gebhart/patrepeval huggingface dataset:
Imaging fluorescence bronchoscopy for localizing early bronchial cancer and carcinoma in situ. (1984)

A system of imaging fluorescence bronchoscopy instrumentation and methods has been devised that has succeeded in localizing very small (1 X 2 mm) areas of bronchial mucosal cancer, in individuals with radiologically occult lung cancer (positive sputum cytology for malignant cells and a negative chest X-ray). These areas were located solely by their fluorescence, and were visibly normal on white-light examination. The detection of lung cancer in individuals with radiologically occult lung cancer depends upon adequate methods of sputum collection and processing. Proving that fluorescing areas show "true positive" fluorescence depends upon accurate brush and forceps biopsies, providing adequate cytological and biopsy material. The entire system of the diagnosis and localization of early or pre-invasive lung cancer (while still confined to a bronchus) rests on skilled cytopathology methods and interpretation, not only skilled fluorescence bronchoscopic examination and adequate instrumentation.
High data-rate transmission with eigenbeam-space division multiplexing (E-SDM) in a MIMO channel (2003)

When channel state information is known at a transmitter in multiple-input multiple-output systems, the optimum capacity is given by eigenmode channel division with water-pouring power control. In this eigenbeam-space division multiplexing (E-SDM), bit assignment to substreams based on the capacity is not optimum due to the fact that the number of assigned bits is expressed by a discrete quantity. In the paper, a method to assign both bit and transmit power to each substream based on the criterion minimizing total bit error rate (BER) is developed, and the BER performance is numerically analyzed in comparison to spatial division multiplexing (SDM). The simulation results assuming 5-transmit and 2-receive antennas show that the E-SDM provides about 10 dB gain compared to the conventional SDM at average BER of 10/sup -3/.
Targeting Mitochondrial Oxidative Metabolism in Melanoma Causes Metabolic Compensation through Glucose and Glutamine Utilization (2014)

Metabolic targets offer attractive opportunities for cancer therapy. However, their targeting may activate alternative metabolic pathways that can still support tumor growth. A subset of human melanomas relies on PGC1α-dependent mitochondrial oxidative metabolism to maintain growth and survival. Herein, we show that loss of viability caused by suppression of PGC1α in these melanomas is rescued by induction of glycolysis. Suppression of PGC1α elevates reactive oxygen species levels decreasing hypoxia-inducible factor-1α (HIF1α) hydroxylation that, in turn, increases its protein stability. HIF1α reprograms melanomas to become highly glycolytic and dependent on this pathway for survival. Dual suppression of PGC1α and HIF1α causes energetic deficits and loss of viability that are partially compensated by glutamine utilization. Notably, triple suppression of PGC1α, HIF1α, and glutamine utilization results in complete blockage of tumor growth. These results show that due to high metabolic and bioenergetic flexibility, complete treatment of melanomas will require combinatorial therapy that targets multiple metabolic components.
CAP1 , an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans (2001)

In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains with CAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in the cap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles of CAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficient cap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.
Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B (2006)

Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the cAMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet perturbations, such as centrally located alpha-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B/2 mice. We conclude that accurate regulation of beta-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance.
Cumene hydroperoxide-mediated inactivation of cytochrome P450 2B1. Identification of an active site heme-modified peptide. (1993)

Cumene hydroperoxide (CuOOH)-mediated inactivation of cytochromes P450 (P450) results in the degradation of their prosthetic heme to products that alkylate the apoprotein. Indirect approaches suggest that this alkylation occurs at the active site. in order to identify the specific apoprotein site(s) alkylated, purified 3H- or 14C-heme-labeled P450 2B1 was incubated with CuOOH and subjected to lysyl endopeptidase-C digestion. Two major peaks (L1 and L2) containing 3H- or 14C-labeled peptides were detected by reverse-phase high pressure liquid chromatography of the digest. L1 contained the highest specific radioactivity and after Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis yielded 3 peptide bands (M(r) approximately 3,500 (P1), 5,000 (P2), and 7,000 (P3)). Although all 3 bands were found radiolabeled, the yield of P1 was higher than that of P2 or P3. Amino acid sequence analysis of the first 13 N-terminal residues of P1 revealed the sequence RICLGEGIARNEL, corresponding to residues 434-446 of the reported 2B1 sequence. A species with the molecular mass of 3771 +/- 1 Da was detected in preliminary electrospray mass spectrometric analysis of L1. Since the theoretical average mass of the predicted peptide (residues 434-466) is 3721.99 Da, the additional 49 +/- 1 Da are considered to be contributed by the alkylating heme fragment. This alkylated 2B1 sequence contains not only Cys436, the conserved residue that provides the SH ligand for heme, but also other highly conserved residues, and therefore corresponds to the heme-sandwiching helix L of P450cam. To our knowledge, this is the first report to localize CuOOH-induced heme alkylation of 2B1 to its active site.
The constitutive expression of the immunomodulatory gp19k protein in E1-, E3- adenoviral vectors strongly reduces the host cytotoxic T cell response against the vector. (1995)

The immune response against cells infected by gene therapy vectors may be a major hindrance for gene therapy, destroying infected cells thus limiting the length of exogene expression and quickly eliminating infected cells on repeat administration. Adenoviruses and many other pathogens have evolved strategies for escape from immune surveillance, including the gp19k gene, found in the adenovirus E3 region, known to down-regulate major histocompatibility complex class 1 expression on the cell surface, and thus reduce lysis of the infected cells by cytotoxic T cells. We have constructed an adenoviral vector expressing the genes for beta-galactosidase and gp19k both under the control of constitutive promoters, and compared the capacity of lymphocytes from DBA/2 mice previously injected with the virus or with Ad-beta gal, a virus expressing beta-galactosidase but not gp19k, to lyse target cells infected with various viruses. Lymphocytes raised against Ad-beta gal fail to lyse target cells infected with Ad-beta gal-gp19k significantly, whereas Ad-beta gal infected target cells and a beta-galactosidase expressing cell line are strongly lysed. The administration of Ad-beta gal-gp19k fails to stimulate the proliferation of anti-vector lymphocytes, and thus these lymphocytes show poor cytotoxic activity against Ad-beta gal or Ad-beta gal-gp19k infected cells.
Periodicity of amide proton exchange rates in a coiled-coil leucine zipper peptide (1991)

The two-stranded coiled-coil motif, which includes leucine zippers, is a simple protein structure that is well suited for studies of helix-helix interactions. The interaction between helices in a coiled coil involves packing of "knobs" into "holes", as predicted by Crick in 1953 and confirmed recently by X-ray crystallography for the GCN4 leucine zipper [O'Shea, E.K., Klemm, J.D., Kim, P.S., & Alber, T. (1991) Science 254, 539]. A striking periodicity, extending over six helical turns, is observed in the rates of hydrogen-deuterium exchange for amide protons in a peptide corresponding to the leucine zipper of GCN4. Protons at the hydrophobic interface show the most protection from exchange. The NMR chemical shifts of amide protons in the helices also show a pronounced periodicity which predicts a short H-bond followed by a long H-bond every seven residues. This variation was anticipated in 1953 by Pauling and is sufficient to give rise to a local left-handed superhelical twist characteristic of coiled coils. The amide protons that lie at the base of the "hole" in the "knobs-into-holes" packing show slow amide proton exchange rates and are predicted to have short H-bond lengths. These results suggest that tertiary interactions can lead to highly localized, but substantial, differences in stability and dynamics within a secondary structure element and emphasize the dominant nature of packing interactions in determining protein structure.
Learning weighted entity lists from web click logs for spoken language understanding (2011)

Named entity lists provide important features for language understanding, but typical lists can contain many ambiguous or incorrect phrases. We present an approach for automatically learning weighted entity lists by mining user clicks from web search logs. The approach significantly outperforms multiple baseline approaches and the weighted lists improve spoken language understanding tasks such as domain detection and slot filling. Our methods are general and can be easily applied to large quantities of entities, across any number of lists. Index Terms: spoken language understanding, domain detection, slot filling, named entity lists, click logs
Structure-Activity Relationship of Fluoroquinolones AgainstK. pneumoniae (2007)

The structure-activity relationship of fluoroquinolones, which show anti-K. pneumoniae activity, was studied by using principal component analysis (PCA) and hierarchical cluster analysis (HCA). The PCA results showed that the lowest unoccupied molecular orbital energy, energy difference between the highest occupied and the lowest unoccupied molecular orbital, dipole moment, net atomic charge on atom I, molecular polarizability, partition coefficient and molecular refractivity of these compounds are responsible for the separation between high-activity and low-activity groups. The HCA results were similar to those obtained with PCA. By using the chemometric results, four synthetic compounds were analyzed through PCA and HCA, and three of them are proposed as active molecules against K. pneumoniae which is consistent with the results of clinical experiments. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-K. pneumoniae activity.
Keystone Symposia: Antibody-based therapeutics for cancer (2003)

This important conference focused on the latest developments in therapeutic antibodies, particularly for their design, production and formulation for cancer therapy. Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent FDA approvals of Zevalin (ibritumomab tiuxetan, IDEC Pharmaceuticals) for cancer radioimmunotherapy and Humira (adalimumab, Abbott Laboratories) for rheumatoid arthritis [1,2]. An impressive array of international speakers was assembled in Banff by the organisers L Weiner (Fox Chase Cancer Center, USA) and P Carter (Amgen and Seattle Genetics). The meeting highlighted emerging new technologies, both for the discovery of novel cancer biomarkers and for innovative immunotherapeutic designs. The latest successes were also presented for antibodies directed to the conventional cancer targets, including CD20, carcinoembryonic antigen (CEA), erbB-family proteins and vascular endothelial growth factor (VEGF). Importantly, recent structural details emerged that will direct future designs of these cancer-targeting molecules, ranging from antibody-dependent cellular-cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) enhancement to improved cytotoxic payloads using radionuclides, toxins, enzymes, drugs and viral delivery. The conference also highlighted the latest in vitro antibody libraries for the selection of high-affinity reagents against refractory cancer targets, and included the design of small domain modules for highly-efficient in vivo targeting to large, high avidity complexes for enhanced cytotoxicity. The major challenges in this rapidly growing area include the need to initiate and sustain innate and adaptive immune responses for the generation of efficient, long-term tumour therapy. This conference was sponsored by Amgen and accredited by the Accreditation Council for Continuing Medical Education (ACCME).
Result of arthroscopic treatment of pigmented villonodular synovitis of the knee (2003)

Arthroscopic synovectomy is an appropriate treatment for knee PVNS. Extended synovectomy must be performed in all cases of diffuse PVNS.
Inhibition of Hepatitis B Virus by Hammerhead Ribozyme Targeted to the Poly(A) Signal Sequence in Cultured Cells (2001)

The deviant poly(A) signal of hepatitis B virus (HBV) not only controls the formation of the 3' end of all the viral RNA, but is also crucial for HBV replication. Hence, a cis-releasing hammerhead ribozyme (RzA) targeted to the poly(A) signal region of HBV subtype adr was investigated for its antiviral effects. In vitro, RzA cleaved HBV RNA at its target site up to 70%, while the disabled ribozyme (dRzA), which had a one-base mutation in the catalytic site, did not cleave the target RNA at all. When the ribozymes were cotransfected into HepG2 cells with the HBV genome-containing plasmid p3.6II, the wild-type ribozyme RzA could effectively decrease HBV RNA levels and inhibit HBV replication, whereas its disabled form, dRzA, had much weaker effects, indicating that the active catalytic domain of the hammerhead ribozyme could markedly increase the extent of antisense-mediated inhibition. In addition, there was a gradient of effectiveness: the higher the amount of released ribozyme, the more the reduction in target HBV RNA in cells as well as progeny DNA reduction. These results suggest the possibility of the hammerhead ribozyme RzA to be used for the gene therapy of HBV infection.
Where do gibberellin biosynthesis and gibberellin signaling occur in rice plants? (2003)

To identify where gibberellin (GA) biosynthesis and signaling occur, we analyzed the expression of four genes involved in GA biosynthesis, GA 20-oxidase1 and GA 20-oxidase2 (OsGA20ox1 and OsGA20ox2), and GA 3-oxidase1 and GA 3-oxidase2 (OsGA3ox1 and OsGA3ox2), and two genes involved in GA signaling, namely, the gene encoding the alpha-subunit of the heterotrimeric GTP-binding protein (Galpha), and SLENDER RICE1 (SLR1), which encodes a repressor of GA signaling. At the vegetative stage, the expression of OsGA20ox2, OsGA3ox2, Galpha, and SLR1 was observed in rapidly elongating or dividing organs and tissues, whereas the expression of OsGA20ox1 or OsGA3ox1 could not be detected. At the inflorescence or floral stage, the expression of OsGA20ox2, OsGA3ox2, Galpha, and SLR1 was also observed in the shoot meristems and stamen primordia. The overlapping expression of genes for GA biosynthesis and signaling indicates that in these tissues and organs, active GA biosynthesis occurs at the same site as does GA signaling. In contrast, no GA-biosynthesis genes were expressed in the aleurone cells of the endosperm; however, the two GA-signaling genes were actively expressed, indicating that the aleurone does not produce bioactive GAs, but can perceive GAs. The expression of OsGA20ox1 and OsGA3ox1 was observed only in the epithelium of the embryo and the tapetum of the anther. Based on the specific expression pattern of OsGA20ox1 and OsGA3ox1 in these tissues, we discuss the unique nature of the epithelium and the tapetum in terms of GA biosynthesis. The epithelium and the tapetum are considered to be an important source of bioactive GAs for aleurone and other organs of the flower, respectively.
A comparison of drug treatment versus electrical stimulation for suppressing seizure activity (2003)

Currently, the management of seizure activity by using pharmacological approaches is in many cases successful. However, it is also known that some patients (up to 30%) do not respond to conventional treatment and are considered drug resistant. For this group other approaches are sometimes attempted, such as surgical resection (not reviewed here) or use of the ketogenic diet (also not reviewed here). More recently, though, procedures that utilize chronic electrical stimulation as a means for suppressing seizure events are being tried. Experiments based on electrical stimulation are being conducted in both animal models and in some limited human trials, but so far it has not been determined if chronic electrical stimulation is more or less effective than conventional drug therapy. This article reviews basic mechanisms of seizure activity, standard antiepileptic drugs (AEDs), and compares conventional AEDs to alternative approaches such as vagal nerve and deep brain stimulation.
A single inductor multiple output converter with adaptive delta current mode control (2006)

The authors propose a single inductor multiple output converter (SIMO) with adaptive delta current mode control. A new time multiplexing scheme is also proposed for this type of control. With this control, the need of off-chip components for stability is eliminated. Use of single inductor for all outputs further eliminates additional magnetic components. This control makes the converter free from line and load regulation problems. It gives a good transient performance and reduces cross-regulation. To the best of authors' knowledge, no multiple output converter has been reported with adaptive delta current mode control. At the switching frequency of 500KHz, it achieves 80% efficiency for 1.5W of output power. The two outputs are regulated to 1.1V and 15V with an input supply of 3.3V. Excluding the inductor and capacitors, it is a fully integrated monolithic circuit, designed in a 3.3V, 0.4 mum, CMOS process
Inhibition of Multidrug‐resistant Human Tumor Growth in Athymic Mice by Anti‐P‐glycoprotein Monoclonal Antibodies (1989)

In an effort to devise an effective treatment for human drug-resistant cancers, we have developed monoclonal antibodies, MRK16 and 17, reactive to the multidrug transporter protein, P-glycoprotein. The monoclonal antibodies given intravenously effectively prevented tumor development in athymic mice inoculated subcutaneously with drug-resistant human ovarian cancer cells 2780AD. Treatment with MRK16 induced rapid regression of established subcutaneous tumors and apparent cures of some animals. Complement-dependent cytotoxicity (MRK16) and antibody-dependent cell-mediated cytolysis (MRK16 and 17) were observed with these antibodies. These monoclonal antibodies may have potential as treatment tools against multidrug resistant human tumors possessing the P-glycoprotein.
ISOLATION OF PLASMA MEMBRANE FRAGMENTS FROM HELA CELLS (1969)

A method for isolating plasma membrane fragments from HeLa cells is described. The procedure starts with the preparation of cell membrane "ghosts," obtained by gentle rupture of hypotonically swollen cells, evacuation of most of the cell contents by repeated washing, and isolation of the ghosts on a discontinuous sucrose density gradient. The ghosts are then treated by minimal sonication (5 sec) at pH 8.6, which causes the ghost membranes to pinch off into small vesicles but leaves any remaining larger intracellular particulates intact and separable by differential centrifugation. The ghost membrane vesicles are then subjected to isopycnic centrifugation on a 20-50% w/w continuous sucrose gradient in tris-magnesium buffer, pH 8.6. A band of morphologically homogeneous smooth vesicles, derived principally from plasma membrane, is recovered at 30-33% (peak density = 1.137). The plasma membrane fraction contained a Na-K-activated ATPase activity of 1.5 micromole Pi/hr per mg, 3% RNA, and 13.8% of the NADH-cytochrome c reductase activity of a heavier fraction from the same gradient which contained mitochondria and rough endoplasmic vesicles. The plasma membranes of viable HeLa cells were marked with (125)I-labeled horse antibody and followed through the isolation procedure. The specific antibody binding of the plasma membrane vesicle fraction was increased 49-fold over that of the original whole cells.