gebhart/patrepeval huggingface dataset:
Boron neutron capture therapy in cancer: past, present and future (2007)

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. 10B is then activated to 11B, which will immediately decay releasing alpha particles and 7Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiforme and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100% of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans.
Human ApoA-I Transfer Attenuates Transplant Arteriosclerosis via Enhanced Incorporation of Bone marrow–derived Endothelial Progenitor Cells (2007)

Human apoA-I transfer increases the number of circulating EPCs, enhances their incorporation into allografts, promotes endothelial regeneration, and attenuates neointima formation in a murine model of transplant arteriosclerosis.
The measurement and use of registered reflectance and range data in scene analysis (1977)

The theory and use of a laser sensor designed to provide arrays of registered intensity and range data for three-dimensional scene analysis are described in this paper. Equations are derived to relate the mean and variance of both the intensity and the range data to the physical properties of the target and the parameters of the sensor. Experimental results that verify these equations are given. Adaptive data smoothing and normalization procedures are presented. These procedures reduce photon noise and correct the intensity data for inverse square-law effects. The resulting intensity data give the product of the diffuse surface reflectance and the cosine of the angle of incidence for each picture element in the scene. Simple procedures are given for finding outlines of occluding objects, obtaining normal views of obliquely sensed planar surfaces, and extracting the images of horizontal surface regions from a scene. These procedures demonstrate the advantages of having registered reflectance and range data for scene analysis.
Is serum fructosamine assay specific for determination of glycated serum protein? (1988)

We compared the fructosamine activity in sera from healthy and diabetic subjects with the degree of protein glycation detected by a liquid-chromatographic method. The latter technique measures furosine as a specific product after hydrolysis of epsilon-amino-fructose-lysine. Our results indicate that the fructosamine assay measures the extent of glycation of purified human serum albumin correctly. On the other hand, we found no correlation between the two methods for sera from healthy subjects, although for diabetics' sera the values obtained with both methods were related. However, only about half of the reducing activity (fructosamine) was due to specific nonenzymatic glycation of proteins in healthy subjects and well-controlled diabetics. The remaining unspecific activity varied from serum to serum. It was not reducible with NaBH4 and was independent of the glycation of albumin, which normally accounts for about 80% of glycated serum proteins. The fructosamine assay is therefore of limited specificity for the exact measurement of glycated proteins in serum.
Biological effects of magnetic fields generated with CoSm magnets. (1981)

Experiments were conducted to determine whether any observable short-term biological effects were caused by a static magnetic field created with CoSm magnets similar to those used in the elbow prosthesis described on pages 69-80. Tissue culture studies of several cell lines showed no obvious effects on cell growth rate, morphology, or the ability to grow and remain confluent; and no deleterious effects of the magnetic field were evident as a result of an in-vivo study of wound and bone healing in rats. Long-term effects, if any, have yet to be determined.
The processivity and fidelity of DNA synthesis exhibited by the reverse transcriptase of bovine leukemia virus (2002)

We have recently expressed in bacteria the enzymatically active reverse transcriptase (RT) of bovine leukemia virus (BLV) [Perach, M. & Hizi, A. (1999) Virology 259, 176-189]. In the present study, we have studied in vitro two features of the DNA polymerase activity of BLV RT, the processivity of DNA synthesis and the fidelity of DNA synthesis. These properties were compared with those of the well-studied RTs of human immunodeficiency virus type 1 (HIV-1) and murine leukaemia virus (MLV). Both the elongation of the DNA template and the processivity of DNA synthesis exhibited by BLV RT are impaired relative to the other two RTs studied. Two parameters of fidelity were studied, the capacity to incorporate incorrect nucleotides at the 3' end of the nascent DNA strand and the ability to extend these 3' end mispairs. BLV RT shows a fidelity of misinsertion higher than that of HIV-1 RT and lower than that of MLV RT. The pattern of mispair elongation by BLV RT suggests that the in vitro error proneness of BLV RT is closer to that of HIV-1 RT. These fidelity properties are discussed in the context of the various retroviral RTs studied so far.
Chemistry of diaminomaleonitrile. II. Preparation of the open-chain adduct with ketone in phosphorus pentoxide-ethanol system (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of diaminomaleonitrile. II. Preparation of the open-chain adduct with ketone in phosphorus pentoxide-ethanol systemYozo. OhtsukaCite this: J. Org. Chem. 1976, 41, 4, 629–633Publication Date (Print):February 20, 1976Publication History Published online1 May 2002Published inissue 20 February 1976https://pubs.acs.org/doi/10.1021/jo00866a010https://doi.org/10.1021/jo00866a010research-articleACS PublicationsRequest reuse permissionsArticle Views439Altmetric-Citations38LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Concentrations of Putative Neurovascular Transmitters in Major Cerebral Arteries and Small Pial Vessels of Various Species (1987)

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.
Advanced Micromachining of Concave Microwells for Long Term On-Chip Culture of Multicellular Tumor Spheroids (2014)

A novel approach based on advanced micromachining is demonstrated to fabricate concave microwell arrays for the formation of high quality multicellular tumor spheroids. Microfabricated molds were prepared using a state-of-the-art CNC machining center, containing arrays of 3D convex micropillars with size ranging from 150 μm to 600 μm. Microscopic imaging of the micropillars machined on the mold showed smooth, curved microfeatures of a dramatic 3D shape. Agarose microwells could be easily replicated from the metallic molds. EMT-6 tumor cells seeded in the primary macrowell sedimented efficiently to the bottom of the concave microwells and formed multicellular spheroids within 48 h. Dense and homogeneous multicellular spheroids were obtained after 10 days of culture, confirming the suitability of the proposed approach. To facilitate long term spheroid culture and reliable on-chip drug assay, polydimethylsiloxane microwells were also replicated from the metallic molds. A solvent swelling method was adapted and optimized to Pluronic F127 towards physically entrapping the block copolymer molecules within the polydimethylsiloxane network and in turn to improve long term cell-binding resistance. Homogeneous multicellular spheroids were efficiently formed in the concave microwells and on-chip drug assays could be reliably carried out using curcumin as a model anti-cancer drug. Advanced micromachining provides an excellent technological solution to the fabrication of high quality concave microwells.
Neutralizing antibody responses to enterovirus and adenovirus in healthy adults in China (2014)

Hand, foot and mouth disease (HFMD) is an important public health problem that has emerged over the past several years. HFMD predominantly infects children under seven years old and occasionally causes severe disease in adults. Among the enteroviruses, enterovirus 71 (EV71) and coxsackievirus 16 (CA16) are the major causative agents of HFMD. In addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for HFMD in some cases. Here, we have investigated the neutralizing antibody responses to both enterovirus and adenovirus in adults, with the aim of exploring the prevalence trends of these viruses and the nature of protective immunity in humans to these viral infections. Sera from 391 healthy adults from 21 provinces and cities in China were tested for the presence of antibodies against EV71, CA16, adenovirus human serotype 5 (AdHu5) and chimpanzee adenovirus pan7 (AdC7) using neutralization tests. High seroprevalence rates of EV71, CA16 and AdHu5 were found in the population (85.7%, 58.8% and 74.2%, respectively). The coseropositivity rate of these three viruses was 39.4% (154 of 391), with median neutralizing antibody titers of 80, 40 and 640, respectively, and the neutralizing antibody titer for EV71 was found to be correlated with those of CA16 and AdHu5. AdC7 was found to be a rare adenovirus serotype in the human population, with a seropositivity rate of 11.8%, suggesting that it could be a good choice for a vaccine carrier that could be used in vaccine development.
Novel N-Linked Aminopiperidine Inhibitors of Bacterial Topoisomerase Type II: Broad-Spectrum Antibacterial Agents with Reduced hERG Activity (2011)

Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. Aminopiperidines that have a bicyclic aromatic moiety linked through a carbon to an ethyl bridge, such as 1, generally show potent broad-spectrum antibacterial activity, including quinolone-resistant isolates, but suffer from potent hERG inhibition (IC(50)= 3 μM for 1). We now disclose the finding that new analogues of 1 with an N-linked cyclic amide moiety attached to the ethyl bridge, such as 24m, retain the broad-spectrum antibacterial activity of 1 but show significantly less hERG inhibition (IC(50)= 31 μM for 24m) and higher free fraction than 1. One optimized analogue, compound 24l, showed moderate clearance in the dog and promising efficacy against Staphylococcus aureus in a mouse thigh infection model.
Direct effects of Bmi1 on p53 protein stability inactivates oncoprotein stress responses in embryonal cancer precursor cells at tumor initiation (2012)

Embryonal cancer can arise from postnatally persistent embryonal remnant or rest cells, which are uniquely characterized by the absence of p53 mutations. Perinatal overexpression of the MycN oncoprotein in embryonal cancer precursor cells causes postnatal rests, and later tumor formation through unknown mechanisms. However, overexpression of Myc in adult tissues normally activates apoptosis and/or senescence signals as an organismal defense mechanism against cancer. Here, we show that perinatal neuroblastoma precursor cells exhibited a transiently diminished p53 response to MycN oncoprotein stress and resistance to trophic factor withdrawal, compared with their adult counterpart cells from the TH-MYCN(+/+) transgenic mouse model of neuroblastoma. The adult stem cell maintenance factor and Polycomb group protein, Bmi1 (B-cell-specific Moloney murine leukemia virus integration site), had a critical role at neuroblastoma initiation in the model, by repressing p53 responses in precursor cells. We further show in neuroblastoma tumor cells that Bmi1 could directly bind p53 in a complex with other Polycomb complex proteins, Ring1A or Ring1B, leading to increased p53 ubiquitination and degradation. Repressed p53 signal responses were also seen in precursor cells for other embryonal cancer types, medulloblastoma and acute lymphoblastic leukemia. Collectively, these date indicate a general mechanism for p53 inactivation in some embryonal cell types and consequent susceptibility to MycN oncogenesis at the point of embryonal tumor initiation.
Disruption of the Rb-Raf-1 Interaction Inhibits Tumor Growth and Angiogenesis (2004)

The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G(1) phase to S phase. Although the signaling events after growth factor stimulation have been well characterized, it is not yet clear how these signals contact the cell cycle machinery. We had found previously that growth factor stimulation of quiescent cells lead to the direct binding of Raf-1 kinase to Rb, leading to its inactivation. Here we show that the Rb-Raf-1 interaction occurs prior to the activation of cyclin and/or cyclin-dependent kinases and facilitates normal cell cycle progression. Raf-1-mediated inactivation of Rb is independent of the mitogen-activated protein kinase cascade, as well as cyclin-dependent kinases. Binding of Raf-1 seemed to correlate with the dissociation of the chromatin remodeling protein Brg1 from Rb. Disruption of the Rb-Raf-1 interaction by a nine-amino-acid peptide inhibits Rb phosphorylation, cell proliferation, and vascular endothelial growth factor-mediated capillary tubule formation. Delivery of this peptide by a carrier molecule led to a 79% reduction in tumor volume and a 57% reduction in microvessel formation in nude mice. It appears that Raf-1 links mitogenic signaling to Rb and that disruption of this interaction could aid in controlling proliferative disorders.
Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells (2005)

HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.
Genes for alkaline protease and neutral protease from Bacillus amyloliquefaciens contain a large open reading frame between the regions coding for signal sequence and mature protein (1984)

The genes for alkaline protease (apr[BamP]) and neutral protease (npr[BamP]) from Bacillus amyloliquefaciens have been isolated and expressed in Bacillus subtilis. The DNA sequences of apr[BamP] and npr[BamP] revealed, in each case, the presence of a large open reading frame. The inferred amino acid sequence of either gene contained a signal sequence and an additional polypeptide sequence ('pro' sequence) preceding the mature protein. Based on DNA sequence, the start point of translation has been identified as amino acid residue - 107 for apr[BamP] and -221 for npr[BamP]. To demonstrate that the start point of translation of apr[BamP] in vivo is probably at codon -107, codon -103 (AAA) was changed to an ochre (TAA) by site-directed mutagenesis. Alkaline protease was produced from this ochre mutant derivative of apr[BamP] only when the host strain was Su+. The presence of a pro sequence may be common to all of the secreted proteases from bacilli.
A fault-tolerant sensory diagnostic system for intelligent vehicle application (2002)

A properly designed automotive sensor monitoring and diagnostic system must be capable of detecting and distinguishing sensor and component malfunctions in the presence of signal noise, varying vehicle operating conditions and multiple faults. The technique presented in this paper addresses these objectives through the implementation of a multivariate state estimation algorithm based upon pattern recognition methodology coupled with a statistically-based hypothesis test. Utilizing a residual signal vector generated from the difference between the estimated and measured current states of a system, disturbances are detected and identified with statistical hypothesis testing. Since the hypothesis testing utilizes the inherent noise on the signals to obtain a conclusion and the state estimation algorithm requires only a majority of the sensors to be functioning to ascertain the current state, this technique has proven to be quite robust and fault-tolerant. Several examples of its application are presented.
Stereocontrolled Synthesis of Piperidine-Condensed Tricyclic Carbapenems (5-Azatrinems) and Their Antibacterial Activities. (2000)

Stereocontrolled synthesis of tricyclic carbapenem (5-azatrinem) derivatives 4, in which a piperidine ring is condensed to the carbapenem skeleton, was achieved. The pivotal tricyclic intermediate 2, allyl (8S,9R,10S)-5-(tert-butoxycarbonyl)-10-(R)-1-(tert-butyldimethylsilyl oxy)ethyl]-11-oxo-1,5-diazatricyclo[7.2.0.0(3,8)]undec-2- ene-2-carboxylate, was synthesized starting from an acetoxyazetidinone chiron 6 in a practical manner based on a C-C bond formation reaction between 6 and piperidinone-ester 5, palladium-catalyzed de(allyloxy)carbonylation of 7b and Wittig-type cyclization via an oxalimide 9. Selective deprotection of the N-Boc group of 2 was found to proceed smoothly by treatment with trimethylsilyl trifluoromethanesulfonate and 2,6-lutidine to give the amino compound 3, whose functionalization on the nitrogen atom to derivatives 10 followed by deprotection led to various 5-azatrinem acids 4. These compounds showed potent in vitro activities against gram-positive and gram-negative bacteria.
Reconstitutively active G protein-coupled receptors purified from baculovirus-infected insect cells. (1991)

The turkey beta-adrenergic receptor (beta-AR), the m1 and m2 forms of the human muscarinic cholingeric receptor (MAChR) and several other mutant and wild-type G protein-coupled receptors were produced in insect Sf9 cells by infection with recombinant baculoviruses. Maximal expression for most receptors was 5-30 pmol receptor/mg protein (2-15 nmol/liter culture). The receptors displayed typical ligand binding characteristics. The beta-AR was glycosylated; electrophoretic behavior of the two MAChRs also suggested glycosylation. The beta-AR stimulated endogenous adenylyl cyclase in response to beta-adrenergic agonists. The beta-AR and both MAChRs were purified and coreconstituted with various purified G proteins in phospholipid vesicles. The recombinant beta-AR catalyzed the agonist-dependent activation of Gs by guanosine 5'-O-(thiotriphosphate) (GTP gamma S) with the same efficiency as did the natural beta-AR. The m2 MAChR efficiently catalyzed GTP gamma S binding to Go and to the recently identified G protein Gz (Gx). The m2 MAChR also catalyzed the activation of Gj,1 and Gj,3 weakly. Activation of these same G proteins by the ml MAChR was much less efficient, consistent with its known selectivity for pertussis toxin-insensitive G proteins ("Gp") that have not yet been isolated. The beta-AR and m2 MAChR were characteristically stimulated by reduction of disulfides. These results demonstrate the general utility of the baculovirus system for production of large quantities of native G protein-coupled receptors.
AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress (2003)

AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that is regulated by hypoxia and other cellular stresses that result in diminished cellular ATP levels. Here, we investigated whether AMPK signaling in endothelial cells has a role in regulating angiogenesis. Hypoxia induced the activating phosphorylation of AMPK in human umbilical vein endothelial cells (HUVECs), and AMPK activation was required for the maintenance of pro-angiogenic Akt signaling under these conditions. Suppression of AMPK signaling inhibited both HUVEC migration to VEGF and in vitro differentiation into tube-like structures in hypoxic, but not normoxic cultures. Dominant-negative AMPK also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. These data identify AMPK signaling as a new regulator of angiogenesis that is specifically required for endothelial cell migration and differentiation under conditions of hypoxia. As such, endothelial AMPK signaling may be a critical determinant of blood vessel recruitment to tissues that are subjected to ischemic stress.