gebhart/patrepeval huggingface dataset:
Strategies in In Vivo Molecular Imaging (2000)

After completing this article, readers should be able to: 

1. Describe the emerging field of in vivo molecular imaging.

2. List the various imaging modalities that have been used to detect molecules and track cells in vivo and discuss the basic molecular strategies and principles.

3. Describe several of the selective events, such as binding, enzymatic activation, or molecular switches, that make in vivo imaging of cells and molecules possible.

4. Delineate the strengths and weakness of current imaging strategies.

5. List combined imaging modalities and their use in molecular imaging.

Following cells and molecules in vivo has been a fundamental difficulty in biomedical research. The technologies in the field of in vivo molecular imaging are aimed at obtaining spatiotemporal information about in vivo processes as they occur; that is, monitoring cellular and molecular changes in response to a variety of stimuli in intact animals and eventually in humans. Understanding basic biologic and biochemical mechanisms is required to develop the tools that will enable access to this information.

Traditional imaging modalities largely depend on physical parameters, such as absorption in ultrasonography, x-ray attenuation, or optical scattering, which reveal primarily structural information. For molecular imaging, unique signatures are generated using molecular biology methods that distinctly label host cells, microbial pathogens, tumor cells, or transplanted tissues. These can be detected in vivo by conventional and novel imaging modalities and can be used to examine molecular mechanisms of pathogenesis, facilitate earlier disease detection, and permit evaluation of therapeutic outcomes. The molecular targets for imaging may include DNA, RNA, protein, or protein function. Imaging of inherent levels of DNA, RNA, and protein is difficult, but protein function can be exploited readily for imaging and can be used in reporter gene approaches to create surrogate markers for processes such as messenger RNA (mRNA) and protein synthesis.1,2, …
Phosphorylation of Ribosomal Protein S6 Is Inhibitory for Autophagy in Isolated Rat Hepatocytes (1995)

In rat hepatocytes, autophagy is known to be inhibited by amino acids. Insulin and cell swelling promote inhibition by amino acids. Each of the conditions leading to inhibition of autophagic proteolysis was found to be associated with phosphorylation of a 31-kDa protein that we identified as ribosomal protein S6. A combination of leucine, tyrosine, and phenylalanine, which efficiently inhibits autophagic proteolysis, was particularly effective in stimulating S6 phosphorylation. The relationship between the percentage inhibition of proteolysis and the degree of S6 phosphorylation was linear. Thus, inhibition of autophagy and phosphorylation of S6 are under the control of the same signal transduction pathway. Stimulation of S6 phosphorylation by the presence of amino acids was due to activation of S6 kinase and not to inhibition of S6 phosphatase. The inhibition by amino acids of both autophagic proteolysis and autophagic sequestration of electro-injected cytosolic [14C]sucrose was partially prevented by rapamycin, a compound known to inhibit activation of p70 S6 kinase. In addition, rapamycin partially inhibited the rate of protein synthesis. We conclude that the fluxes through the autophagic and protein synthetic pathways are regulated in an opposite manner by the degree to which S6 is phosphorylated. Possible mechanisms by which S6 phosphorylation can cause inhibition of autophagy are discussed.
A deep-coverage tomato BAC library and prospects toward development of an STC framework for genome sequencing. (2000)

Recently a new strategy using BAC end sequences as sequence-tagged connectors (STCs) was proposed for whole-genome sequencing projects. In this study, we present the construction and detailed characterization of a 15.0 haploid genome equivalent BAC library for the cultivated tomato, Lycopersicon esculentum cv. Heinz 1706. The library contains 129,024 clones with an average insert size of 117.5 kb and a chloroplast content of 1.11%. BAC end sequences from 1490 ends were generated and analyzed as a preliminary evaluation for using this library to develop an STC framework to sequence the tomato genome. A total of 1205 BAC end sequences (80.9%) were obtained, with an average length of 360 high-quality bases, and were searched against the GenBank database. Using a cutoff expectation value of <10(-6), and combining the results from BLASTN, BLASTX, and TBLASTX searches, 24.3% of the BAC end sequences were similar to known sequences, of which almost half (48.7%) share sequence similarities to retrotransposons and 7% to known genes. Some of the transposable element sequences were the first reported in tomato, such as sequences similar to maize transposon Activator (Ac) ORF and tobacco pararetrovirus-like sequences. Interestingly, there were no BAC end sequences similar to the highly repeated TGRI and TGRII elements. However, the majority (70.3%) of STCs did not share significant sequence similarities to any sequences in GenBank at either the DNA or predicted protein levels, indicating that a large portion of the tomato genome is still unknown. Our data demonstrate that this BAC library is suitable for developing an STC database to sequence the tomato genome. The advantages of developing an STC framework for whole-genome sequencing of tomato are discussed.
A model for the tertiary structure of the 28 residue DNA-binding motif (‘zinc finger’) common to many eukaryotic transcriptional regulatory proteins (1988)

Many eukaryotic transcriptional activator proteins, including the Xenopus 5S RNA gene activator protein TFIIIA and the HeLa cell protein Sp1, have an approximately 30 amino acid repeating motif which binds to short, specific DNA sequences. Over 150 of these sequences are now known. Based on the observed distribution of amino acid residues, a series of constraints and predictions can be proposed for the structure of the motif. A compatible three-dimensional structural model has been developed by a combination of interactive model building and refinement by molecular dynamics. The model structure consists of a two-stranded beta-hairpin stabilizing a C-terminal alpha-helix by both zinc ligands and hydrophobic interactions. Four of the residue positions on the helix N-terminus and exposed face are predicted to provide base specific ligands. Further implications of the model for DNA binding are discussed.
Migratory neighbors and distant invaders: tumor-associated niche cells (2008)

The cancer environment is comprised of tumor cells as well as a wide network of stromal and vascular cells participating in the cellular and molecular events necessary for invasion and metastasis. Tumor secretory factors can activate the migration of host cells, both near to and far from the primary tumor site, as well as promote the exodus of cells to distant tissues. Thus, the migration of stromal cells and tumor cells among specialized microenvironments takes place throughout tumor and metastatic progression, providing evidence for the systemic nature of a malignancy. Investigations of the tumor-stromal and stromal-stromal cross-talk involved in cellular migration in cancer may lead to the design of novel therapeutic strategies.
Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis. (1997)

These data support previous research with dietary questionnaire methodology, suggesting that specific dietary fatty acids may be associated with breast cancer promotion. Further research with long-term clinical follow-up is necessary to investigate these observations in large, diverse populations before dietary recommendations can be envisioned.
Growth factors in the extracellular matrix (1997)

Much recent research has focused on the study of the expression of growth factor genes and on the identification of growth factor signaling mechanisms inside cells. However, growth factor signaling can also be regulated outside of cells by extracellular matrix proteins and proteolytic enzymes. The ability of extracellular proteins to process complex information in the absence of new protein synthesis is illustrated in blood clotting and complement pathways. An increasing number of growth factors, including IGFs, FGFs, TGF-beta's, and HGF, have been found to associate with the extracellular matrix proteins or with heparan sulfate. Rapid and localized changes in the activity of these factors can be induced by release from matrix storage and/or by activation of latent forms. These growth factors, in turn, control cell proliferation, differentiation, and synthesis and remodeling of the extracellular matrix. It is therefore likely that much of the information processing necessary for construction of complex multicellular organisms occurs in the extracellular environment. This suggests that extracellular matrix plays a major role in the control of growth factor signaling.
Ubiquitin carboxyl‐terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases (1990)

The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases. Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity in cortical Lewy bodies, neurofibrillary tangles, Rosenthal fibres, Pick bodies, spinal inclusions in motor neurone disease, and Mallory's hyaline in alcoholic liver disease were immunostained to localize PGP 9.5. The majority of cortical Lewy bodies in diffuse Lewy body disease showed immunoreactivity for PGP 9.5. In Alzheimer's disease, only a minority of loosely arranged globose-type neurofibrillary tangles were immunostained together with a minority of neurites surrounding senile plaques. In cerebellar astrocytomas, the periphery of the majority of Rosenthal fibers was immunostained in addition to strong diffuse cytoplasmic immunostaining in some astrocytes lacking apparent Rosenthal fibers. In Pick's disease, there was no immunostaining of inclusions but there was intense immunostaining of swollen Pick cells. No spinal inclusions in motor neurone disease were stained; however, anterior horn neurones appear to show increased levels of PGP 9.5 compared with those from control cases. No immunostaining of hepatic Mallory's hyaline was demonstrable, which accords with suggestions that PGP 9.5 is a tissue-specific ubiquitin C-terminal hydrolase isoenzyme. The differential detection of a ubiquitin C-terminal hydrolase in different forms of ubiquitinated inclusion body in the nervous system may form the basis of a method for assessment of the staging of inclusion body biogenesis and give insight into the dynamics of inclusion body formation.(ABSTRACT TRUNCATED AT 250 WORDS)
138. The search for chemotherapeutic amidines. Part X. Substituted 4 : 4′-diamidino-αω-diphenoxyalkanes and -diphenyl ethers (1949)

S. S. Berg and G. Newbery, J. Chem. Soc., 1949, 642 DOI: 10.1039/JR9490000642
One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial (2004)

Estradiol 2 mg and promegestone 0.5 mg per day is an effective and safe add-back therapy, which can be proposed for prolonged leuprorelin treatment over 6 months in severe endometriosis.
Selective One-Electron and Two-Electron Reduction of C60 with NADH and NAD Dimer Analogues via Photoinduced Electron Transfer (1998)

The selective one-electron reduction of C60 to C60•- is attained through photoinduced electron transfer from an NADH analogue, 1-benzyl-1,4-dihydronicotinamide (BNAH), and the dimer analogue [(BNA)2] to the triplet excited state of C60. The limiting quantum yield for formation of C60•- in the case of (BNA)2 exceeds unity; Φ∞ = 1.3. In this case, the initial electron transfer from (BNA)2 to the triplet excited state (3C60*) is followed by fast C−C bond cleavage in the resulting (BNA)2•+ to give BNA• and BNA+ and the second electron transfer from BNA• to C60 yields BNA+ and C60•-, when (BNA)2 acts as a two-electron donor to produce 2 equiv of C60•-. When BNAH is replaced by 4-tert-butylated BNAH (t-BuBNAH), the photochemical reaction with C60 yields not C60•- but instead the tert-butylated anion (t-BuC60-) selectively. In this case, the initial electron transfer from t-BuBNAH to 3C60* is also followed by fast C−C bond cleavage in t-BuBNAH•+ to give t-Bu•, which is coupled with C60•- produced in the electron transfer to yield t-BuC60-. The selective two-electron reduction of C60 to 1,2-dihydro[60]fullerene (1,2-C60H2) is also attained with the use of another NADH analogue, 10-methyl-9,10-dihydroacridine (AcrH2), under visible light irradiation in deaerated benzonitrile solution containing trifluoroacetic acid. The studies on the quantum yields, the kinetic deuterium isotope effects, and the quenching of the triplet−triplet absorption of C60 by AcrH2 have revealed that the photochemical reduction proceeds via photoinduced electron transfer from 10-methyl-9,10-dihydroacridine to the triplet excited state of C60, which is followed by proton transfer from AcrH2•+ to C60•- and a second electron transfer from the deprotonated acridinyl radical (AcrH•) to C60H• in the presence of trifluoroacetic acid to yield the final products 10-methylacridinium ion (AcrH+) and 1,2-C60H2. The transient spectra of the radical ion pair formed in the photoinduced electron transfer have been detected successfully in laser flash photolysis of each NADH analogue−C60 system. The mechanistic difference between the selective one- and two-electron reductions of C60 is discussed on the basis of the difference in the redox and acid−base properties of NADH and the dimer analogues.
Induction of Vascular Endothelial Growth Factor in Human Astrocytes by Lead (2000)

The mechanism(s) underlying lead neurotoxicity are not fully elucidated. cDNA expression microarray analysis identified lead-sensitive genes in immortalized human fetal astrocytes (SV-FHA). Of the represented genes expressed, vascular endothelial growth factor (VEGF) was one of the most sensitive. Lead induced VEGF mRNA 3-fold and VEGF protein approximately 2-fold with maximum mRNA induction following incubation with 10 micrometer lead acetate for 24 h. Phorbol 12-myristate 13-acetate (PMA), a potent protein kinase C (PKC) activator, increased VEGF mRNA 2-fold and PKC inhibition by GF-109203 completely blocked VEGF induction by lead. Expression of dominant-negative PKC-epsilon, but not PKC-alpha, completely inhibited VEGF mRNA induction by lead. Lead activated the transcription factor AP-1 and increased AP-1-dependent luciferase expression >2-fold. Transfection of cells with a c-jun dominant-negative effectively inhibited both AP-1 activation and VEGF mRNA induction by lead. Hypoxia-inducible factor 1 (HIF-1) activity in SV-FHAs was moderately increased by lead (86%) and PMA (96%). Pretreatment with GF-109203 completely inhibited these effects of lead and PMA. However, lead did not alter HIF-1-dependent luciferase expression and a HIF-1alpha dominant-negative had no effects on the induction of VEGF mRNA by lead. These findings indicate that lead induces VEGF expression in SV-FHAs via a PKC/AP-1-dependent and HIF-1-independent signaling pathway.
Molecular transport and flow past hard and soft surfaces: computer simulation of model systems (2011)

The equilibrium and flow of polymer films and drops past a surface are characterized by the interface and surface tensions, viscosity, slip length and hydrodynamic boundary position. These parameters of the continuum description are extracted from molecular simulations of coarse-grained models. Hard, corrugated substrates are modelled by a Lennard-Jones solid while polymer brushes are studied as prototypes of soft, deformable surfaces. Four observations are discussed. (i) If the surface becomes strongly attractive or is coated with a brush, the Navier boundary condition fails to describe the effect of the surface independently of the strength and type of the flow. This failure stems from the formation of a boundary layer with an effective, higher viscosity. (ii) In the case of brush-coated surfaces, flow induces a cyclic, tumbling motion of the tethered chain molecules. Their collective motion gives rise to an inversion of the flow in the vicinity of the grafting surfaces and leads to strong, non-Gaussian fluctuations of the molecular orientations. The flow past a polymer brush cannot be described by Brinkman's equation. (iii) The hydrodynamic boundary condition is an important parameter for predicting the motion of polymer droplets on a surface under the influence of an external force. Their steady-state velocity is dictated by a balance between the power that is provided by the external force and the dissipation. If there is slippage at the liquid-solid interface, the friction at the solid-liquid interface and the viscous dissipation of the flow inside the drop will be the dominant dissipation mechanisms; dissipation at the three-phase contact line appears to be less important on a hard surface. (iv) On a soft, deformable substrate like a polymer brush, we observe a lifting-up of the three-phase contact line. Controlling the grafting density and the incompatibility between the brush and the polymer liquid we can independently tune the softness of the surface and the contact angle and thereby identify the parameters for maximizing the deformation at the three-phase contact.
Computer modeling of ventricular rhythm during atrial fibrillation and ventricular pacing (2006)

We propose a unified atrial fibrillation (AF)-ventricular pacing (VP) (AF-VP) model to demonstrate the effects of VP on the ventricular rhythm during atrial fibrillation AF. In this model, the AV junction (AVJ) is treated as a lumped structure characterized by refractoriness and automaticity. Bombarded by random AF impulses, the AVJ can also be invaded by the VP-induced retrograde wave. The model includes bidirectional conduction delays in the AVJ and ventricle. Both refractory period and conduction delay of the AVJ are dependent upon its recovery time. The electrotonic modulation by blocked impulses is also considered in the model. Our simulations show that, with proper parameter settings, the present model can account for most principal statistical properties of the RR intervals during AF. We further demonstrate that the AV conduction property and the ventricular rate in AF depend on both AF rate and the degree of electrotonic modulation in the AVJ. Finally, we show that multilevel interactions between AF and VP can generate various patterns of ventricular rhythm that are consistent with previous experimental observations.
Molybdenum–strontium multilayer mirrors for the 8–12-nm extreme-ultraviolet wavelength region (2001)

Mo-Sr multilayer mirrors were successfully deposited by dc-magnetron sputtering and characterized in situ with synchrotron radiation. Normal-incidence (3.6 degrees ) reflectance of 23.0% at 8.8 nm, 40.8% at 9.4 nm, and 48.3% at 10.5 nm were measured before the samples were exposed to air. After exposure, as a result of the reactivity of Sr with oxygen and water vapor, the reflectance of these multilayers decreased rapidly. Attempts to use thin layers of C to passivate the surface of these Mo-Sr multilayers were unsuccessful.
Prolonged Operative Time Correlates with Increased Infection Rate after Total Knee Arthroplasty (2005)

Risk stratification has proven to be a useful tool in surgical site infection prevention. The duration of the surgical procedure has been recommended for use in surgical site infection (SSI) risk stratification (Infect Control Hosp Epidemiol 20:247-248, 1999). A retrospective analysis of 6489 patients who underwent total knee replacement (TKR) between 1993 and 1999 assessed the association between the duration of the surgical procedure and the risk of postoperative infection. One hundred thirteen infected patients were matched with 236 controls, and nominal variables were statistically processed. Patients without infections (n = 236) had surgery durations of 94 +/- 28 min, and patients with infection (n = 104) had durations of 127 +/- 45 min (p < 0.001). Operation time has positive correlations with weight (r = 0.3, p < 0.001), body mass index (r = 0.3, p < 0.001), and the total number of comorbidities (r = 0.2, p < 0.001; n = 340). The results confirm that the duration of the surgical procedure can be used as a risk predictor for SSI in TKR.
Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone–insulin‐like growth factor I axis in growth hormone–deficient children (2001)

Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH) secretagogue, stimulates GH release through a pituitary and hypothalamic receptor that is different from the GH-releasing hormone receptor. We evaluated the safety and tolerability and the GH-insulin-like growth factor (IGF) responses to two dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to 8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height < 10th percentile for age, and a maximum GH response of < or = 10 microg/L to two different GH stimulation tests. The children were assigned as follows to one of three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day 15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in groups I and II were studied first to assess safety at the low dose before advancement to the high dose. Hormonal profiles were evaluated on day -1 (baseline) and day 15, and the results were expressed as the change from baseline within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8 days (group III), the median increases (on day 15) from baseline were as follows: 3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3 microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to 116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum cortisol, and insulin concentrations or 24-hour urinary free cortisol after administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We conclude that short-term administration of ibutamoren mesylate can increase GH, IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound is applicable for testing its effect on growth velocity.
Nanoparticle-Cored Dendrimers:  Synthesis and Characterization (2003)

The synthesis and characterization of a group of new dendrimers-namely, nanoparticle-cored dendrimers (NCDs)-are described. These materials were obtained by the reduction of hydrogen tetrachloroaurate phase-transferred into toluene in the presence of Fréchet-type polyaryl ether dendritic disulfide wedges of generation 1-5. These materials, possessing nanometer-sized gold clusters at the core and dendritic wedges radially connected to the core by Au-S bonds, were analyzed by TEM and TGA, and by UV, IR, and NMR spectroscopies. The number of branching units connected to the core decreased with the generation of the dendritic wedge, and this number changed from 2.18/nm(2) for Au-G-2 to 0.27/nm(2) for Au-G-5. This result suggests that, in the higher-generation NCDs, a large fraction of the surface area of the metal cluster is not passivated and is therefore available for catalytic activity.