gebhart/patrepeval huggingface dataset:
Cancer biomarker discovery: Opportunities and pitfalls in analytical methods (2011)

Many diseases result in specific and characteristic changes in the chemical and biochemical profiles of biological fluids and tissues prior to development of clinical symptoms. These changes are often useful diagnostic and prognostic biomarkers. Identifying biomarkers that can be used for the early detection of cancer will result in more efficient treatments, reduction in suffering, and lower mortality rates. An ideal screening test should be non-invasive with high sensitivity and specificity. Proteomic and metabolomic analyses of biological samples can reveal changes in abundance levels of metabolites and proteins that when validated and confirmed through clinical trials can function as clinical tests for early detection, diagnosis, monitoring disease progression, and predicting therapeutic response. While the past decade has seen great advancements in proteomics and metabolomics research producing potential biomarkers for cancer, most of the identified biomarkers have failed to replace existing clinical tests. To become a clinically approved test, a potential biomarker should be confirmed and validated using hundreds of specimens and should be reproducible, specific, and sensitive. A search of the scientific and medical literature indicates that many studies report the discovery of potential biomarkers without proper validation and/or they do not meet the above criteria. In this manuscript, we will discuss the successes and the pitfalls of biomarker research and comment on study and experimental design, which in most cases is lacking, resulting in suboptimal biomarkers.
The magnetosome membrane protein, MmsF, is a major regulator of magnetite biomineralization in <i>Magnetospirillum magneticum</i> AMB‐1 (2012)

Magnetotactic bacteria (MTB) use magnetosomes, membrane-bound crystals of magnetite or greigite, for navigation along geomagnetic fields. In Magnetospirillum magneticum sp. AMB-1, and other MTB, a magnetosome gene island (MAI) is essential for every step of magnetosome formation. An 8-gene region of the MAI encodes several factors implicated in control of crystal size and morphology in previous genetic and proteomic studies. We show that these factors play a minor role in magnetite biomineralization in vivo. In contrast, MmsF, a previously uncharacterized magnetosome membrane protein encoded within the same region plays a dominant role in defining crystal size and morphology and is sufficient for restoring magnetite synthesis in the absence of the other major biomineralization candidates. In addition, we show that the 18 genes of the mamAB gene cluster of the MAI are sufficient for the formation of an immature magnetosome organelle. Addition of MmsF to these 18 genes leads to a significant enhancement of magnetite biomineralization and an increase in the cellular magnetic response. These results define a new biomineralization protein and lay down the foundation for the design of autonomous gene cassettes for the transfer of the magnetic phenotype in other bacteria.
High capacitance density metal-insulator-metal structure based on Al2O3–HfTiO nanolaminate stacks (2007)

The authors describe metal-insulator-metal (MIM) capacitors comprising a five layer Al2O3–HfTiO nanolaminate stack with a total thickness of ∼29nm. At room temperature they demonstrate a capacitance density of ∼14fF∕μm2, a leakage current density of ∼1×10−6A∕cm2 at 1V, a temperature capacitance coefficient of 380ppm∕°C as well as corresponding linear and quadratic voltage coefficients of 350ppm∕V and 570ppm∕V2, respectively. They compare the structure to a MIM capacitor having a uniform HfTiO insulator film. That device exhibits a larger capacitance density (∼28fF∕μm2) but its electrical properties are found to be poorer than those of the structures utilizing the nanolaminate stack.
Photonic surface-wave excitation: photonic crystal–metal interface (2003)

We demonstrate the existence of electromagnetic surface modes and surface plasma waves in the interface of a one-dimensional photonic crystal and a metal. These modes can exist in the region in which bandgaps of the photonic crystal overlap and in the region below the plasma frequency of a metal in the frequency wave-vector space. An analytic dispersion relation to determine the existence of these electromagnetic surface modes is obtained, and it is shown that these modes can be excited and observed without prism or grating configurations even under normal incidence from vacuum.
Synthesis and Properties of Dithieno-Fused 1,4-Azaborine Derivatives (2018)

The first synthesis of dithieno[3,2- b:2',3'- e][1,4]azaborinine (DTAB) derivatives has been achieved by Buchwald-Hartwig coupling and subsequent Friedel-Crafts-type C-H borylation. A facile method for further π-extension of DTAB was also developed via stannylation and subsequent Kosugi-Migita-Stille cross-coupling reaction. The fundamental properties of DTAB derivatives were also investigated.
A High Power Density Intermediate‐Temperature Solid Oxide Fuel Cell with Thin (La<sub>0.9</sub>Sr<sub>0.1</sub>)<sub>0.98</sub>(Ga<sub>0.8</sub>Mg<sub>0.2</sub>)O<sub>3‐δ</sub> Electrolyte and Nano‐Scale Anode (2014)

Solid oxide fuel cells (SOFCs) with thin (La 0.9 Sr 0.1 ) 0.98 Ga 0.8 Mg 0.2 O 3‐δ (LSGM) electrolytes are primary candidates for achieving high (> 1 W cm ‐2 ) power density at intermediate (< 650 °C) temperatures. Although high power density LSGM‐electrolyte SOFCs have been reported, it is still necessary to develop a fabrication process suitable for large‐scale manufacturing and to minimize the amount of LSGM used. Here we show that SOFCs made with a novel processing method and a Sr 0.8 La 0.2 TiO 3‐ α (SLT) oxide support can achieve high power density at intermediate temperature. The SLT support is advantageous, especially compared to LSGM supports, because of its low materials cost, electronic conductivity, and good mechanical strength. The novel process is to first co‐fire the ceramic layers – porous SLT support, porous LSGM layer, and dense LSGM layer – followed by infiltration of nano‐scale Ni into the porous layers. Low polarization resistance of 0.188 Ωcm 2 was achieved at 650 °C for a cell with an optimized anode functional layer (AFL) and an (La,Sr)(Fe,Co)O 3 cathode. Maximum power density reached 1.12 W cm −2 at 650 °C, limited primarily by cathode polarization and ohmic resistances, so there is considerable potential to further improve the power density.
Lateral whiplash (1968)

<h3>To the Editor:—</h3> I have read with pleasure the story of Castleton Medical College (<b>204</b>:698,1968). As you probably know the medical college at Woodstock, Vt, like that at Castleton, contributed much to the life of Vermont and New England. The memory of these institutions ought to be kept alive. These two medical colleges sent comparatively well-trained physicians out into the state to care, as best they could, for the people. I sometimes wonder whether one can say as much for most of our modern American medical schools! I hope that a goodly number of people will be stimulated by your article to contribute money to save the chapel.
Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex (2011)

The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.
Two Pathways for Base Excision Repair in Mammalian Cells (1996)

Abasic sites (apurinic/apyrimidinic, AP sites) are the most common DNA lesions generated by both spontaneous and induced base loss. In a previous study we have shown that circular plasmid molecules containing multiple AP sites are efficiently repaired by Chinese hamster extracts in an in vitro repair assay. An average patch size of 6.6 nucleotides for a single AP site was calculated. To define the exact repair patch, a circular DNA duplex with a single AP site was constructed. The repair synthesis carried out by hamster and human cell extracts was characterized by restriction endonuclease analysis of the area containing the lesion. The results indicate that, besides the repair events involving the incorporation of a single nucleotide at the lesion site, repair synthesis occurred also 3' to the AP site and involved a repair patch of approximately 7 nucleotides. This alternative repair pathway was completely inhibited by the presence in the repair reaction of a polyclonal antibody raised against human proliferating cell nuclear antigen. These data give the first evidence that mammalian cell extracts repair natural AP sites by two distinct pathways: a single nucleotide gap filling reaction targeted at the AP site and a proliferating cell nuclear antigen-dependent pathway that removes a short oligonucleotide containing the abasic site and 3'-flanking nucleotides.
Kinetic study of interaction between BRL 42715, beta-lactamases, and D-alanyl-D-alanine peptidases (1995)

A detailed kinetic study of the interactions between BRL 42715, a beta-lactamase-inhibiting penem, and various beta-lactamases (EC 3.5.2.6) and D-alanyl-D-alanine peptidases (DD-peptidases, EC 3.4.16.4) is presented. The compound was a very efficient inactivator of all active-site serine beta-lactamases but was hydrolyzed by the class B, Zn(2+)-containing enzymes, with very different kcat values. Inactivation of the Streptomyces sp. strain R61 extracellular DD-peptidase was not observed, and the Actinomadura sp. strain R39 DD-peptidase exhibited a low level of sensitivity to the compound.
Effect of Poloxamer 407 on the Adherence of Pseudomonas aeruginosa to Corneal Epithelial Cells (1995)

The effect of poloxamer 407 on Pseudomonas aeruginosa adherence to cultured epithelial cells from rabbit corneas was investigated. Three methods of bacterial quantification were used to assess P. aeruginosa adherence: scanning electron microscopy (SEM) counts, radioactivity counts, and viable bacteria counts. Confluent monolayers of rabbit corneal epithelial cells were incubated in agitation for 30 min at room temperature with H3-labeled or nonradiolabeled P. aeruginosa (10(10) bacteria/ml) in a solution of poloxamer 407 [2% or 4% in phosphate-buffered saline (PBS)] or PBS as control. Cell monolayers were washed to remove nonadherent bacteria and fixed with 2.5% glutaraldehyde and processed for SEM or processed for radioactivity counting or for culture on agar plates. The results showed that both solutions of poloxamer 407 inhibited approximately 75% of the bacterial adherence to epithelial cells (p < 0.05). Similar percentages of bacterial inhibition were obtained using the three methods of bacterial quantification. The use of an antiadherent agent such as poloxamer 407 in eye drops could possibly be a prophylactic approach to P. aeruginosa keratitis.
Effects of <i>Helminthosporium maydis</i> Race T Toxin on Electron Transport in Susceptible Corn Mitochondria and Prevention of Toxin Actions by Dicyclohexylcarbodiimide (1989)

The effect of Helminthosporium maydis race T toxin on electron transport in susceptible cytoplasmic male-sterile Texas corn (Zea mays L.) mitochondria was investigated, using dichlorophenol indophenol and ferricyanide as electron acceptors. Succinate-dependent electron transport was stimulated by the toxin, consistent with the well described increase in membrane permeability induced by the toxin. Malate-dependent electron transport was inhibited. This inhibition of electron transport increased as a function of time of exposure to the toxin. Mitochondria from normal-fertile (N) corn were not affected by the toxin. Both the inhibition of electron transport and the increase in ion permeability, such as dissipation of membrane potential and Ca(2+) gradients, induced by the toxin in T corn was prevented by N,N'-dicyclohexylcarbodiimide, a hydrophobic carbodiimide. A water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, was ineffective in preventing dissipation of membrane potential by the toxin. These results suggest that the various toxin actions are mediated via interaction of the toxin with one target site, most probably a 13 kilodalton polypeptide unique to T mitochondria. N,N'-dicyclohexylcarbodiimide may confer protection by modifying an amino acid residue in a hydrophobic portion of the target site.
Justified lives: morality & narrative in the films of Sam Peckinpah (1994)

In first book critically examine each of fourteen feature films Sam Peckinpah directed during his career, Michael Bliss stresses persistent moral structural elements that permeate Peckinpah s work.By examining films in great detail, Bliss makes clear moral framework of temptation redemption which Peckinpah was concerned while revealing director s attention narrative. Bliss shows that each of Peckinpah s protagonists is involved attempting, in words of Ride the High Country s Steve Judd, to enter my house justified.The validity of this systematic method is clearly demonstrated in chapter devoted Wild Bunch. By enumerating doublings triplings of action dialogue found in film, Bliss underscores its symbolic structural complexity. Beginning chapters treating Junior Bonner and Getaway with analyses of their important title sequences, Bliss shows how these frequently disregarded pieces present in miniature major moral narrative concerns of films. In his chapter on Osterman Weekend, Bliss makes apparent Peckinpahs awareness of concern self-reflexive nature of filmmaking itself.Bliss shows that like John Ford, Peckinpah moved from optimism pessimism. The films of director s early period, from Deadly Companions to Cable Hogue, support romantic ideals of adventure camaraderie affirm a potential for goodness in America. In his second group of films, which begins Straw Dogs ends Bring Me Head of Alfredo Garcia, both heroes hope have vanished. It is only in Osterman Weekend that Peckinpah appears finally have renewed his capacity for hope, allowing his career close in a positive way.
Formation of Neutral and Cationic Methyl Derivatives of Titanium Containing Cyclopentadienyl and Aryloxide Ancillary Ligation (2004)

The series of dimethyltitanium compounds [CpTi(OAr)Me2], ligated by one cyclopentadienyl (Cp) and one 2,6-disubstituted aryloxide (OAr), have been prepared by the reaction of [CpTi(OAr)Cl2] with 2 equiv of LiMe or by the addition of parent phenol (HOAr) to a cold ether solution of [CpTiMe3]. The compounds are stable, except for those containing less bulky o-methyl substituents; the compounds [CpTi(OC6H2Me2-2,6-X-4)Me2] (X = H (19), Br (20)) undergo ligand exchange to produce [CpTi(OC6H2Me2-2,6-X-4)2Me] (X = H (22), Br (23)) and [CpTiMe3]. X-ray crystal structures have been obtained for the dimethyl compounds [CpTi(OC6H2Np-2-But2-4,6)Me2] (13), [CpTi(OC6H2{C10H9}-2-But2-4,6)Me2] (14), [Cp*Ti(OC6HPh2-2,6-But2-3,5)Me2] (15), [CpTi(OC6Ph4-2,3,5,6-Br-4)Me2] (18), [CpTi(OC6H2Me2-2,6-Br-4)Me2] (20), [CpTi(OC6H3Pri2-2,6)Me2] (21), and the monomethyl species 23. Reaction of the dimethyl compounds with [B(C6F5)3] generates the corresponding cationic methyl species [CpTi(OAr)Me][MeB(C6F5)3]. The compound [CpTi(OC6HPh4-2,3,5,6)Me][MeB(C6F5)3] (27) was studied via solution VT-NMR spectroscopy, and the free energy of activation for methyl exchange was estimated to be 14.4(5) kcal mol-1 at 10 °C. These thermally unstable cationic derivatives readily eliminate methane at room temperature, affording compounds of the type [CpTi(OAr)(C6F5){CH2B(C6F5)2}]. A kinetic study of the conversion of 27 to [CpTi(OC6HPh4-2,3,5,6)(C6F5){CH2B(C6F5)2}] (31) was undertaken. Toluene-d8 solutions of 27 were found to cleanly convert to 31 and methane, as monitored by 1H NMR spectroscopy. A first-order rate constant of [7.6(2)] × 10-4 s-1 was measured at 25.0(5) °C. The solid-state structure of [CpTi(OC6HPh2-2,6-Me2-3,5)(C6F5)(CH2B{C6F5}2)] (28) confirms this formulation and reveals a trigonal-planar boron atom exhibiting no interaction with the adjacent Ti−C6F5 unit.
Identification of Ganglioside GM3 Molecular Species in Human Serum Associated with Risk Factors of Metabolic Syndrome (2015)

Serum GM3 molecular species were quantified in 125 Japanese residents using tandem mass spectrometry multiple reaction monitoring. Individuals were categorized by the presence or absence of metabolic disease risk factors including visceral fat accumulation, hyperglycemia and dyslipidemia. A total of 23 GM3 molecular species were measured, of these, eight were found to be significantly elevated in individuals with visceral fat accumulation and metabolic disease, defined as the presence of hyperglycemia and dyslipidemia. All of the GM3 molecular species were composed of the sphingoid base sphingosine (d18:1 (Δ4)) and, interestingly, six of the eight elevated GM3 molecular species contained a hydroxylated ceramide moiety. The hydroxylated GM3 species were, in order of decreasing abundance, d18:1-h24:0 ≈ d18:1-h24:1 > d18:1-h22:0 » d18:1-h20:0 > d18:1-h21:0 > d18:1-h18:1. Univariate and multiple linear regression analyses were conducted using a number of clinical health variables associated with obesity, type 2 diabetes, metabolic disease, atherosclerosis and hypertension. GM3(d18:1-h24:1) was identified as the best candidate for metabolic screening, proving to be significantly correlated with intima-media thickness, used for the detection of atherosclerotic disease in humans, and a number of metabolic disease risk factors including autotaxin, LDL-c and homeostatic model assessment insulin resistance (HOMA-IR).
Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial (2008)

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, doubleblind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score <or= -2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p <or= 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.
Dopamine D3 receptor‐preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal‐regulated kinase phosphorylation (2008)

Clinical improvements in Parkinson's disease produced by dopamine D3 receptor-preferring agonists have been related to their neuroprotective actions and, more recently, to their neuroregenerative properties. However, it is unclear whether dopamine agonists produce their neurotrophic effects by acting directly on receptors expressed by the mesencephalic dopaminergic neurons or indirectly on receptors expressed by astrocytes, via release of neurotrophic factors. In this study, we investigated the effects of the dopamine D3 receptor-preferring agonists quinpirole and 7-hydroxy-N,N-di-propyl-2-aminotetralin (7-OH-DPAT), as well as of the indirect agonist amphetamine, on dopaminergic neurons identified by tyrosine hydroxylase immunoreactivity (TH-IR). Experiments were performed on neuronal-enriched primary cultures containing less than 0.5% of astrocytes prepared from the mouse embryo mesencephalon. After 3 days of incubation, both quinpirole (1-10 microm) and 7-OH-DPAT (5-500 nm) dose-dependently increased the maximal dendrite length (P < 0.001), number of primary dendrites (P < 0.01) and [3H]dopamine uptake (P < 0.01) of TH-IR-positive mesencephalic neurons. Similar effects were observed with 10 microm amphetamine. All neurotrophic effects were blocked by the unselective D2/D3 receptor antagonist sulpiride (5 microm) and by the selective D3 receptor antagonist SB-277011-A at a low dose (50 nm). Quinpirole and 7-OH-DPAT also increased the phosphorylation of extracellular signal-regulated kinase (ERK) within minutes, an effect blocked by pretreatment with SB-277011-A. Inhibition of the D2/D3 receptor signalling pathway to ERK was obtained with PD98059, GF109203 or LY294002, resulting in blockade of neurotrophic effects. These data suggest that dopamine agonists increase dendritic arborizations of mesencephalic dopaminergic neurons via a direct effect on D2/D3 receptors, preferentially involving D3 receptor-dependent neurotransmission.
Electromagnetic energy exposure of simulated users of portable cellular telephones (1995)

Describes a method to quantify the RF exposure of the users of portable cellular phones in terms of specific absorption rate (SAR). The method involves a robotic system to accurately position an isotropic E-field probe within equivalent biological tissue. The user of cellular phones is simulated by a simple human model (a phantom) consisting of a thin shell of fibreglass filled with a liquid having the complex dielectric constant of human brain tissue. The authors present the results of the dosimetric assays conducted using current and previous models of cellular telephones. The peak SAR values detected using the measurement method described are below the limits recommended by the National Council for Radiation Protection and Measurements (NCRP) Report 86 for the protection of humans exposed to RF electromagnetic energy.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>