gebhart/patrepeval huggingface dataset:
Functional significance of different human CYPlAl genotypes (1994)

At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms.
Selective Cytotoxicity of Dermaseptin S3 toward IntraerythrocyticPlasmodium falciparum and the Underlying Molecular Basis (1997)

The antimicrobial activity of various naturally occurring microbicidal peptides was reported to result from their interaction with microbial membrane. In this study, we investigated the cytotoxicity of the hemolytic peptide dermaseptin S4 (DS4) and the nonhemolytic peptide dermaseptin S3 (DS3) toward human erythrocytes infected by the malaria parasite Plasmodium falciparum. Both DS4 and DS3 inhibited the parasite's ability to incorporate [3H]hypoxanthine. However, while DS4 was toxic toward both the parasite and the host erythrocyte, DS3 was toxic only toward the intraerythrocytic parasite. To gain insight into the mechanism of this selective cytotoxicity, we labeled the peptides with fluorescent probes and investigated their organization in solution and in membranes. In Plasmodium-infected cells, rhodamine-labeled peptides interacted directly with the intracellular parasite, in contrast to noninfected cells, where the peptides remained bound to the erythrocyte plasma membrane. Binding experiments to phospholipid membranes revealed that DS3 and DS4 had similar binding characteristics. Membrane permeation studies indicated that the peptides were equally potent in permeating phosphatidylserine/phosphatidylcholine vesicles, whereas DS4 was more permeative with phosphatidylcholine vesicles. In aqueous solutions, DS4 was found to be in a higher aggregation state. Nevertheless, both DS3 and DS4 spontaneously dissociated to monomers upon interaction with vesicles, albeit with different kinetics. In light of these results, we propose a mechanism by which dermaseptins permeate cells and affect intraerythrocytic parasites.
Fluidic Timers for Time-Dependent, Point-of-Care Assays on Paper (2010)

This article describes an integrated approach to tracking the end point of a time-based assay that is conducted on an analytical device made out of paper. The timing mechanism is built directly into a paper-based analytical device and does not require starting, stopping, reset buttons, batteries, or maintenance; the timer simply starts once the sample is added to the device. These "fluidic timers" are composed of paraffin wax and a signaling feature (e.g., a dye). The timing function is made possible by the specific time required for a liquid sample to wick through predefined regions in the device. This time period can be anywhere between 1 min and 2 h and is controlled by the quantity of wax present in the timer. Because both the fluidic timers and paper-based assays depend on the wicking rate of the sample, the fluidic timers automatically calibrate themselves (relative to the assay) to account for differences in wicking rates that are caused by variations in humidity. Fluidic timers are 97% accurate (with respect to the time required for the assay) and provide slightly better accuracy than an external timer when used to track an assay that measured the level of glucose in a sample.
Efficient synthesis of cytotoxic quinones: 2‐Acetyl‐4H,9H‐naphtho[2,3‐b]furan‐4,9‐dione (6) and (±)‐2‐(1‐hydroxyethyl)‐4H,9H‐naphtho[2,3‐b]furan‐4,9‐dione (7) (1984)

Abstract From the ethanol extract of the stem bark of Tabebuia cassinoides (Lam.) DC (Bignoniaceae), Kingston and Rao [1] isolated two new furonaphthoquinones 6 and 7 that showed activity in KB cell culture assay (ED 50 1.0 and 2.0 μg/ml, respectively). These values may be significant since lapachol, which has an ED 50 value of 4.4 μg/ml in the same assay, showed sufficient in vivo activity to reach clinical trial at the National Cancer Institute of the United States. The syntheses of these compounds ( 6 and 7 ) were realized in 36% overall yield starting from furan and phthalic anhydride.
Novel Ridge-Type InGaN Multiple-Quantum-Well Laser Diodes Fabricated by Selective Area Re-Growth on n-GaN Substrates (2001)

A novel ridge structure fabricated by selective-area epitaxial re-growth is proposed for InGaN multiple-quantum-well (MQW) laser diodes (LDs). This technique is capable of precisely controlling the active ridge width and height, thus enabling stable single tran sverse-mode operation. Together with a backside n-contact on a low-dislocation-density GaN substrate, this structure provides high productivity and performance for GaN-based blue-violet LDs. A stable fundamental transverse mode up to 40 mW was demonstrated for the certain range of ridge dimensions. The minimum aspect ratio of the far-field patterns (FFPs) was about 2.1 in the fabricated ridge-type InGaN MQW LDs.
Human rheumatoid B-1a (CD5+ B) cells make somatically hypermutated high affinity IgM rheumatoid factors. (1993)

To analyze the structure and formally ascertain the B-1a cellular origin of IgM rheumatoid factor (RF) autoantibodies, we generated 4 IgM RF mAb-producing cell lines using sorted (surface CD5+) B-1a cells from a patient with active rheumatoid arthritis. The RF mAb111, mAb112, mAb113, and mAb114 were monoreactive and displayed a relatively high affinity for human IgG Fc fragment (Kd, 3.1 x 10(-7) to 6.8 x 10(-7) M). The B-1a origin of the lymphocytes that gave rise to the IgM RF was confirmed by the expression of surface CD5 and specific CD5 mRNA by all mAb-producing cell lines. Analysis of the genes encoding the RF mAb VH and VL regions revealed that members of the VHI and VHIII families were utilized in conjunction with V kappa IIIa, V kappa IIIb, or V lambda I genes. JH3 and JH4 genes were each utilized twice. The H chain CDR3 sequences were divergent and variable in length. The RF mAb VH genes were identical or closely related to those expressed in the "restricted" fetal B cell repertoire and/or were JH-proximal. For instance, mAb111 VH gene likely constituted a mutated variant of the expressed fetal 20P3 which is the second most JH-proximal gene (125 kb from JH). In addition, the expressed VH and VL genes were among those that have been found to encode other RF, different autoantibodies, high affinity antibodies induced by exogenous Ag, and natural autoantibodies in the adult and neonatal B cell repertoires. When compared with those of known germline genes, the expressed V gene sequences displayed a number of differences. By cloning and sequencing DNA from PMN of the same patient whose B lymphocytes were used for the mAb generation, we showed that such differences resulted from somatic hypermutation in the RF mAb112 VH gene. The germline gene (112GL) that presumably gave rise to the RF mAb112 VH segment was identical to the expressed fetal 51P1 gene. The distribution and the high replacement to silent mutation ratio of the nucleotide mutations in RF mAb112 VH segment were highly consistent with their selection by Ag. RF mAb113 was clonally related to RF mAb112, as shown by the utilization of the same sets of VHI-D-JH4 and V kappa IIIb-J kappa 4 genes, displaying identical junctional sequences, and the presence of two identical replacement and one silent mutations.(ABSTRACT TRUNCATED AT 400 WORDS)
Isolation of two forms of basement membrane proteoglycans. (1985)

Sequential extractions of the basement membrane producing Engelbreth-Holm-Swarm tumor yielded heparan sulfate proteoglycans with different size core proteins, but the same size heparan sulfate side chains. Saline, a nondenaturing solvent, extracted a small high density proteoglycan with a heterodisperse core protein of Mr = 95,000-130,000 whereas subsequent extraction with 7 M urea, a denaturing solvent, removed a large, low density proteoglycan with a Mr = 350,000-400,000 protein core. The denaturing conditions required for extraction of the large proteoglycan suggest that it interacts strongly with other basement membrane components. Antibodies to these proteoglycans cross-react with both proteoglycans, but the large proteoglycan has additional antigenic sites not present on the small proteoglycan. These proteoglycans may be derived from the same or similar gene products.
Optimizing the use of erythropoietic agents - pharmacokinetic and pharmacodynamic considerations (2002)

Erythropoietic agents have transformed the management of renal anaemia. Two forms of recombinant human erythropoietin (rHuEPO) have been available since the early 1990s, and more recently, a second-generation erythropoietic agent, darbepoetin alfa, has been granted a licence for treating this condition. The endogenous erythropoietin molecule may contain anything from 4 to 14 sialic acid residues. The various isoforms have different biological potencies in vivo owing to their different metabolic clearance rates. However, there is a continuing debate about those organs potentially involved in the metabolism of the erythropoietin molecule; the kidneys, liver, and bone marrow have all been suggested as possible participants. Darbepoetin alfa contains two extra N-linked glycosylation consensus sequences increasing the potential maximum number of sialic acid residues from 14 up to 22. In vitro, the affinity of darbepoetin alfa for the erythropoietin receptor is less than for the natural ligand, but this is more than compensated for by the increased potency in vivo. One of the most important factors determining the biological activity of erythropoiesis-stimulating agents is the length of time that the serum concentration of the protein remains above the threshold necessary for erythropoiesis. The pharmacokinetic profile of darbepoetin alfa is distinct from that of rHuEPO, the major difference being the much longer elimination half-life and slower clearance in vivo of darbepoetin alfa leading to prolonged erythropoietic activity. Stimulation of erythropoiesis depends both on an ambient circulating level of erythropoietin and on the mechanisms governing the interaction of the hormone with its receptor. Our knowledge regarding the latter is limited and it is difficult to predict the optimum frequency of administration for an erythropoietic agent. In general, rHuEPO is given two or three times weekly. A small number of studies have supported the once-weekly use of rHuEPO. All clinical trials so far conducted on darbepoetin alfa have demonstrated success with once-weekly and once every other week dosing.
Calcium Chloride in Neonatal Parenteral Nutrition Solutions with and without Added Cysteine: Compatibility Studies Using Laser and Micro-Flow Imaging Methodology (2015)

Calcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus.
Exploiting domain geometry in analogical route planning (1997)

Abstract Abstract. Automated route planning consists of using real maps to automatically find good map routes. Two shortcomings to standard methods are (1) that domain information may be lacking, and (2) that a 'good' route can be hard to define. Most on-line map representations do not include information that may be relevant for the purpose of generating good realistic routes, such as traffic patterns, construction, and one-way streets. The notion of a good route is dependent not only on geometry (shortest path),but also on a variety of other factors, such as the day and time, weather conditions,and perhaps most importantly,user-dependent preferences. These features can be learned by evaluating real-world execution experience. These difficulties motivate our work on applying analogical reasoning to route planning. Analogical reasoning is a method of using past experience to improve problem solving performance in similar new situations.Our approach consists of the accumulation and reuse of previously traversed routes. We exploit the geometric characteristics of the map domain in the storage, retrieval, and reuse phases of the analogical reasoning process. Our route planning method retrieves and reuses multiple past routing cases that collectively form a good basis for generating a new routing plan. To find a good set of past routes, we have designed a similarity metric that takes into account the geometric and continuous-valued characteristics of a city map. The metric evaluates its own performance and uses execution experience to improve its prediction of case similarity, adaptability and executability. The planner uses a replay mechanism to produce a route plan based on analogy with past routes retrieved by the similarity metric. We use illustrative examples and show some empirical results from a detailed on-line map of the city of Pittsburgh, containing over 18,000 intersections and 25,000 street segments. Keywords: Case-based ReasoningAutomated Route PlanningAdaptive Similarity MetricsAnalogical ReasoningPath Planning
Immunoscintigraphy: Importance for researchers and patients (1996)

One of the subtle differences between the cancer cell surface and the normal cell is exploited by immunoscintigraphy. The clinical role and some technical aspects of imaging cancer with radiolabelled antibodies are reviewed. 99mTc is the best radiolabel for immunoscintigraphy. Specificity is added to the general sensitivity of nuclear medicine techniques by this approach to imaging cancer.
Adenovirus Vector Pseudotyping in Fiber-Expressing Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed B Cells (2000)

While adenovirus (Ad) gene delivery vectors are useful in many gene therapy applications, their broad tropism means that they cannot be directed to a specific target cell. There are also a number of cell types involved in human disease which are not transducible with standard Ad vectors, such as Epstein-Barr virus (EBV)-transformed B lymphocytes. Adenovirus binds to host cells via the viral fiber protein, and Ad vectors have previously been retargeted by modifying the fiber gene on the viral chromosome. This requires that the modified fiber be able to bind to the cell in which the vector is grown, which prevents truly specific vector targeting. We previously reported a gene delivery system based on a fiber gene-deleted Ad type 5 (Ad5) vector (Ad5.betagal.DeltaF) and packaging cells that express the viral fiber protein. Expression of different fibers in packaging cells will allow Ad retargeting without modifying the viral chromosome. Importantly, fiber proteins which can no longer bind to the producer cells can also be used. Using this approach, we generated for the first time pseudotyped Ad5.betagal.DeltaF particles containing either the wild-type Ad5 fiber protein or a chimeric fiber with the receptor-binding knob domain of the Ad3 fiber. Particles equipped with the chimeric fiber bound to the Ad3 receptor rather than the coxsackievirus-adenovirus receptor protein used by Ad5. EBV-transformed B lymphocytes were infected efficiently by the Ad3-pseudotyped particles but poorly by virus containing the Ad5 fiber protein. The strategy described here represents a broadly applicable method for targeting gene delivery to specific cell types.
Happy mapping: linkage mapping using a physical analogue of meiosis (1993)

We have devised a simple method for ordering markers on a chromosome and determining the distances between them. It uses haploid equivalents of DNA and the polymerase chain reaction, hence 'happy mapping'. Our approach is analogous to classical linkage mapping; we replace its two essential elements, chromosome breakage and segregation, by in vitro analogues. DNA from any source is broken randomly by gamma-irradiation or shearing. Markers are then segregated by diluting the resulting fragments to give aliquots containing approximately 1 haploid genome equivalent. Linked markers tend to be found together in an aliquot. After detecting markers using the polymerase chain reaction, map order and distance can be deduced from the frequency with which markers 'co-segregate'. We have mapped 7 markers scattered over 1.24 Mbp using only 140 aliquots. Using the 'whole-genome' chain reaction, we also show how the approach might be used to map thousands of markers scattered throughout the genome. The method is powerful because the frequency of chromosome breakage can be optimized to suit the resolution required.
Mapping of single-copy DNA sequences on human chromosomes by in situ hybridization with biotinylated probes: enhancement of detection sensitivity by intensified-fluorescence digital-imaging microscopy. (1989)

Two single-copy DNA segments of 6 kilobases (kb) and 2.3 kb were labeled with biotin-labeled dUTP (Bio11-dUTP) and hybridized to human chromosomes. These probes were detected by immunofluorescence and directly mapped on chromosomes by using classical fluorescence microscopy and a microchannel-plate-intensified video camera. By a subsequent R-banding, the 6-kb and 2.3-kb fragments were precisely localized to the 18p11.3 band and to the 22q11.2 band, respectively, in agreement with previous results obtained with radioactive probes. The adaptation of fluorescence intensification and digital image processing (frame integration to enhance signal-to-noise ratio and linear contrast stretching) to microscopy makes it possible to detect very weak fluorescent spots on chromosomes. This system allows a high spatial resolution (less than 0.6 micron), even at very low fluorescence levels. The efficiency and the specificity of the hybridization and detection methodology give a direct and precise localization of the short single-copy sequences on human chromosomes.
Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status (2010)

Breast cancer is a highly heterogeneous disease, with several different subtypes being characterized by distinct histology, gene expression patterns, and genetic alterations. The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost in both luminal-B and triple-negative tumor (TNT; i.e., estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative) breast cancer subtypes. However, a causal role for RB1 loss in different subtypes remains undefined. Here we report that deletion of Rb alone or together with its relative p107 in mouse mammary stem/bipotent progenitor cells induced focal acinar hyperplasia with squamous metaplasia. These lesions progressed into histologically diverse, transplantable mammary tumors with features of either luminal-B or TNT subtypes. The TNTs included basal-like tumors as well as tumors that exhibited epithelial-to-mesenchymal transition (EMT). The EMT-type tumors and a subset of the basal-like tumors, but not luminal-B-like tumors, expressed mutant forms of the tumor suppressor p53. Accordingly, targeted deletion of both Rb and p53 in stem/bipotent progenitors led to histologically uniform, aggressive, EMT-type tumors. Reintroduction of Rb into these tumor cells suppressed growth in vitro and tumor formation in vivo. These results establish a causal role for Rb loss in breast cancer in mice and demonstrate that cooperating oncogenic events, such as mutations in p53, dictate tumor subtype after Rb inactivation.
Glutamate Receptor Gating (2004)

Ionotropic glutamate receptors (iGluRs) mediate the vast majority of fast excitatory synaptic transmissions within the mammalian central nervous system (CNS). As for other ion channel protein families, there has been astounding progress in recent years in elucidating the details of protein structure through the crystallization of at least part of the ion channel protein complex. The result is a new framework for the interpretation of both classic and emerging functional data. Here we summarize, compare, and contrast recent findings for the AMPA, kainate, and NMDA subtypes of glutamate receptor ion channels, with an emphasis on the functional and structural aspects of how agonist binding controls channel gating.
Multichannel analysis of surface waves (MASW)—active and passive methods (2007)

The conventional seismic approaches for near-surface investigation have usually been either high-resolution reflection or refraction surveys that deal with a depth range of a few tens to hundreds meters. Seismic signals from these surveys consist of wavelets with frequencies higher than 50 Hz. The multichannel analysis of surface waves (MASW) method deals with surface waves in the lower frequencies (e.g., 1–30 Hz) and uses a much shallower depth range of investigation (e.g., a few to a few tens of meters).
Direct geminal dimethylation of ketones and exhaustive methylation of carboxylic acid chlorides using dichlorodimethyltitanium (1985)

Abstract The reaction of ketones with an excess of (CH 3 ) 2 TiCl 2 ( 6 ) leads to the replacement of the carbonyl oxygen atom by two methyl groups. This mild method of direct geminal dimethylation involves Grignard‐type addition followed by formation of tertiary carbocations which are captured by methyltitanium species. Additional functional groups such as primary alkyl chlorides, thioethers, aromatics, ethers, and esters are tolerated, but not thioketals. The procedure has been applied to the synthesis of (±)‐cuparene ( 44 ). Similarly, carboxylic acid chlorides are converted to tert ‐butyl derivatives.
Xanthine Oxidase Inhibition With Oxypurinol Improves Endothelial Vasodilator Function in Hypercholesterolemic but Not in Hypertensive Patients (1997)

Hypercholesterolemic and hypertensive patients have impaired endothelium-dependent vasorelaxation because of decreased nitric oxide activity, but the mechanism underlying this abnormality is unknown. This study sought to determine whether an increased breakdown of nitric oxide by xanthine oxidase-generated superoxide anions could participate in these forms of endothelial dysfunction. We studied vascular responses to intrabrachial infusion of acetylcholine (an endothelium-dependent vasodilator, 7.5 to 30 microg/min) and sodium nitroprusside (a direct smooth muscle dilator, 0.8 to 3.2 microg/min) by strain-gauge plethysmography before and during the combined administration of oxypurinol (300 microg/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients, 20 essential hypertensive patients, and 20 normal subjects. The vasodilator response to acetylcholine was blunted in hypercholesterolemic (highest flow, 8.2+/-8 mL x min(-1) x dL(-1)) and hypertensive (8.5+/-4 mL x min(-1) x dL(-1)) patients compared with control subjects (13.8+/- 6.6 mL x min(-1) x dL(-1)) (both P<.001); however, no differences were observed in the response to sodium nitroprusside. Oxypurinol did not change the response to acetylcholine in control subjects (P=.26) and improved, but did not normalize, its vasodilator effect in hypercholesterolemic patients (P<.01). Oxypurinol did not affect the response to acetylcholine in hypertensive patients (P=.34) and did not modify the response to sodium nitroprusside in any group. These results suggest that xanthine oxidase-generated superoxide anions are partly responsible for the impaired endothelial vasodilator function of hypercholesterolemic patients. In contrast, this mechanism does not appear to play a significant role in essential hypertension.