gebhart/patrepeval huggingface dataset:
Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells (2006)

Perifosine is a synthetic novel alkylphospholipid, a new class of antitumor agents which targets cell membranes and inhibits Akt activation. Here we show that baseline phosphorylation of Akt in multiple myeloma (MM) cells is completely inhibited by perifosine [octadecyl-(1,1-dimethyl-piperidinio-4-yl)-phosphate] in a time- and dose-dependent fashion, without inhibiting phosphoinositide-dependent protein kinase 1 phosphorylation. Perifosine induces significant cytotoxicity in both MM cell lines and patient MM cells resistant to conventional therapeutic agents. Perifosine does not induce cytotoxicity in peripheral blood mononuclear cells. Neither exogenous interleukin-6 (IL-6) nor insulinlike growth factor 1 (IGF-1) overcomes Perifosine-induced cytotoxicity. Importantly, Perifosine induces apoptosis even of MM cells adherent to bone marrow stromal cells. Perifosine triggers c-Jun N-terminal kinase (JNK) activation, followed by caspase-8/9 and poly (ADP)-ribose polymerase cleavage. Inhibition of JNK abrogates perifosine-induced cytotoxicity, suggesting that JNK plays an essential role in perifosine-induced apoptosis. Interestingly, phosphorylation of extracellular signal-related kinase (ERK) is increased by perifosine; conversely, MEK inhibitor synergistically enhances Perifosine-induced cytotoxicity in MM cells. Furthermore, perifosine augments dexamethasone, doxorubicin, melphalan, and bortezomib-induced MM cell cytotoxicity. Finally, perifosine demonstrates significant antitumor activity in a human plasmacytoma mouse model, associated with down-regulation of Akt phosphorylation in tumor cells. Taken together, our data provide the rationale for clinical trials of perifosine to improve patient outcome in MM.
A possible physiological function of lysozyme. (1976)

A possible physiological function of lysozyme might consist of an indirect effect arising in the course of its action on bacteria, as some of the bacterial reaction products behave as adjuvants or immunostimulating substances.
Network Time Protocol (NTP) (1985)

This document describes the Network Time Protocol (NTP), a protocol
for synchronizing a set of network clocks using a set of distributed
clients and servers. NTP is built on the User Datagram Protocol (UDP),
which provides a connectionless transport mechanism. It is evolved
from the Time Protocol and the ICMP Timestamp message and is a
suitable replacement for both. This RFC suggests a proposed protocol
for the ARPA-Internet community, and requests discussion and
suggestions for improvements.
Use of a Single Solution for Oral Rehydration and Maintenance Therapy of Infants With Diarrhea and Mild to Moderate Dehydration (1995)

The two maintenance oral electrolyte solutions (Pedialyte and Infalyte) most commonly used in the United States are effective as rehydration solutions for infants with mild to moderate dehydration. We speculate that a strategy for oral rehydration therapy in the United States, based on the use of a single solution during the rehydration and maintenance phase, might gain additional acceptance by practicing pediatricians and family physicians.
Examining Menstrual Tracking to Inform the Design of Personal Informatics Tools (2017)

We consider why and how women track their menstrual cycles, examining their experiences to uncover design opportunities and extend the field's understanding of personal informatics tools. To understand menstrual cycle tracking practices, we collected and analyzed data from three sources: 2,000 reviews of popular menstrual tracking apps, a survey of 687 people, and follow-up interviews with 12 survey respondents. We find that women track their menstrual cycle for varied reasons that include remembering and predicting their period as well as informing conversations with healthcare providers. Participants described six methods of tracking their menstrual cycles, including use of technology, awareness of their premenstrual physiological states, and simply remembering. Although women find apps and calendars helpful, these methods are ineffective when predictions of future menstrual cycles are inaccurate. Designs can create feelings of exclusion for gender and sexual minorities. Existing apps also generally fail to consider life stages that women experience, including young adulthood, pregnancy, and menopause. Our findings encourage expanding the field's conceptions of personal informatics.
Theoretical Limits on Extrasolar Terrestrial Planet Detection with Coronagraphs (2006)

Many high contrast coronagraph designs have recently been proposed. In this paper, their suitability for direct imaging of extrasolar terrestrial planets is reviewed. We also develop a linear-algebra based model of coronagraphy that can both explain the behavior of existing coronagraphs and quantify the coronagraphic performance limit imposed by fundamental physics. We find that the maximum theoretical throughput of a coronagraph is equal to one minus the non-aberrated non-coronagraphic PSF of the telescope. We describe how a coronagraph reaching this fundamental limit may be designed, and how much improvement over the best existing coronagraph design is still possible. Both the analytical model and numerical simulations of existing designs also show that this theoretical limit rapidly degrades as the source size is increased: the ``highest performance'' coronagraphs, those with the highest throughput and smallest Inner Working Angle (IWA), are the most sensitive to stellar angular diameter. This unfortunately rules out the possibility of using a small IWA (lambda/d) coronagraph for a terrestrial planet imaging mission. Finally, a detailed numerical simulation which accurately accounts for stellar angular size, zodiacal and exozodiacal light is used to quantify the efficiency of coronagraph designs for direct imaging of extrasolar terrestrial planets in a possible real observing program. We find that in the photon noise limited regime, a 4m telescope with a theoretically optimal coronagraph is able to detect Earth-like planets around 50 stars with 1hr exposure time per target (assuming 25% throughput and exozodi levels similar to our solar system). We also show that at least 2 existing coronagraph design can approach this level of performance in the ideal monochromatic case considered in this study.
Single-Domain Antibodies (2009)

The antigen-binding entity of an antibody, reduced in size to one single domain, is referred to as a “single-domain antibody.” Various strategies have been explored with variable success to arrive at functional single-domain antibodies. The potential of single-domain antibodies, as research tools or in medicine, is reflected by the three companies – founded in Europe – with a mission to bring these molecules to the market. Domantis using human VH-derived single-domain antibodies started in 2000 and was bought by GSK for £300M in December 2007. Haptogen employing shark single-domain antibodies was acquired by Wyeth, and Ablynx focusing on llama-derived single-domain antibodies received over €70M in three rounds of venture capitalist investments and another €80M on the Euronext stock market in November 2007. Regarding therapeutic applications, Arana Therapeutics in Australia entered a Phase 2 clinical trial with its single-domain antibody derivative. In this chapter, we will review (1) the various antibodies used for generating single-domain antibodies, (2) the properties of single-domain antibodies that create an added value for use in immunotherapy, and (3) a number of therapeutic applications.
Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep. Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation. (1988)

When protamine (2 mg/kg) was injected intravenously into awake sheep 5 minutes after infusing heparin (200 units/kg), there was transient diffuse pulmonary vasoconstriction with mean pulmonary arterial pressure increasing from 18.0 +/- 0.7 to 43.8 +/- 2.7 mm Hg at 1 minute (x +/- SEM; n = 10). In addition, there was profound leukopenia (36.9 +/- 7.7% of baseline values at 2 minutes) with transpulmonary leukocyte sequestration and transiently elevated plasma concentrations of C3a (from 420 +/- 146 to 1,599 +/- 249 ng/ml; n = 3, p less than 0.01) and thromboxane B2 (from 0.30 +/- 0.05 to 6.3 +/- 2.8 ng/ml; n = 10, p less than 0.0001), without significant increases of plasma 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, leukotrienes, or histamine. Intravenous injection of protamine alone produced no hemodynamic effects and did not increase plasma levels of vasoconstrictor eicosanoids. Intravenous pretreatment with either a cyclooxygenase inhibitor or a hydrogen peroxide scavenger (dimethylthiourea) blocked both the increases of thromboxane levels and the pulmonary vasoconstriction.
Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human (2014)

Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground-state transcription factors, TFCP2L1 or KLF4, has marginal impact on conventional human pluripotent stem cells but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground-state pluripotency in human cells.
Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. (1996)

It has been known for many years that adipocytes express high affinity ACTH and alpha-melanocyte stimulating hormone (MSH) binding sites, and that ACTH, alpha-MSH, and beta-lipotropin are potent lipolytic hormones. We show here that the adipocyte response to the melanocortin peptides results from the expression of both the MC2 (ACTH) receptor as well as the newly discovered MC5 receptor. Using RT-PCR and Northern blot hybridization, high levels of MC2 receptor messenger RNA (mRNA) were found in all adipose tissues examined in the mouse, whereas MC5 receptor mRNA was found in a subset of these. Both receptors mRNAs were also found in the 3T3-L1 cell line but only after the cells had been induced to differentiate into adipocytes. This cell line was then used to characterize the pharmacological properties of the MC2 and MC5 receptor sites in situ. The MC2 receptor exhibits properties similar to the ACTH receptor characterized in adrenocortical cells, coupling to activation of adenylyl cyclase with an EC50 of approximately 1 nM. An MSH binding site characterized in these cells is presumably the MC5 receptor, based on the observation that this is the only other melanocortin receptor mRNA detected in these cells. The MC5 receptor in the 3T3-L1 adipocyte activated adenylyl cyclase in response to alpha-MSH stimulation. Interestingly, Nle4, D-Phe7-alpha-MSH (NDP-MSH), a commonly used synthetic alpha-MSH agonist, was a potent antagonist of the MC5 receptor expressed in the 3T3-L1 cell line. Although the agouti signaling peptide is a potent antagonist of NDP-MSH binding to the MC1 and MC4 melanocortin receptors, agouti was unable to block NDP-MSH binding in the 3T3-L1 adipocyte.
Book notes (1991)

Hansson, Desiree and Van Zyl Smit, Dirk. (Eds). 1990. TOWARDS JUSTICE? CRIME AND STATE CONTROL IN SOUTH AFRICA. Cape Town: Oxford University Press. Pp. 278. Paper. Beresford, Melanie. 1988. VIETNAM: POLITICS, ECONOMICS AND SOCIETY. London: Pinter, pp.x + 242. Illustrations and tables, basic data, Vietnamese terms, abbreviations and glossary. Index and select bibliography. R44.75. Paper. Schoeman, Elna. (Compiler). 1990. ECONOMIC INTERDEPENDENCE IN SOUTHERN AFRICA, 1961–1989. A Select and Annotated Bibliography. Bibliographical Series No. 20. Johannesburg: South African Institute of International Affairs. Pp.377. Author and Subject Indexes. R60.00. Paper.
MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-XL, and Mcl-1 and promotes survival of human pancreatic cancer cells (2000)

Our data suggest that activation of the ERK pathway functions to protect pancreatic tumor cells from apoptosis as well as to regulate their progression in the cell cycle.
Assessment of spinal cord damage in MS using MRI (2000)

Spinal cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the spinal cord. Conventional measures used in the assessment of damage to the spinal cord include quantification of: (1) high intensity on T2 weighted images; (2) spinal cord enhancement; and (3) spinal cord atrophy. Although not presently implemented, newer methods including magnetization transfer, diffusion, and proton spectroscopy offer the potential for more specific classification of spinal cord MS. Assessment of spinal cord damage using MR still remains behind the development of brain methodology and represents both a challenge and an opportunity.
Intrinsic Activity of Human Immunodeficiency Virus Type 1 Protease Heterologous Fusion Proteins in Mammalian Cells (1995)

We have generated various mammalian expression constructs that produce fusion proteins of human immunodeficiency virus type 1 (HIV-1) protease (PR) with the HIV-1 Nef protein. The expression of these proteins is inducible by the HIV-1 Tat protein. High-level expression of proteolytically active PR was produced from PR imbedded into Nef coding sequences, flanked by PR cleavage sites. The fusion protein was cleaved nearly to completion and did not exhibit the regulated processing that is seen with the virally encoded PR. No cytotoxic effect of PR expression was detected. The self-cleavage of PR could be inhibited by a specific inhibitor of HIV-1 PR (U75875). Elimination of the aminoterminal PR cleavage site did not have a measurable effect on cleavage of the precursor fusion protein. The cleaved fusion proteins appeared to be extremely unstable in the transfected cells. These findings demonstrate the intrinsic activity of HIV-1 PR in mammalian cells, in the context of a heterologous fusion protein.
Characterization of IS 1515 , a Functional Insertion Sequence in Streptococcus pneumoniae (1998)

We describe the characterization of a new insertion sequence, IS1515, identified in the genome of Streptococcus pneumoniae I41R, an unencapsulated mutant isolated many years ago (R. Austrian, H. P. Bernheimer, E. E. B. Smith, and G. T. Mills, J. Exp. Med. 110:585-602, 1959). A copy of this element located in the cap1EI41R gene was sequenced. The 871-bp-long IS1515 element possesses 12-bp perfect inverted repeats and generates a 3-bp target duplication upon insertion. The IS encodes a protein of 271 amino acid residues similar to the putative transposases of other insertion sequences, namely IS1381 from S. pneumoniae, ISL2 from Lactobacillus helveticus, IS702 from the cyanobacterium Calothrix sp. strain PCC 7601, and IS112 from Streptomyces albus G. IS1515 appears to be present in the genome of most type 1 pneumococci in a maximum of 13 copies, although it has also been found in the chromosome of pneumococcal isolates belonging to other serotypes. We have found that the unencapsulated phenotype of strain 141R is the result of both the presence of an IS1515 copy and a frameshift mutation in the cap1EI41R gene. Precise excision of the IS was observed in the type 1 encapsulated transformants isolated in experiments designed to repair the frameshift. These results reveal that IS1515 behaves quite differently from other previously described pneumococcal insertion sequences. Several copies of IS1515 were also able to excise and move to another locations in the chromosome of S. pneumoniae. To our knowledge, this is the first report of a functional IS in pneumococcus.
Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers (1997)

Hydrophilic nanoparticulate carriers have important potential applications for the administration of therapeutic molecules. The recently developed hydrophobic-hydrophilic carriers require the use of organic solvents for their preparation and have a limited protein-loading capacity. To address these limitations a new approach for the preparation of nanoparticles made solely of hydrophilic polymers is presented. The preparation technique, based on an ionic gelation process, is extremely mild and involves the mixture of two aqueous phases at room temperature. One phase contains the polysaccharide chitosan (CS) and a diblock copolymer of ethylene oxide and propylene oxide (PEO-PPO) and, the other, contains the polyanion sodium tripolyphosphate (TPP). Size (200–1000 nm) and zeta potential (between +20 mV and +60 mV) of nanoparticles can be conveniently modulated by varying the ratio CS/PEO-PPO. Furthermore, using bovine serum albumin (BSA) as a model protein it was shown that these new nanoparticles have a great protein loading capacity (entrapment efficiency up to 80% of the protein) and provide a continuous release of the entrapped protein for up to 1 week. © 1997 John Wiley & Sons, Inc.
On the charge storage and decay mechanism in silicon dioxide electrets (1992)

A mechanism for both the storage and the decay of charge in a charged silicon dioxide layer is proposed. The oxide layer needs neutral electron traps to obtain stable trapped negative charge, after having been charged, resulting in an electret that can be applied in microphones. The deprotonization of the silanol groups, followed by charge injection, results in an electrochemical reaction with immobile SiO/sup -/ as one of the reaction products. Decay of the stable charge thus obtained can occur by the clustering of water molecules at inner silanol groups, resulting in a conductive hydrogen bonded network, which eventually leads to the discharge of the electret. Measurement results are presented, showing a considerable decrease in surface conductivity, after having grafted the SiO/sub 2/ surface, resulting in covalently bonded, relatively long octadecyl silane chains.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Epigenetic inactivation of 14-3-3 sigma in oral carcinoma: association with p16(INK4a) silencing and human papillomavirus negativity. (2002)

In vitro studies have identified 14-3-3sigma as a regulator of senescence in human keratinocytes. To assess its contribution to squamous neoplasia, we have analyzed genetic and epigenetic changes in this gene in squamous cell carcinomas (SCCs) and dysplastic lesions of the oral cavity. No mutations were detected in the coding sequence of 14-3-3sigma in 20 oral carcinomas, and there was loss of heterozygosity in only 7 of 40 informative cases. In contrast to the absence of genetic change, aberrant methylation within 14-3-3sigma was detected in 32 of 92 squamous cell carcinomas and in 3 of 6 oral dysplasias and was associated with reduced or absent expression at both mRNA and protein levels. Methylation was not detected in matched, normal epithelial tissue controls. Carcinomas in which 14-3-3sigma was methylated were significantly more likely to lack DNA sequences from human papillomavirus and to have coincident methylation of p16(INK4a) than cases that expressed 14-3-3sigma. Methylation was detected in SCC, both wild-type and mutant for p53, but was more commonly detected in cancers with wild-type p53. These results implicate coincident epigenetic abrogation of function in both sigma and p16(INK4a) in a subset of SCCs of the oral cavity.
N‐Heterocyclic Carbenes (1997)

Abstract The chemistry of N‐heterocyclic carbenes has long been limited to metal coordination compounds derived from azolium precursors, a development that was started by Öfele and Wanzlick in 1968. Since free carbenes are now available through the work of Arduengo (1991), a renaissance in this little‐recognized area of chemistry has occurred. A leading motive is the advantages of N‐heterocyclic carbenes as ligands in organometallic catalysts, where they extend the scope of application reached by phosphanes (functionalized, chiral, water‐soluble, and immobilized derivatives). The present review summarizes the state of the art with regard to synthesis, structure, bonding theory, metal coordination chemistry, and catalysis. Chelating, functionalized, chiral, and immobilized ligands can be generated and attached to metal centers in straightforward procedures under mild conditions. A wealth of new chemistry is thus opened. It is also shown how carbenes derived from imidazoles and triazoles behave as ligands in catalysis. It is reasonable to assume that N‐heterocyclic carbenes surpass the ubiquitous phosphanes as ligands in a number of organometallic catalytic reactions.
Etch Rate Retardation of Ga[sup +]-Ion Beam-Irradiated Silicon (2005)

Surface chemistry during wet chemical etching in alkaline KOH solution and dry etching in plasma of high-dose -implanted Si has been investigated by means of secondary ion mass spectroscopy (SIMS) and X-ray photoelectron spectroscopy (XPS). During wet chemical etching in a solution a thin layer of of thickness is formed, which has been investigated in more detail by angle-resolved XPS. In the case of dry reactive ion etching (RIE) the surface chemistry is quite different. In this case a more enhanced oxidation of Ga takes place due to the high reactivity of atomic oxygen from the plasma. SIMS results show that during RIE a Ga-rich surface layer forms, and therefore an enhanced Ga oxidation takes place, leading to a thicker layer compared to wet chemical treatment. XPS depth profiling reveals a stoichiometry of almost completely oxidized Ga layer free from Si with a thickness of about . The etch rate lowering in as-implanted silicon is ascribed to the formation of gallium oxide at the Si surface during the etch processes.