gebhart/patrepeval huggingface dataset:
Proton:  A Major Factor for the Racemization and the Dehydration at the Cyclization/Cleavage Stage in the Edman Sequencing Method (1996)

The racemization of the liberated 7-[(N,N-dimethylamino)sulfonyl]-4-(2,1,3-benzoxadiazolyl)-thiazoli none (DBD-TZ) amino acid during the cyclization/cleavage reaction with trifluoroacetic acid (TFA) in the Edman sequencing procedure has been carefully investigated, and evidence is presented to show conclusively that the racemization is caused by the replacement of a hydrogen atom by TFA. The fluorescent reagent 7-[N,N-dimethylamino)sulfonyl]-4-(2,1,3-benzoxadiazolyl) isothiocyanate (DBD-NCS) was used for amino acid sequencing, and DBD-TZ amino acid was used for sequence and configuration determination. DBD-thiocarbamoylated peptides were cyclized and cleaved with deuterated TFA, and the protonated pseudomolecular ions (M-d1 + H)+ of DBD-TZ amino acids were detected by LC/MS. Furthermore, in the reaction kinetics study, we confirmed that the replacement reaction by TFA correlated sufficiently with the racemization of DBD-TZ amino acids. For the purpose of retaining D/L-amino acid configuration in sequencing, we used an aprotic acid, i.e., the Lewis acid boron trifluoride (BF3), for the cyclization/cleavage reaction. When we used BF3, the derivatized DBD-TZ amino acid was scarcely racemized under cyclization/cleavage conditions. Using this method, amino acid sequencing of D-Phe-Met-Arg-Phe-amide could be performed, retaining the D/L-configuration of the amino acid residues.
Is there a rationale for combined TNF and IL-1 blocking in arthritis? (2004)

TNF and IL-1 are master cytokines in chronic destructive arthritis. Therapeutic approaches have so far focused mainly on TNF which is a major inflammatory mediator in RA and a potent inducer of IL-1. Anti-TNF treatment shows great efficacy in RA patients. However, it is not effective in all patients, nor does it fully control the arthritic process in affected joints of good responders. Although TNF is an early mediator and often crucial in onset of experimental arthritis, studies in rodent models revealed that TNF independent IL-1 production does occur in many arthritic situations. These include direct, innate macrophage activation by phlogistic stimuli, but also immune driven conditions of immune complex and T cell mediated arthritis. If elements of the models apply to the arthritic process in RA patients, it is necessary to block IL-1 in addition to TNF.
A novel concurrent TMS‐fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation (2018)

Major depressive disorder (MDD) is a severe mental disorder associated with high morbidity and mortality rates, which remains difficult to treat, as both resistance and recurrence rates are high. Repetitive transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) provides a safe and effective treatment for selected patients with treatment-resistant MDD. Little is known about the mechanisms of action of TMS provided to the left DLPFC in MDD and we can currently not predict who will respond to this type of treatment, precluding effective patient selection. In order to shed some light on the mechanism of action, we applied single pulse TMS to the left DLPFC in 10 healthy participants using a unique TMS-fMRI set-up, in which we could record the direct effects of TMS. Stimulation of the DLPFC triggered activity in a number of connected brain regions, including the subgenual anterior cingulate cortex (sgACC) in four out of nine participants. The sgACC is of particular interest, because normalization of activity in this region has been associated with relief of depressive symptoms in MDD patients. This is the first direct evidence that TMS pulses delivered to the DLPFC can propagate to the sgACC. The propagation of TMS-induced activity from the DLPFC to sgACC may be an accurate biomarker for rTMS efficacy. Further research is required to determine whether this method can contribute to the selection of patients with treatment resistant MDD who will respond to rTMS treatment.
What is Twitter, a social network or a news media? (2010)

Twitter, a microblogging service less than three years old, commands more than 41 million users as of July 2009 and is growing fast. Twitter users tweet about any topic within the 140-character limit and follow others to receive their tweets. The goal of this paper is to study the topological characteristics of Twitter and its power as a new medium of information sharing.
Mechanism of estrogen activation of c-myc oncogene expression. (1992)

The estrogen receptor complex is a known trans-acting factor that regulates transcription of specific genes through an interaction with a specific estrogen-responsive cis-acting element (ERE). In previous studies we have shown that in estrogen-responsive human breast cancer cells estrogen rapidly activates c-myc expression. This activated expression occurs through enhanced transcription and does not require the synthesis of new protein intermediates; therefore, an ERE is present in the human c-myc gene regulatory region. To localize the ERE, constructs containing varying lengths of the c-myc 5'-flanking region ranging from -2327 to +25 (relative to the P1 promoter) placed adjacent to the chloramphenicol acetyl transferase reporter gene (CAT) were prepared. They were used in transient transfection studies in MCF-7 and HeLa cells co-transfected with an estrogen receptor expression vector. These studies reveal that all constructs containing the P2 promoter region exhibited estrogen-regulated CAT expression and that a 116-bp region upstream and encompassing the P2 TATA box is necessary for this activity. Analysis of this 116-bp region failed to identify a cis-acting element with sequences resembling the consensus ERE; however, co-transfection studies with mutant estrogen receptor expression vectors showed that the DNA-binding domain of the receptor is essential for estrogen-regulated CAT gene expression. We have also observed that anti-estrogen receptor complexes can weakly trans-activate from this 116-bp region but fail to do so from the ERE-containing ApoVLDLII-CAT construct. To explain these results we propose a new mechanism of estrogen trans-activation in the c-myc gene promoter.
In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord (2002)

Stem cells isolated from the fourth ventricle and spinal cord form neurospheres in vitro in response to basic fibroblast growth factor (FGF2)+heparin (H) or epidermal growth factor (EGF)+FGF2 together. To determine whether these growth factor conditions are sufficient to induce stem cells within the fourth ventricle and spinal cord to proliferate and expand their progeny in vivo, we infused EGF and FGF2, alone or together, with or without H, into the fourth ventricle for 6 days via osmotic minipumps. Animals were injected with bromodeoxyuridine (BrdU) on days 4, 5 and 6 of infusion in order to label cells proliferating in response to the growth factors. Infusions of EGF+FGF2+H into the fourth ventricle resulted in the largest proliferative effect, a 10.8-fold increase in the number of BrdU+ cells around the fourth ventricle, and a 33.5-fold increase in the number of BrdU+ cells around the central canal of the spinal cord, as compared to vehicle infused controls. The majority of the cells were nestin+ after 6 days of infusion. Seven weeks post-infusion, 22 and 30% of the number of BrdU+ cells induced to proliferate after 6 days of EGF+FGF2+H infusions were still detected around the fourth ventricle and central canal of the spinal cord, respectively. Analysis of the fates of the remaining cells showed that a small percentage of BrdU+ cells around the fourth ventricle and in the white matter of the spinal cord differentiated into astrocytes and oligodendrocytes. BrdU+ neurons were not found in the brainstem or in the grey matter of the cervical spinal cord 7 weeks post-infusion. These results show that endogenous stem cells and progenitors around the fourth ventricle and central canal of the spinal cord proliferate in response to exogenously applied growth factors, but unlike in the lateral ventricle where they generate some new neurons, they only produce new astrocytes and oligodendrocytes at 7 weeks post-infusion.
Differential priming of RNA templates during cDNA synthesis markedly affects both accuracy and reproducibility of quantitative competitive reverse-transcriptase PCR (1999)

Quantitative competitive reverse-transcriptase PCR is the most sensitive method for studying gene expression. To investigate whether the accuracy of the calculated target mRNA copy number is affected by the cDNA priming process, we utilized primers of different lengths, concentrations and primer sequences to prime cDNA synthesis reactions. Our results show a ≈ 19-fold increase in the calculated mRNA copy number from cDNA synthesis reactions primed with random hexamers (P< 0.001, n = 4), and a ≈ 4-fold increase in copy number with a specific hexamer (P< 0.001, n = 4) compared with that obtained with a 22-mer-sequence-specific primer. The increase in calculated mRNA copy number obtained by priming cDNA synthesis with the shorter specific and non-specific primers could be explained largely by the synthesis of truncated standard cDNA molecules lacking a requisite binding site for amplification with PCR primers. Since these truncated standard cDNA molecules could not be amplified and standard RNA is used to quantify target mRNA copy number, this phenomenon resulted in overestimation of target mRNA copy number. In conclusion, accurate determination of target mRNA copy number is most likely if a long specific antisense primer is used to prime cDNA synthesis.
A technique to build a secret key in integrated circuits for identification and authentication applications (2004)

This paper describes a technique that exploits the statistical delay variations of wires and transistors across ICs to build a secret key unique to each IC. To explore its feasibility, we fabricated a candidate circuit to generate a response based on its delay characteristics. We show that there exists enough delay variation across ICs implementing, the proposed circuit to identify individual ICs. Further. the circuit, functions reliably over a practical range of environmental variation such as temperature and voltage.
Asymmetric Synthesis of Helical Poly(quinoxaline-2,3-diyl)s by Palladium-Mediated Polymerization of 1,2-Diisocyanobenzenes:  Effective Control of the Screw-Sense by a Binaphthyl Group at the Chain-End (1998)

Aromatizing polymerization of 1,2-diisocyanobenzene derivatives was mediated by optically active organopalladium(II) complexes bearing 1,1‘-binaphth-2-yl groups to give optically active poly(quinoxaline-2,3-diyl)s with varying screw-sense selectivities, which crucially depended upon the substituents on the binaphthyl groups. The most effective catalyst, which has 7‘-methoxy-1,1‘-binaphthyl group, induced the formation of a single screw-sense. Isolation and structural analyses (single-crystal X-ray diffraction and 1H NMR spectroscopy) of intermediary [oligo(quinoxalinyl)]palladium complexes revealed that the screw-sense selection in the polymerization may be decisively governed by the diastereomeric ratios of the (terquinoxalinyl)palladium(II) complex intermediate.
Streptolysin O:  A Proposed Model of Allosteric Interaction between a Pore-Forming Protein and Its Target Lipid Bilayer (1998)

Streptolysin O, a polypeptide of 571 amino acids, belongs to the family of thiol-activated toxins that permeabilize animal cell membranes. The protein binds as a monomer to membrane cholesterol. Binding involves a conserved region close to the C-terminus and triggers subsequent polymerization into large arc- and ring-shaped structures surrounding pores of up to 30 nm. Besides the C-terminus, a distantly located region spanning residues 213-305 is involved in oligomerization and in membrane insertion. Here, we searched for conformational effects of monomer binding to the latter functionally important region. To this end, single cysteine substitution mutants were produced and derivatized with the polarity-sensitive fluorophore acrylodan. Fluorimetric measurements revealed that binding of the monomer to membranes is accompanied by distinct environmental changes at amino acid residues 218, 248, 266, and 277. Conspicuously, the environment of residues 218 and 266 became more hydrophilic, suggesting movement of these residues out of hydrophobic protein pockets. Upon oligomerization, further alterations in all side-chain environments were observed. The membrane-bound monomer thus differs in conformation from both the monomer in solution and the subunit of the oligomer. The putative binding site of the molecule is linked to remote domains involved in oligomerization and membrane insertion in an apparently allosteric fashion. It is proposed that allostery is responsible for restricting oligomerization to the membrane-bound state of the toxin.
Synthesis and antiviral activity of certain 9-.beta.-D-ribofuranosylpurine-6-carboxamides (1981)

To examine the structural parameters necessary for antiviral efficacy of certain purine nucleosides, several 9-beta-D-ribofuranosylpurine-6-carboxamides have been synthesized. Glycosylation of the Me3Si derivative of purine--6-carboxamide with protected ribofuranose in the presence of a Lewis acid gave the blocked nucleoside which on deprotection furnished 9-beta-D-ribofuranosyl-6-iodopurine with cyanide ion. Certain 2-amino- and 2-methyl-9-beta-D-ribofuranosylpurine-6-carboxamides have also been prepared. 8-Carbamoylguanosine (16) has been prepared by homolytic acylation of the parent nucleoside. These compounds were tested against several RNA and DNA viruses in cell culture. 9-beta-D-Ribofuranosylpurine-6-carboxamide (6a), the corresponding 6-thiocarboxamide (7b), and 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (8) showed significant in vitro antiviral activity at nontoxic dosage levels. 6a employed in the treatment of Rift Valley fever virus infected mice at 50 (mg/kg)/day gave a 55% survival rate on day 21 compared to a 30% survival in the controls.
Quorum sensing, communication and cross-kingdom signalling in the bacterial world (2007)

Although unicellular, bacteria are highly interactive and employ a range of cell-to-cell communication or 'quorum sensing (QS)' systems for promoting collective behaviour within a population. QS is generally considered to facilitate gene expression only when the population has reached a sufficient cell density and depends on the synthesis of small molecules that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of QS signal molecules and consequently, their concentration in the external environment increases. Once a critical threshold concentration is reached, a target sensor kinase or response regulator is activated, so facilitating the expression of QS-dependent target genes. Several chemically distinct families of QS signal molecules have been described, of which the N-acylhomoserine lactone (AHL) family in Gram-negative bacteria have been the most intensively investigated. QS contributes to environmental adaptation by facilitating the elaboration of virulence determinants in pathogenic species and plant biocontrol characteristics in beneficial species as well as directing biofilm formation and colony escape. QS also crosses the prokaryotic-eukaryotic boundary in that QS signal molecules influence the behaviour of eukaryotic organisms in both the plant and mammalian worlds such that QS signal molecules may directly facilitate bacterial survival by promoting an advantageous lifestyle within a given environmental niche.
Serum Interleukin-2, Interleukin-6, Tumour Necrosis Factor-Alpha and Nitric Oxide Levels in Patients With Behçet’s Disease (2004)

Our results suggest that elevated levels of IL-2, IL-6, TNF-alpha, and nitric oxide in Behcet's disease appear to be related to the disease.
Design Study of Low-Speed Direct-Driven Permanent-Magnet Motors with Concentrated Windings (2005)

Abstract— In this study, different designs of radial-flux direct-driven permanent magnet (PM) motors are compared. They should replace an induction motor and its gearbox for an industrial application requiring 5 kW and 50 rpm. The goal is to show if the use of concentrated windings brings some benefits for this application, the PM motors having a high number of poles. Different combinations of the number of slots and number of poles are investigated for the concentrated windings designs. Neodymium Iron Boron PM and ferrite PM are tested and the cost of the different machines is estimated. 1. INTRODUCTION Replacing induction machines with permanent magnet (PM) synchronous machines has recently gained great interest, as the environmental concern increases worldwide and the price of PM materials decreases. For low speed applications, using PM machines may further eliminate the need of a gearbox, which is traditionally coupled to a standard induction machine. Since the gearbox is costly, decreases the efficiency of the drive, and needs maintenance, a direct-driven PM machine is an attractive solution that can compete with the induction motor and the gearbox. Direct-driven PM machines are nowadays mostly used for boat propulsion, wind turbines and elevators [1]. In the present paper, the industrial application is a mixer used in wastewater treatment plants, which requires 5 kW and a rated speed of 50 rpm. Since the speed is very low, the machines are lighter when they have a high number of poles. Different radial-flux PM machines with high pole number, distributed windings, and different PM positions in the rotor were investigated in [2]. The present study shows how concentrated windings can improve the designs of high pole number direct-driven PM machines. The advantages and drawbacks of the concentrated windings are well known when the number of poles is under 30 [3], [4]. With a higher number of poles, the possibilities in the design of permanent magnet machines with concentrated windings are wider. Especially there are many more combinations of number of slots and number of poles to choose between. The choice of the number of poles and number of slots of the investigated designs is therefore justified in detailed. Designs with surface mounted and buried PM magnets with different concentrated windings are compared using results from finite element methods (FEM) simulations. The cost of the active material of different designs is also given and different PM materials are investigated. The benefits that bring the use of concentrated windings in the direct-driven PM machines are emphasized.
Fluoroscopy based accuracy assessment of electromagnetic tracking (2006)

Tracking organ motion due to respiration is important to enable precise interventions in the regions of the abdomen and thorax. Respiratory induced motion in these regions may limit the accuracy of interventions which do not employ some type of tracking. One method of tracking organ motion is to use a predictive model based on external tracking that is correlated to internal motion. This approach depends on the accuracy of the model used for correlating the two motions. Ideally, one would track the internal motion directly. We are investigating the use of electromagnetically tracked fiducials to enable real-time tracking of internal organ motion. To investigate the in-vivo accuracy of this approach we propose to use stereo-fluoroscopy. In this paper we show that stereo-fluoroscopy is accurate enough to serve as a validation method, displaying sub-millimetric accuracy (maximal error of 0.66mm). We study the effect of the bi-plane fluoroscopes on the electromagnetic systems' accuracy, and show that placing the bi-plane fluoroscopes in a typical intra-operative setup has a negligible effect on the tracking accuracy (maximal error of 1.4mm). Finally, we compare the results of stereo-fluoroscopy tracking and electromagnetic tracking of needles in an animal study, showing a mean (std) difference of 1.4 (1.5)mm between modalities. These results show that stereo-fluoroscopy can be used in conjunction with electromagnetic tracking with minimal effect, and that the electromagnetic system is accurate enough for motion tracking of internal organs.
Superparamagnetic Sub-5 nm Fe@C Nanoparticles: Isolation, Structure, Magnetic Properties, and Directed Assembly (2008)

A method for isolating single crystalline sub-5 nm carbon coated iron nanoparticles (Fe@C NPs) from a carbon nanotube matrix has been developed. The isolation of such particles allows for their characterization by high resolution electron microscopy methods and SQUID magnetometry. While the NPs are superparamagnetic at room temperature, at 10 K they exhibit a coercivity nearly 30 times greater than that of commercial Fe3O4 NPs of comparable size. A novel nanotemplate directed assembly method for manipulating the particles at the individual particle level is also reported.
In vitro degradation of thin poly(DL-lactic-co-glycolic acid) films (1999)

This study was designed to investigate the in vitro degradation of thin poly(DL-lactic-co-glycolic acid) (PLGA) films for applications in retinal pigment epithelium transplantation and guided tissue regeneration. PLGA films of copolymer ratios of 75:25 and 50:50 were manufactured with thickness levels of 10 microm (thin) and 100 microm (thick). Degradation of the films occurred during sample processing, and thin films with a higher surface area to volume ratio degraded faster. Sample weight loss, molecular weight loss, dimensional, and morphological changes were analyzed over a 10-week period of degradation in 0.2 M of phosphate-buffered saline (PBS), pH 7.4, at 37 degrees C. All PLGA films degraded by heterogeneous bulk degradation. Sample weights remained relatively constant for the first several weeks and then decreased dramatically. The molecular weights of PLGA films decreased immediately upon placement in PBS and continued to decrease throughout the time course. PLGA 50:50 films degraded faster than 75:25 films due to their higher content of hydrophilic glycolic units. The results also demonstrated that thick films degrade faster than corresponding thin films with the same composition. This was attributed to the greater extent of the autocatalytic effect, which further was confirmed by heterogeneous gel permeation chromatograms. These studies suggest that the degradation rate of thin films can be engineered by varying film thicknesses.