gebhart/patrepeval huggingface dataset:
DNA melting initiates the RAG catalytic pathway. (2018)

The mechanism for initiating DNA cleavage by DDE-family enzymes, including the RAG endonuclease, which initiates V(D)J recombination, is not well understood. Here we report six cryo-EM structures of zebrafish RAG in complex with one or two intact recombination signal sequences (RSSs), at up to 3.9-Å resolution. Unexpectedly, these structures reveal DNA melting at the heptamer of the RSSs, thus resulting in a corkscrew-like rotation of coding-flank DNA and the positioning of the scissile phosphate in the active site. Substrate binding is associated with dimer opening and a piston-like movement in RAG1, first outward to accommodate unmelted DNA and then inward to wedge melted DNA. These precleavage complexes show limited base-specific contacts of RAG at the conserved terminal CAC/GTG sequence of the heptamer, thus suggesting conservation based on a propensity to unwind. CA and TG overwhelmingly dominate terminal sequences in transposons and retrotransposons, thereby implicating a universal mechanism for DNA melting during the initiation of retroviral integration and DNA transposition.
Electrospray ionization mass spectrometric observation of ligand exchange of zinc pyrithione with amino acids (2009)

Zinc pyrithione (ZnPT) is widely used as an antidandruff or antifouling reagent. However, this compound is considered toxic, such as the teratogenic effect, to aquatic lives, and it is important to clarify the mechanism of its toxicity. In this study, the interactions between ZnPT and amino acids were observed using electrospray ionization mass spectrometry (ESI-MS) in order to obtain information on the activity of ZnPT within the living body. The ZnPT complex ([ZnPT-ligand+Amino acid]+), in which the ligand of ZnPT was exchanged by the amino acid, was detected in ZnPT solutions mixed with one of 20 amino acids by ESI-MS. Histidine and cysteine, in particular, showed a high reactivity with ZnPT, while serine and glycine showed a low reactivity. The complexes of ZnPT and a peptide were also observed by the ESI-MS measurement of the solution containing ZnPT with the peptide. These results would be useful to understand the mechanism of ZnPT toxicities to living creatures.
A sustainable model for antibiotics (2015)

How can we foster the development of novel drugs against resistant bacteria? [Also see Perspective by Baker ]
Effects of AMN107, a Novel Aminopyrimidine Tyrosine Kinase Inhibitor, on Human Mast Cells Bearing Wild-Type or Mutated Codon 816 c-kit. (2005)

Abstract Background. Majority of adult patients with systemic mastocytosis (SM) have activating mutation in codon 816 of c-kit (CD117), a receptor on the surface of mast cells. This abnormality is responsible for the pathogenesis of the disease. Methods. We investigated the effects of a newly designed tyrosine kinase inhibitor, AMN107, by comparing its in vitro inhibitory potency on c-kit mutated mast cell lines and patient samples with that of imatinib mesylate, another tyrosine kinase inhibitor, effective in some patients with SM. Two cell lines, subclones of HMC-1 cells, were used: HMC-1560 carrying juxtamembrane domain mutation in codon 560 of c-kit, and HMC-1560, 816 carrying both codon 560 mutation and tyrosine kinase domain mutation in codon 816 of c-kit. Results. In HMC-1560 mast cell line carrying wild-type codon 816, AMN107 was as potent as imatinib in inhibiting cellular proliferation, with IC50 values of 108 and 74 nM respectively, while in HMC-1560, 816 cell line carrying 816 mutation, neither medication had an effect. AMN107 was also as effective as imatinib in inhibiting phosphorylation of c-kit tyrosine kinase in HMC-1560 cells. The inhibition of cellular proliferation was associated with induction of apoptosis in HMC-1560 cells. AMN107 in concentrations up to 1 uM had no effect on bone marrow mast cells carrying D816V c-kit mutation obtained from patients with mastocytosis. Conclusions. Our results suggest similar potency of AMN107 and imatinib in mast cells that carry wild-type codon 816, but no activity against codon 816 mutation carrying cells.
Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin (2006)

Osteoclast motility is thought to depend on rapid podosome assembly and disassembly. Both mu-calpain and m-calpain, which promote the formation and disassembly of focal adhesions, were observed in the podosome belt of osteoclasts. Calpain inhibitors disrupted the podosome belt, blocked the constitutive cleavage of the calpain substrates filamin A, talin, and Pyk2, which are enriched in the podosome belt, induced osteoclast retraction, and reduced osteoclast motility and bone resorption. The motility and resorbing activity of mu-calpain(-/-) osteoclast-like cells were also reduced, indicating that mu-calpain is required for normal osteoclast activity. Histomorphometric analysis of tibias from mu-calpain(-/-) mice revealed increased osteoclast numbers and decreased trabecular bone volume that was apparent at 10 weeks but not at 5 weeks of age. In vitro studies suggested that the increased osteoclast number in the mu-calpain(-/-) bones resulted from increased osteoclast survival, not increased osteoclast formation. Calcitonin disrupted the podosome ring, induced osteoclast retraction, and reduced osteoclast motility and bone resorption in a manner similar to the effects of calpain inhibitors and had no further effect on these parameters when added to osteoclasts pretreated with calpain inhibitors. Calcitonin inhibited the constitutive cleavage of a fluorogenic calpain substrate and transiently blocked the constitutive cleavage of filamin A, talin, and Pyk2 by a protein kinase C-dependent mechanism, demonstrating that calcitonin induces the inhibition of calpain in osteoclasts. These results indicate that calpain activity is required for normal osteoclast activity and suggest that calcitonin inhibits osteoclast bone resorbing activity in part by down-regulating calpain activity.
Katalysierte Dehalogenierungen mit Natriumborhydrid (1968)

Abstract Sodium tetrahydroborate has a poor reduction capacity for the elimination of aromatic halogens. The addition of metal catalysts (in particular Pd, Co, Ni, Cu) accelerates this reaction to such an extent that even the rather stable aromatic chlorine can be exchanged by hydrogen at room temperature. An activity order of catalysts (the best is palladium on charcoal), a reactivity comparison of iodine, bromine and chlorine, and the influence of ortho, meta or para position in halogenobenzoic acids in relation to halogenobenzenes and to several other halogen compounds are given. Two preparative examples are described.
Increased Carbon Monoxide in Exhaled Air of Asthmatic Patients (1997)

Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients receiving or not receiving inhaled corticosteroids and in nonsmoking and smoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids (5.6+/-0.6 ppm, p < 0.001) and similar in asthmatic patients receiving inhaled corticosteroids (1.7+/-0.1 ppm) compared with those in nonsmoking healthy control subjects (1.5+/-0.1 ppm). Smoking healthy control subjects had the highest levels of exhaled CO concentration among the groups (21.6+/-2.8 ppm, p < 0.001). To examine whether inhaling corticosteroids reduce exhaled CO concentration in a given asthmatic patient, 12 patients with symptomatic asthma who were being treated by inhaled beta2-agonists alone underwent measurements of exhaled CO concentration before and 4 wk after the initiation of inhaled corticosteroid treatment. All patients had reductions in exhaled CO concentration (p < 0.001) and eosinophil cell counts in sputum (p < 0.01) that were accompanied by an improvement in airway obstruction. Changes in exhaled CO concentration were significantly related to those in the eosinophil cell counts in sputum (p < 0.001). The present study shows an elevation of exhaled CO in asthmatic patients that decreases with corticosteroid therapy. Increases in the exhaled CO levels therefore may reflect inflammation in the asthmatic lung.
Selective and Homogeneous Fluorescent DNA Detection by Target-Induced Strand Displacement Using Cationic Conjugated Polyelectrolytes (2008)

A new methodology has been developed for DNA detection that interfaces optical amplification properties of cationic conjugated polyelectrolytes with highly selective target-induced DNA strand displacement. The probe solution contains a cationic conjugated polyelectrolyte (CCP-1), partly hybridized duplex DNA labeled with a fluorescein at the 5'-terminus, and endonuclease Hae III. Excitation of the CCP-1 leads to efficient energy transfer from CCP-1 to fluorescein. In the presence of a complementary DNA strand to one strand of the probe duplex, a hairpin DNA with the recognition site of endonuclease Hae at the double-stranded stem is released following its cleavage by Hae III to generate short DNA fragment carrying fluorescein. The relatively weak electrostatic interactions between the DNA fragment and CCP-1 lead fluorescein far away from CCP-1 and inefficient energy transfer between them is present. Thus, the DNA can be detected by fluorescence spectra in view of the observed CCP-1 or fluorescein emission changes in aqueous solutions. To avoid utilizing unstable Hae III endonuclease, a new system based on RNA-cleaving DNAzyme was further developed. The protocol offers a convenient approach for homogeneous, selective, and sensitive DNA assay in aqueous solution without using any denaturation steps. Compared with previously reported DNA sensors based on conjugated polyelectrolytes, our new method is highly sequence specific and a single-nucleotide mismatch can be clearly detected in target DNA.
Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels (2018)

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.<b>SIGNIFICANCE STATEMENT</b> BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD.
Statistical Modeling of Resilient Behavior of Unbound Granular Material (2012)

The resilient behavior of an unbound granular material is a primary input used in the mechanistic analysis of pavements incorporating such layers. Various models exist for the determination of the resilient behavior based on mainly the output of tri-axial laboratory testing. This paper describes an investigation where basic engineering properties such as grading, laboratory compaction characteristics and optimum moisture content are incorporated into the resilient behavior model to quantify the effect of basic material properties on the resilient response of unbound granular materials. Such a resilient behavior model will enable practitioners to estimate behavior material specific, which might enable the use of available quality material that was discarded in the past. Data from tri-axial laboratory tests on materials originating from the Long Term Pavement Performance test sections are combined with basic engineering parameters of typical unbound granular material through a statistical modeling process to develop a model for the prediction of the resilient behavior that can be used as a practical predictor of the expected behavior during Level 2 and/or Level 3 Mechanistic Empirical Pavement Design analysis. The work illustrates the process and the potential to develop a general resilient behavior model for unbound granular materials incorporating saturation effects.
A new look at the modification of polyethylene terephthalate by sodium hydroxide (2009)

Weight reduction is an alkali treatment of polyethylene terephthalate (PET) fabric with the aim of improving drape, handle and touch. The reaction of aqueous alkaline such as sodium hydroxide on PET is reported to be of the topochemical type meaning that the chemical reaction, hydrolysis, is limited to the fibre surface, and alkali does not affect the PET fibre core. Moreover, it is also reported that roughening of the fibre surface is a result of excess PET oligomers on the fibre surface after hydrolysis. New evidence obtained from small and wide angle X-ray scattering, wide angle X-ray scattering and atomic force microscopy reported in this article reveals that the bulk microstructure of PET is indeed affected by the weight reduction process and the roughening of the surface is a result of the new topology formed after weight reduction. A wide range of mechanical properties are measured. The wetting time is reduced from an average of 30 seconds to less than 1 second as a result of weight reduction. It was also found that dimensions of the PET fabrics were not affected by the weight reduction process.
2244 – Maternal Prenatal Anxiety And Epigenetic Modification Glucocorticoid Receptor Gene: The Shaping Of The Biological Stress Response (2013)

Background The methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene. Methods We examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells. Results Univariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p=0.023) during T1. Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) - (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE: 8.9%) in T3. Conclusion These data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.
Design and Baseline Characteristics of the HELP Study: An Extended and Long-Term Observation of Pathological Myopia in Caucasians (2018)

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; To assess the natural disease progression of high myopia in Caucasians considered at risk for the development of myopic choroidal neovascularization (mCNV). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Subjects were recruited in 25 clinical sites between June 2014 and June 2016. Main inclusion criteria included axial length of ≥26 mm, best-corrected visual acuity ≥0.05 decimal equivalent and presence of at least one out of five predefined morphological disease risk criteria. These were (1) subfoveal choroidal thinning &amp;#x3c; 50 µm, (2) enhanced choroidal curvature length &amp;#x3e; 6,300 µm, (3) lacquer cracks, (4) patchy atrophy &amp;#x3e; 5 mm&lt;sup&gt;2&lt;/sup&gt; and (5) preexisting mCNV in the fellow eye (German Clinical Trial Register DRKS00007761). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 150 participants (66% females) with a mean age of 57.2 (±12.7) years (range 21.9–86.2 years) were included. The disease criteria most frequently encountered were choroidal thinning (33.3%) and lacquer cracks (32.7%). Enhanced choroidal curvature length was detected in only 8 subjects and always occurred in combination with other disease criteria. Presence of patchy atrophy was found to be more common in older subjects (&lt;i&gt;p&lt;/i&gt; = 0.0012) and also associated with a more severe disease manifestation. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The baseline data of this study indicate that enhanced choroidal curvature might be less common in Caucasians than in Asian populations. Further, disease severity in patients with high myopia is relatively high in the presence of patchy atrophy.
Optimized Microstrip Ring-Star 5-Ports for Broadband 6-Port Measurement Applications (2005)

Results of computer-aided analysis and optimization of symmetrical 5-port microstrip rings with external matching and inner star coupling are presented. Over one octave operational bandwidth with power balance within 1dB and matching better than -20dB has been achieved in theory and measurement for two different design concepts.
Advanced liquid crystal on silicon optical phased arrays (2003)

Non-mechanical beamsteering eliminates the need for massive optomechanical components to steer the field of view of optical systems. This benefit is to come in the form of compact, low-power, light-weight optical phased arrays (OPAs) that provide better control with greater flexibility in their steering capability than their mechanical counterparts. Due to such benefits, there is a need to develop technologies that provide this capability without greatly sacrificing other parameters such as aperture size, efficiency, and scanning range. One technology being explored for OPA implementation is liquid crystal on silicon (LCoS). The LCoS technology provides a means for manufacturing high-resolution backplanes using high-volume semiconductor processes commonly used for very large scale integrated (VLSI) circuits. VLSI production minimizes the cost of backplane fabrication and allows integration of electronic circuits into the backplane structure to provide individual addressing of each pixel while minimizing interconnects to the OPA. Since each pixel is individually addressed, the phase modulation is not restricted to phase ramps but provides any type of phase profile. This capability is useful for dynamic correction of phase distortions across the aperture due to heating effects, for example. Also, it allows the reset period to be randomized to minimize sidelobe amplitudes. However, VLSI technology has its own set of limitations that have slowed the development of highspeed, high-resolution, non-mechanical beamsteerers having good optical efficiency and a large scanning range. This paper discusses the benefits and limitations of the LCoS approach and methods for improving the state-of-the-art.
XOR retransmission in multicast error recovery (2002)

A growing number of network applications require the use of a reliable multicast protocol to disseminate data from a source to a potentially large number of receivers. We present a new error recovery mechanism, called XOR, which is based on the selective repeat ARQ protocols. The idea is to combine several NACKed packets by XORing them. The analytical and simulative result show that XOR achieves a better throughput than both 'N1' and 'N2' do.
The Magnetic Susceptibilities of Chlorine Trifluoride, Bromine Trifluoride, Bromine Pentafluoride and Iodine Pentafluoride1 (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Magnetic Susceptibilities of Chlorine Trifluoride, Bromine Trifluoride, Bromine Pentafluoride and Iodine Pentafluoride1Max T. Rogers, Morton B. Panish, and John L. SpeirsCite this: J. Am. Chem. Soc. 1955, 77, 20, 5292–5293Publication Date (Print):October 1, 1955Publication History Published online1 May 2002Published inissue 1 October 1955https://doi.org/10.1021/ja01625a026RIGHTS & PERMISSIONSArticle Views26Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (222 KB) Get e-Alerts Get e-Alerts
Handheld diffuse reflectance spectroscopy system for noninvasive quantification of neonatal bilirubin and hemoglobin concentrations: a pilot study (2022)

The prevalence rate of neonatal jaundice can reach 80%, of which 5% may develop dangerous hemolytic jaundice. The blood test for obtaining bilirubin and hemoglobin concentration is the gold standard for diagnosing hemolytic jaundice; however, frequently drawing blood from jaundice neonates for the screening purpose is not practical. We have developed a handheld diffuse reflectance spectroscopy system to noninvasively determine the bilirubin and hemoglobin levels in neonates. Our study showed that the correlation coefficients were 0.95 and 0.80 for bilirubin and hemoglobin between the results from the blood tests and our handheld system, respectively. This handheld system could be an effective tool for screening hemolytic jaundice.