gebhart/patrepeval huggingface dataset:
Induced Fit Conformational Changes of a “Reversed Amidine” Heterocycle:  Optimized Interactions in a DNA Minor Groove Complex (2007)

To better understand the molecular basis for recognition of the DNA minor groove by heterocyclic cations, a series of "reversed amidine" substituted heterocycles has been prepared. Amidine derivatives for targeting the minor groove have the amidine carbon linked to a central heterocyclic system, whereas in the reverse orientation, an amidine nitrogen provides the link. The reverse system has a larger dihedral angle as well as a modified spatial relationship with the groove relative to amidines. Because of the large dihedral, the reversed amidines should have reduced binding to DNA relative to similar amidines. Such a reduction is observed in footprinting, circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetric (ITC) experiments with DB613, which has a central phenyl-furan-phenyl heterocyclic system. The reduction is not seen when a pyrrole (DB884) is substituted for the furan. Analysis of a number of derivatives defines the pyrrole and a terminal phenyl substituent on the reversed amidine groups as critical components in the strong binding of DB884. ITC and SPR comparisons showed that the better binding of DB884 was due to a more favorable binding enthalpy and that it had exceptionally slow dissociation from DNA. Crystallographic analysis of DB884 bound to an AATT site shows that the compound was bound in the minor groove in a 1:1 complex as suggested by CD solution studies. Surprisingly, unlike the amidine derivative, the pyrrole -NH of DB884 formed an H-bond with a central T of the AATT site and this accounts for the enthalpy-driven strong binding. The structural results and molecular modeling studies provide an explanation for the differences in binding affinities for related amidine and reversed amidine analogues.
Optical Frequency Synthesizer for Precision Spectroscopy (2000)

We have used the frequency comb generated by a femtosecond mode-locked laser and broadened to more than an optical octave in a photonic crystal fiber to realize a frequency chain that links a 10 MHz radio frequency reference phase-coherently in one step to the optical region. By comparison with a similar frequency chain we set an upper limit for the uncertainty of this new approach to 5. 1x10(-16). This opens the door for measurement and synthesis of virtually any optical frequency and is ready to revolutionize frequency metrology.
[A method based on independent component analysis for processing fMRI data]. (2002)

Independent component analysis (ICA) is a new technique in statistical signal processing to extract independent components from multidimensional measurements of mixed signals. In this paper, for the processing of functional magnetic resonance imaging(fMRI) data, two signals of near voxels are used as the mixed signals and are separated by ICA. The correlation coefficients between the reference signal and the separated signals are calculated and those voxels whose correlation coefficients are greater than a threshold are considered to be the activated voxels by the stimulation, and so the functional localization of the stimulation is completed. The validity of the method was primarily proved by trial of real brain functional magnetic resonance imaging data.
Synthesis of a NovelC2-Symmetric Thiourea and Its Application in the Pd-Catalyzed Cross-Coupling Reactions with Arenediazonium Salts under Aerobic Conditions (2003)

[reaction: see text] A novel thiourea-based C2-symmetric ligand was synthesized, and its application in the palladium-catalyzed Heck and Suzuki coupling reactions of arenediazonium salts was evaluated. The reactions, which were performed at room temperature, without added base, and under aerobic conditions, produced product in 4 h with good yield. The corresponding arenediazonium salts were easily generated in one step from anilines.
A Defined Methodology for Reliable Quantification of Western Blot Data (2013)

Chemiluminescent western blotting has been in common practice for over three decades, but its use as a quantitative method for measuring the relative expression of the target proteins is still debatable. This is mainly due to the various steps, techniques, reagents, and detection methods that are used to obtain the associated data. In order to have confidence in densitometric data from western blots, researchers should be able to demonstrate statistically significant fold differences in protein expression. This entails a necessary evolution of the procedures, controls, and the analysis methods. We describe a methodology to obtain reliable quantitative data from chemiluminescent western blots using standardization procedures coupled with the updated reagents and detection methods.
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2 (1999)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.
L-Cysteine Biosynthesis in Escherichia coli: Nucleotide Sequence and Expression of the Serine Acetyltransferase (cysE) Gene from the Wild-type and a Cysteine-excreting Mutant (1987)

Serine acetyltransferase (SAT) from Escherichia coli is subject to feedback inhibition by L-cysteine. A mutant was isolated which excretes L-cysteine because of a lesion in cysE, the structural gene for SAT, rendering the enzyme less feedback sensitive. To analyse the structural basis for this mutation the cysE genes both from wild-type E. coli and the mutant strain were cloned and their nucleotide sequences determined. The cysE gene contained an open reading frame consisting of 819 bp, equivalent to a protein of 273 amino acids. The mutant gene showed a single base change in position 767 resulting in a methionine to isoleucine substitution. A causal connection between this SAT sequence alteration, feedback insensitivity and L-cysteine excretion was demonstrated. The SAT from the wild-type strain was purified. It was composed of a single polypeptide chain migrating in SDS gels according to an Mr of 34,000. As in Salmonella typhimurium, the enzyme was associated in a bifunctional complex with O-acetylserine (thiol)-lyase.
Correction: Contribution of Corticospinal Tract and Functional Connectivity in Hand Motor Impairment after Stroke (2014)

Background: Motor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14).
Novel 2-Phenylimidazo[1,2-a]pyridine Derivatives as Potent and Selective Ligands for Peripheral Benzodiazepine Receptors:  Synthesis, Binding Affinity, and in Vivo Studies (1999)

The substituent effects at positions 6 and 8 (compounds 17-31) as well as at the amide nitrogen (compounds 32-40) of a series of 2-phenylimidazo[1,2-a]pyridineacetamides were evaluated at both central (CBR) and peripheral (PBR) benzodiazepine receptors. The structure-activity relationship studies detailed herein indicate the key structural features required for high affinity and selectivity for PBR. Substitution on the imidazopyridine nucleus at position 8 with lipophilic substituents and the presence of one chlorine atom at the para position of the phenyl ring at C(2) are crucial features for high binding affinity and selectivity toward PBR. A small subset of active ligands (i.e., 17, 20, 26, 34, and 35) were evaluated in vitro in Xenopus oocytes expressing cloned human GABA(A) receptors for their effects at CBR and in vivo for their ability to stimulate the synthesis of neurosteroids such as pregnenolone, progesterone, allopregnanolone, and allotetrahydrodeoxycorticosterone (THDOC). Compounds 17, 20, 26, and 34 markedly increased the levels of neuroactive steroids in plasma and cerebral cortex, unlike compound 35.
Arrhythmogenic right ventricular cardiomyopathy (ARVC): cardiovascular magnetic resonance update (2014)

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is one of the most arrhythmogenic forms of inherited cardiomyopathy and a frequent cause of sudden death in the young. Affected individuals typically present between the second and fourth decade of life with arrhythmias coming from the right ventricle. Pathogenic mutations in genes encoding the cardiac desmosome can be found in approximately 60% of index patients, leading to our current perception of ARVC as a desmosomal disease. Although ARVC is known to preferentially affect the right ventricle, early and/or predominant left ventricular involvement is increasingly recognized. Diagnosis is made by combining multiple sources of diagnostic information as prescribed by the "Task Force" criteria. Recent research suggests that electrical abnormalities precede structural changes in ARVC. Cardiovascular Magnetic Resonance (CMR) is an ideal technique in ARVC workup, as it provides comprehensive information on cardiac morphology, function, and tissue characterization in a single investigation. Prevention of sudden cardiac death using implantable cardioverter-defibrillators is the most important management consideration. This purpose of this paper is to provide an updated review of our understanding of the genetics, diagnosis, current state-of-the-art CMR acquisition and analysis, and management of patients with ARVC.
Bioelectric Control of Metastasis in Solid Tumors (2019)

As the leading cause of death in cancer, there is an urgent need to develop treatments to target the dissemination of primary tumor cells to secondary organs, known as metastasis. Bioelectric signaling has emerged in the last century as an important controller of cell growth, and with the development of current molecular tools we are now beginning to identify its role in driving cell migration and metastasis in a variety of cancer types. This review summarizes the currently available research for bioelectric signaling in solid tumor metastasis. We review the steps of metastasis and discuss how these can be controlled by bioelectric cues at the level of a cell, a population of cells, and the tissue. The role of ion channel, pump, and exchanger activity and ion flux is discussed, along with the importance of the membrane potential and the relationship between ion flux and membrane potential. We also provide an overview of the evidence for control of metastasis by external electric fields (EFs) and draw from examples in embryogenesis and regeneration to discuss the implications for endogenous EFs. By increasing our understanding of the dynamic properties of bioelectric signaling, we can develop new strategies that target metastasis to be translated into the clinic.
31P-NMR analysis of bio-oils obtained from the pyrolysis of biomass (2010)

Background: The use of 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane followed by 31P-NMR analysis has been frequently employed to quantitatively characterize the structure of hydroxyl groups in lignin and, more recently, biodiesel. This technique serves as a valuable tool to determine aliphatic hydroxyls, phenolics and carboxylic acid groups in lignin and aliphatic hydroxyl groups in partially substituted glycerols. Results: This study demonstrates the application of this analytical technique to pyrolysis oils to allow efficient analysis and identification of important functional groups present in bio-oils and the measurement of moisture content. Conclusion: Phosphitylation followed by 31P-NMR analysis was used to show that the moisture content of the loblolly pine bio-oil used in this study was 11.94%. The results also established that the bio-oils obtained from loblolly pine cellulose had higher levoglucosan content than the bio-oil obtained from the starting pine itself. In addition, the total phenolic content of bio-oil derived from loblolly pine milled wood lignin was greater than that obtained from the bio-oil from the loblolly pine cellulose. The data also highlighted the ability to track chemical transitions that take place during pyrolysis using 31P-NMR.
Foot-And-Mouth Disease (1968)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Structure of 5-hydroxymethyl-7,7-dimethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid (1990)

C 11 H 18 O 4 cristallise dans P2 1 /c avec a=6,832, b=14,933, c=11,315, β=106,74°, Z=4; affinement jusqu'a R=0,069. La conformation du cycle a cinq chai←nons est tordue de type torsion, l'axe de symetrie d'ordre 2 etant la bissectrice de la liaison entre les deux atomes C 5 et C 6 , situes hors du plan du cycle. Quant au cycle a six chai←nons, il est dans une conformation chaise, deformee, aplanie en C 3 . Chaque molecule participe a quatre liaisons hydrogene du type OH--O
Rates of Behavior and Aging Specified by Mitochondrial Function During Development (2002)

To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood.
Treatment with Monoclonal Antibodies against Clostridium difficile Toxins (2010)

The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection. (ClinicalTrials.gov number, NCT00350298.)
イロニー考 : トーマス・マンを中心として (2007)

In der vorliegenden Arbeit wird versucht, Betrachtungen über Ironie, vor allem über Thomas Manns Ironie, anhand seiner Werke und Essays anzustellen. Zuerst werden die Bedeutung der Ironie überhaupt und ihre Geschichte kurz beschrieben. Ironie heißt eigentlich eironeia im Griechischen und wird mit dissimulatio, Verstellung, ins Lateinische übersetzt. Sokrates' "Nichtwissen" ist ein typisches Beispiel der klassischen Ironie. Ende des 18. Jahrhunderts entwickelt Friedrich Schlegel die rhetorische Ironie zur sogenannten romantischen Ironie weiter. Schlegel behauptet, dass man in der Mitte schwebend alles übersehen solle. Dieses Verhalten führt zu Thomas Manns Ironie, als deren Merkmale Mitte, Vorbehalt und Abstand zu verstehen sind. Tonio Kröger steht in der Mitte zwischen zwei Polen: Bürger und Künstler, und hält Abstand von beiden. Er behält sich die Entscheidung für einen Pol vor. In der Erzählung wird häufig die Wendung "einerseits A, andererseits B" benutzt: einerseits liebt Tonio seine Mutter, aber andererseits findet er den Zorn seines Vaters würdiger. Darin kann man seinen ironischen Stil erkennen. Als Künstler liebt Tonio das Leben, aber in dieser Liebe steckt immer ein wenig Verachtung. Vor seiner Ehe schreibt Thomas Mann seiner künftigen Frau, Tonios Worte anführend, dass die ironische Liebe sein eigentlichstes Gefühlsgebiet gewesen sei und gesteht, dass er seine ironische Stellung verlasse, um ihre Liebe zu gewinnen. Diese Episode zeigt die Grenze der Ironie. In "Lotte in Weimar" wird Goethe von verschiedenen Personen von verschiedenen Standpunkten aus betrachtet. Sowohl sein Verehrer als auch seine Kritikerin, sein Sekretär und sein Sohn treten auf und sprechen über ihn. Durch diese perspektivischen ironischen Darstellungen versucht der Autor, den großen Dichter in seiner Totalität zu schildern. Thomas Manns ironische Stellung kann man auch z.B. an seinem Verhalten gegenüber den okkulten Sitzungen und Nietzsches Philosophie erkennen. Bei Thomas Mann können Sympathie und Kritik nebeneinander stehen. In "Joseph und seine Brüder" kann Joseph durch sein Wissen um die mythischen Begebenheiten voraussehen, was in Zukunft geschehen wird. Am Ende des Romans gesteht er aber vor seinen Brüdern, es sei sträflich gewesen, dass er zu gut gewusst habe, was da gespielt wurde. Im letzten Abschnitt des Romans "Der Zauberberg" nennt sich der Erzähler, der die jungen Soldaten im Feld schildert, einen schauenden Schatten am Weg und schämt sich seiner ironischen Schattensicherheit. An Thomas Manns Ironie kann Kritik geübt werden: die Ironie ist zwar eine sinnvolle Lebensanschauung, aber im Ernstfall kann man nicht in der Ironie verharren. Aber aus den oben genannten Texten, Thomas Manns Brief an seine Frau, Josephs Geständnis und der Selbstkrititk des Erzählers des "Zauberbergs" kann man begreifen, wie gut Thomas Mann selbst die Probleme der Ironie kennt.
Stable and highly sensitive gas sensors based on semiconducting oxide nanobelts (2002)

Gas sensors have been fabricated using the single-crystalline SnO2 nanobelts. Electrical characterization showed that the contacts were ohmic and the nanobelts were sensitive to environmental polluting species like CO and NO2, as well as to ethanol for breath analyzers and food control applications. The sensor response, defined as the relative variation in conductance due to the introduction of the gas, is 4160% for 250 ppm of ethanol and −1550% for 0.5 ppm NO2 at 400 °C. The results demonstrate the potential of fabricating nanosized sensors using the integrity of a single nanobelt with a sensitivity at the level of a few ppb.
A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal. (1993)

We investigated the association between expression of a novel M(r) 32,000 nuclear phosphoprotein (pp32) and cell proliferation in vivo using the well-characterized physiological model of androgen-dependent regeneration of prostate in orchiectomized rats, pp32 is expressed at high levels in neoplastic cell lines and in certain anatomically defined stem cell compartments of normal human tissues such as intestinal crypt epithelial cells. Immunohistochemistry and in situ hybridization were used to monitor pp32 expression in rat ventral prostatic epithelium following castration and androgen restoration. Castrated rats retained only 6% of prostate wet weight compared to intact controls but were capable of complete gland restoration upon androgen replacement. In intact controls, pp32 expression localized to small acini at the periphery of the gland and to rare basal cells in the central regions. Ten days following castration, there was a 3,5-fold enrichment in the frequency of pp32-positive cells with greater than 56% of remaining epithelial cells expressing pp32 protein. In situ hybridization showed that all remaining epithelial cells contained pp32 mRNA. Upon testosterone replacement, pp32 expression and localization returned to that of intact controls. In order to determine the association between pp32 expression and cell division, DNA synthesis was monitored by bromodeoxyuridine incorporation during prostate involution and regeneration. Bromodeoxyuridine incorporation peaked 3 days after androgen replacement and occurred diffusely throughout the gland. Thus, pp32-positive cells are anatomically distinguishable from the population of terminally differentiating cells undergoing rapid expansion. Preliminary immunohistochemical studies of human prostatic neoplasia demonstrated increased expression of pp32 in human prostatic adenocarcinoma and prostatic intraepithelial neoplasia compared to benign prostatic hypertrophy and normal human prostate. The highest degree of expression occurred in the higher Gleason grades and prostatic intraepithelial neoplasia. This work suggests that pp32 is a nuclear protein which has a selective but presently undefined role in cells competent for self-renewal.
Heparin-Induced Thrombocytopenia (1978)

Two patients with underlying thromboembolic disorders developed severe thrombocytopenia while receiving heparin sodium; one of these patients developed recurrence of the thrombocytopenia and possible heparin-induced pulmonary emboli when heparin was restarted. In a prospective study of patients receiving heparin in a coronary care unit (CCU), nine of 37 patients developed transient mild thrombocytopenia (platelet counts ranging from 88,000 to 150,000/cu mm). Heparin added to citrated platelet-rich plasma caused platelet aggregation in the two original patients. In three of six CCU patients tested, and in 17 of 87 other subjects, with maximum aggregation at concentrations of heparin likely to be present in vivo during therapy. We herein discuss evidence that suggests that heparin may cause or aggravate thrombosis by causing platelet aggregation. The occurrence of severe heparin-induced thrombocytopenia is well documented, and mild transient thrombocytopenia may be more common than has been recognized. Studies of heparin efficacy should take these responses into account.
Nonprecipitating Asymmetric Antibodies (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Comparison of schizotypal relatives of schizophrenic versus affective probands (1994)

In order to investigate possible heterogeneity in schizotypal personality disorder (SPD), two groups of schizotypals, one related to schizophrenic probands (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14), ascertained in the same family study, were compared. The FSPD group had more inadequate rapport; the groups did not differ in the frequency of any other symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher rates of anxiety disorders. There was a higher risk of bipolar disorder in the relatives of NFSPDs and higher risk for anxiety disorders in the relatives of FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and atypical PDs and for having at least one PD.
A low power 13-Gb/s 2^7-1 pseudo random bit sequence generator IC in 120 nm bulk CMOS (2004)

We present a pseudo random bit sequence (PRBS) generator with a sequence length of 2^7-1. The circuit uses a 7 bit full rate shift register with a linear xor feedback and works up to data rates of 13Gb/s. The PRBS generator features a divide by 2 trigger divider, two 3 bit shifted outputs and an auto start logic. The circuit draws 137mA from a single 1.5V supply. The circuit is manufactured in 120nm bulk CMOS technology.