gebhart/patrepeval huggingface dataset:
Eight‐year median survival in multiple myeloma after total therapy 2: roles of thalidomide and consolidation chemotherapy in the context of total therapy 1 (2008)

In comparison to total therapy 1 (TT1), the phase 3 trial total therapy 2 (TT2) evaluated the benefit of up-front administration of thalidomide (THAL); TT2 also introduced post-transplant consolidation chemotherapy. With median follow-up times of 5 and 12 years, respectively, outcome comparisons were made of 668 patient's enrolled on TT2 and 231 patients treated on TT1. Complete response (CR) rates were similar at 40% for TT1 and TT2 without THAL versus 60% on the THAL arm of TT2. CR durations were similar with either TT2 arm and both were superior to results of TT1. Event-free and overall survivals were extended from 2.6 to 5.7 years, respectively, with TT1 to 4.8 and 8.0 years with TT2. TT2's major advance vis-à-vis TT1 pertained to the subgroup without cytogenetic abnormalities (CA), supporting the role of post-transplant consolidation therapy, whereas the improved survival of the CA subgroup on the experimental versus control arm of TT2 attests to the role of THAL in this setting. Adjusting for prognostic variables in multivariate and pair-mate analyses, TT2 was superior to TT1 in terms of CR duration, event-free and overall survival. These results provide a basis for the prospective evaluation of the consolidation strategy in a randomized clinical trial design.
Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in Alzheimer's disease (2003)

The principal pathological features of Alzheimer's disease (AD) are extracellular amyloid plaques and intracellular neurofibrillary tangles, the latter composed of the microtubule-binding protein tau assembled into paired helical and straight filaments. Recent studies suggest that these pathological entities may be functionally linked, although the mechanisms by which amyloid deposition promotes pathological tau filament assembly are poorly understood. Here, we report that tau is proteolyzed by multiple caspases at a highly conserved aspartate residue (Asp421) in its C terminus in vitro and in neurons treated with amyloid-beta (Abeta) (1-42) peptide. Tau is rapidly cleaved at Asp421 in Abeta-treated neurons (within 2 h), and its proteolysis appears to precede the nuclear events of apoptosis. We also demonstrate that caspase cleavage of tau generates a truncated protein that lacks its C-terminal 20 amino acids and assembles more rapidly and more extensively into tau filaments in vitro than wild-type tau. Using a monoclonal antibody that specifically recognizes tau truncated at Asp421, we show that tau is proteolytically cleaved at this site in the fibrillar pathologies of AD brain. Taken together, our results suggest a novel mechanism linking amyloid deposition and neurofibrillary tangles in AD: Abeta peptides promote pathological tau filament assembly in neurons by triggering caspase cleavage of tau and generating a proteolytic product with enhanced polymerization kinetics.
REGULATION OF NEWLY EVOLVED ENZYMES. III EVOLUTION OF THE ebg REPRESSOR DURING SELECTION FOR ENHANCED LACTASE ACTIVITY (1977)

The evolution of lactose utilization by lacZ deletion strains of E. coli occurs via mutations in the ebg genes. We show that one kind of mutation in the regulatory gene ebgR results in a repressor which retains the ability to repress synthesis of ebg enzymes, but which permits 4.5-fold more ebg enzyme synthesis during lactose induction than does the wild-type repressor. A comparison between the growth rate of various ebg+ strains on lactose and the amount of ebg enzyme synthesized by these strains shows that the rate of enzyme synthesis permitted by the wild-type repressor is insufficient for growth on lactose as a sole carbon source by a cell with the most active ebg lactase yet isolated. We conclude, therefore, that the evolution of lactose utilization requires both a structural and a regulatory mutation.
Only a Portion of the Small Seatbelt Loop in Human Choriogonadotropin Appears Capable of Contacting the Lutropin Receptor (2004)

Twenty residues of the human choriogonadotropin (hCG) beta-subunit that are wrapped around alpha-subunit loop 2 like a "seatbelt" stabilize the heterodimer and enable the hormone to distinguish lutropin (LHR), follitropin, and thyrotropin receptors. The N-terminal portion of the seatbelt contains a small disulfide-stabilized loop needed for heterodimer assembly and is thought to mediate hCG-LHR interactions. To test the latter notion, we compared the LHR binding and signal transduction activities of hCG analogs in which the alpha-subunit C terminus (alphaCT) was cross-linked to residues in the small seatbelt loop. Analogs having an intersubunit disulfide between a cysteine in place of alphaCT residue alphaSer-92 and cysteines substituted for loop residues betaArg-94, betaArg-95, or betaSer-96 had high activities in LHR binding and signaling assays despite the fact that both portions of the hormone are thought to be essential for hCG activity. Use of a larger probe blocked hormone activity when the alphaCT was cross-linked to cysteines in place of residues betaArg-95 and betaAsp-99, but not to cysteines in place of residues betaArg-94, betaSer-96, or betaThr-97. This suggested that the side chains of residues betaArg-95 and betaAsp-99, which face in the same outward direction from the heterodimer, are nearer than the others to the LHR interface. The finding that residue 95 can be cross-linked to small alphaCT probes without eliminating hormone activity indicates its side chain does not participate in essential LHR contacts. We suggest that contacts between the small seatbelt loop and the LHR, if any, involve its backbone atoms and possibly the side chain of residue betaAsp-99.
Dynamic query evaluation plans (1989)

In most database systems, a query embedded in a program written in a conventional programming language is optimized when the program is compiled. The query optimizer must make assumptions about the values of the program variables that appear as constants in the query, the resources that can be committed to query evaluation, and the data in the database. The optimality of the resulting query evaluation plan depends on the validity of these assumptions. If a query evaluation plan is used repeatedly over an extended period of time, it is important to determine when reoptimization is necessary. Our work aims at developing criteria when reoptimization is required, how these criteria can be implemented efficiently, and how reoptimization can be avoided by using a new technique called dynamic query evaluation plans . We experimentally demonstrate the need for dynamic plans and outline modifications to the EXODUS optimizer generator required for creating dynamic query evaluation plans.
Immunoassay Readout Method Using Extrinsic Raman Labels Adsorbed on Immunogold Colloids (1999)

An immunoassay readout method based on surface-enhanced Raman scattering (SERS) is described. The method exploits the SERS-derived signal from reporter molecules that are coimmobilized with biospecific species on gold colloids. This concept is demonstrated in a dualanalyte sandwich assay, in which two different antibodies covalently bound to a solid substrate specifically capture two different antigens from an aqueous sample. The captured antigens in turn bind selectively to their corresponding detection antibodies. The detection antibodies are conjugated with gold colloids that are labeled with different Raman reporter molecules, which serve as extrinsic labels for each type of antibody. The presence of a specific antigen is established by the characteristic SERS spectrum of the reporter molecule. A near-infrared diode laser was used to excite efficiently the SERS signal while minimizing fluorescence interference. We show that, by using different labels with little spectral overlap, two different antigenic species can be detected simultaneously. The potential of this concept to function as a readout strategy for multiple analytes is briefly discussed.
α-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models (2006)

Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following alphaSyn expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.
A Survey on Context Learning (2016)

Learning semantics based on context information has been researched in many research areas for decades. Context information can not only be directly used as the input data, but also sometimes used as auxiliary knowledge to improve existing models. This survey aims at providing a structured and comprehensive overview of the research on context learning. We summarize and group the existing literature into four categories, Explicit Analysis, Implicit Analysis, Neural Network Models, and Composite Models, based on the underlying techniques adopted by them. For each category, we talk about the basic idea and techniques, and also introduce how context information is utilized as the model input or incorporated into the model to enhance the performance or extend the domain of application as auxiliary knowledge. In addition, we discuss the advantages and disadvantages of each model from both the technical and practical point of view.
The sequence of human caveolin reveals identity with VIP21, a component of transport vesicles (1992)

Caveolin is a protein present in membrane specializations termed caveolae where it may play a structural role. Previous studies on the cDNA sequence of chicken caveolin demonstrated that it is an integral membrane protein without significant homology to any known protein. The cDNA sequence of human lung caveolin is presented here. A striking sequence homology is observed with the chicken protein, as well as a very recently reported protein termed VIP21 [(1992) J. Cell Biol. 118, 1003-1014], a putative vesicle transport protein isolated from MDCK cells. Genomic Southern blots suggest that caveolin is present in a single copy, and Northern blots confirm that the caveolin mRNA is elevated in muscle.
Nonsedating histamine H1-receptor antagonists. (1989)

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating histamine H1-receptor antagonists terfenadine, astemizole, loratadine, and acrivastine are reviewed. Terfenadine and astemizole are chemically unrelated to histamine H1-receptor antagonists such as diphenhydramine and chlorpheniramine. Loratadine is structurally related to the antihistamine azatadine, and acrivastine is a side-chain-reduced metabolite of the antihistamine triprolidine. Like other histamine H1-receptor antagonists, they competitively block histamine receptor sites rather than inhibiting histamine release. All four drugs have relatively long half-lives and are rapidly absorbed after oral administration. Terfenadine, astemizole, and loratadine are metabolized extensively in the liver; terfenadine and astemizole are both 97% protein bound. Terfenadine 60 mg twice daily has been shown to be as effective as conventional antihistamines for the treatment of seasonal allergic rhinitis. In clinical trials, astemizole 10 mg daily was comparable to or better than chlorpheniramine for treatment of chronic rhinitis. Both terfenadine and astemizole were effective for treatment of chronic urticaria. For treatment of seasonal allergic rhinitis, loratadine combined with pseudoephedrine may be preferable to triprolidine-pseudoephedrine and acrivastine-pseudoephedrine combinations that require more frequent dosing. Acrivastine must be administered more frequently than the other nonsedating antihistamines. None of these four agents impairs psychomotor activity. Infrequently reported adverse effects include dry mouth, skin reactions, and weight gain. The absence of substantial sedative effects and the less-frequent dosing schedules make these agents good alternatives to the classic antihistamines for treatment of seasonal and chronic rhinitis and chronic urticaria.
Efficient, deep-blue organic electrophosphorescence by guest charge trapping (2003)

We demonstrate efficient, deep-blue organic electrophosphorescence using a charge-trapping phosphorescent guest, iridium(III) bis(4′,6′-difluorophenylpyridinato)tetrakis(1-pyrazolyl)borate (FIr6) doped in the wide-energy-gap hosts, diphenyldi(o-tolyl)silane (UGH1) and p-bis(triphenylsilyly)benzene (UGH2), where exciton formation occurs directly on the guest molecules. Charge trapping on the guest is confirmed by the dependence of the drive voltage and electroluminescence spectrum on guest concentration. Ultraviolet photoemission spectroscopy measurements establish the relative highest occupied molecular orbital positions of FIr6 in UGH1 and UGH2. Peak quantum and power efficiencies of (8.8±0.9)% and (11.0±1.1) lm/W in UGH1 and (11.6±1.2)% and (13.9±1.4) lm/W in UGH2 are obtained, while the emission in both cases is from FIr6 and is characterized by Commission Internationale de l’Eclairage coordinates of (x=0.16, y=0.26) in UGH2.
Realization and Application of Large-Scale Fast Optical Circuit Switch for Data Center Networking (2018)

Applying optical switching to data center networks can greatly expand network bandwidth and reduce electrical power consumption, both of which are needed to meet the explosive traffic increase. The optical switch offers large bandwidth switching capability, and so eliminates the multistage switch network architecture needed with electrical switching. Furthermore, the single stage architecture of the optical switch greatly simplifies operating costs, which include cabling, while substantially reducing the number of transponders needed. Data center networks place very different demands on optical systems than communication networks. Grasping the right direction to proceed is of paramount importance. To realize the full potential of optical switches, such as scalability and cost effectiveness, we analyze the role of large-scale optical circuit switches and discuss the realization technologies that combine the two dimensions of space and wavelength. Our recent advances in large port-count optical switches are presented.
MAGE-11 protein is highly conserved in higher organisms and located predominantly in the nucleus (1998)

The MAGE-11 gene belongs to a family whose products were identified first in tumor tissue. The MAGE-11 gene product has not been characterized in detail. We have isolated MAGE-11 cDNA from HeLa cells and confirmed the presence of MAGE-11 protein and of at least 2 other MAGE proteins (MAGE-1 and MAGE-3) in this cell line. Monoclonal antibodies (MAbs), obtained by using a GST-MAGE-11 fusion protein, detect MAGE-11 protein in HeLa cells as a 48 kDa protein. In contrast to other known proteins of the MAGE family, MAGE-11 is found mainly in the nucleus. Immunoprecipitation out of whole-cell extracts from different species reveals that MAGE-11 protein is highly conserved among mammalian cells, suggesting a conserved and important function.
Intranasal immunization using the B subunit of the Escherichia coli heat‐labile toxin fused to an epitope of the Bordetella pertussis P.69 antigen (1991)

The plasmid pBRD026, which directs expression of the B subunit of the Escherichia coli heat-labile toxin (LTB), was modified so that DNA encoding epitopes could be inserted at the 3' end of the gene. An oligonucleotide linker containing restriction sites for BglII and SpeI was inserted at the SpeI site at the 3' end of the LTB gene to form plasmid pFV1. This linker also encodes the amino acid sequence Gly-Pro-Gly-Pro which we propose acts as a 'hinge' between the LTB and the foreign epitope. Oligonucleotides specifying an epitope from the Bordetella pertussis P.69 outer membrane protein were cloned into pFV1 to form pFV169. The resultant fusion protein (LTB69) was partially purified from the periplasm of E. coli strains in a soluble pentameric form which could bind GM1 gangliosides. Mice immunized intranasally with purified LTB69 produced antibodies against both LTB and the P.69 protein. In addition, ELISPOT assays demonstrated the presence of LTB-specific and P.69-specific antibody-secreting cells in the lungs of immunized mice.
Genetic Transformation of Rice (1994)

Abstract Rice was the first major monocot crop species to be transformed and regenerated. Initially, rice transformation was limited to japonica cultivars. Subsequently, a number of indica and javanica cultivars have also been transformed and regenerated into fertile transgenic plants. Most transformation studies in rice have used direct DNA uptake into protoplasts, induced by polyethylene glycol treatment or electroporation. Recently, other transformation methods have been developed that are less genotype dependent, such as microprojectile bombardment of cell suspensions and immature embryos. This review summarizes progress in both protoplast-based and other transformation methods.
Affinity of LDL to a human arterial proteoglycan among male survivors of myocardial infarction (1989)

In the present study, the hypothesis that the affinity of LDL to arterial proteoglycans might discriminate myocardial infarction patients from controls were tested. The patients were 52 men who had sustained a myocardial infarction at an age of 50 years or less and the controls, selected from a random population sample, were matched to the patients for age and sex. Serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and apoB discriminated patients from controls. In addition, LDL reactivity with arterial proteoglycans was significantly higher in patients than in controls. In a multiple regression analysis, with patient or control as the dependent variable, apoB levels, LDL proteoglycan reactivity and serum triglycerides appeared as independent contributors to the regression. These observations indicate that LDL reactivity with arterial proteoglycans is a new, highly significant factor which discriminates between young myocardial infarction patients and controls.
The starch-related R1 protein is an α-glucan, water dikinase (2002)

To determine the enzymatic function of the starch-related R1 protein it was heterologously expressed in Escherichia coli and purified to apparent homogeneity. Incubation of the purified protein with various phosphate donor and acceptor molecules showed that R1 is capable of phosphorylating glucosyl residues of alpha-glucans at both the C-6 and the C-3 positions in a ratio similar to that occurring naturally in starch. Phosphorylation occurs in a dikinase-type reaction in which three substrates, an alpha-polyglucan, ATP, and H(2)O, are converted into three products, an alpha-polyglucan-P, AMP, and orthophosphate. The use of ATP radioactively labeled at either the gamma or beta positions showed that solely the beta phosphate is transferred to the alpha-glucan. The apparent K(m) of the R1 protein for ATP was calculated to be 0.23 microM and for amylopectin 1.7 mg x ml(-1). The velocity of in vitro phosphorylation strongly depends on the type of the glucan. Glycogen was an extremely poor substrate; however, the efficiency of phosphorylation strongly increased if the glucan chains of glycogen were elongated by phosphorylase. Mg(2+) ions proved to be essential for activity. Incubation of R1 with radioactively labeled ATP in the absence of an alpha-glucan showed that the protein phosphorylates itself with the beta, but not with the gamma phosphate. Autophosphorylation precedes the phosphate transfer to the glucan indicating a ping-pong reaction mechanism.
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins (2004)

The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) provides a non-redundant collection of sequences representing genomic data, transcripts and proteins. Although the goal is to provide a comprehensive dataset representing the complete sequence information for any given species, the database pragmatically includes sequence data that are currently publicly available in the archival databases. The database incorporates data from over 2400 organisms and includes over one million proteins representing significant taxonomic diversity spanning prokaryotes, eukaryotes and viruses. Nucleotide and protein sequences are explicitly linked, and the sequences are linked to other resources including the NCBI Map Viewer and Gene. Sequences are annotated to include coding regions, conserved domains, variation, references, names, database cross-references, and other features using a combined approach of collaboration and other input from the scientific community, automated annotation, propagation from GenBank and curation by NCBI staff.
Chiral synthesis of the key intermediate for 1β-methylcarbapenem antibiotics starting from (–)-carvone (1991)

A stereoselective synthesis of the key intermediate for the preparation of 1β-methylcarbapenem antibiotics was achieved by using a cyclopentanone derivative, easily derived from (–)-carvone, as a starting material.
Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes (2003)

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies.
The Therapeutic Potential of Antigen‐Oligonucleotide Conjugates (2003)

Conjugation of protein antigen with immunostimulatory oligonucleotides creates a potent immunogen that elicits antigen-specific antibody responses, a Th1-biased cytokine profile, and CD8 cytotoxic T lymphocyte activity. The wide range of humoral and cellular immune responses induced by these conjugates suggests they can be used to create effective vaccines against infectious pathogens and tumors and to beneficially modulate the immune responses seen in allergic diseases. This review summarizes the available data on the use of antigen-oligonucleotide conjugates and discusses their potential use for the treatment of infectious, oncologic, and allergic diseases in humans.