gebhart/patrepeval huggingface dataset:
Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives. (1999)

Six halogenated derivatives of cannabidiol (CBD, 1) substituted on the aromatic ring at the 3' and/or 5' position, 3'-chloro- (2), 3',5'-dichloro- (3), 3'-bromo- (4), 3',5'-dibromo- (5), 3'-iodo- (6) and 3',5'-diiodo-CBD (7) were synthesized and their pharmacological effects of barbiturate-induced sleep prolongation, anticonvulsant effects and locomotor activity were evaluated by intravenous (i.v.) injection in mice. 2 (10 mg/kg, i.v., 69 +/- 10 min) significantly prolonged pentobarbital-induced sleeping time by 3.1-fold, compared to control (22 +/- 2 min), although other 1 derivatives used did not significantly affect the sleeping time. 2, 4 and 6 (10 mg/kg, i.v.) significantly prolonged hexobarbital-induced sleeping time by 2.0-, 2.0- and 2.3-fold, respectively, compared with control (52 +/- 5 min). On the other hand, 1 and all halogenated derivatives did not significantly prolong barbital-induced sleeping time. The monohalogenated derivatives, 2, 4 and 6 were able to prolong pentobarbital and hexobarbital-induced sleeping time, although the dihalogenated derivatives, 3, 5 and 7 did not exhibit a prolongation of the sleeping time. All halogenated derivatives of 1 except for brominated derivatives (2, 3, 6, 7) tended to prolong tonic seizure latency induced by pentylenetetrazol. 1 and its halogenated derivatives did not exhibit any prolongation of seizure latency induced by picrotoxin or strychnine. Maximal electroshock test demonstrated that 1 and 4 exhibited almost the same potency in their anticonvulsant effects, although other 1 derivatives 2, 3, 5, 6 and 7 did not show significant effect up to a dose of 63 mg/kg, i.v. The ED50 values (mg/kg, i.v.) of 1 and 4 were 38 and 44, respectively. 1 and 4 also showed anticonvulsant effect in minimal and maximal electroshock-threshold tests. 2, 4 and 6 tended to decrease the total distance (horizontal activity) and number of rearings (vertical activity) of mice, whereas 3, 5 and 7 tended to increase the number of rearings. However, the effects of all derivatives were not statistically significant from the control. 2 and 4 were the most potent derivatives on pharmacological activities among the synthetic cannabinoids examined in the present study. These results indicate that monohalogenation of 1 leads to some modification of the pharmacological profile of CBD.
Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation (2019)

In first-in-human trials, PFA preferentially affected myocardial tissue, allowing facile ultra-rapid PV isolation with excellent durability and chronic safety. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation; NCT03700385; and PEFCAT: A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation; NCT03714178).
High-Riter Bicistronic Retroviral Vectors Employing Foot-and-Mouth Disease Virus Internal Ribosome Entry Site (1996)

Bicistronic retroviral vectors were constructed containing the foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES) followed by the coding region of beta-galactosidase (beta-gal) or therapeutic genes, with the selectable neomycin phosphotransferase gene under the control of the viral long terminal repeat (LTR) promoter. LNFX, a vector with a multiple cloning site 3' to foot-and-mouth disease virus IRES, was used to construct vectors encoding rat erythropoietin (EP), rat granulocyte colony-stimulating factor (G-CSF), human adenosine deaminase (ADA) and beta-gal. In transduced primary rat vascular smooth muscle cells the cytokines were expressed at high levels, similar to those obtained from vectors employing the viral LTR promoter. LNFZ, a vector encoding beta-gal, had a 10-fold increase in titer over that of LNPoZ, a comparable vector containing the poliovirus (Po) internal ribosome entry site. Primary canine vascular smooth muscle cells infected with LNFZ and LNPoZ expressed similar activities of beta-gal and neomycin phosphotransferase (NPT). Overall, these vectors had titers between 10(6) and 2 x 10(7) c.f.u./ml, indicating that foot-and-mouth disease virus IRES provides high-titer bicistronic vectors with high-level two gene expression.
Directed evolution of novel adeno-associated viral vectors for gene therapy (2014)

Click to launch & play an online audio visual presentation by Prof. David Schaffer on Directed evolution of novel adeno-associated viral vectors for gene therapy, part of a collection of multimedia lectures.
Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation (2012)

The threat of emerging pathogens and microbial drug resistance has spurred tremendous efforts to develop new and more effective antimicrobial strategies. Recently, a novel ultrashort pulsed (USP) laser technology has been developed that enables efficient and chemical-free inactivation of a wide spectrum of viral and bacterial pathogens. Such a technology circumvents the need to introduce potentially toxic chemicals and could permit safe and environmentally friendly pathogen reduction, with a multitude of possible applications including the sterilization of pharmaceuticals and blood products, and the generation of attenuated or inactivated vaccines.
A Safer Generation of Wettability Alteration Chemical Treatments (2017)

Abstract Substantial natural gas reserves are found in gas condensate reservoirs. As gas production takes place from these reservoirs, single phase gas flows as long as the bottomhole pressure is greater than the dew point pressure. With production, the flowing bottomhole pressure decreases and once it decreases below the dew point pressure, condensation of some of the heavy components in the gas stream occurs. This liquid condensate will accumulate in the area near the wellbore and form condensate banking, which adversely affects both the gas relative permeability and the well productivity. Numerous methods have been utilized to mitigate the problem of condensate banking. One of the most effective methods is the use of wettability alteration chemicals to change the rock wettability from water/oil wet to preferentially gas wet. The main problem with the current wettability alteration chemical treatment is the treatment's low flash point, which makes it unsafe to be used in the summer time when temperatures in some parts of the world can be as high as 130°F (54.5°C). The main objective of the current work is to develop a wettability alteration chemical with a high flash point to address this safety concern. Several additives and alternatives intended to increase the flash point were tested. The flash point temperature was measured for these new formulations, and contact angle, interfacial tension and coreflood experiments were performed to evaluate the newly developed treatment formulations. Lab tests indicated that the flash point temperature of the treatment fluids increased from 22°C to approximately 67°C. The contact angle measurements indicated that the modified wettability alteration chemicals treatment fluid was able to modify the wettability of rock surfaces from complete water wetting to mixed wettability or even gas wetting. The contact angle between water and sandstone rock surfaces increased from 10° to 114° after treating the rocks with some of the new formulations. The pressure drop encountered while injecting different fluid systems decreased after treating the rock sample with a formulation that has 67°C flash point temperature. As an example, the formulation that has a flash point temperature of 67°C achieved an improvement factor of 1.55 in the condensate and gas relative permeabilities compared to an improvement factor of 1.7 that was achieved by using the low flash point fluid (flash point temperature is 22°C). A higher flash point chemical treatment was developed to be used to mitigate the condensate banking problem. The newly developed formulations were able to modify the rock wettability from water and oil wetting to intermediate wettability or preferentially gas wetting.
Applied Optimal Estimation (1974)

This is the first book on the optimal estimation that places its major emphasis on practical applications, treating the subject more from an engineering than a mathematical orientation. Even so, theoretical and mathematical concepts are introduced and developed sufficiently to make the book a self-contained source of instruction for readers without prior knowledge of the basic principles of the field. The work is the product of the technical staff of the The Analytic Sciences Corporation (TASC), an organization whose success has resulted largely from its applications of optimal estimation techniques to a wide variety of real situations involving large-scale systemsArthur Gelb writes in the Foreword that It is our intent throughout to provide a simple and interesting picture of the central issues underlying modern estimation theory and practice. Heuristic, rather than theoretically elegant, arguments are used extensively, with emphasis on physical insights and key questions of practical importance.Numerous illustrative examples, many based on actual applications, have been interspersed throughout the text to lead the student to a concrete understanding of the theoretical material. The inclusion of problems with built-in answers at the end of each of the nine chapters further enhances the self-study potential of the text.After a brief historical prelude, the book introduces the mathematics underlying random process theory and state-space characterization of linear dynamic systems. The theory and practice of optimal estimation is them presented, including filtering, smoothing, and prediction. Both linear and non-linear systems, and continuous- and discrete-time cases, are covered in considerable detail. New results are described concerning the application of covariance analysis to non-linear systems and the connection between observers and optimal estimators. The final chapters treat such practical and often pivotal issues as suboptimal structure, and computer loading considerations.This book is an outgrowth of a course given by TASC at a number of US Government facilities. Virtually all of the members of the TASC technical staff have, at one time and in one way or another, contributed to the material contained in the work
Live cell ultraviolet microscopy: A comparison between two‐ and three‐photon excitation (2003)

We compare conventional infrared laser based three-photon excitation with a visible laser based two-photon excitation scheme for imaging the ultraviolet fluorophore serotonin in solution and in live cells. To obtain a signal level of 1000 photons per second per mM serotonin solution, we need a back aperture power of 5 mW at 550 nm (for two-photon excitation) and 33 mW at 740 nm (for three-photon excitation). The detectivity of serotonin (defined as the concentration of serotonin that yields a signal equivalent to three times the standard deviation of the signal obtained from the buffer alone) is 12 microM for two-photon, and 220 microM for three-photon excitation. Surprisingly, for live cell imaging of vesicular serotonin in serotonergic cells, three-photon excitation appears to provide better image contrast than two-photon excitation. The origin of this is traced to the concentration-dependent shift of the serotonin emission spectrum.
Activating and dominant inactivating c-KITcatalytic domain mutations in distinct clinical forms of human mastocytosis (1999)

Human mastocytosis is characterized by increased mast cells. It usually occurs as a sporadic disease that is often transient and limited in children and persistent or progressive in adults. The c-KIT protooncogene encodes KIT, a tyrosine kinase that is the receptor for mast cell growth factor. Because mutated KIT can transform cells, we examined c-KIT in skin lesions of 22 patients with sporadic mastocytosis and 3 patients with familial mastocytosis. All patients with adult sporadic mastocytosis had somatic c-KIT mutations in codon 816 causing substitution of valine for aspartate and spontaneous activation of mast cell growth factor receptor (P = 0.0001). A subset of four pediatric onset cases with clinically unusual disease also had codon 816 activating mutations substituting valine, tyrosine, or phenylalanine for aspartate. Typical pediatric patients lacked 816 mutations, but limited sequencing showed three of six had a novel dominant inactivating mutation substituting lysine for glutamic acid in position 839, the site of a potential salt bridge that is highly conserved in receptor tyrosine kinases. No c-KIT mutations were found in the entire coding region of three patients with familial mastocytosis. We conclude that c-KIT somatic mutations substituting valine in position 816 of KIT are characteristic of sporadic adult mastocytosis and may cause this disease. Similar mutations causing activation of the mast cell growth factor receptor are found in children apparently at risk for extensive or persistent disease. In contrast, typical pediatric mastocytosis patients lack these mutations and may express inactivating c-KIT mutations. Familial mastocytosis, however, may occur in the absence of c-KIT coding mutations.
Development of a Forced Choice Photographic Questionnaire for Photic Phenomena and Its Testing – Repeatability, Reliability and Validity (2004)

The photographic images of photic phenomena analyser is an acceptable, validated measure for the assessment of photic phenomena, in both pseudophakic patients and those with cataract.
Evidence of covalent interaction of fumaric acid esters with sulfhydryl groups in peptides (2005)

Fumaric acid esters, namely dimethylfumarate, have been used for the treatment of psoriasis for many years. Still, their mode of action is not fully clear. Because addition of nucleophiles to the double bonds of fumarates can occur (Michael analogous addition), a study of the interaction of fumarates with cysteine and cysteine-containing peptides possessing nucleophilic sulfhydryl group was carried out. Experiments were performed in aqueous medium at pH 7.4 and at 37 degrees C to simulate physiological conditions. It was proven by mass spectrometric measurements using an ion-trap and time-of-flight instrument that a covalent bond can form between fumarates and the sulfhydryl group of cysteine or cysteinyl residues in peptides. Structures of the interaction products were elucidated by multistage mass spectrometry applying collision-induced dissociation. Higher reactivity of dimethylfumarate in comparison to monomethylfumarate and fumaric acid was observed.
A Bayesian framework for automatic concept discovery in image collections (2004)

This paper develops a Bayesian framework for automatic hidden semantic concept discovery to address effective semantics-intensive content-based image retrieval. Each image in the database is segmented to regions associated with homogenous color, texture, and shape features. By employing self-organization map learning, a uniform and sparse region-based representation is obtained. With this representation a probabilistic model based on the statistical-hidden-class assumptions of the image database is developed, to which expectation-maximization technique is applied to analyze semantic concepts hidden in the database. An elaborated retrieval algorithm is designed to support the probabilistic model. The semantic similarity is measured through integrating the posterior probabilities of the transformed query image, as well as a constructed negative vector, to the discovered semantic concepts. The proposed approach has a solid statistical foundation and the experimental evaluations on a database of 10,000 general-purposed images demonstrate its promise of the retrieval effectiveness.
Conversion between two cytochalasin B‐binding states of the human GLUT1 glucose transporter (2000)

Two cytochalasin B-binding states of the human red blood cell facilitative glucose transporter GLUT1 were studied, one exhibiting one cytochalasin B-binding site on every second GLUT1 monomer (state 1) and the other showing one site per monomer (state 2). Quantitative affinity chromatography of cytochalasin B was performed on (a) biotinylated red blood cells, (b) cytoskeleton-depleted red blood cell membrane vesicles, and (c) GLUT1 proteoliposomes. The cells were adsorbed on streptavidin-derivatized gel beads, and the vesicles and proteoliposomes entrapped in dextran-grafted agarose gel beads. Cytochalasin B binding to free vesicles and proteoliposomes was analyzed by Hummel and Dreyer size-exclusion chromatography and ultracentrifugation. Analysis of the biotinylated cells indicated an equilibrium between the two GLUT1 states. GLUT1 in free membrane vesicles attained state 2, but was converted into state 1 on entrapment of the vesicles. Purification of GLUT1 in the presence of non-ionic detergent followed by reconstitution produced GLUT1 in state 1. This state was maintained after entrapment of the proteoliposomes. Finally, GLUT1 showed slightly higher affinity for cytochalasin B in state 1 than in state 2. In summary, the cytochalasin B-binding state of GLUT1 seemed to be affected by (a) biotinylation of the cell surface, (b) removal of the cytoskeleton at high pH and low ionic strength, (c) interaction between the dextran-grafted agarose gel matrix and the membrane vesicles, and (d) reconstitution to form proteoliposomes.
Structure−Activity Relationship Studies of Gonadotropin-Releasing Hormone Antagonists ContainingS-Aryl/Alkyl Norcysteines and Their Oxidized Derivatives (2007)

A series of acyline analogues incorporating l- and d-isomers of S-arylated/alkylated norcysteines [Ncy(R), where R is 2-naphthyl, methyl, and isopropyl] at positions 1, 4, 7, and 10 were synthesized. Some of these analogues were mono- and dioxidized to sulfoxides and sulfones. All of the analogues of acyline were screened for the antagonism of the GnRH-induced response in a reporter gene assay in HEK-293 cells expressing the human GnRH receptor. Nine of the analogues (9, 11, 15, 16, 17, 19, 20, 21, and 22) had antagonistic potency (IC50 < 2 nM) similar to that of acyline (IC50 = 0.52 nM) in this assay. Selected analogues (9, 11, 15, 16, 19, and 21) were tested in vitro for their antagonism at the rat GnRH-R in a reporter gene assay as well as in an in vivo intact male rat assay. Analogues 9 and 15 were the most potent in suppressing testosterone levels.
CA 125: The past and the Future (1998)

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.
Serum 4-Hydroxy-2-Nonenal-Modified Albumin Is Elevated in Patients with Type 2 Diabetes Mellitus (2000)

4-Hydroxy-2-nonenal (HNE) is one of the major lipid peroxidation products with cytotoxic and mutagenic activity. It further reacts with protein residues such as histidine to generate stable Michael adducts. To evaluate the status of oxidative stress in the serum of type 2 diabetes mellitus, we constructed a sandwich enzyme-linked immunosorbent assay to measure serum HNE-modified albumin by the use of a specific monoclonal antibody (HNEJ-2) against HNE-histidine adducts as well as an antibody against human serum albumin. Serum of type 2 diabetes outpatients revealed significantly higher levels of HNE-modified albumin (736.1 +/- 34.2 pmol/ml, n = 54) than the matched nondiabetics (611.4 +/- 39.1 pmol/ml, n = 30; means +/- SEM; p = 0.018). However, no significant correlation was observed in diabetic outpatients between the levels of HNE-modified albumin and clinical parameters such as fasted blood glucose, HbA1c, diabetes duration, or complications. Our data demonstrated the increased formation of serum HNE-modified albumin in type 2 diabetic outpatients in the milieu between liver and vascular lumina, indicating the presence of oxidative stress.
Electrical detection of deoxyribonucleic acid hybridization with AlGaN∕GaN high electron mobility transistors (2006)

Au-gated AlGaN∕GaN high electron mobility transistor (HEMT) structures were functionalized in the gate region with label-free 3′-thiol-modified oligonucleotides. This serves as a binding layer to the AlGaN surface for hybridization of matched target deoxyribonucleic acid (DNA). X-ray photoelectron spectroscopy shows the immobilization of thiol-modified DNA covalently bonded with gold on the gated region. Hybridization between probe DNA and matched or mismatched target DNA on the Au-gated HEMT was detected by electrical measurements. The HEMT drain-source current showed a clear decrease of 115μA as this matched target DNA was introduced to the probe DNA on the surface, showing the promise of the DNA sequence detection approach for biological sensing.
Mesh optimization (1993)

We present a method for solving the following problem: Given a set of data points scattered in three dimensions and an initial triangular mesh M0, produce a mesh M, of the same topological type as M0, that fits the data well and has a small number of vertices. Our approach is to minimize an energy function that explicitly models the competing desires of conciseness of representation and fidelity to the data. We show that mesh optimization can be effectively used in at least two applications: surface reconstruction from unorganized points, and mesh simplification (the reduction of the number of vertices in an initially dense mesh of triangles).