gebhart/patrepeval huggingface dataset:
Dose‐Proportional and Stereospecific Pharmacokinetics of Methylphenidate Delivered Using an Osmotic, Controlled‐Release Oral Delivery System (2000)

Methylphenidate hydrochloride (HCl) is frequently used for the treatment of attention deficit/hyperactivity disorder (ADHD). A study was conducted in healthy subjects to evaluate the dose-ranging pharmacokinetics of 18, 36, and 54 mg methylphenidate HCl delivered using an oral, osmotic, controlled-release formulation (OROS). Plasma concentrations of l-methylphenidate were 40-fold lower than those of d-methylphenidate, whereas plasma concentrations of d-alpha-phenyl-2-piperidine acetic acid (d-PPA) and l-PPA, the major metabolite of methylphenidate, were comparable. Mean AUCinf values for d-methylphenidate were 42.2, 80.9, and 120 ng.h/mL for the 18, 36, and 54 mg doses, respectively, increasing dose proportionally. AUCinf values for l-methylphenidate were only approximately 1% of d-methylphenidate (0.43, 0.96, and 1.82 ng.h/mL for the 18, 36, and 54 mg dose groups, respectively). In contrast, AUCinf values of d- and l-PPA were comparable. The dose-normalized d- and l-methylphenidate plasma concentration-time profiles for the three treatment groups were superimposable. Similarly, dose-normalized plasma concentrations of d- and l-PPA were superimposable. Methylphenidate metabolism, measured as the ratio of d-methylphenidate AUCinf to d-PPA AUCinf and as l-methylphenidate AUCinf to l-PPA AUCinf, was similar for the three dose groups, indicating that methylphenidate metabolism was not affected by increasing dose. OROS (methylphenidate HCl) exhibits dose-proportional and linear pharmacokinetics.
Periodontopathic Bacteria and Their Potential Involvement in Atherosclerosis (2002)

Based initially on epidemiological studies, an association between periodontitis and atherosclerosis has been suggested. In addition, several recent murine model studies have indicated that one periodontopathic bacterium, Porphyromonas gingivalis, can exacerbate heart lesion formation. This organism, as well as other suspected periodontopathogens, can also be demonstrated in human atheromas. Therefore, though not unequivocal, the present data from a variety of approaches are consistent with a role for periodontitis in cardiovascular disease. This review will discuss potential mechanisms which could explain a role for periodontitis in atherosclerosis. Both general inflammatory mechanisms as well as specific bacterial interactions with cardiac tissue, primarily mediated by Porphyromonas gingivalis, will be described. In addition, the complex nature of atherosclerosis suggests that it will be difficult to precisely define the relationship between these two diseases.
Monte Carlo Tree Search in Continuous Spaces Using Voronoi Optimistic Optimization with Regret Bounds (2020)

Many important applications, including robotics, data-center management, and process control, require planning action sequences in domains with continuous state and action spaces and discontinuous objective functions. Monte Carlo tree search (MCTS) is an effective strategy for planning in discrete action spaces. We provide a novel MCTS algorithm (voot) for deterministic environments with continuous action spaces, which, in turn, is based on a novel black-box function-optimization algorithm (voo) to efficiently sample actions. The voo algorithm uses Voronoi partitioning to guide sampling, and is particularly efficient in high-dimensional spaces. The voot algorithm has an instance of voo at each node in the tree. We provide regret bounds for both algorithms and demonstrate their empirical effectiveness in several high-dimensional problems including two difficult robotics planning problems.
Nanoparticle-Infused UHMWPE Layer as Multifunctional Coating for High-Performance PPTA Single Fibers (2019)

High-performance fibers made of poly-(p-phenylene terephthalamide) (PPTA) with high stiffness and high strength are widely used in body armor for protection due to their high degree of molecular chain alignment along the fiber direction. However, their poor mechanical properties in the transverse direction and low surface friction are undesirable for applications requiring resistance to ballistic impact. Here we provide a simple yet effective surface engineering strategy to improve both the transverse mechanical properties and the tribological property by coating PPTA fibers with ultra-high molecular weight polyethylene (UHMWPE) embedded with silica nanoparticles. The coated-PPTA fiber shows remarkable enhancement in transverse mechanical properties including ~127% increase of Young's modulus, which is attributed to both the alignment of UHMWPE chains in the transverse direction and the embeded ceramic nanoparticles. Meanwhile, the surface friction of the coated fiber increases twofold as a result of the ceramic nanoparticles. In addition, the coated fibers exhibit an enhanced chemical resistance to external harsh environment. The improved transverse mechanical properties, surface frictional characteristics, and chemical resistance demonstrate that coating with UHMWPE and ceramic nanoparticles can be used as an effective approach to enhance the performance of PPTA and other high-performance polymer fibers for body armor applications.
HAIC - High Altitude Ice Crystals (2013)

Commercial aircraft have been experiencing inservice events while flying in the vicinity of deep convective clouds since at least the early 1990s. Heated probes and engines are the areas of aircraft most prone to mixed phase and glaciated icing threat. In anticipation of regulation changes according to mixed phase and glaciated icing conditions, the HAIC project will provide to the European Aeronautical industry Acceptable Means of Compliance (numerical and test capabilities) and appropriate ice particle detection/awareness technologies for use on-board of commercial aircraft in order to enhance safety when an aircraft is flying in such weather conditions. HAIC will achieve high Technology Readiness Level (TRL6) for technologies (radar, detector) and capabilities (numerical models and tools, test facilities) developed as part of the project HAIC is a 4 years integrated project comprising 37 partners representing the European stakeholders of the Aeronautical industry from 14 European countries.HAIC will also develop international cooperation and collaboration thanks to the involvement of key international organizations and companies as partner of the project or through the advisory board. Finally, HAIC will complement the work performed as part of existing international projects and working groups, notably EASA-HighIWC, HIWC, Engine Icing Working Group and Ice Crystals Consortium, and pave the way towards the ACARE 2020 and Flight Path 2050 safety objectives.
Pancreatic cancer detection using EpiDetect signatures in plasma-derived cell free DNA in high-risk patients with new onset diabetes. (2021)

e16265 Background: Pancreatic cancer (PaCa) is the third leading cause of cancer death in the United States despite its low incidence rate, owing to a 5-year survival rate of 10%. It is often asymptomatic in early stage, resulting in the majority of diagnoses occurring when cancer has already metastasized to distant organs. Late diagnosis deprives patients of potentially curative treatments such as surgery and impacts survival rates. Diabetes can be an early symptom of PaCa. Indeed, 25% of PaCa patients had a preceding diabetes diagnosis. Among all people with new onset diabetes (NOD), 0.85% will be diagnosed with PaCa within 3 years, which represents 6-8 fold increased risk for PaCa compared to the general population. Surveillance of the NOD population for PaCa presents an opportunity to shift PaCa diagnosis to earlier stage by finding it sooner. Methods: Whole blood was obtained from a cohort of 117 PaCa patients as well as 800 non-cancer controls with and without NOD. Plasma was processed to isolate cfDNA and 5hmC and low pass whole genome libraries were generated and sequenced. The EpiDetect assay combines 5hmC and whole genome sequencing data and were generated using Bluestar Genomics’s technology platform. Results: To investigate whether PaCa can be detected in plasma, we interrogated plasma-derived cfDNA epigenomic and genomic signal from PaCa patients and non-cancer controls. We first trained stacked ensemble models on PaCa and non-cancer samples utilizing 5hmC, fragmentation and CNV-based biomarkers from cfDNA. These models performed stably with a median of 72.8% sensitivity and 90.1% specificity measured across 25 outer fold iterations using the training data set, which was composed of 50% early stage (Stages I &amp; II) disease. The final binomial ensemble model was trained using all of the training data, yielding an area under the receiver operating characteristic curve (auROC) of 0.9, with 75% sensitivity and 89% specificity. This model was then tested on an independent validation data set from 33 PaCa patients (24 with diabetes, 15 of which was NOD) and 202 non-cancer control patients (76 with diabetes, 51 of which was NOD) and yielded a classification performance auROC of 0.9 with 67% sensitivity at 92% specificity. Lastly, model performance in the subset of patient cohort with NOD only had an auROC of 0.87 with 60% sensitivity at 88% specificity. Conclusions: Our results indicate that 5hmC profiles along with CNV and fragmentation patterns from cfDNA can be used to detect PaCa in plasma-derived cfDNA. Overall, model performance was stable and consistent between the training and independent validation datasets. A larger clinical study is under development to investigate the utility of the model described in this pilot study in identifying occult PaCa within the NOD population, with the aim of shifting diagnosis to early stage and potentially improving patient outcomes.
Identification of an Antigenic and Immunogenic Motif Expressed by Two 7-Mer Rituximab-Specific Cyclic Peptide Mimotopes: Implication for Peptide-Based Active Immunotherapy (2007)

Two 7-mer cyclic peptides-Rp15-C and Rp13-C-which bear the antigenic motif recognized by the anti-CD20 mAb rituximab, but have different motif-surrounding amino acids, show a comparable avidity for rituximab and inhibit the binding of rituximab to raft-associated CD20 and rituximab-induced membrane ceramide on human lymphoid Daudi cells. Their immunogenic profiles differed: Abs recognizing CD20 were induced in two and five of five BALB/c mice immunized with Rp15-C and Rp13-C, respectively. Analysis of immunogenic motif, performed by panning a 7-mer phage-display peptide library with purified anti-peptide IgGs, showed that the motif defined by anti-Rp15-C mostly included amino acids surrounding the rituximab-specific antigenic motif <aNPS>, whereas that defined by anti-Rp13-C was <NPS>. These data indicate that their motif-surrounding amino acids can markedly influence the specificity of Abs, even when elicited with a short 7-mer peptide. Because these anti-peptide Abs are of IgG isotype, their specificity is likely to reflect how peptides are processed at the T cell level and suggest that, within a short peptide, the motifs defined by T cells during the initial phase and upon their stimulation may be different. Our findings may account for the failure of most forms of peptide-based immunotherapy in cancer and autoimmune diseases in which anti-mimotope Abs are expected to play a relevant therapeutic effect. They also suggest strategies to implement the specificity of peptide-induced Abs against the target Ag.
Intestinal flora in very low‐birth weight infants (2009)

In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.
HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19 (2021)

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.
Surgical Revolutions: A Historical and Philosophical View (2011)

Introduction Surgical Revolutions De Humani Corporis Fabrica Surgical Revolution Exercitatio Anatomica De Motus Cordis et Sanguinis in Animalibus Surgical Revolution The Strange Little Animals of Antony van Leeuwenhoek Surgical Revolution Anesthesia Surgical Revolution Introduction A L'Etude de la Medicine Experimentale Surgical Revolution, Part I Introduction A L'Etude de la Medicine Experimentale, Surgical Revolution, Part II Antiseptic Surgical Revolution (Lister) Birth of Scientific Surgery American Surgical Research William Roentgen Surgical Revolution Arpad Gerster and Max Thorek Contributions to American Surgery Michael E DeBakey Christiaan Barnard Heart Transplantation Art, Surgery and Transplantation Believing in Yourself Mentoring Gentlemen Surgeons Concluding Remarks.
Role of the RNA-binding protein HuR in human renal cell carcinoma (2010)

Human conventional renal cell carcinoma (CRCC) remains resistant to therapy. The RNA-binding protein HuR regulates the stability and/or translation of multiple messenger RNAs involved in malignant transformation. In this study, we aimed to evaluate the potential role of HuR in this pathology. Using seven human CRCC cell lines expressing or not the von Hippel-Lindau (VHL) tumor suppressor gene as well as 15 normal/renal cell carcinoma tumor pairs, we showed that HuR is overexpressed in all tumors independently of the VHL status. Futhermore, HuR cytoplasmic presence appears to be more common in early tumor stages, suggesting a role in tumor promotion. We then assessed the effect of HuR knockdown using small interfering RNA in cultured cell and in tumor-bearing mice. Both in vitro and in vivo, we observed that cell growth was inhibited by 60% and that this effect was obtained through an inhibition of cell proliferation and an induction of cell apoptosis. Finally, we found that expression of vascular endothelium growth factor, tumor growth factor-beta and of the hypoxia-induced transcription factor-2alpha as well as the constitutive activation of the oncogenic phosphoinositide 3-kinase/Akt, nuclear factor-kappaB and mitogen-activated protein kinase pathways were decreased in HuR-depleted cells and tumors. All these results suggest a pivotal role for HuR in human CRCC.
Methods for the Calculation and Use of the Articulation Index (1962)

Speech-intelligibility testing is an expensive and time-consuming operation that requires laboratory test conditions. In an attempt to short-cut or make unnecessary this type of testing, a procedure was developed by French and Steinberg [J. Acoust. Soc. Am. 19, 90–119 (1949)] for calculating from physical and acoustical measurements made on a communication system a measure that is indicative of the intelligibility scores that would be obtained for that system under actual test conditions. This measure is called the “Articulation Index” (AI). Methods of calculating AI have been improved and elaborated to the point where several methods for its calculation, herein reported, can be proposed for use in the evaluation of most speech communication systems.
High performance of Mg3Bi1.5Sb0.5 based materials for power generation: Revealing the counter-intuitive effect of tuning Bi content on the thermoelectric properties (2023)

Recently, Mg3Sb2-xBix alloys have attracted intensive attention, with the aim of maximizing the electrical transport performance via donor element doping, increasing the grain size, as well as electronic band structure engineering. However, less attention has been paid to other significant factors, like how these intrinsic point defects and accompanied secondary phases influence thermoelectric properties. In this study, the microstructure and thermoelectric transport properties of Mg3.2Sb0.5Bi1.495-xTe0.005 (x = 0 ∼ 0.2) compounds were systematically investigated, where tuning the Bi content shows the counter-intuitive impact on the thermoelectric properties. It was found that the Bi-poor environment associated with Bi impurities facilitated the increment of cation vacancy formation energy and then increased the carrier concentration, leading to the enhancement of power factor. Simultaneously, the reduction of Bi-rich second phase content weakened the carrier scattering by grain boundaries whereas high carrier mobility was maintained. Moreover, the bipolar thermal conductivity decreased obviously due to the increased majority carrier concentration to suppress the intrinsic excitation. The synergistic optimization pushes the average ZT value (300–573 K) up to 0.95 in the Mg3.2Sb0.5Bi1.295Te0.005 sample. Moreover, the calculated single-leg conversion efficiency is increased up to 9.7% with the hot-side temperature of 573 K, as the record-high value in this system.
Multicompartment micelles from A2-star-(B-alt-C) block terpolymers in selective solvents (2011)

The ability of multiblock ABC terpolymers to self-assemble into multicompartment micelles in an A-selective solvent is of great current interest. We have used dissipative particle dynamics (DPD) to explore the morphologies adopted by a particular block terpolymer architecture, A2-star-(B-alt-C), where the two A blocks form the micelle corona and the alternating B and C blocks segregate within the core. Parameters of interest include the strength of the pairwise interactions among A, B, and C, the relative length of the A blocks compared to B + C, and the relative selectivity of the solvent towards B and C. A rich suite of structures are observed, including those with either spherical or wormlike cores, and with internally segregated B and C domains. Within the spherical micelle family, the B and C domains adopt various packings, including concentric layers, the “hamburger” motif (B–C–B layers and C–B–C layers), and a bicontinuous network. For wormlike micelles, the B and C domains are arranged as stacked alternating disks, or as intertwined helices. The choice of morphology is rationalized in terms of the relative block volume fractions and interaction energies. The DPD algorithm is a promising approach to screen ABC terpolymer architectures for the ability to produce potentially useful hierarchical structures.
Do Pharmacokinetics Explain Persistent Restenosis Inhibition by a Single Dose of Paclitaxel? (2012)

After a single local administration with coated balloons, paclitaxel stays in the vessel wall of pigs long enough to explain persistent inhibition of neointimal proliferation. The pharmacokinetics of paclitaxel does, however, not exclude other reasons for sustained efficacy such as early blocking of processes initiating excessive and prolonged neointimal proliferation.
Metallocene Catalysts Used for the Hydrogenation of Polystyrene-b-Polybutadiene-b-Polystyrene Block Copolymers (2000)

Catalytic effectiveness of three metallocenes (Cp2Co, Cp2Ni, and Cp2TiCl2), in the presence of various reducing agents (n-butyllithium, phenyllithium, and triethylaluminum), have been studied for hydrogenating polystyrene-b-polybutadiene-b-polystyrene (SBS) thermoplastic elastomers. The CP2Co / n-butyllithium system was found the most active. A n-butyllithium to cobaltocene molar ratio of 1~2, a 15~25 kg/cm2 H2 pressure, and a minimal 80°C temperature were necessary in order to achieve a high extent of hydrogenation. UV spectroscopy of the catalyst system showed the formation of CpLi indicating that some Cp ligands in the original Cp2Co were displaced by n-butyllithium.
Enhancement of writing margin for low switching toggle magnetic random access memories using multilayer synthetic antiferromagnetic structures (2006)

We developed synthetic antiferromagnets (SAFs) with a multilayer structure where more than three magnetic layers were coupled in an antiparallel configuration for use as a free layer of toggle magnetic random access memories, with the aim of reducing the switching field. The SAFs consisted of a magnetic layer of NiFe∕CoFe with a spacer layer of Ru and were deposited on the Al-oxide barrier layer in magnetic tunnel junctions. Conventional bilayer SAFs did not realize a large writing margin with a low spin flop field (Hflop). On the other hand, multilayer SAFs increased the saturation field (Hs) significantly with increases in both the number of magnetic layers (N) and the antiferromagnetic coupling (AFC) strength between the inner magnetic layers while maintaining a low Hflop. This is because strong AFCs involved in the inner magnetic layers and weak AFCs of the outer magnetic layers determine Hs and Hflop of these, respectively. To control an AFC of each spacer layer, we chose an appropriate thickness for each Ru layer in the multilayer SAFs according to the Ru crystalline structure that was responsible for its AFC strength.
Use of hydrogenated soya phospholipids as a diluent: Preparation of sustained-release tablets of theophylline and sodium diclofenac. (1987)

Sustained-release tablets (SR-tablet), prepared with hydrogenated soya phospholipids, gave slow release of theophylline and sodium diclofenac into a solvent at pH 6.8, in an in vitro study. The release profile of theophylline from the SR-tablet remained unchanged at pH values between 2.0 and 6.8. However, the release of diclofenac from the SR-tablet into a solvent at pH 2.0 was very slight, due to the low solubility at pH 2.0. The release of both drugs seems to occur predominantly by a leaching mechanism, as proposed by Higuchi. The oral administration of SR-tablets to dogs avoided a transient peak of drug concentration in the plasma and maintained plasma drug concentrations at higher levels for a longer period, in comparison with the oral administration of theophylline in suspension form or a commercial tablet of sodium diclofenac.
Few-Cycle femtosecond waveform synthesizer (2008)

A waveform synthesizer consisting of an octave-spanning Ti:sapphire oscillator and a prism-based pulse shaper is presented. Combined with CEO-phase stabilization the system allows for full control of the electric field on a sub-femtosecond time-scale.