gebhart/patrepeval huggingface dataset:
Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate (1990)

Naturally occurring strains of human immunodeficiency virus (HIV) can vary considerably in their in vitro biological properties, and such differences may also be reflected in their in vivo pathogenesis. In an attempt to define genetic determinants of viral pathogenicity, we have molecularly cloned, sequenced, and characterized an attenuated isolate of HIV type 2 (HIV-2/ST) that differs from prototype HIV-2 strains in its inability to fuse with and kill susceptible CD4-bearing target cells. A proviral clone, termed JSP4-27, was identified to be transfection competent and to fully exhibit the noncytopathic and nonfusogenic properties of its parental isolate. Nucleotide sequence analysis of this clone revealed a genomic organization very similar to that of cytopathic HIV-2 strains and an overall nucleotide sequence homology of 88 to 90%. Amino acid sequence comparison confirmed the integrity of all major viral gene products in JSP4-27 but identified two amino acid sequence substitutions in its envelope fusion region. To investigate whether these mutations were responsible for the nonfusogenic phenotype of JSP4-27, we amplified, cloned, and sequenced the envelope fusion regions of four additional HIV-2/ST strains, two of which represented in vitro-generated, fusogenic and cytopathic variants of HIV-2/ST. The analysis showed that all HIV-2/ST strains examined, including the fusogenic variants, contained the same amino acid sequence changes. On the basis of these findings, we conclude that the attenuated phenotype of JSP4-27, and that of its parental virus, is not due to a direct alteration of the envelope fusion domain. Our results also show, for the first time, that individual replication-competent proviral clones can be representative of attenuated strains of HIV.
From animal models to human disease: a genetic approach for personalized medicine in ALS (2016)

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.
Ultrafast Extraction of Proteins from Tissues Using Desorption by Impulsive Vibrational Excitation (2014)

A picosecond IR laser (PIRL) can be used to blast proteins out of tissues through desorption by impulsive excitation (DIVE) of intramolecular vibrational states of water molecules in the cell in less than a millisecond. With PIRL-DIVE proteins covering a range of a few kDa up to several MDa are extracted in high quantities compared to conventional approaches. The chemical composition of extracted proteins remains unaltered and even enzymatic activities are maintained.
Scaling laws for jet pulsations associated with high-resolution electrohydrodynamic printing (2008)

This paper presents simple scaling laws that describe the intrinsic pulsation of a liquid jet that forms at the tips of fine nozzles under electrohydrodynamically induced flows. The jet diameter is proportional to the square root of the nozzle size and inversely proportional to the electric field strength. The fundamental pulsation frequency is proportional to the electric field strength raised to the power of 1.5. These scaling relationships are confirmed by experiments presented here and by data from the literature. The results are important for recently developed high-resolution ink jet printing techniques and other applications using electrohydrodynamics.
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 (2017)

Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Blind separation of convolved sources based on information maximization (2002)

Blind separation of independent sources from their convolutive mixtures is a problem in many real world multi-sensor applications. In this paper we present a solution to this problem based on the information maximization principle, which was proposed by Bell and Sejnowski (1995) for the case of blind separation of instantaneous mixtures. We present a feedback network architecture capable of coping with convolutive mixtures, and we derive the adaptation equations for the adaptive filters in the network by maximizing the information transferred through the network. Examples using speech signals are presented to illustrate the algorithm.
Definitive-like erythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin (2006)

Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic marker emergence suggest that CD45+ hematopoiesis peaks at late D14EB differentiation stages, although low-level CD45- erythroid differentiation can be seen before that stage. By morphologic criteria, hES-derived erythroid cells were of definitive type, but these cells both at mRNA and protein levels coexpressed high levels of embryonic (epsilon) and fetal (gamma) globins, with little or no adult globin (beta). This globin expression pattern was not altered by the presence or absence of fetal bovine serum, vascular endothelial growth factor, Flt3-L, or coculture with OP-9 during erythroid differentiation and was not culture time dependent. The coexpression of both embryonic and fetal globins by definitive-type erythroid cells does not faithfully mimic either yolk sac embryonic or their fetal liver counterparts. Nevertheless, the high frequency of erythroid cells coexpressing embryonic and fetal globin generated from embryonic stem cells can serve as an invaluable tool to further explore molecular mechanisms.
Universal Antibodies to Human Interferon-α Subtypes— The Production of Antipeptide Antibodies to Conserved Regions of Interferon-α (1991)

Antibodies to three conserved regions of all human interferon (IFN)-alpha 1 subtypes were raised by immunizing rabbits with short synthetic peptides coupled to a carrier. These peptides correspond to amino acid residues 29-36, 31-36, 126-131, 139-151, and 142-151 of the consensus sequence of IFN-alpha 1. The antibodies were tested for reactivity with IFN-alpha 1, -alpha 2a, -alpha 2b, -alpha 4a, and -alpha 14 and IFN-beta. Most antipeptide antibodies react only weakly with IFN-alpha subtypes; only the antibodies raised against the peptide corresponding to residues 142-151 conjugated to keyhole limpet hemocyanin using glutaraldehyde react appreciably with all IFN-alpha subtypes tested. These antipeptide antibodies are potentially universal antibodies to the human IFN-alpha 1 subtypes, since they exhibit similar binding affinity to all the IFN-alpha subtypes tested and do not react with IFN-beta.
Analysis of human papillomavirus sequences in cell lines recently derived from cervical cancers. (1988)

The DNA and RNA from four cell lines recently derived from cervical carcinomas (HX151c, HX155c, HX156c, and HX160c) were analyzed for the presence of human Papillomavirus DNA. Each contained HPV-16 DNA in a multicopy integrated form of varying complexity. Each also expressed RNA transcripts of similar sizes to CaSki cell transcripts. The splice acceptor position within the E6 coding region of the cell line HX156c was identical to CaSki, SiHa, and HeLa cells as well as a cell line derived from mouse fibroblasts transformed with HPV-16 sequences in a retrovirus vector. Immunoprecipitation with an anti-HPV-16 E6 polyclonal antiserum demonstrated that HX160c cells contain the E6 polypeptide derived from unspliced transcripts.
Recent Progress on Anticancer Candidates in Patents of Herbal Medicinal Products (2011)

Herbal medicines in treatment of cancer as complementary and alternative therapy are accepted increasingly with growing scientific evidences of biomedical research and clinical trials. Anticancer drugs discovered from herbal medicines have a long history and some of them have been used in clinical setting as the conventional anticancer drugs. Actually, herbal medicines are a source for anticancer drug discovery and drug development. Recently, research continuously focuses on clues from traditional use of herbal medicines to develop new anticancer drugs in single pure compounds. On the other hand, standardized various extracts or fractions with anticancer effects or with adjuvant therapy in cancer treatment coming from single or mixed herbs are also accepted forms as dietary supplements and botanical drug products in the US for current statutory regulations. In the present paper, we analyzed the patented agents in the US from herbal medicines in recent ten years, both as potential anticancer extracts/fractions (containing multi-components) and single pure compound(s) that act as new anticancer substances. This review also highlighted the advances in knowledge about quality control, safety, efficacy and recent progress in anticancer candidates in patents of botanical drug products from herbal medicines.
Assembly and peptide binding of major histocompatibility complex class II heterodimers in an in vitro translation system. (1994)

In vitro transcription/translation of HLA-DR1 cDNAs in the presence of microsomal membranes was used to study the association of major histocompatibility complex class II molecules with peptide and invariant chain (Ii) in the endoplasmic reticulum (ER). HLA-DR alpha and HLA-DR beta subunits assembled into SDS-unstable heterodimers in the absence of exogenous peptide. The inclusion of synthetic peptides during the alpha/beta assembly process promoted their conversion to SDS-resistant heterodimers. Addition of Ii RNA during the translation of HLA-DR alpha and HLA-DR beta RNAs resulted in the formation of alpha/beta/Ii complexes. Peptide binding by class II molecules was detected even when excess Ii was present during alpha/beta assembly. These findings indicate that peptides can bind alpha/beta heterodimers in the ER microenvironment and suggest that peptides derived from cytosolic proteins that are presented by class II molecules at the cell surface may have bound to HLA-DR in the ER.
Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha. (1994)

A sphingomyelin (SM)-signaling cycle has been described in human leukemia-derived HL-60 cells (Okazaki, T., Bell, R.M., and Hannun, Y.A. (1989) J. Biol. Chem. 264, 19076-19080). Activation of the cycle by tumor necrosis factor alpha (TNF alpha) occurs rapidly, with peak levels of approximately 30% SM hydrolysis observed within 45-60 min. The mechanisms by which TNF alpha induces this SM turnover remain largely unexplored. In this study, arachidonic acid (AA) was investigated as a potential mediator of TNF alpha effects on SM turnover. In HL-60 cells, 30 nM TNF alpha stimulated the release of AA within 5-10 min. In turn, AA stimulated SM hydrolysis and concomitant ceramide generation within 20 min of addition to cells. Other fatty acids, notably oleate, mimicked the effects of AA on SM hydrolysis, but the methyl ester and alcohol analogs of fatty acids were inactive. Diacylglycerol, a candidate mediator of TNF alpha responses, AA activated a cytosolic sphingomyelinase dose dependently, with 10-100 microM AA including 3-4-fold activation, thus suggesting a direct effect of AA on sphingomyelinase. Melittin, a potent phospholipase A2 activator, induced SM hydrolysis at concentrations as low as 35 nM. However, unlike AA, melittin was unable to stimulate sphingomyelinase activation in an in vitro assay system. Finally, exogenous addition of AA also produced antiproliferative effects reminiscent of ceramide effects. Thus, a role for the phospholipase A2/AA pathway in mediating TNF alpha induction of the SM cycle is supported by multiple lines of evidence. These studies begin to elucidate a mechanism of TNF alpha signaling and identify a close relationship between glycerophospholipid and sphingolipid signaling. AA, therefore, may be pivotal to understanding the sphingomyelin-signaling cascade.
Effect of finite size of ion chambers used for neutron dosimetry (1980)

The effective point of measurement for spherical ionisation chambers was determined free-in-air for d + T neutrons and inside a human water phantom for d + T neutrons and 60Co gamma rays. Measurements were performed with spherical chambers of different diameters and a disc-type chamber. For spherical ion chambers free-in-air, the geometrical centre of the chamber was found to be the point of measurement for sufficiently great distances from the neutron source. In-phantom for spherical ion chambers, displacement correction factors of 1 - (0.25 +/- 0.06) x 10(-2) r for d + T neutrons and of 1 - (0.37 +/- 0.04) x 10(-2) r for 60Co gamma rays (r being the cavity radius in mm) were observed. The differences in displacement for d + T neutrons and 60Co gamma rays can be attributed to differences in attenuation and scatter characteristics of these radiation qualities. The replacement of phantom material by the cavity of an ion chamber was simulated by introducing Styrofoam spheres of comparable dimensions into the phantom. The dose distributions measured over the cavities could explain the different displacement corrections for 60Co gamma rays and 15 MeV neutrons.
A substance P-opioid chimeric peptide as a unique nontolerance-forming analgesic (2000)

To elucidate mechanisms of acute and chronic pain, it is important to understand how spinal excitatory systems influence opioid analgesia. The tachykinin substance P (SP) represents the prototypic spinal excitatory peptide neurotransmitter/neuromodulator, acting in concert with endogenous opioid systems to regulate analgesic responses to nociceptive stimuli. We have synthesized and pharmacologically characterized a chimeric peptide containing overlapping NH(2)- and COOH-terminal functional domains of the endogenous opioid endomorphin-2 (EM-2) and the tachykinin SP, respectively. Repeated administration of the chimeric molecule YPFFGLM-NH(2), designated ESP7, into the rat spinal cord produces opioid-dependent analgesia without loss of potency over 5 days. In contrast, repeated administration of ESP7 with concurrent SP receptor (SPR) blockade results in a progressive loss of analgesic potency, consistent with the development of tolerance. Furthermore, tolerant animals completely regain opioid sensitivity after post hoc administration of ESP7 alone, suggesting that coactivation of SPRs is essential to maintaining opioid responsiveness. Radioligand binding and signaling assays, using recombinant receptors, confirm that ESP7 can coactivate mu-opioid receptors (MOR) and SPRs in vitro. We hypothesize that coincidental activation of the MOR- and SPR-expressing systems in the spinal cord mimics an ongoing state of reciprocal excitation and inhibition, which is normally encountered in nociceptive processing. Due to the ability of ESP7 to interact with both MOR and SPRs, it represents a unique prototypic, anti-tolerance-forming analgesic with future therapeutic potential.
RGD AND OTHER RECOGNITION SEQUENCES FOR INTEGRINS (1996)

Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
Identification of Nicotinamide N -Methyltransferase as a Novel Serum Tumor Marker for Colorectal Cancer (2005)

It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.
Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine (1994)

T. D. James, K. R. A. S. Sandanayake and S. Shinkai, J. Chem. Soc., Chem. Commun., 1994, 477 DOI: 10.1039/C39940000477
Multiplex PCR and Emerging Technologies for the Detection of Respiratory Pathogens (2011)

Molecular methods are becoming more widely used for the detection of respiratory pathogens, in part because of their superior sensitivity, relatively rapid turnaround time, and ability to identify pathogens that are slow growing or difficult to culture. The recent novel H1N1 influenza A pandemic served to underscore how quickly new molecular tests can become available for clinical use. Over the years PCR has been the dominant amplification method. Recently, modifications of this technology have emerged, some of which allow for the rapid detection of multiple pathogens in a single test. This review will focus on emerging multiplex molecular technologies and their clinical utility for the detection of respiratory pathogens.
PRODUCTION AND CHARACTERIZATION OF MULTIPLE-LAYERED POPULATIONS OF ANIMAL CELLS (1965)

Dense populations containing 129 x 10(6) Jensen sarcoma, 134 x 10(6) DON Chinese hamster, 28.9 x 10(6) WI-38 human diploid, 61.8 x 10(6) HEp-2 human carcinoma, and 67.4 x 10(6) WISH human amnion cells were produced from dilute inocula, 0.85 to 5.33 x 10(6), in 7 to 8 days in a perfusion system using replicate T-60 flasks. Perfusion rates as high as 560 ml medium/day/T-60 were required to maintain pH (to ca +/-0.1 unit) and adequate nutrient supplies. The cell densities encountered are described by the term "monolayer equivalents" (M.E.), defined as number of cells per culture divided by number of cells in a monolayer. The M.E.'s for T-60 cultures containing unusually dense populations of 40 x 10(6) WI-38 and 250 x 10(6) DON cells (9-day perfusion) were 5 and 17, respectively, and numbers of cells in illustrations of stained cross-sections of membranes from these cultures were in excellent agreement. Threshold M.E.'s exist below which proliferation is the chief cellular activity and above which one or more cell functions may predominate even though proliferation persists. Cellular nutrition and metabolism may change with changes in M.E., as illustrated in different patterns of glutamic acid, proline, and glycine utilization or production in dense vs. dilute WI-38 cell populations. The results indicated that the role of contact inhibition phenomena in arresting cellular proliferation was diminished in perfusion system environments.
Optimizing object queries using an effective calculus (2000)

Object-oriented databases (OODBs) provide powerful data abstractions and modeling facilities, but they generally lack a suitable framework for query processing and optimization. The development of an effective query optimizer is one of the key factors for OODB systems to successfully compete with relational systems, as well as to meet the performance requirements of many nontraditional applications. We propose an effective framework with a solid theoretical basis for optimizing OODB query languages. Our calculus, called the monoid comprehension calculus, captures most features of ODMG OQL, and is a good basis for expressing various optimization algorithms concisely. This article concentrates on query unnesting (also known as query decorrelation), an optimization that, even though it improves performance considerably, is not treated properly (if at all) by most OODB systems. Our framework generalizes many unnesting techniques proposed recently in the literature, and is capable of removing any form of query nesting using a very simple and efficient algorithm. The simplicity of our method is due to the use of the monoid comprehension calculus as an intermediate form for OODB queries. The monoid comprehension calculus treats operations over multiple collection types, aggregates, and quantifiers in a similar way, resulting in a uniform method of unnesting queries, regardless of their type of nesting.
A comparison of rat small intestinal insulin and insulin-like growth factor I receptors during fasting and refeeding (1995)

Insulin-like growth factor I (IGF-I) and insulin may be important regulators of intestinal growth. To investigate small intestinal IGF-I receptors (IGF-IR) and insulin receptors (IR) during intestinal cell atrophy and regeneration, we compared indexes of IGF-IR and IR expression in rat jejunum after 72 h of fasting and 24-72 h of enteral refeeding. Fasting induced intestinal atrophy, reduced plasma insulin and IGF-I concentrations, and markedly decreased jejunal IGF-I messenger RNA (mRNA) levels; these changes were reversed by refeeding. Fasting significantly increased jejunal specific insulin binding, IR content (to 230% of the fed control value), and the 9.6- and 7.4-kilobase IR mRNA transcript levels (to 202% and 218% of control values, respectively). These IR indexes rapidly decreased to control levels with refeeding. Levels of IGF-IR (by Scatchard analysis) and IGF-I-R mRNA were not significantly altered with fasting. The 11-kilobase IGF-IR mRNA transcript increased significantly during the first 24 h of refeeding (to 166% of the control value), and IGF-IR number rose 3-fold. We conclude that rat jejunal IR and IGF-IR are differentially regulated by nutrient availability. Up-regulation of jejunal IGF-I and IGF-IR expression during refeeding suggests a role for the IGF action pathway in gut trophic responses to enteral nutrients.