gebhart/patrepeval huggingface dataset:
Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low‐dose methotrexate (1989)

Neovascularization in the rheumatoid synovium plays an important role in the propagation of rheumatoid synovitis because the emigration of mononuclear cells and the growth of pannus are critically dependent on the development of small blood vessels. Inhibition of local vascular endothelial cell (EC) proliferation, which is essential for growth of these vessels, therefore, would have the potential to suppress rheumatoid inflammation. We investigated the effects of methotrexate (MTX), low doses of which are commonly administered to rheumatoid arthritis patients, on DNA synthesis by human umbilical vein EC in vitro and on rabbit corneal neovascularization in vivo. MTX inhibited both basal and EC growth factor-stimulated tritiated deoxyuridine (3H-UdR) incorporation into EC in a dose-dependent manner. Significant inhibition was observed at a concentration of 5 x 10(-9) M, which is that attained in the serum of treated patients. Neovascularization in vivo was also suppressed by low-dose intramuscular injections. These results suggest that MTX has an antiangiogenic effect, and may suppress rheumatoid inflammation through the reduction of synovial small blood vessels responsible for mononuclear cell infiltration and proliferation of synovial tissue.
Novel biomarkers of metastatic cancer (2010)

Once metastatic disease is documented, cure is no longer the goal and the disease is generally associated with poor outcomes, with the majority of patients dying of their disease rather than other causes. The last three decades have seen significant advances in the genomics, proteomics and molecular pathology of biomarkers in cancer, allowing for individualization of therapy that has significantly and positively impacted survival outcomes. Genetic signatures have been identified that can predict not only the future development of metastases, but also the development of specific sites of metastases. Protein biomarkers have been identified that are in use clinically for the monitoring of both disease progression and therapeutic efficacy. DNA- and RNA-based biomarkers have also been identified. This review will focus on some of the novel biomarkers that have been developed over the last decade.
Stokes vectors, Mueller matrices, and polarized scattered light (1985)

The complete characterization of scattered light is described in the context of Stokes vectors and Mueller matrices which highly motivates the measuring procedures. The most general form of the scattering matrix coupled with polarizers and quarter wave plates elegantly demonstrates the physical relationship among the matrix elements and polarization measurements.
Domain inversion effects in Ti-LiNbO3 integrated optical devices (1985)

Significant degradation in the cumulative electro-optic effect attributable to domain inversion has been observed in integrated optical devices fabricated by Ti diffusion in c+-LiNbO3. The c− surface was found to be considerably more immune to domain inversion than the c+ surface under similar diffusion conditions. Domain inversion was found to be dependent on diffusion temperature, time, and Ti concentration. A large increase in the Vπ voltage was observed in Mach–Zehnder interferometers fabricated on c+ substrates compared to that of c− substrates under the same fabrication conditions. The effect of domain inversion on crosstalk in directional coupler switches is also discussed.
Phase I study of liposome irinotecan (PEP02) in combination with weekly infusion of 5-FU/LV in advanced solid tumors. (2010)

e13024 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved PK and tumor biodistribution of CPT-11 and its active metabolite-SN38 with encouraging safety and tumor response in preclinical studies and a single-agent phase I study. The study is to define the DLT, MTD, and PK of PEP02 when in combination with high-dose fluorouracil/leucovorin (HDFL) in patients (pt) with advanced solid tumors. Methods: Pts who had failed to standard chemotherapy, ECOG PS 0-1 and adequate organ functions, no prior CPT-11, were eligible. PEP02 was given as 90 mins i.v. infusion on D1 in combination with 24-hr infusion of 5FU (2,000 mg/m2)/ LV (200 mg/m2) on D1 and D8, every 3 weeks. Cohorts of 3-6 pts were treated at 60, 80, 100, and 120 mg/m2. PK and PGx samples were collected. Results: A total of 16 pts were enrolled, with 3, 6, 5, and 2 at 60, 80, 100, and 120 mg/m2. DLTs were observed in 4 pts, including 2 each at 100 and 120 mg/m2 dose levels. DLTs were mainly G3 diarrhea and G4 hematologic toxicities. MTD was determined as 80 mg/m2. Grade 3 or above adverse events at the MTD dose and all dose levels were 10.6% and 18.4%, respectively. The PK of total CPT-11 after PEP02 (at 80 mg/m2) in combination with HDFL was characterized by low clearance (mean = 116.4 mL/m2/hr) and small volume of distribution (mean = 2.93 L/m2, similar to plasma volume) as did of PEP02 monotherapy study. Compared to the PK of SN-38 after 250 mg/m2 of CPT-11 (in combination with capecitabine, Ann Oncol 2005; 16: 1123-32), the Cmax after 80 mg/m2 of PEP02 was lower (7.98 ± 4.39 vs 62.0 ± 37.4 ng/mL), but the AUC0→t was similar (354.77 ± 145.35 vs 396 ± 247 ng×h/mL). The correlation of UGT1A family with PK and toxicity was not observed. However, the only subject with the coexistence of two variants of UGT1A1*6 and *28 had higher dose-normalized AUCSN-38and experienced DLT. The best response of 15 evaluable pts was PR in 2 (gastric cancer and breast cancer) and SD in 9. Conclusions: The MTD of PEP02 in combination with HDFL given every-3-week is 80 mg/m2. The observation of tumor response in two heavily pre-treated patients suggests the combination deserves further exploration in advanced solid tumor patients who are refractory to standard therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaEngine PharmaEngine PharmaEngine PharmaEngine
Poststroke Depression: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2016)

Poststroke depression (PSD) is common, affecting approximately one third of stroke survivors at any one time after stroke. Individuals with PSD are at a higher risk for suboptimal recovery, recurrent vascular events, poor quality of life, and mortality. Although PSD is prevalent, uncertainty remains regarding predisposing risk factors and optimal strategies for prevention and treatment. This is the first scientific statement from the American Heart Association on the topic of PSD. Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion. This multispecialty statement provides a comprehensive review of the current evidence and gaps in current knowledge of the epidemiology, pathophysiology, outcomes, management, and prevention of PSD, and provides implications for clinical practice.
Implant alignment in total elbow arthroplasty: conventional vs. navigated techniques (2009)

Incorrect selection of the native flexion-extension axis during implant alignment in elbow replacement surgery is likely a significant contributor to failure of the prosthesis. Computer and image-assisted surgery is emerging as a useful surgical tool in terms of improving the accuracy of orthopaedic procedures. This study evaluated the accuracy of implant alignment using an image-based navigation technique compared against a conventional non-navigated approach. Implant alignment error was 0.8 &plusmn; 0.3 mm in translation and 1.1 &plusmn; 0.4&deg; in rotation for the navigated alignment, compared with 3.1 &plusmn; 1.3 mm and 5.0 &plusmn; 3.8&deg; for the non-navigated alignment. Five (5) of the 11 non-navigated alignments were malaligned greater than 5&deg; while none of the navigated alignments were placed with an error of greater than 2.0&deg;. It is likely that improved implant positioning will lead to reduced implant loading and wear, resulting in fewer implantrelated complications and revision surgeries.
Development of a new type of biosensors based on ATR-FTIR spectroscopy (2012)

Les biosenseurs sont des dispositifs analytiques utilisés pour la détection de reconnaissance moléculaire. Ils consistent en un élément biologique immobilisé en contact intime avec un transducteur approprié qui convertit un signal biochimique en un signal électrique quantifiable. Leur principe est basé sur la reconnaissance d'une ou plusieurs molécules d'intérêt en solution (le ligand), par un composant biologique (le récepteur) étroitement lié au substrat transducteur. Le senseur réagit aux interactions récepteur-ligand et produit un signal mesurable, généralement proportionnel à la concentration du ligand fixé. Les biosenseurs sont déjà utilisés dans beaucoup de domaines différents, notamment dans le domaine médical (diagnostique et thérapeutique), le contrôle de l’environnement, et l’analyse et le monitoring de processus biotechnologiques. &lt;p&gt;&lt;p&gt;La recherche concerne la mise au point d’un nouveau type de biosenseurs polyvalents à haute performance. Ces senseurs utilisent un élément de transduction optique dont la surface a été fonctionnalisée en vue de permettre la détection sélective d'interactions récepteur-ligand ainsi que le dosage des molécules fixées aux récepteurs. La technique utilisée pour la détection et le dosage est celle de la Spectroscopie ATR-FTIR (Spectroscopie Infra Rouge à Transformée de Fourrier en Réflexion Total Atténuée). Le système permet la détection directe, en temps réel, et sans marquage des molécules ciblées. La spectroscopie ATR-FTIR fournit une analyse des molécules sur base de leur empreinte spectrale infra rouge (IR) caractéristique, ce qui offre une mine d'informations pour identifier les ligands. Ce nouveau système de biosenseur, appelé BIA-ATR (Biospecific Interaction Analysis – Attenuated Total Reflection) est original et offre des avantages majeurs par rapport à la plus part des biosenseurs commercialement disponibles. Il fournit à l’utilisateur le spectre IR entier du ligand étudié, permettant non seulement le dosage quantitatif de ce dernier, mais aussi d’identifier sa nature intrinsèque. Un autre avantage est sa grande sensibilité ;le senseur BIA-ATR peut détecter la fixation de petites molécules et dans certains cas, aussi les réactions chimiques associées. &lt;p&gt;&lt;p&gt;Le potentiel de cette nouvelle technologie de senseur est évalué dans ce travail par son application à plusieurs systèmes d’intérêt biologique et médical :la détection de protéines en milieux complexes, appliquée à la détection du Facteur VIII de coagulation du sang impliqué dans l’hémophilie de type A ;la fixation d’une petite molécule, le phosphate (phosphorylation), sur l’ATPase gastrique, un récepteur protéique de grande taille responsable de la sécrétion d’acide dans l’estomac et la détection et dosage d’un antibiotique, la vancomycine, utilisé en soins intensifs hospitaliers dans les cas d’infections bactériennes sévères à Staphylocoques dorés.&lt;p&gt;
A fast algorithm for the implementation of filter banks based on 'time domain aliasing cancellation' (1991)

Several data compression techniques are in competition for coding high-quality audio signals (sampling rate >or=32 kHz) down to a 64 kb/s bit rate. The authors concentrate on the subband/transform coding scheme using filter banks known as time domain aliasing cancellation (TDAC). This scheme first involves a window on a set of N data, overlapping by N/2 with the previous one, followed by a TDAC transform. First, it is shown that the transform turns out to be a doubly odd DCT, for which a fast algorithm is provided. Then, it is shown how the windowing and the overlap can be merged with the first step of the first algorithm. The total number of operations (multiplications plus additions) required by this algorithm for computing a length-N TDAC plus windowing is exactly N log/sub 2/ N. Implementation considerations are provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sex Steroids and Afferent Input: Their Roles in Brain Sexual Differentiation (1987)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
High Affinity Mimotope of the Polysaccharide Capsule of Cryptococcus neoformans Identified from an Evolutionary Phage Peptide Library (2002)

Abstract Cryptococcus neoformans causes a life-threatening meningoencephalitis in a significant percentage of AIDS patients. Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid (TT) produce Abs that, based on the epitope recognized, can be either protective or nonprotective. Since nonprotective Abs block the efficacy of protective Abs, we are interested in developing a vaccine that would focus the immune response specifically to protective epitopes. Previously, we screened a phage display library with 2H1, a protective anti-GXM mAb, and isolated PA1, a representative peptide that had a Kd of 295 nM for 2H1. Mice immunized with PA1 conjugated to keyhole limpet hemocyanin developed high anti-peptide (1/13,000), but low anti-GXM (maximum, 1/200) titers. We now report our efforts to improve this vaccine by screening a sublibrary with six random amino acids added to either end of the PA1 motif to identify higher affinity peptides. P206.1, a peptide isolated from this sublibrary, had 80-fold higher affinity for 2H1 (Kd = 3.7 nM) than PA1. P206.1 bound protective, but not nonprotective, anti-GXM Abs. Mice immunized with P206.1 conjugated to various carriers did not mount an Ab response to GXM despite developing high anti-peptide titers. However, mice primed with GXM-TT and boosted with P206.1-TT developed significant anti-GXM titers (maximum, 1/180,000). This latter immunization scheme focused the immune response on protective epitopes, since only 2–5% of these titers were directed against nonprotective de-O-acetylated GXM epitopes compared with 20–60% in animals primed and boosted with GXM-TT.
Short low loss AM antenna (1989)

An exploration is made of ways to improve the performance of a relatively small transmitting or receiving AM antenna system. Short vertical towers can be top-loaded to increase the radiation resistance and lower the base input capacitive reactance. An insulated counterpoise is connected to the coupling unit and to ground through an inductance which is tuned so as to maximize the field strength radiated in the far field.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Plaque assay of neonatal calf diarrhea virus and the neutralizing antibody in human sera (1977)

Neonatal calf diarrhea virus (a bovine rotavirus) formed distinct plaques in monolayers of MA-104 cells, an established macacus rhesus monkey kidney cell line, when diethylaminoethyl dextran and trypsin were included in the overlay medium. By using this plaque assay method, titration of neutralizing antibody to neonatal calf diarrhea virus was made feasible. It was demonstrated that some human sera contained neutralizing antibody to this agent.
Effect of Drastic Sequence Alteration andd-Amino Acid Incorporation on the Membrane Binding Behavior of Lytic Peptides (2004)

The amphipathic alpha-helix is a common motif found in many cell lytic peptides including antimicrobial peptides. We have recently shown that significantly altering the amphipathic structure of a lytic peptide by reshuffling its sequence and/or replacing a few l-amino acids with their D-enantiomers did not significantly affect the antimicrobial activity of the peptides nor their ability to bind and permeate negatively charged (PE/PG) membranes. However, a pronounced effect was observed regarding their hemolytic activity and their ability to bind and permeate zwitterionic (PC/Cho) membranes. To shed light on these findings, here we used surface plasmon resonance (SPR) with mono- and bilayer membranes. We found that the L-amino acid (aa) peptides bound 10-25-fold stronger to PC/Cho bilayers compared with monolayers, whereas the diastereomers bound similarly to both membranes. A two-state reaction model analysis of the data indicated that this difference is due to the insertion of the L-aa peptides into the PC/Cho bilayers, whereas the diastereomers are surface-localized. In contrast, only an approximately 2-fold difference was found with negatively charged membranes. Changes in the amphipathicity markedly affected only the insertion of the L-aa peptides into PC/Cho bilayers. Furthermore, whereas the all-L-aa peptides bound similarly to the PC/Cho and PE/PG membranes, the diastereomers bound approximately 100-fold better to PE/PG compared with PC/Cho membranes, and selectivity was determined only in the first binding step. The effect of the peptides on the lipid order determined by using ATR-FTIR studies supported these findings. Besides shedding light on the mode of action of these peptides, the present study demonstrates SPR as a powerful tool to differentiate between non-cell-selective compared with bacteria-selective peptides, based on differences in their membrane binding behavior.
A DNA-Based Archival Storage System (2016)

Demand for data storage is growing exponentially, but the capacity of existing storage media is not keeping up. Using DNA to archive data is an attractive possibility because it is extremely dense, with a raw limit of 1 exabyte/mm 3 (109 GB/mm 3 ), and long-lasting, with observed half-life of over 500 years. This paper presents an architecture for a DNA-based archival storage system. It is structured as a key-value store, and leverages common biochemical techniques to provide random access. We also propose a new encoding scheme that offers controllable redundancy, trading off reliability for density. We demonstrate feasibility, random access, and robustness of the proposed encoding with wet lab experiments involving 151 kB of synthesized DNA and a 42 kB random-access subset, and simulation experiments of larger sets calibrated to the wet lab experiments. Finally, we highlight trends in biotechnology that indicate the impending practicality of DNA storage for much larger datasets.
Synergistic Inhibition of HIV-1 Reverse Transcriptase DNA Polymerase Activity and Virus Replication in Vitro by Combinations of Carboxanilide Nonnucleoside Compounds (1995)

The carboxanilides UC84 and UC38 are nonnucleoside inhibitors of both the RNA-dependent and DNA-dependent DNA polymerase activities of HIV-1 reverse transcriptase (RT). We have previously shown that UC84 and UC38 bind to the same site as nevirapine but interact with different RT mechanistic forms, with UC84 preferentially binding to the RT-primer/template complex and UC38 binding only to the RT-primer/template-dNTP ternary complex [Fletcher, R. S., et al. (1995) Biochemistry 34, 4346-4353]. Here we demonstrate that combinations of UC84 and UC38 inhibit RT DNA polymerase activity in vitro in a synergistic manner. This synergy was noted primarily in reactions containing high concentrations of primer/template and Km levels of dNTP substrate and was independent of both primer/template identity and the molar ratio of UC84:UC38. Combination indices were in the range of 0.4-0.6, indicating substantial synergy in the inhibition of RT activity. More importantly, combinations of UC84 and UC38 also showed a high degree of synergy in inhibiting HIV-1 replication in both MT-4 and cord blood mononuclear cells. We believe this to be the first example of synergistic inhibition of HIV-1 RT by combinations of structurally related nonnucleoside inhibitors.
A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis (2001)

Standard therapy in the United States for malignancy-associated hyperuricemia consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes the enzymatic oxidation of uric acid to a 5 times increased urine soluble product, allantoin. Rasburicase is a new recombinant form of urate oxidase available for clinical evaluation. This multicenter randomized trial compared allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at high risk for tumor lysis. Patients received the assigned uric acid-lowering agent for 5 to 7 days during induction chemotherapy. The primary efficacy end point was to compare the area under the serial plasma uric acid concentration curves during the first 96 hours of therapy (AUC(0-96)). Fifty-two patients were randomized at 6 sites. In an intent-to-treat analysis, the mean uric acid AUC(0-96) was 128 +/- 70 mg/dL.hour for the rasburicase group and 329 +/- 129 mg/dL.hour for the allopurinol group (P <.0001). The rasburicase versus allopurinol group experienced a 2.6-fold (95% CI: 2.0-3.4) less exposure to uric acid. Four hours after the first dose, patients randomized to rasburicase compared to allopurinol achieved an 86% versus 12% reduction (P <.0001) of initial plasma uric acid levels. No antirasburicase antibodies were detected at day 14. This randomized study demonstrated more rapid control and lower levels of plasma uric acid in patients at high risk for tumor lysis who received rasburicase compared to allopurinol. For pediatric patients with advanced stage lymphoma or high tumor burden leukemia, rasburicase is a safe and effective alternative to allopurinol during initial chemotherapy.
Effect of Surfactants on the Interfacial Tension and Emulsion Formation between Water and Carbon Dioxide (1998)

The lowering of the interfacial tension (γ) between water and carbon dioxide by various classes of surfactants is reported and used to interpret complementary measurements of the capacity, stability, and average drop size of water-in-CO2 emulsions. γ is lowered from ∼20 to ∼2 mN/m for the best poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(propylene oxide) (PPO-b-PEO-b-PPO) and PEO-b-PPO-b-PEO Pluronic triblock copolymers, 1.4 mN/m for a poly(butylene oxide)-b-PEO copolymer, 0.8 mN/m for a perfluoropolyether (PFPE) ammonium carboxylate and 0.2 mN/m for PDMS24-g-EO22. The hydrophilic−CO2-philic balance (HCB) of the triblock Pluronic and PDMS-g-PEO−PPO surfactants is characterized by the CO2-to-water distribution coefficient and “V-shaped” plots of log γ vs wt % EO. A minimum in γ is observed for the optimum HCB. As the CO2-philicity of the surfactant tail is increased, the molecular weight of the hydrophilic segment increases for an optimum HCB. The stronger interactions on both sides of the interface lead to a lower γ. Consequently, more water was emulsified for the PDMS-based copolymers than either the PPO- or PBO-based copolymers.