evaluated using computed tomography myelography. Results. Nine discectomies were performed in two cadaveric specimens, from T5–T6–T9–T10. Operative times ranged from 46 to 77 minutes (mean 60 minutes). The procedure required removing 3.4 mm (±1.9 mm) of the ipsilateral facet, which amounted to 35.4% (±17.5%) of the facet complex. Canal decompression averaged 73.5% (±7.9%). Conclusions. Thoracic microendoscopic discectomy allows for a posterolateral approach to thoracic disc herniation without entry into the chest cavity that consistently gives access to the majority of the canal while requiring only a minimal amount of bone removal. This technique provides an approach angle similar to that obtained with other posterolateral discectomy techniques while limiting the morbidity associated with exposure. The authors describe a new microendoscopic technique for the treatment of thoracic disc herniations. Adequate decompression of the spinal canal is possible with minimal soft tissue dissection and bone removal. Morbidities associated with entry into the chest are avoided with this technique.
Immunological effects and activity of multiple doses of zolbetuximab in combination with zoledronic acid and interleukin-2 in a phase 1 study in patients with advanced gastric and gastroesophageal junction cancer (2023)

NCT01671774.
Reverse Prostheses in Arthropathies With Cuff Tear: Are Survivorship and Function Maintained Over Time? (2011)

Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
High density of immobilized galactose ligand enhances hepatocyte attachment and function (2003)

Galactosylated surface is an attractive substrate for hepatocyte culture because of the specific interaction between the galactose ligand and the asialoglycoprotein receptor on hepatocytes. In this study, we described a scheme to achieve high density of immobilized galactose ligands on polyethylene terephthalate (PET) surface by first surface-grafting polyacrylic acid on plasma-pretreated PET film under UV irradiation, followed by conjugation of a galactose derivative (1-O-(6'-aminohexyl)-D-galactopyranoside) to the grafted polyacrylic acid chains. A high galactose density of 513 nmol/cm(2) on the PET surface was used in this study to investigate the behavior of cultured hepatocyte. This engineered substrate showed high affinity to fluorescein isothiocyanate-lectin binding. Primary rat hepatocytes, when seeded at a density of 2 x 10(5) cells/cm(2), attached to the galactosylated PET substrate at a similar efficiency compared with collagen-coated substrate. The hepatocytes spontaneously formed aggregates 1 day after cell seeding and showed better maintenance of albumin secretion and urea synthesis functions than those cultured on collagen-coated surface.
Micropulverizador de precisão para aplicação de entomopatógenos (2013)

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-03-20T11:48:11Z No. of bitstreams: 2 Artigo - Gabriel Moura Mascarin - 2013.pdf: 513679 bytes, checksum: ab8ecc46b6dff4c90109a6fa51635553 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)
Palladium‐Catalyzed Intramolecular CH Difluoroalkylation: Synthesis of Substituted 3,3‐Difluoro‐2‐oxindoles (2014)

The synthesis of 3,3-difluoro-2-oxindoles through a robust and efficient palladium-catalyzed CH difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate-determining step for this process.
Active-State Model of a Dopamine D2 Receptor - Gαi Complex Stabilized by Aripiprazole-Type Partial Agonists (2014)

Partial agonists exhibit a submaximal capacity to enhance the coupling of one receptor to an intracellular binding partner. Although a multitude of studies have reported different ligand-specific conformations for a given receptor, little is known about the mechanism by which different receptor conformations are connected to the capacity to activate the coupling to G-proteins. We have now performed molecular-dynamics simulations employing our recently described active-state homology model of the dopamine D 2 receptor-Ga i protein-complex coupled to the partial agonists aripiprazole and FAUC350, in order to understand the structural determinants of partial agonism better. We have compared our findings with our model of the D2R-Ga i -complex in the presence of the full agonist dopamine. The two partial agonists are capable of inducing different conformations of important structural motifs, including the extracellular loop regions, the binding pocket and, in particular, intracellular G-protein-binding domains. As G-protein-coupling to certain intracellular epitopes of the receptor is considered the key step of allosterically triggered nucleotide-exchange, it is tempting to assume that impaired coupling between the receptor and the G-protein caused by distinct ligand-specific conformations is a major determinant of partial agonist efficacy.
Pharmacologic Exhaustion of Suppressor Cells with Tasquinimod Enhances Bacterial Clearance during Tuberculosis (2018)

the radiology department.This, arguably, limits the optimization of respiratory support during neonatal intensive care with existing monitoring tools focusing on ventilation alone.A further strength of this case report is the lack of any adjunctive respiratory support during the measurements.EIT demonstrated an almost complete lack of tidal ventilation in the left lung.EIT has been repeatedly shown to be able to differentiate single-lung ventilation in animal and human reports (5).Interestingly, EIT detected some residual tidal ventilation that clinicians would not have seen without the EIT recordings.The pulmonary artery infarct likely occurred after the pseudoglandular period and airway development.The residual ventilation likely represents bronchial tidal air movement and collateral ventilation via pores of Kohn.This suggests that EIT is able to image complex ventilation patterns within the lung at a resolution not currently possible within a bedside tool.EIT holds potential in monitoring ventilation and perfusion development in conditions characterized by unilateral lung differences and altered pulmonary blood flow, such as congenital diaphragmatic hernia and after cardiac surgery, over longer time periods.To date, the use of EIT to measure lung perfusion has been limited to human observations in which the perfusion state was not known (2) or animal models with selective occlusion of a single pulmonary artery and injection of an electrical impedance contrast agent (3).Our data support the preclinical data demonstrating the ability of EIT to selectively measure lung perfusion.The clear differentiation between the heartbeat-related signals within the left and right lung suggests that the cardiac-domain impedance measures within the anatomical regions of the chest containing lung are not exclusively due to heart movement being transmitted through lung regions.Conclusions.This case report describes the first report of EIT to measure perfusion and ventilation patterns in a newborn with a known loss of both in a single lung.EIT was able to demonstrate the perfusion and ventilation defects found on static radiological imaging.Importantly, EIT recordings within the heart-rate domain were independent of heart movement and at a respiratory resolution able to identify small areas of tidal ventilation.This suggests that EIT may hold promise as the first tool able to dynamically measure ventilation-perfusion matching over time in infants.
Physical-Parameter Design in 2-D (2005)

Free-space micromachined optical switching technol- ogy has emerged as a promising candidate for the transparent optical cross connects that are needed in next-generation optical transport networks. This paper deals with the system design of two-dimensional (2-D) microelectromechanical system (MEMS)- based cross connects. In particular, we propose a method, ap- plicable to any kind of 2-D MEMS switching architectures, which finds the best choices of the basic geometrical parameters of the device (such as mirror radius and beam-waist size) allowing the achievement of given insertion-loss and differential-loss target values for the overall switching matrix. Our proposal is based on a widely used model of the loss mechanisms in a 2-D MEMS switch, keeping Gaussian-beam divergence and free-space/fiber mode mismatching into account. By adopting the proposed design technique, we compare various 2-D MEMS architectures recently proposed in the technical literature in terms of cost and feasibility of large port count optical switches. Index Terms—Microelectromechanical systems (MEMSs), net- work architectures, system design, transparent optical switching.
Tri-linear representations for the Laser Interferometer Space Antenna (2022)

Abstract The Laser Interferometer Space Antenna (LISA) is a space-borne observatory of gravitational waves to be launched by ESA and NASA in the 2030s. Interferometric measurements are made between three spacecraft orbiting the Sun. The measurements are dependent on the geometric information due to the relative locations between the spacecraft as well as the intrinsic parameters of the astrophysical objects that generate the gravitational waves. We show that the measurements of mildly chirping gravitational waves can be approximated by means of a tri-linear representation, where the geometric information about the location of the observed object as well as that of the spacecraft locations are separated by different factors. We discuss that for low frequencies the relative approximation error is proportional to the square of the signal’s carrier frequency and illustrate this accuracy in numerical experiments. For the sake of illustration, we outline a simple algorithm for extracting parameters from the observed gravitational waves.
Supplementary Methods from Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma (2023)

&lt;p&gt;Supplementary Methods&lt;/p&gt;
Kinetics of Insulin Secretion in Chronic Pancreatitis and Mild Maturity Onset Diabetes (Evidence for “Gut Hormone” Action Beyond Glucoreceptor and Cyclic Adenosine Monophosphate Mediated Insulin Release) (1976)

Abstract We studied insulin responses to glucose with and without cholecystokinin‐pancreozymin and aminophyllin infusions in normal, chronic pancreatitic and genetic (maturity‐onset) diabetic subjects. Glucose was given alone as separate 5 and 10 g boluses followed by infusion at 250 mg/min. and 500 mg/min., respectively. Chronic pancreatitis patients and genetic diabetic patients had decreased Imax values, indicating a decreased insulin reserve. Sensitivity to glucose was normal in pancreatitic subjects, but the diabetic subjects had a raised G50 value, compatible with glucoreceptor dysfunction. Infusions of aminophyllin enhanced insulin responses (Imax) to glucose injection in normal subjects and to a lesser degree in pancreatitic subjects, but decreased sensitivity to glucose (increase in G50) in both groups. Although the Imax value in pancreatitic subjects was significantly lower than in the control subjects during the glucose plus aminophyllin infusion, the blood glucose concentration in the pancreatitic subjects was nonetheless decreased. This suggests that pancreatitic subjects have increased endogenous insulin sensitivity. Aminophyllin had no effect in diabetic subjects. Crude cholecystokinin‐pancreozymin changed the shape of the glucose/insulin dose response curve in normal, pancreatitic and diabetic subjects. These findings further suggest that the defect in insulin secretion in pancreatitic subjects is partly situated at the cyclic adenosine monophosphate stage of insulin release. Crude cholecystokin‐pan‐creozymin seems to affect insulin release at a point beyond the cyclic adenosine monophosphate stage.
Lightweight Call-Graph Construction for Multilingual Software Analysis (2018)

Analysis of multilingual codebases is a topic of increasing importance. In prior work, we have proposed the MLSA (MultiLingual Software Analysis) architecture, an approach to the lightweight analysis of multilingual codebases, and have shown how it can be used to address the challenge of constructing a single call graph from multilingual software with mutual calls. This paper addresses the challenge of constructing monolingual call graphs in a lightweight manner (consistent with the objective of MLSA) which nonetheless yields sufficient information for resolving language interoperability calls. A novel approach is proposed which leverages information from a compiler-generated AST to provide the quality of call graph necessary, while the program itself is written using an Island Grammar that parses the AST providing the lightweight aspect necessary. Performance results are presented for a C/C++ implementation of the approach, PAIGE (Parsing AST using Island Grammar Call Graph Emitter) showing that despite its lightweight nature, it outperforms Doxgen, is robust to changes in the (Clang) AST, and is not restricted to C/C++.
Organic-inorganic hybrid photovoltaics based on organometal halide perovskites (2013)

This thesis details the development of a novel photovoltaic device based on organometal halide perovskites. The initial focus of this thesis begins with the study of lighttrapping strategies in solid-state dye-sensitised solar cells (detailed in chapter 3). While I report enhancement in device performance through the application of near and far-ﬁeld light-trapping techniques, I ﬁnd that improvements remain step-wise due to fundamental limitations currently employed in dye-sensitised solar cell technology— notably, the available light-sensitising materials. I found a promising yet under researched family of materials in the methyl ammonium tri-halide plumbate perovskite (detailed in chapter 4). The perovskite light-sensitiser was applied to the traditional mesoscopic sensitised solar cell device architecture as a replacement to conventional dye yielding world-record breaking photo-conversion e!ciencies for solid-state sensitised solar cells as high as 8.5%. The system was further developed leading to the conception of a novel device architecture, termed the mesoporous superstructured solar cell (MSSC), this new architecture replaces the conventional mesoporous titanium dioxide semiconductor with a porous insulating oxide in aluminium oxide, resulting in very low fundamental losses evidenced through high photo-generated open-circuit voltages of over 1.1 V. This development has delivered striking photo-conversion ef- ﬁciencies of 10.9% (detailed in chapter 6).
An Integrative Framework Reveals Signaling-to-Transcription Events in Toll-like Receptor Signaling (2017)

Building an integrated view of cellular responses to environmental cues remains a fundamental challenge due to the complexity of intracellular networks in mammalian cells. Here, we introduce an integrative biochemical and genetic framework to dissect signal transduction events using multiple data types and, in particular, to unify signaling and transcriptional networks. Using the Toll-like receptor (TLR) system as a model cellular response, we generate multifaceted datasets on physical, enzymatic, and functional interactions and integrate these data to reveal biochemical paths that connect TLR4 signaling to transcription. We define the roles of proximal TLR4 kinases, identify and functionally test two dozen candidate regulators, and demonstrate a role for Ap1ar (encoding the Gadkin protein) and its binding partner, Picalm, potentially linking vesicle transport with pro-inflammatory responses. Our study thus demonstrates how deciphering dynamic cellular responses by integrating datasets on various regulatory layers defines key components and higher-order logic underlying signaling-to-transcription pathways.
Real-time monitoring of insulin using a graphene aptameric nanosensor (2017)

We present a new approach for real-time, specific and sensitive detection of insulin using a graphene aptameric nanosensor. The nanosensor is configured as a graphene field effect transistor, where the graphene conducting channel was functionalized with a guanine-rich aptamer IGA3 that would form an anti-parallel G-quadruplex upon insulin binding. The aptamer conformational changes altered the electrical conductance of graphene by varying the carrier density of the graphene. The nanosensor allowed us to perform real-time, label-free and specific detection of insulin concentrations as low as 1 nM.
Precessional spin-transfer switching in a magnetic tunnel junction with a synthetic antiferromagnetic perpendicular polarizer (2012)

This paper reports sub-nanosecond precessional spin-transfer switching in elliptical magnetic tunnel junction nanopillars. This result is obtained in samples integrating a synthetic antiferromagnetic perpendicular polarizer and a tunnel junction with in-plane magnetized electrodes. The out-of-plane precession of the free layer magnetization results in oscillations of the switching probability as a function of the pulse width. At 9.25 MA/cm2 current density, these oscillations have a period of 1 ns with a high degree of coherence.
Micellar structure and transformations in sodium alkylbenzenesulfonate (NaLAS) aqueous solutions: effects of concentration, temperature, and salt (2020)

We investigate the shape, dimensions, and transformation pathways of micelles of linear sodium alkylbenzenesulfonate (NaLAS), a common anionic surfactant, in aqueous solution. Employing Small Angle Neutron Scattering (SANS) and surface tensiometry, we quantify the effects of surfactant concentration (0.6-15 wt%), temperature (5-40 °C) and added salt (≤0.35 M Na2SO4). Spherical micelles form at low NaLAS (≤2.6 wt%) concentration in water, and become elongated with increasing concentration and decreasing temperature. Addition of salt reduces the critical micelle concentration (CMC) and thus promotes the formation of micelles. At fixed NaLAS concentration, salt addition causes spherical micelles to grow into cylindrical micelles, and then multilamellar vesicles (MLVs), which we examine by SANS and cryo-TEM. Above a threshold salt concentration, the MLVs reach diameters of 100 s of nm to few μm, eventually causing precipitation. While the salt concentrations associated with the micelle-to-cylinder transformation increase only slightly with temperature, those required for the cylinder-to-MLV transformation exhibit a pronounced, linear temperature dependence, which we examine in detail. Our study establishes a solution structure map for this model anionic surfactant in water, quantifying the combined roles of concentration, temperature and salt, at practically relevant conditions.
Combined stereotactic biopsy and stepping-source interstitial irradiation of glioblastoma multiforme. (2018)

Patients diagnosed with glioblastoma multiforme receiving stereotactic biopsy only either due to tumor localization or impaired clinical status face a devastating prognosis with very short survival times. One strategy to provide an initial cytoreductive and palliative therapy at the time of the stereotactic biopsy is interstitial irradiation through the pre-defined trajectory of the biopsy channel. We designed a novel treatment planning system and evaluated the treatment potential of a fixed-source and a stepping-source algorithm for interstitial radiosurgery on non-spherical glioblastoma in direct adjacency to risk structures. Using both setups, we show that radiation doses delivered to 100% of the gross tumor volume shifts from sub-therapeutic (10-12 Gy) to sterilizing single doses (25-30 Gy) when using the stepping source algorithm due to improved sparing of organs-at-risk. Specifically, the maximum doses at the brain stem were 100% of the PTV dose when a fixed central source and 38% when a stepping-source algorithm was used. We also demonstrated precision of intracranial target points and stability of superficial and deep trajectories using both a phantom and a body donor study. Our setup now for the first time provides a basis for a clinical proof-of-concept trial and may widen palliation options for patients with limited life expectancy that should not undergo time-consuming therapies.
Predicting TCP throughput from non-invasive network sampling (2003)

In this paper, we wish to derive analytic models that predict the performance of TCP flows between specified endpoints using routinely observed network characteristics such as loss and delay. The ultimate goal of our approach is to convert network observables into representative user and application relevant performance metrics. The main contributions of this paper are in studying which network performance data sources are most reflective of session characteristics, and then in thoroughly investigating a new TCP model based on Padhye et al. (2000) that uses non-invasive network samples to predict the throughput of representative TCP flows between given end-points.