gebhart/patrepeval huggingface dataset:
Safety and Efficacy of the Neuraminidase Inhibitor GG167 in Experimental Human Influenza (1996)

Direct respiratory administration of the selective neuraminidase inhibitor GG167 appears safe and effective for both prevention and early treatment of experimental influenza. Influenza virus neuraminidase is important for viral replication in humans.
Base-calling for next-generation sequencing platforms (2011)

Next-generation sequencing platforms are dramatically reducing the cost of DNA sequencing. With these technologies, bases are inferred from light intensity signals, a process commonly referred to as base-calling. Thus, understanding and improving the quality of sequence data generated using these approaches are of high interest. Recently, a number of papers have characterized the biases associated with base-calling and proposed methodological improvements. In this review, we summarize recent development of base-calling approaches for the Illumina and Roche 454 sequencing platforms.
Drug-Antibody-Platelet Interaction in Quinine- and Quinidine-induced Thrombocytopenia (1982)

Binding of quinine- and quinidine-dependent antibodies to platelets was studied using an electroimmunoassay to measure platelet-bound IgG. Antibodies from four patients with drug-induced thrombocytopenia differed significantly in their interaction with platelets: association constants for binding to platelets at high drug concentrations ranged from 0.29 to 2.6 x 10(7) M(-1), the maximum number of antibody molecules bound ranged from 36,000 to 161,000/platelet, the amount of drug necessary to achieve half-maximum binding of antibodies to platelets ranged from 2 to 60 muM, and only one of the antibodies cross-reacted with the stereoisomer of the drug to which the patient was sensitized. Binding of the antibodies to platelets was enhanced at the highest achievable molar ratio of drug:antibody, 10,000:1, rather than being inhibited, as would be expected in a conventional, hapten-dependent reaction. The drug-antibody-platelet reaction was unaffected by Factor VIII/von Willebrand protein, nonspecifically aggregated IgG, or heat-labile complement components. After pretreatment with tritiated quinine, platelets retained several hundred thousand molecules of drug each, but failed to bind detectable amounts of antibody. However, platelets treated simultaneously with quinine-dependent antibody and tritiated quinine retained significantly more drug after repeated washes than platelets treated with drug and normal serum. These findings support the proposition that in quinine- and quinidine-induced thrombocytopenia, drug and antibody combine first in the soluble phase to form a complex, which then binds with high affinity to a receptor on the platelet surface (innocent bystander reaction), and demonstrate that these antibodies are heterogeneous in respect to the amount of drug required to promote their binding to platelets, the number of platelet receptors they recognize, and their binding affinities.
Conformational Preconditioning by Electrophoresis of DNA through a Finite Obstacle Array (2008)

We investigate the effectiveness of DNA conformational preconditioning by electrophoresis through an obstacle array on the later stretching of molecules in a microchannel contraction. The control, reproducibility, and ability to compare with the well-studied single postcollision problem make this a model system for conformational preconditioning studies. We find that the obstacle array increases the average deformation applied to the DNA in the contraction through elimination of slower stretching DNA conformations. In the current device, a dramatic change in the resulting polymer behavior occurs at a predeformation in the obstacle array of about 20% relative extension. We show that the hooking probability in the array is geometrically limited at large electric fields and that modification of the geometrical parameters shows promise for optimization of a second-generation device.
High-field MRI of brain cortical substructure based on signal phase (2007)

The ability to detect brain anatomy and pathophysiology with MRI is limited by the contrast-to-noise ratio (CNR), which depends on the contrast mechanism used and the spatial resolution. In this work, we show that in MRI of the human brain, large improvements in contrast to noise in high-resolution images are possible by exploiting the MRI signal phase at high magnetic field strength. Using gradient-echo MRI at 7.0 tesla and a multichannel detector, a nominal voxel size of 0.24 x 0.24 x 1.0 mm3 (58 nl) was achieved. At this resolution, a strong phase contrast was observed both between as well as within gray matter (GM) and white matter (WM). In gradient-echo phase images obtained on normal volunteers at this high resolution, the CNR between GM and WM ranged from 3:1 to 20:1 over the cortex. This CNR is an almost 10-fold improvement over conventional MRI techniques that do not use image phase, and it is an approximately 100-fold improvement when including the gains in resolution from high-field and multichannel detection. Within WM, phase contrast appeared to be associated with the major fiber bundles, whereas contrast within GM was suggestive of the underlying layer structure. The observed phase contrast is attributed to local variations in magnetic susceptibility, which, at least in part, appeared to originate from iron stores. The ability to detect cortical substructure from MRI phase contrast at high field is expected to greatly enhance the study of human brain anatomy in vivo.
OFDM spread spectrum communications using lapped transforms and interference excision (2002)

Two systems that use orthogonal frequency division multiplexing (OFDM) as a spread spectrum technique are described and their performance is evaluated in the presence of tone and pulsed Gaussian interference. One system obtains frequency diversity by sending the same data bit simultaneously on all the carriers while a second system obtains both time and frequency diversity by sequentially sending a given data bit on different carriers until it is sent on all possible carriers. Interference excision, in which some of the transform bins are removed in the detection process, is used in the receivers. Simulated BER performance in AWGN and interference is presented for systems that use a number of different block transforms and the modulated lapped transform (MLT) and it is shown that the MLT provides much better performance due to its ability to confine the interference energy to a few transform bins.
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications (2001)

The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
Observation of Liver Pathology after Praziquantel Treatment in Experimental Clonorchis sinensis Infection in Guinea Pigs (1988)

The liver of guinea pigs infected experimentally with Clonorchis sinensis was&#13;\ngrossly and histologically examined after treatment with praziquanteL Total 38 male guinea&#13;\npigs were infected each with 300-500 metacercariae. Five weeks later praziquantel treatment&#13;\nwas done on 28 animals, and repeated if needed. Remaining 10 were used for untreated&#13;\ncontrols, while 3 others were for uninfected controls. Liver examinations were done at 1, 2,&#13;\n4 and/or 9 weeks following the treatment.&#13;\nCompared with uninfected controls, C sinensis-infected guinea pigs grossly revealed remarkably&#13;\nenlarged and swollen liver, with yellowish discolorations at surrounding portions of&#13;\ninfected sites. Histologically these livers showed cystic hyperplasia of the bile ducts accompanied&#13;\nby irregular dilatation, glandular and/or papillary hyperplasia of the lining epithelia as&#13;\nwell as periductal fibrosis.&#13;\nThe livers of praziquantel-treated animals grossly revealed more of less recovering features&#13;\nlater than 2 weeks after the treatment. Histologically, although adenomatous hyperplasia was&#13;\nquite subsided, other bile duct changes such as cystic hyperplasia and fibrosis were persistently&#13;\nretained in most animals until 9 weeks after the treatment. The results suggest that the&#13;\nliver damage induced by C sinensis is persistent for at least a few months after deworming&#13;\nwith praziquantel.
Antigen-Antibody Affinity for Dry Eye Biomarkers by Label Free Biosensing. Comparison with the ELISA Technique (2015)

The specificity and affinity of antibody-antigen interactions is a fundamental way to achieve reliable biosensing responses. Different proteins involved with dry eye dysfunction: ANXA1, ANXA11, CST4, PRDX5, PLAA and S100A6; were validated as biomarkers. In this work several antibodies were tested for ANXA1, ANXA11 and PRDX5 to select the best candidates for each biomarker. The results were obtained by using Biophotonic Sensing Cells (BICELLs) as an efficient methodology for label-free biosensing and compared with the Enzyme-Linked Immuno Sorbent Assay (ELISA) technique.
Changes in Infestation, Cell Cap Condition, and Reproductive Status of Varroa destructor (Mesostigmata: Varroidae) in Brood Exposed to Honey Bees with Varroa Sensitive Hygiene (2012)

Abstract Honey bees (Apis mellifera L.) bred for Varroa sensitive hygiene (VSH) selectively remove pupae infested with Varroa destructor Anderson &amp; Trueman (Mesostigmata: Varroidae) from capped brood that is inserted into the nest. After 1 wk, remaining brood cells tend to have been uncapped and recapped, and remaining mites are mostly infertile. A primary goal of this experiment was to compare the reproductive status of mites that remained in recapped and normally capped cells after a 1-wk exposure to VSH and control colonies. Differences in distribution of fertile mites in normally capped brood cells between VSH bees and control bees may suggest that the stimulus for hygiene is related to reproduction by mites. Identification of stimuli triggering VSH behavior could be used to develop new bioassays for selective breeding of this important resistance mechanism. Combs of capped brood that were exposed to control bees had 10 times more pupae with fertile mites in normally capped brood as did VSH bees (6.7 and 0.7%, respectively). They also had 3 times more pupae with infertile mites in normally capped brood than did VSH bees (1.4 and 0.5%, respectively). Thus, VSH bees targeted fertile mites by a 3:1 ratio by either removing or uncapping and recapping their host pupae. Biased removal of mite-infested pupae with fertile mites suggested that stimuli triggering VSH behavior were enhanced by the presence of mite offspring within the brood cell. This bias for fertile mites is not seen during experiments of short 3-h duration. The differing results are discussed relative to a behavioral threshold model for hygienic behavior in honey bees in which different experimental protocols may reflect activities of honey bees having different sensitivities to pupae infested by fertile mites. In addition, mortality of mite offspring was significantly higher in recapped cells than in normally capped cells and contributed to decreased reproduction by the mites.
The functional network of ion channels in T lymphocytes (2009)

For more than 25 years, it has been widely appreciated that Ca2+ influx is essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiation, intensity, and duration of the Ca2+ signal. Five distinct types of ion channels--Kv1.3, KCa3.1, Orai1+ stromal interacting molecule 1 (STIM1) [Ca2+-release activating Ca2+ (CRAC) channel], TRPM7, and Cl(swell)--comprise a network that performs functions vital for ongoing cellular homeostasis and for T-cell activation, offering potential targets for immunomodulation. Most recently, the roles of STIM1 and Orai1 have been revealed in triggering and forming the CRAC channel following T-cell receptor engagement. Kv1.3, KCa3.1, STIM1, and Orai1 have been found to cluster at the immunological synapse following contact with an antigen-presenting cell; we discuss how channels at the synapse might function to modulate local signaling. Immuno-imaging approaches are beginning to shed light on ion channel function in vivo. Importantly, the expression pattern of Ca2+ and K+ channels and hence the functional network can adapt depending upon the state of differentiation and activation, and this allows for different stages of an immune response to be targeted specifically.
Nucleotide Sequence and Expression of the Diphtheria tox 228 Gene in Escherichia coli (1983)

The complete nucleotide sequence of the diphtheria tox228 gene encoding the nontoxic serologically related protein CRM228 has been determined. A comparison of the predicted amino acid sequence with the available amino acid sequences from the wild-type toxin made it possible to deduce essentially the entire nucleotide sequence of the wild-type tox gene. The signal peptide of pro-diphtheria toxin and the putative tox promoter have been identified, a highly symmetrical nucleotide sequence downstream of the toxin gene has been detected; this region may be the corynebacteriophage beta attachment site (attP). The cloned toxin gene was expressed at a low level in Escherichia coli.
Complete Genome Sequence of the Broad-Host-Range Vibriophage KVP40: Comparative Genomics of a T4-Related Bacteriophage (2003)

The complete genome sequence of the T4-like, broad-host-range vibriophage KVP40 has been determined. The genome sequence is 244,835 bp, with an overall G+C content of 42.6%. It encodes 386 putative protein-encoding open reading frames (CDSs), 30 tRNAs, 33 T4-like late promoters, and 57 potential rho-independent terminators. Overall, 92.1% of the KVP40 genome is coding, with an average CDS size of 587 bp. While 65% of the CDSs were unique to KVP40 and had no known function, the genome sequence and organization show specific regions of extensive conservation with phage T4. At least 99 KVP40 CDSs have homologs in the T4 genome (Blast alignments of 45 to 68% amino acid similarity). The shared CDSs represent 36% of all T4 CDSs but only 26% of those from KVP40. There is extensive representation of the DNA replication, recombination, and repair enzymes as well as the viral capsid and tail structural genes. KVP40 lacks several T4 enzymes involved in host DNA degradation, appears not to synthesize the modified cytosine (hydroxymethyl glucose) present in T-even phages, and lacks group I introns. KVP40 likely utilizes the T4-type sigma-55 late transcription apparatus, but features of early- or middle-mode transcription were not identified. There are 26 CDSs that have no viral homolog, and many did not necessarily originate from Vibrio spp., suggesting an even broader host range for KVP40. From these latter CDSs, an NAD salvage pathway was inferred that appears to be unique among bacteriophages. Features of the KVP40 genome that distinguish it from T4 are presented, as well as those, such as the replication and virion gene clusters, that are substantially conserved.
Energy conversion from catalytic reaction to hot electron current with metal-semiconductor Schottky nanodiodes (2006)

Exothermic catalytic reactions induce electronic excitation at the metal surface, leading to the production of energetic hot electrons. We monitored the flow of hot electrons for over several hours using two types of metal-semiconductor Schottky diodes, Pt∕TiO2 or Pt∕GaN, during the platinum catalyzed oxidation of carbon monoxide. The thickness of Pt film used as the catalyst was 5nm, less than the electron mean free path, resulting in the ballistic transport of hot electrons through the metal. The electron flow was detected as a chemicurrent if the excess electron kinetic energy generated by the exothermic reaction was larger than the effective Schottky barrier formed at the metal-semiconductor interface. The measurement of continuous chemicurrent indicated that chemical energy of exothermic catalytic reaction was directly converted into hot electron flux in the catalytic nanodiode. The chemicurrent was well correlated with the turnover rate of CO oxidation separately measured by gas chromatography, suggesting the possibility of application as chemical sensors with high sensitivity.
Size, shape, and stability of InAs quantum dots on the GaAs(001) substrate (2000)

We study the energetics of island formation in Stranski-Krastanow growth of highly mismatched heteroepitaxy within a parameter-free approach. It is shown that the (frequently found) rather narrow size distribution of the self-assembled coherent islands can be understood as the result of the system being trapped in a constrained equilibrium state with a fixed island density. If allowing for variations of the island density, we find that larger islands combined with a lower island density are more stable; this implies that Ostwald ripening will take place on time scales sufficiently long for exchange of atoms between different islands to occur. Moreover, we show how to select the island size by controlling the growth conditions and the amount of deposited material. Our study also indicates that the island shape depends on the island size, i.e., an island with larger volume has a higher value of the height-to-base ratio.
No‐carrier added synthesis of 18F‐labelled nucleosides using Stille cross‐coupling reactions with 4‐[18F]fluoroiodobenzene (2004)

Abstract The radiosyntheses of 5‐(4′‐[ 18 F]fluorophenyl)‐uridine [ 18 F]‐11 and 5‐(4′‐[ 18 F]fluorophenyl)‐2′‐deoxy‐uridine [ 18 F]‐12 are described. The 5‐(4′‐[ 18 F]fluoro‐phenyl)‐substituted nucleosides were prepared via a Stille cross‐coupling reaction with 4‐[ 18 F]fluoroiodobenzene followed by basic hydrolysis using 1 M potassium hy‐droxide. The Stille cross‐coupling reaction was optimized by screening various palladium complexes, additives and solvents. By using optimized labelling conditions (Pd 2 (dba) 3 /CuI/AsPh 3 in DMF/dioxane (1:1), 20 min at 65°C), 550 MBq of [4‐ 18 F]fluoroiodobenzene could be converted into 120 MBq (33%, decay‐corrected) of 5‐(4′‐[ 18 F]fluorophenyl)‐2′‐deoxy‐uridine [ 18 F]‐12 within 40 min, including HPLC purification. Copyright © 2004 John Wiley &amp; Sons, Ltd.
High-Affinity Small-Molecule Inhibitors of the Menin-Mixed Lineage Leukemia (MLL) Interaction Closely Mimic a Natural Protein–Protein Interaction (2014)

The protein-protein interaction (PPI) between menin and mixed lineage leukemia (MLL) plays a critical role in acute leukemias, and inhibition of this interaction represents a new potential therapeutic strategy for MLL leukemias. We report development of a novel class of small-molecule inhibitors of the menin-MLL interaction, the hydroxy- and aminomethylpiperidine compounds, which originated from HTS of ∼288000 small molecules. We determined menin-inhibitor co-crystal structures and found that these compounds closely mimic all key interactions of MLL with menin. Extensive crystallography studies combined with structure-based design were applied for optimization of these compounds, resulting in MIV-6R, which inhibits the menin-MLL interaction with IC50 = 56 nM. Treatment with MIV-6 demonstrated strong and selective effects in MLL leukemia cells, validating specific mechanism of action. Our studies provide novel and attractive scaffold as a new potential therapeutic approach for MLL leukemias and demonstrate an example of PPI amenable to inhibition by small molecules.
Further Characterization of Surface Membrane Structures Expressed on Human Basophils and Mast Cells (1990)

Recently, we were able to establish the immunologic surface marker profile of human basophils and mast cells. In the present study, the characterization of these cell types was extended by the use of monoclonal antibodies (mAbs) to hemopoietic differentiation antigens. Basophils and mast cells were enriched by mAbs and complement from chronic myeloid leukemia blood (n = 5) and dispersed lung tissue (n = 4), respectively. A panel of 80 mAbs was tested for being reactive with purified cell populations using flow cytometry and/or a combined toluidine blue-immunofluorescence staining procedure. In addition to previous findings, basophils were found to react with mAbs directed against the 126-kilodalton dipeptidylpeptidase IV (CD26), platelet glycoprotein IIa (CD31), CD40 antigen known to share sequence homology with nerve growth factor receptor, leukosialin (CD43), CD44 antigen, the ICAM-1 antigen (CD54) and VIM2-reactive gangliosides involving the sialofucooligosaccharide sequence (CDw65L). Bsp-1 was found to be a specific marker for human basophils, whereas mast cells were not stained by this reagent. Basophils apparently lack CD22 antigen, gangliosides detected by CDw65 mAbs (except CDw65L) and CD71 antigen (transferrin receptor). Mast cells were found to express CD43 and CD44 antigen. In contrast, mast cells lack CD22, CD26, CD31, CD40 and CDw65 antigen. These results provide further evidence that both blood basophils and mast cells express a unique immunologic surface marker profile including binding sites for a variety of immunomodulating ligands and adhesion molecules.
Toxic effect of the bloom‐forming Trichodesmium sp. (cyanophyta) to the copepod Acartia tonsa (1994)

The toxicity of the marine cyanobacterium Trichodesmium sp. to the copepod Acartia tonsa was assessed in a series of experiments during a Trichodesmium bloom off the North Carolina coast in late October 1992. Healthy intact cells of Trichodesmium sp. were not toxic to A. tonsa and were ingested by A. tonsa when no other foods were available. However, homogenized Trichodesmium cells were toxic to A. tonsa, suggesting that Trichodesmium sp. contains certain type(s) of intracellular biotoxins. This hypothesis was consistent with the observed high mortality when A. tonsa was treated with aging Trichodesmium sp. cells or with filtered cell homogenate. The affected copepods showed weakness, recumbency, and reduced responsiveness. Many were observed to have distended intestines. Bioassays using aged Trichodesmium sp. cells and filtered homogenate demonstrated a dose-dependent effect on A. tonsa survival.